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Tang J, Fang X, Feng J, Liu Y, Yu J, Fu H, Su T, Feng Y, Zhao L. Case Report: Multiple Autoimmune Syndrome-A Multidisciplinary Clinical Approach to a Spectrum of Organ Involvement. Int J Rheum Dis 2025; 28:e70027. [PMID: 39912263 DOI: 10.1111/1756-185x.70027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 11/19/2024] [Accepted: 12/16/2024] [Indexed: 02/07/2025]
Affiliation(s)
- Jia Tang
- Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Xiucai Fang
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Jun Feng
- Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Yingxian Liu
- Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Jie Yu
- Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Hanhui Fu
- Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Tong Su
- Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Yunlu Feng
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Lidan Zhao
- Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Ahn SH, Halgren K, Grzesiak G, MacRenaris KW, Sue A, Xie H, Demireva E, O'Halloran TV, Petroff MG. Autoimmune regulator deficiency causes sterile epididymitis and impacts male fertility through disruption of inorganic physiology. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2025:2025.01.11.632558. [PMID: 39868100 PMCID: PMC11761525 DOI: 10.1101/2025.01.11.632558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/28/2025]
Abstract
Autoimmune regulator (AIRE), a transcription factor expressed by medullary thymic epithelial cells, is required for shaping the self-antigen tolerant T cell receptor repertoire. Humans with mutations in AIRE suffer from Autoimmune Polyglandular Syndrome Type 1 (APS-1). Among many symptoms, men with APS-1 commonly experience testicular insufficiency and infertility, but the mechanisms causing infertility are unknown. Using an Aire -deficient mouse model, we demonstrate that male subfertility is caused by sterile epididymitis characterized by immune cell infiltration and extensive fibrosis. In addition, we reveal that the presence of autoreactive immune cells and inflammation in epididymides of Aire- deficient mice are required for iron (Fe) deposition in the interstitium, which is brought on by macrophages. We further demonstrate that male subfertility is associated with a decrease in metals zinc (Zn), copper (Cu), and selenium (Se) which serve as cofactors in several antioxidant enzymes. We also show increase in DNA damage of epididymal sperm of Aire -/- animals as a key contributing factor to subfertility. The absence of Aire results in autoimmune attack of the epididymis leading to fibrosis, Fe deposition, and Cu, Zn and Se imbalance, ultimately resulting in sperm DNA damage and subfertility. These results highlight the requirement of Aire to promote immune tolerance throughout the epididymis, disruption of which causes an imbalance of inorganic elements with resulting consequence on male fertility. Key points Breakdown of epididymal self-tolerance promotes disruption of inorganic elements. Autoimmunity causes interstitial fibrosis resulting in sperm DNA damage and subfertility. Elevated interstitial iron and macrophages contribute to fibrosis.
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Yang Y, Jiang H, Yang W, Wang H, Wang M, Li X, Huang P, Fang S, Hao W, Yang Y, Zhao F, He W. The IVIG treatment response in autoimmune polyendocrine syndromes type 2 with anti-GAD65 antibody-associated stiff person syndrome: a case report and literature review. Front Immunol 2025; 15:1471115. [PMID: 39840065 PMCID: PMC11746041 DOI: 10.3389/fimmu.2024.1471115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 12/12/2024] [Indexed: 01/23/2025] Open
Abstract
Autoimmune polyendocrine syndromes (APS) is a rare group of disorders caused by impaired function of multiple endocrine glands due to disruption of immune tolerance. Of which, type 2 (APS-2) is the most common. Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA). Anti-GAD antibodies are associated with various neurological disorders, including stiff person syndrome (SPS). SPS is characterized by axial muscle stiffness, rigidity, and intermittent painful muscle spasms, with a prevalence of one to two in a million, making it an extremely rare neurological disorder. The comorbidity of APS-2 with SPS is even rarer. Most practicing neurologists encounter only one or two cases of APS-2 combined with anti-GAD65 antibody-associated SPS in their careers, resulting in underdiagnosis and undertreatment, leading to severe disability and suffering. This case report describes a young male who initially exhibited hair loss, vitiligo, and previously unreported eosinophilia. Before his diagnosis, he was admitted multiple times, with symptoms improving following the addition of intravenous immunoglobulin (IVIG) therapy to a poor treatment regimen. This paper aims to increase physicians' awareness of this condition, enhancing the likelihood of early diagnosis and treatment.
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Affiliation(s)
- Yulong Yang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
| | - Hailin Jiang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
| | - Wenming Yang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
- Key Laboratory of Xin’An Medicine, Ministry of Education Hefei, Anhui, China
- Center for Xin’an Medicine and Modernization of Traditional Chinese Medicine, Institute of Health and Medicine Hefei Comprehensive National Science Center, Hefei, Anhui, China
| | - Han Wang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
- Key Laboratory of Xin’An Medicine, Ministry of Education Hefei, Anhui, China
| | - Meixia Wang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
- Key Laboratory of Xin’An Medicine, Ministry of Education Hefei, Anhui, China
| | - Xiang Li
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
| | - Peng Huang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
| | - Shuzhen Fang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
| | - Wenjie Hao
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
| | - Yue Yang
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
| | - Furong Zhao
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
| | - Wei He
- Department of Neurology, The First Affiliated Hospital of Anhui University of Traditional, Chinese Medicine, Hefei, Anhui, China
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Sieber‐Ruckstuhl NS, Riond B, Fracassi F, Kuemmerle‐Fraune C, Meunier S, Hofmann‐Lehmann R, Reusch CE, Mueller C, Hofer‐Inteeworn N, Boretti FS. Longitudinal assessment of thyroid function in dogs with hypoadrenocorticism: Clinical outcomes and prevalence of autoantibodies. J Vet Intern Med 2025; 39:e17232. [PMID: 39531378 PMCID: PMC11627518 DOI: 10.1111/jvim.17232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 10/07/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Knowledge about primary hypoadrenocorticism coexisting with immune-mediated thyroiditis (Schmidt's syndrome) in dogs is limited. OBJECTIVE To evaluate thyroid function in dogs with naturally occurring hypoadrenocorticism before and during treatment. ANIMALS Sixty-six client-owned dogs. METHODS Measurement of canine thyroid stimulating hormone (cTSH), total thyroxine (T4), free thyroxine, and autoantibodies against thyroglobulin, T4, and total triiodothyronine. RESULTS Thirty-eight dogs were assessed before and 28 during treatment. Follow-up data were available for 24/38 and 17/28 dogs, with median follow-up duration of 3.8 years (range, <1.0-8.8 years) and 4 years (range, 1.1 weeks to 10.5 years), respectively. Canine thyroid stimulating hormone was above the reference range at the time of diagnosis of hypoadrenocorticism in 10 of 38 dogs but decreased into the reference range in 7 for which follow-up data was available. Hypothyroidism was confirmed in 5 dogs at a median age of 11 years (range, 7-15 years). In 4 dogs, the condition was diagnosed after a median treatment duration of 5.75 years (range, 2.6-10 years), while in 1 dog, the diagnosis was made concurrently. One dog had detectable thyroid autoantibodies. CONCLUSIONS AND CLINICAL RELEVANCE Hypothyroidism occurs as a rare concurrent condition in dogs with hypoadrenocorticism, potentially at any phase of treatment. Close monitoring of cTSH levels in these dogs could be beneficial, as early changes might indicate the onset of hypothyroidism. The low prevalence of detectable thyroid autoantibodies suggests that nonimmune mechanisms might contribute to thyroid dysfunction.
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Affiliation(s)
| | - Barbara Riond
- Clinical Laboratory, Vetsuisse FacultyUniversity of ZurichZurichSwitzerland
| | - Federico Fracassi
- Department of Veterinary Medical SciencesUniversity of BolognaBolognaItaly
| | - Claudia Kuemmerle‐Fraune
- Clinic for Small Animal Internal Medicine, Vetsuisse FacultyUniversity of ZurichZurichSwitzerland
| | - Solène Meunier
- Clinic for Small Animal Internal Medicine, Vetsuisse FacultyUniversity of ZurichZurichSwitzerland
| | | | - Claudia E. Reusch
- Clinic for Small Animal Internal Medicine, Vetsuisse FacultyUniversity of ZurichZurichSwitzerland
| | - Claudia Mueller
- Clinic for Small Animal Internal Medicine, Vetsuisse FacultyUniversity of ZurichZurichSwitzerland
| | - Natalie Hofer‐Inteeworn
- Clinic for Small Animal Internal Medicine, Vetsuisse FacultyUniversity of ZurichZurichSwitzerland
| | - Felicitas S. Boretti
- Clinic for Small Animal Internal Medicine, Vetsuisse FacultyUniversity of ZurichZurichSwitzerland
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ElSayed NA, McCoy RG, Aleppo G, Bajaj M, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Cusi K, Echouffo-Tcheugui JB, Ekhlaspour L, Fleming TK, Garg R, Khunti K, Lal R, Levin SR, Lingvay I, Matfin G, Napoli N, Pandya N, Parish SJ, Pekas EJ, Pilla SJ, Pirih FQ, Polsky S, Segal AR, Jeffrie Seley J, Stanton RC, Verduzco-Gutierrez M, Younossi ZM, Bannuru RR. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S59-S85. [PMID: 39651988 PMCID: PMC11635044 DOI: 10.2337/dc25-s004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
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Huang X, Chen Y, Huang X, Tang J. Case report: management of a young male patient with diabetic ketoacidosis and thyroid storm. Front Endocrinol (Lausanne) 2024; 15:1403893. [PMID: 38952386 PMCID: PMC11215015 DOI: 10.3389/fendo.2024.1403893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 05/23/2024] [Indexed: 07/03/2024] Open
Abstract
This report describes a case of concomitant diabetic ketoacidosis (DKA) and thyroid storm (TS) in a 20-year-old male patient that presented both diagnostic and management challenges owing to their intricate interrelationship in endocrine-metabolic disorders. The patient, previously diagnosed with type 1 diabetes mellitus (T1DM) and hyperthyroidism, was admitted to the emergency department with symptoms of DKA and progressive exacerbation of TS. Initial treatment focused on correcting DKA; as the disease progressed to TS, it was promptly recognized and treated. This case emphasizes the rarity of simultaneous occurrence of DKA and TS, as well as the challenges in clinical diagnosis posed by the interacting pathophysiological processes and overlapping clinical manifestations of DKA and TS. The patient's treatment process involved multiple disciplines, and after treatment, the patient's critical condition of both endocrine metabolic diseases was alleviated, after which he recovered and was eventually discharged from the hospital. This case report aims to emphasize the need for heightened awareness in patients with complex clinical presentations, stress the possibility of concurrent complications, and underscore the importance of prompt and collaborative treatment strategies.
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Affiliation(s)
- Xiaoyu Huang
- Emergency & Disaster Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yan Chen
- Department of Endocrinology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xinwei Huang
- Department of Endocrinology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Jiahao Tang
- Department of Endocrinology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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Murata Y, Haneda M, Miyakawa N, Nishida S, Kajihara N, Maeda S, Ono K, Hanatani S, Igata M, Takaki Y, Motoshima H, Kishikawa H, Araki E. Autoimmune Polyglandular Syndrome Type 3 Complicated with IgG4-related Disease. Intern Med 2024; 63:425-431. [PMID: 37344441 PMCID: PMC10901709 DOI: 10.2169/internalmedicine.1270-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/23/2023] Open
Abstract
A 52-year-old Japanese woman developed type 1 diabetes mellitus (type 1 DM) at 41 years old. She became complicated with Hashimoto's disease and showed swelling of both submandibular glands, which was diagnosed as IgG4-related disease (IgG4-RD). This is a rare case of a Japanese patient with autoimmune polyglandular syndrome type 3A (APS-3A) coexisting with autoimmune thyroid disease (AITD) and type 1 DM complicated by IgG4-RD. Bilateral submandibular gland resection was successfully performed without steroid therapy. We discuss the possibility that the immunological pathogenic mechanisms of APS-3A and IgG4-RD are related.
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Affiliation(s)
- Yusuke Murata
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Masaki Haneda
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Nobukazu Miyakawa
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Saiko Nishida
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Nobuhiro Kajihara
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Sarie Maeda
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Kaoru Ono
- Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Japan
| | - Satoko Hanatani
- Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Japan
| | - Motoyuki Igata
- Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Japan
| | | | | | | | - Eiichi Araki
- Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Japan
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Pallotta DP, Granito A, Raiteri A, Boe M, Pratelli A, Giamperoli A, Monaco G, Faggiano C, Tovoli F. Autoimmune Polyendocrine Syndromes in Adult Italian Celiac Disease Patients. J Clin Med 2024; 13:488. [PMID: 38256623 PMCID: PMC10815968 DOI: 10.3390/jcm13020488] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 01/10/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
Celiac disease (CD) is frequently associated with other autoimmune disorders. Different studies have explored the association between CD and single autoimmune endocrine disease (AED), especially autoimmune thyroiditis (AIT) and type-1 diabetes mellitus (T1DM). Data about CD as a component of autoimmune polyendocrine syndrome (APS) are scant. We analyzed a large dataset including prospectively collected data from 920 consecutive adult CD patients diagnosed in a third-level Italian institution in the 2013-2023 period, The prevalence of isolated autoimmune endocrine diseases and APS were collected. A total of 262 (28.5%) CD patients had at least one associated AED, with AIT (n = 223, 24.2%) and T1DM (n = 27, 2.9%) being the most frequent conditions. In most cases (n = 173, 66%), AEDs were diagnosed after CD. Thirteen patients (1.4%) had at least two of the requested three endocrinopathies, satisfying the diagnosis of type 2 APS. APS-2 is a rare but not exceptional occurrence among Italian CD patients, underscoring the intricate and multifaceted nature of autoimmune disorders. Periodic evaluations of thyroid function and glycaemia should be recommended after the diagnosis of CD together with testing for autoantibodies that may be helpful in assessing disease risk before disease onset. Likewise, implementation of a systematic screening for CD amongst T1DM and other autoimmune endocrine diseases are paramount.
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Affiliation(s)
- Dante Pio Pallotta
- Unit of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.P.P.); (A.R.); (M.B.); (A.P.); (A.G.); (G.M.); (C.F.); (F.T.)
| | - Alessandro Granito
- Unit of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.P.P.); (A.R.); (M.B.); (A.P.); (A.G.); (G.M.); (C.F.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Alberto Raiteri
- Unit of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.P.P.); (A.R.); (M.B.); (A.P.); (A.G.); (G.M.); (C.F.); (F.T.)
| | - Maria Boe
- Unit of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.P.P.); (A.R.); (M.B.); (A.P.); (A.G.); (G.M.); (C.F.); (F.T.)
| | - Agnese Pratelli
- Unit of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.P.P.); (A.R.); (M.B.); (A.P.); (A.G.); (G.M.); (C.F.); (F.T.)
| | - Alice Giamperoli
- Unit of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.P.P.); (A.R.); (M.B.); (A.P.); (A.G.); (G.M.); (C.F.); (F.T.)
| | - Giovanni Monaco
- Unit of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.P.P.); (A.R.); (M.B.); (A.P.); (A.G.); (G.M.); (C.F.); (F.T.)
| | - Chiara Faggiano
- Unit of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.P.P.); (A.R.); (M.B.); (A.P.); (A.G.); (G.M.); (C.F.); (F.T.)
| | - Francesco Tovoli
- Unit of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (D.P.P.); (A.R.); (M.B.); (A.P.); (A.G.); (G.M.); (C.F.); (F.T.)
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
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ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Cusi K, Ekhlaspour L, Fleming TK, Hilliard ME, Johnson EL, Khunti K, Lingvay I, Matfin G, McCoy RG, Napoli N, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Stanton RC, Verduzco-Gutierrez M, Younossi ZM, Gabbay RA. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S52-S76. [PMID: 38078591 PMCID: PMC10725809 DOI: 10.2337/dc24-s004] [Citation(s) in RCA: 45] [Impact Index Per Article: 45.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Slouma M, Hannech E, Gharsallah I. Hypoparathyroidism: Musculoskeletal Manifestations Related to Parathormone Deficiency. Curr Rheumatol Rev 2024; 20:488-500. [PMID: 38279727 DOI: 10.2174/0115733971267895231227102539] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 11/01/2023] [Accepted: 11/08/2023] [Indexed: 01/28/2024]
Abstract
BACKGROUND Hypoparathyroidism is a rare metabolic disorder that can be responsible for musculoskeletal manifestations. AIM We present a systematic review of musculoskeletal manifestations of adult-onset nonsurgical nongenetic hypoparathyroidism. METHODS A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the MEDLINE database, including manuscripts describing musculoskeletal manifestations of adult-onset nonsurgical nongenetic hypoparathyroidism. RESULTS Musculoskeletal manifestations included myopathy, shoulder disorder, immune-negative non-erosive peripheral arthritis, axial involvement simulating spondylarthritis, and diffuse ligamentous ossifications. An association between hypoparathyroidism and spondyloarthritis or autoimmune diseases is possible. T-cell activation, seen in patients with hypoparathyroidism, may explain the co-occurrence of hypoparathyroidism with other autoimmune diseases. The treatment of these manifestations is based on calcium and active vitamin D supplementation. Parathyroid hormone may have an anabolic effect on muscle atrophy and muscle weakness. Parathyroid hormone can also promote bone formation and bone resorption by stimulating osteoclast differentiation by increasing RANKL (receptor activator for nuclear factor kappa-B ligand) expression. Therefore, hypoparathyroidism can be responsible for an increase in bone mineral density. However, the risk of fractures does not appear to be reduced due to changes in bone microarchitecture and the high risk of falls. Treatment with parathyroid hormone has been shown to improve bone microarchitecture. CONCLUSION Our review showed that musculoskeletal manifestations are frequent in patients with hypoparathyroidism, including muscular, axial, peripheral articular, and entheseal manifestations.
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Affiliation(s)
- Maroua Slouma
- Department of Rheumatology Military Hospital, El Manar University of Tunis, Tunis, Tunisia
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
| | - Emna Hannech
- Department of Rheumatology Military Hospital, El Manar University of Tunis, Tunis, Tunisia
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
| | - Imen Gharsallah
- Department of Rheumatology Military Hospital, El Manar University of Tunis, Tunis, Tunisia
- Faculty of Medicine of Tunis, Tunis El Manar University, Tunisia
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Øksnes M, Husebye ES. Approach to the Patient: Diagnosis of Primary Adrenal Insufficiency in Adults. J Clin Endocrinol Metab 2023; 109:269-278. [PMID: 37450570 PMCID: PMC10735307 DOI: 10.1210/clinem/dgad402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 06/28/2023] [Accepted: 07/05/2023] [Indexed: 07/18/2023]
Affiliation(s)
- Marianne Øksnes
- Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway
- Department of Medicine Haukeland, University Hospital, N-5021 Bergen, Norway
| | - Eystein S Husebye
- Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway
- Department of Medicine Haukeland, University Hospital, N-5021 Bergen, Norway
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Sapana T, Li W, Tian F, Yan W, Dou B, Hua S, Zhuo Z. A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review. Front Immunol 2023; 14:1274672. [PMID: 38077387 PMCID: PMC10703372 DOI: 10.3389/fimmu.2023.1274672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 10/30/2023] [Indexed: 12/18/2023] Open
Abstract
Background Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extra limbic encephalitis. While there are few case reports and research on anti-GAD65 antibody-associated encephalitis in adults, such cases are extremely rare in pediatric cases. Methods For the first time, we report a case of anti-GAD65-positive autoimmune encephalitis associated with autoimmune polyendocrine syndrome (APS) type II. We reviewed previously published pediatric cases of anti-GAD65 autoimmune encephalitis to discuss their clinical features, laboratory tests, imaging findings, EEG patterns, and prognosis. Case presentation An 8-year-old, male child presented to the outpatient department after experiencing generalized convulsions for twenty days. The child was admitted for epilepsy and had received oral sodium valproate (500 mg/day) in another center, where investigations such as USG abdomen and MRI brain revealed no abnormalities, however, had abnormal EEG with diffuse mixed activity in the left anterior middle prefrontal temporal region. On the follow-up day, a repeat blood test showed a very low serum drug concentration of sodium valproate hence the dose was increased to 750 mg/day. Then, the child experienced adverse effects including increased sleep, thirst, and poor appetite, prompting the parents to discontinue the medication. A repeat MRI showed increased signals on FLAIR sequences in the right hippocampus hence admitted for further management. The child's past history included a diagnosis of hypothyroidism at the age of 4, and receiving levothyroxine 75 mcg once daily. His parents are healthy with no history of any similar neurological, autoimmune, or genetic diseases, but his uncle had a history of epilepsy. At presentation, he had uncontrolled blood glucose levels with elevated HbA1c levels. Additionally, the serum and CSF autoantibodies were positive against the anti-GAD65 antibody with the titer of 1:100 and 1:32 respectively. The patient was managed with a mixed type of insulin regimen and received first-line immunotherapy (intravenous immunoglobulin, IVIG) for five consecutive days, followed by oral prednisone and sodium valproate as an antiepileptic drug. Upon achieving a favorable clinical outcome, the patient was discharged with oral medications. Results Among the 15 pediatric patients reported in this literature, nine presented with limbic encephalitis (LE), three with extralimbic encephalitis (ELE), and three with a combination of limbic and extralimbic encephalitis. Most of these cases exhibited T2-W FLAIR hyperintensities primarily localized to the temporal lobes in the early phase, progressing to hippocampal sclerosis/atrophy in the later phase on MRI. EEG commonly showed slow or spike waves on frontotemporal lobes with epileptic discharges. Prognostic factors varied among patients, with some experiencing persistent refractory seizures, type-1 diabetes mellitus (T1DM), persistent memory impairment, persistent disability requiring full assistance, and, in severe cases, death. Conclusion Our findings suggest that anti-GAD65 antibody-positive autoimmune encephalitis patients may concurrently present with other APS. Our unique case presented with multiple endocrine syndromes and represents the first reported occurrence in children. Early diagnosis and timely initiation of immunotherapy are crucial for improving clinical symptoms and reducing the likelihood of relapses or permanent disabilities. Therefore, emphasis should be placed on prompt diagnosis and appropriate treatment implementation to achieve better patient outcomes.
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Affiliation(s)
- Tamang Sapana
- Department of Pediatric, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Wei Li
- Department of Pediatric, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Fengyan Tian
- Department of Pediatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Wenhao Yan
- Department of Pediatric, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Binghua Dou
- Department of Pediatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Shuang Hua
- Department of Pediatric, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Zhihong Zhuo
- Department of Pediatric, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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Shi L, Wang S, Zhang S, Wang J, Chen Y, Li Y, Liu Z, Zhao S, Wei B, Zhang L. Research progress on pharmacological effects and mechanisms of cepharanthine and its derivatives. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:2843-2860. [PMID: 37338575 DOI: 10.1007/s00210-023-02537-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 05/16/2023] [Indexed: 06/21/2023]
Abstract
Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid compound found in plants of the Stephania genus, which has biological functions such as regulating autophagy, inhibiting inflammation, oxidative stress, and apoptosis. It is often used for the treatment of inflammatory diseases, viral infections, cancer, and immune disorders and has great clinical translational value. However, there is no detailed research on its specific mechanism and dosage and administration methods, especially clinical research is limited. In recent years, CEP has shown significant effects in the prevention and treatment of COVID-19, suggesting its potential medicinal value waiting to be discovered. In this article, we comprehensively introduce the molecular structure of CEP and its derivatives, describe in detail the pharmacological mechanisms of CEP in various diseases, and discuss how to chemically modify and design CEP to improve its bioavailability. In summary, this work will provide a reference for further research and clinical application of CEP.
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Affiliation(s)
- Liangliang Shi
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Shuaizhe Wang
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Shangzu Zhang
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Jiawei Wang
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yaping Chen
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Yangyang Li
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Zhiwei Liu
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Sichen Zhao
- Gansu University of Traditional Chinese Medicine, Lanzhou, China
| | - Benjun Wei
- Gansu University of Traditional Chinese Medicine, Lanzhou, China.
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Lanzhou, China.
| | - Liying Zhang
- Gansu University of Traditional Chinese Medicine, Lanzhou, China.
- Key Laboratory of Traditional Chinese Medicine Exploration and Innovation Transformation in Gansu Province, Lanzhou, China.
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Wang X, Ye H, Chen R, Yang S, Zhang T, Xiao W, Yang H. HbA1c: an independent risk factor for dysthyroid optic neuropathy. Front Endocrinol (Lausanne) 2023; 14:1251209. [PMID: 37881496 PMCID: PMC10597662 DOI: 10.3389/fendo.2023.1251209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 09/07/2023] [Indexed: 10/27/2023] Open
Abstract
Background We aimed to explore the frequencies of islet β-cell autoantibodies and insulin resistance (IR) in thyroid-associated ophthalmopathy (TAO) and identify specific diabetes mellitus (DM) indicators as early predictors for dysthyroid optic neuropathy (DON). Methods Ninety-eight TAO patients (57 DON and 41 non-DON patients) and 48 healthy control (HC) participants were recruited for this prospective cross-sectional study. Serum thyroxine, serum thyroid autoantibodies, serum humoral immune markers against islet β-cell, fasting plasma glucose (FPG), fasting serum insulin (FINS), fasting c-peptide (FCP), and glycosylated hemoglobin A1 (HbA1c) were measured. Logistic regression analysis was used to evaluate the correlation of patients' age, body mass index (BMI), FPG, HbA1c, and related indexes of islet β-cell function to the occurrence of DON. Results The DON group had higher FPG (P<0.001, 0.016) and HbA1c (P<0.0001, P<0.001) levels than the HC and non-DON groups. The homeostasis model assessment (HOMA)-IR level was the highest in the DON group (HC 2.15 ± 0.89, non-DON 2.41 ± 1.24, and DON 2.82 ± 2.65), while the HOMA-β level was the lowest (HC 101.8 ± 44.75%, non-DON 102.9 ± 54.61%, and DON 88.29 ± 52.75%), with no significant differences (P=1, P>0.05). On univariate analysis, age (P=0.006), BMI (P=0.022), history of steroid use (P=0.014), FPG (P=0.013), and HbA1c (P=0.001) levels were significantly associated with the presence/absence of DON. In addition, after adjusting for potential confounds, the HbA1c level was an independent factor associated with DON (P=0.009, OR=4.012). Conclusions HbA1c is an independent risk factor for DON. Given the interconnected link between thyroid dysfunction and DM, the use of HbA1c as a potential biomarker for DON warrants further investigation.
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Affiliation(s)
- Xing Wang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
- Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, China
| | - Huijing Ye
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Rongxin Chen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Shenglan Yang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Te Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Wei Xiao
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
| | - Huasheng Yang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China
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Strey S, Mischke R, Rieder J. [Polyendocrine syndromes in dogs]. TIERARZTLICHE PRAXIS. AUSGABE K, KLEINTIERE/HEIMTIERE 2023; 51:313-325. [PMID: 37956663 DOI: 10.1055/a-2183-0654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
The autoimmune polyendocrine syndrome (APS) refers to a combination of autoimmune endocrine disorders. It is rarely described in dogs. The most common combinations are hypoadrenocorticism and hypothyroidism, followed by diabetes mellitus, and less often hypoparathyroidism and orchitis. The diagnosis of the APS is based on the diagnosis of each endocrinopathy, as is the therapy, which involves the substitution of deficient hormones. If a patient was previously stable under treatment and is showing further signs (e.g. polyuria, polydipsia, or weight loss), the development of additional endocrinopathies like hypoadrenocorticism or diabetes mellitus should be considered. The diagnosis of the initially diagnosed endocrinopathy should also be critically questioned. This article summarizes some cases of our own animal hospital and selected cases published in the available literature.
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Affiliation(s)
- Sina Strey
- Klinik für Kleintiere, Stiftung Tierärztliche Hochschule Hannover, Hannover
| | - Reinhard Mischke
- Klinik für Kleintiere, Stiftung Tierärztliche Hochschule Hannover, Hannover
| | - Johanna Rieder
- Klinik für Kleintiere, Stiftung Tierärztliche Hochschule Hannover, Hannover
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Espenschied T, Lawford R, Zacharin M, Gray LE. Simultaneous diagnosis of primary adrenal insufficiency and Type 1 diabetes mellitus. J Paediatr Child Health 2023; 59:1175-1177. [PMID: 37638614 DOI: 10.1111/jpc.16482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 08/13/2023] [Indexed: 08/29/2023]
Affiliation(s)
- Tahlia Espenschied
- Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, Australia
| | - Robyn Lawford
- Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, Australia
| | - Margaret Zacharin
- Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, Australia
- Department of Endocrinology, Royal Children's Hospital, Parkville, Victoria, Australia
| | - Lawrence Ek Gray
- Women's and Children's Services, Barwon Health, University Hospital Ryrie Street, Geelong, Victoria, Australia
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Shi H, Korejo NA, Kamboh AA, Korejo RA, Shi F. Effects of hyperthyroidism and diabetes mellitus on spermatogenesis in peri- and post-pubertal mice. Front Endocrinol (Lausanne) 2023; 14:1191571. [PMID: 37654561 PMCID: PMC10465343 DOI: 10.3389/fendo.2023.1191571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 07/24/2023] [Indexed: 09/02/2023] Open
Abstract
Introduction Diabetes and thyroid dysfunction often co-exist. One autoimmune disorder always invites another and it has been reported that such co-morbid ailments always become detrimental to the health of the patients. Materials and methods In our previous work, we elucidated the interactions of diabetes and hypothyroidism on testicular development and spermatogenesis. However, the present study illuminates the interface between diabetes and hyperthyroidism, where 16 ICR pregnant primiparous mice were used and subsequently 48 male pups were randomly selected (n=12/group) and separated into 4 groups: control (C), diabetic (D), diabetic + hyperthyroidism (DH) and hyperthyroidism (H). Results Computerized sperm analyses showed significant reductions in count by 20% and increases of 15% in D and H animals, respectively, vs. controls. However, rapid progressive sperm motility was significantly lower only in D (30%) compared with C mice. Our histomorphometric investigation depicted damaging effects on testicular and epididymal tissues; the stroma adjacent to the seminiferous tubules of the D mice revealed edematous fluid and unstructured material. However, in the epididymis, germ cell diminution contraction of tubules, compacted principal and clear cells, lipid vacuolization, atypical cellular connections, exfoliated epithelial cells, and round spermatids were conspicuous in DH mice. Discussion Collectively, our experiment was undertaken to ultimately better recognize male reproductive disorders in diabetic-hyperthyroid patients.
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Affiliation(s)
- Hanhao Shi
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Nazar Ali Korejo
- Faculty of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University Tandojam, Hyderabad, Pakistan
| | - Asghar Ali Kamboh
- Faculty of Animal Husbandry and Veterinary Sciences, Sindh Agriculture University Tandojam, Hyderabad, Pakistan
| | - Rashid Ali Korejo
- Department of Animal Nutrition, Faculty of Animal Production and Technology, Shaheed Benazir Bhutto University of Veterinary and Animal Sciences, Sakrand, Pakistan
| | - Fangxiong Shi
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
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Arram N, Riyaz R, khatroth S, Shrestha AB. A case report on autoimmune polyglandular syndrome type 2 with pernicious anemia. Clin Case Rep 2023; 11:e7413. [PMID: 37305884 PMCID: PMC10250687 DOI: 10.1002/ccr3.7413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 04/09/2023] [Accepted: 05/08/2023] [Indexed: 06/13/2023] Open
Abstract
Autoimmune polyglandular syndrome type 2 (APS II) is a rare autoimmune disease that affects many endocrine glands. We present a case of a 32-year-old man with Addison's disease, autoimmune thyroiditis, and pernicious anemia. Multi-line and timely management are crucial for each association.
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Affiliation(s)
- Niharikha Arram
- Apollo Institute of Medical Sciences and ResearchHyderabadIndia
| | - Romana Riyaz
- Shadan Institute of Medical Sciences and ResearchHyderabadIndia
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Ovakimyan A, Patel NA, Brown NJ, Reardon T, Fote G, Gendreau J. Acute Mania and Psychosis in the Context of Primary Adrenal Insufficiency: A Systematic Review of the Literature. Cogn Behav Neurol 2023; 36:85-92. [PMID: 37026774 DOI: 10.1097/wnn.0000000000000340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 12/28/2022] [Indexed: 04/08/2023]
Abstract
BACKGROUND Given the sparse nature of acute mania or psychosis in primary adrenal insufficiency (PAI), physicians may not be aware of the association of these two entities. OBJECTIVE To conduct a systematic review of the literature for the purpose of identifying all studies reporting mania and/or psychosis in individuals with PAI. METHOD We conducted a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using the PubMed, Embase, and Web of Science databases from June 22, 1970 to June 22, 2021, for the purpose of identifying all studies reporting instances of mania or psychosis associated with PAI. RESULTS We identified nine case reports featuring nine patients (M age = 43.3 years, male = 44.4%) over eight countries that fit our inclusion/exclusion criteria. Eight (89%) of the patients had experienced psychosis. Manic and/or psychotic symptom resolution was achieved in 100% of the cases, of which steroid replacement therapy was efficacious in seven (78%) cases and was sufficient in six (67%). CONCLUSION Acute mania and psychosis in the context of PAI is a very rare presentation of an already uncommon disease. Resolution of acute psychiatric change is reliably achieved with the correction of underlying adrenal insufficiency.
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Affiliation(s)
- Andrew Ovakimyan
- School of Medicine, University of California, Irvine, Orange, California
| | - Neal A Patel
- School of Medicine, Mercer University, Columbus, Georgia
| | - Nolan J Brown
- School of Medicine, University of California, Irvine, Orange, California
| | - Taylor Reardon
- Kentucky College of Osteopathic Medicine, University of Pikeville, Pikeville, Kentucky
| | - Gianna Fote
- School of Medicine, University of California, Irvine, Orange, California
| | - Julian Gendreau
- Department of Biomedical Engineering, Johns Hopkins Whiting School of Engineering, Baltimore, Maryland
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Fyvie MJ, Gillespie KM. The importance of biomarker development for monitoring type 1 diabetes progression rate and therapeutic responsiveness. Front Immunol 2023; 14:1158278. [PMID: 37256143 PMCID: PMC10225507 DOI: 10.3389/fimmu.2023.1158278] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 03/28/2023] [Indexed: 06/01/2023] Open
Abstract
Type 1 diabetes (T1D) is an autoimmune condition of children and adults in which immune cells target insulin-producing pancreatic β-cells for destruction. This results in a chronic inability to regulate blood glucose levels. The natural history of T1D is well-characterized in childhood. Evidence of two or more autoantibodies to the islet antigens insulin, GAD, IA-2 or ZnT8 in early childhood is associated with high risk of developing T1D in the future. Prediction of risk is less clear in adults and, overall, the factors controlling the progression rate from multiple islet autoantibody positivity to onset of symptoms are not fully understood. An anti-CD3 antibody, teplizumab, was recently shown to delay clinical progression to T1D in high-risk individuals including adults and older children. This represents an important proof of concept for those at risk of future T1D. Given their role in risk assessment, islet autoantibodies might appear to be the most obvious biomarkers to monitor efficacy. However, monitoring islet autoantibodies in clinical trials has shown only limited effects, although antibodies to the most recently identified autoantigen, tetraspanin-7, have not yet been studied in this context. Measurements of beta cell function remain fundamental to assessing efficacy and different models have been proposed, but improved biomarkers are required for both progression studies before onset of diabetes and in therapeutic monitoring. In this mini-review, we consider some established and emerging predictive and prognostic biomarkers, including markers of pancreatic function that could be integrated with metabolic markers to generate improved strategies to measure outcomes of therapeutic intervention.
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Affiliation(s)
| | - Kathleen M. Gillespie
- Diabetes and Metabolism, Bristol Medical School, University of Bristol, Bristol, United Kingdom
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Bowden SA. Current Screening Strategies for the Diagnosis of Adrenal Insufficiency in Children. Pediatric Health Med Ther 2023; 14:117-130. [PMID: 37051221 PMCID: PMC10084833 DOI: 10.2147/phmt.s334576] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 03/21/2023] [Indexed: 04/08/2023] Open
Abstract
Adrenal insufficiency can arise from a primary adrenal disorder, secondary to adrenocorticotropic hormone deficiency, or by suppression of hypothalamic-pituitary-adrenal axis due to exogenous glucocorticoids. Diagnosis of adrenal insufficiency is usually delayed because the initial presentation is often subtle and nonspecific. Clinician awareness and recognition is crucial for timely diagnosis to avoid adrenal crisis. Current screening strategies for the diagnosis of adrenal insufficiency in children in various clinical situations are discussed in this review.
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Affiliation(s)
- Sasigarn A Bowden
- Division of Endocrinology, Department of Pediatrics, Nationwide Children’s Hospital/The Ohio State University College of Medicine, Columbus, OH, USA
- Correspondence: Sasigarn A Bowden, Nationwide Children’s Hospital, Division of Endocrinology, 700 Children’s Drive, Columbus, OH, 43205, USA, Tel +1 614-722-4118, Fax +1 614-722-4440, Email
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Paparella R, Menghi M, Micangeli G, Leonardi L, Profeta G, Tarani F, Petrella C, Ferraguti G, Fiore M, Tarani L. Autoimmune Polyendocrine Syndromes in the Pediatric Age. CHILDREN 2023; 10:children10030588. [PMID: 36980146 PMCID: PMC10047132 DOI: 10.3390/children10030588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/13/2023] [Accepted: 03/17/2023] [Indexed: 03/22/2023]
Abstract
Autoimmune polyendocrine syndromes (APSs) encompass a heterogeneous group of rare diseases characterized by autoimmune activity against two or more endocrine or non-endocrine organs. Three types of APSs are reported, including both monogenic and multifactorial, heterogeneous disorders. The aim of this manuscript is to present the main clinical and epidemiological characteristics of APS-1, APS-2, and IPEX syndrome in the pediatric age, describing the mechanisms of autoimmunity and the currently available treatments for these rare conditions.
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Affiliation(s)
- Roberto Paparella
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Michela Menghi
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Ginevra Micangeli
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Lucia Leonardi
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Giovanni Profeta
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Francesca Tarani
- Department of Experimental Medicine, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Carla Petrella
- Institute of Biochemistry and Cell Biology, IBBC-CNR, 00185 Rome, Italy
| | - Giampiero Ferraguti
- Department of Experimental Medicine, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
| | - Marco Fiore
- Institute of Biochemistry and Cell Biology, IBBC-CNR, 00185 Rome, Italy
- Correspondence: (M.F.); (L.T.)
| | - Luigi Tarani
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
- Correspondence: (M.F.); (L.T.)
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Yang Y, Zhao W, Yang N, Cui S, Jin H, Li L. Associations between bullous pemphigoid and hematological diseases: Literature review on mechanistic connections and possible treatments. Front Immunol 2023; 14:1155181. [PMID: 36969223 PMCID: PMC10030799 DOI: 10.3389/fimmu.2023.1155181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 02/22/2023] [Indexed: 03/11/2023] Open
Abstract
Bullous pemphigoid is an autoimmune blistering disorder that primarily occurs in elderly patients. Reports indicate that BP coexists with various hematological diseases, including acquired hemophilia A, hypereosinophilic syndrome, aplastic anemia, autoimmune thrombocytopenia, and hematological malignancies. Early identification of these comorbidities contributes to a better control and reduced mortality. This article details the atypical clinical manifestations of BP when associated with hematological diseases, specific diagnostic strategies, underlying mechanistic connections, and possible treatments. Cross-reactivity between autoantibodies and exposed abnormal epitopes, shared cytokines and immune cells, together with genetic susceptibility are the most common connections between BP and hematological diseases. Patients were most often successfully treated with oral steroids combined with medications specifically targeting the hematological disorders. However, the individual comorbidities require specific considerations.
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Affiliation(s)
- Yuyan Yang
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Wenling Zhao
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
- Department of Dermatology, Shunyi Maternal and Children’s Hospital of Beijing Children’s Hospital, Beijing, China
| | - Nan Yang
- Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Shengnan Cui
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Hongzhong Jin
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
| | - Li Li
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China
- *Correspondence: Li Li,
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Lee HJ, Stefan-Lifshitz M, Li CW, Tomer Y. Genetics and epigenetics of autoimmune thyroid diseases: Translational implications. Best Pract Res Clin Endocrinol Metab 2023; 37:101661. [PMID: 35459628 PMCID: PMC9550878 DOI: 10.1016/j.beem.2022.101661] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Hashimoto's thyroiditis (HT) and Graves' disease (GD) are prevalent autoimmune disorders, representing opposite ends of the clinical spectrum of autoimmune thyroid diseases (AITD). The pathogenesis involves a complex interplay between environment and genes. Specific susceptibility genes have been discovered that predispose to AITD, including thyroid-specific and immune-regulatory genes. Growing evidence has revealed that genetic and epigenetic variants can alter autoantigen presentation during the development of immune tolerance, can enhance self-peptide binding to MHC (major histocompatibility complex), and can amplify stimulation of T- and B-cells. These gene-driven mechanistic discoveries lay the groundwork for novel treatment targets. This review summarizes recent advances in our understanding of key AITD susceptibility genes (Tg1, TSHR, HLA-DR3, and CD40) and their translational therapeutic potential.
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Affiliation(s)
- Hanna J Lee
- Department of Medicine, The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, New York, NY, USA.
| | - Mihaela Stefan-Lifshitz
- Department of Medicine, The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, New York, NY, USA.
| | - Cheuk Wun Li
- Department of Medicine, The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, New York, NY, USA.
| | - Yaron Tomer
- Department of Medicine, The Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, New York, NY, USA.
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25
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Ilias I, Milionis C, Zabuliene L, Rizzo M. Does Iodine Influence the Metabolism of Glucose? MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020189. [PMID: 36837391 PMCID: PMC9966122 DOI: 10.3390/medicina59020189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/05/2023] [Accepted: 01/13/2023] [Indexed: 01/19/2023]
Abstract
Thyroid function and glucose status are linked; experimental, clinical, and epidemiological studies have shown this. Iodine is a vital trace element that is inextricably linked to thyroid hormone synthesis. The latter is also associated with glucose metabolism and diabetes. Recently, some-but not all-studies have shown that iodine is linked to glucose metabolism, glucose intolerance, impaired fasting glucose, prediabetes, diabetes mellitus, or gestational diabetes. In this concise review, we review these studies, focusing on iodine and glucose metabolism and prediabetic conditions or type 2 diabetes mellitus. The potential beneficial effect of iodine on glucose metabolism may be attributed to its antioxidant properties.
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Affiliation(s)
- Ioannis Ilias
- Department of Endocrinology, Diabetes and Metabolism, Elena Venizelou Hospital, GR-11521 Athens, Greece
- Correspondence:
| | - Charalampos Milionis
- Department of Endocrinology, Diabetes and Metabolism, Elena Venizelou Hospital, GR-11521 Athens, Greece
| | - Lina Zabuliene
- Faculty of Medicine, Vilnius University, M. K. Čiurlionio St. 21/27, LT-03101 Vilnius, Lithuania
| | - Manfredi Rizzo
- Department of Health Promotion Sciences, Maternal and Infantile Care, Internal Medicine and Medical Specialties (Promise), School of Medicine, University of Palermo, Via del Vespro, 141, 90127 Palermo, Italy
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26
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ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Cusi K, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46:S49-S67. [PMID: 36507651 PMCID: PMC9810472 DOI: 10.2337/dc23-s004] [Citation(s) in RCA: 112] [Impact Index Per Article: 56.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Lechleitner M, Kaser S, Hoppichler F, Roden M, Weitgasser R, Ludvik B, Fasching P, Winhofer Y, Kautzky-Willer A, Schernthaner G, Prager R, Wascher TC, Clodi M. [Diagnosis and insulin therapy of type 1 diabetes mellitus (Update 2023)]. Wien Klin Wochenschr 2023; 135:98-105. [PMID: 37101030 PMCID: PMC10133075 DOI: 10.1007/s00508-023-02182-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2023] [Indexed: 04/28/2023]
Abstract
This guideline summarizes diagnosis of type 1 diabetes, including accompanying autoimmune disorders, insulin therapy regimens and glycemic target values.
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Affiliation(s)
- Monika Lechleitner
- Avomed - Arbeitskreis für Vorsorgemedizin zbd Gesundheitsförderung in Tirol, Innsbruck, Österreich
| | - Susanne Kaser
- Department für Innere Medizin 1, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Friedrich Hoppichler
- Abteilung für Innere Medizin, Krankenhaus der Barmherzigen Brüder Salzburg, Salzburg, Österreich
| | - Michael Roden
- Klinik für Endokrinologie und Diabetologie, Medizinische Fakultät, Heinrich-Heine-Universität, Düsseldorf, Deutschland
- Institut für Klinische Diabetologie, Deutsches Diabetes-Zentrum (DDZ), Leibniz-Zentrum für Diabetesforschung, Düsseldorf, Deutschland
- Deutsches Zentrum für Diabetesforschung (DZD e. V.), München-Neuherberg, Deutschland
| | - Raimund Weitgasser
- Abteilung für Innere Medizin, Privatklinik Wehrle-Diakonissen, Salzburg, Österreich
- Universitätsklinik für Innere Medizin I, LKH Salzburg - Universitätsklinikum der Paracelsus Medizinischen Privatuniversität, Salzburg, Österreich
| | - Bernhard Ludvik
- 1. Medizinische Abteilung mit Diabetologie, Endokrinologie und Nephrologie, Klinik Landstraße, Wien, Österreich
| | - Peter Fasching
- 5. Medizinische Abteilung für Endokrinologie, Rheumatologie und Akutgeriatrie, Wilhelminenspital der Stadt Wien, Wien, Österreich
| | - Yvonne Winhofer
- Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Wien, Österreich
| | - Alexandra Kautzky-Willer
- Gender Medicine Unit, Klinische Abteilung für Endokrinologie und Stoffwechsel, Universitätsklinik für Innere Medizin III, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090, Wien, Österreich.
| | - Guntram Schernthaner
- 1. Medizinische Abteilung mit Diabetologie, Endokrinologie und Department für Nephrologie, Krankenanstalt Rudolfstiftung, Wien, Österreich
| | - Rudolf Prager
- 3. Medizinische Abteilung mit Stoffwechselerkrankungen und Nephrologie, Krankenhaus Hietzing, Wien, Österreich
- Karl Landsteiner Institut für Stoffwechselerkrankungen und Nephrologie, Wien, Österreich
| | - Thomas C Wascher
- 1. Medizinische Abteilung, Hanusch-Krankenhaus, Wien, Österreich
| | - Martin Clodi
- ICMR - Institute for Cardiovascular and Metabolic Research, Johannes Kepler Universität Linz, Linz, Österreich
- Abteilung für Innere Medizin, Konventhospital der Barmherzigen Brüder Linz, Linz, Österreich
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Al-Dubayee M, Babiker A, Alkewaibeen A, Alkhalifah A, Alanazi T, Nogoud M, Alotaibi A, Alotaibi F, Almetairi F, Alrowaily MA, Masuadi E, Nasr A. Correlation analysis between cytokines' profile, autoimmune antibodies and the duration of type 1 diabetes: A case control study in a specialized children's centre in Riyadh. Int J Immunopathol Pharmacol 2023; 37:3946320231209821. [PMID: 37953627 PMCID: PMC10644762 DOI: 10.1177/03946320231209821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 10/06/2023] [Indexed: 11/14/2023] Open
Abstract
OBJECTIVE The aim of this study was to investigate the role of cytokines in children with T1D living in Saudi Arabia and their correlation with disease duration and autoimmune antibody markers. METHODS A case-control study was conducted in the endocrine clinic of King Abdullah Specialized Children's Hospital in Riyadh. A total of 274 T1D and healthy control children were enrolled in the study. 5 mL of venous blood samples were collected in the morning after 9 to 12 h of fasting in BD Vacutainer® EDTA tubes and centrifuged at 250g for 15 min at. Plasma was then stored at -20°C for detection of anti-islet, anti-GAD antibodies (Abs), and C-peptide using commercial ELISA kits from Thermo Fisher Scientific. The levels of cytokines were measured using commercial sandwich ELISA kits from Abcam. RESULTS Median differences in cytokine levels (IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, IL-18, IL-21, IL-35, and IL-37) were significantly higher in T1D patients compared with healthy controls (p-value < .001). Spearman's Rho correlation indicated that TNFα, IL-1β, IL-4, IL-10, IL-13, and IL-21 correlated significantly with T1D Abs (p-value = .01). HbA1C correlated negatively with IL-35 and IL-37, and positively with IL-18 (p-value = .01). Linear regression analysis showed a significant increase in anti-glutamic acid antibodies (GAD) in patients with >3 years of T1D duration. CONCLUSION Autoantibodies remained positive at high levels in our patients over a 3-year duration of the disease and correlated with specific cytokines. The clear correlations with disease duration and profile of specific cytokines could be targets for future therapeutic interventions.
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Affiliation(s)
- Mohammed Al-Dubayee
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia
- Ministry of National Guard Health Affairs, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Amir Babiker
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia
- Ministry of National Guard Health Affairs, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Abdulaziz Alkewaibeen
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia
| | - Abdulrahman Alkhalifah
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia
| | - Tammam Alanazi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia
| | - Maysa Nogoud
- Ministry of National Guard-Health Affairs (MNGHA), King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia
| | - Anas Alotaibi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia
| | - Faisal Alotaibi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia
| | - Firas Almetairi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia
| | - Mohammed A Alrowaily
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- Ministry of National Guard Health Affairs, King Abdulaziz Medical City, Riyadh, Saudi Arabia
| | - Emad Masuadi
- Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Amre Nasr
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdullah International Medical Research Centre (KAIMRC), Riyadh, Saudi Arabia
- Ministry of National Guard Health Affairs, King Abdulaziz Medical City, Riyadh, Saudi Arabia
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Park E, Kim MS, Noh ES, Lee JE, Kim SJ, Kwon YS, Cho SY. Multiple endocrine neoplasia type 2 and autoimmune polyendocrine syndromes (type 1 diabetes mellitus and Graves' disease) in a 16-year-old male with Kabuki syndrome. Endocr J 2022; 69:1211-1216. [PMID: 35676000 DOI: 10.1507/endocrj.ej22-0084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Multiple endocrine neoplasia type 2A (MEN2A) is caused by germline pathogenic variants in the RET proto-oncogene and is characterized by medullary thyroid cancer (MTC), pheochromocytoma, and hyperparathyroidism. Autoimmune polyendocrine syndromes (APS) are defined as multiple endocrine gland insufficiency associated with loss of immune tolerance. APS type 2 (APS-2) consists of at least two of the following diseases: type 1 diabetes mellitus (T1DM), autoimmune thyroid disease, and Addison's disease. We describe the clinical, molecular, and biochemical findings of MEN2A, APS-2, and Kabuki syndrome (KS) in a 16-year-old male. Whole exome sequencing was performed to identify the genetic cause of the pheochromocytoma and syndromic features including facial dysmorphism, developmental delay, and epilepsy. RET pathogenic variant and KMT2D pathogenic variant were identified, and he was diagnosed with MEN2A and KS. This is the first case of association between MEN2 and APS in adolescence and the second proven case in humans. In addition, this is the first report of MEN2 and APS in KS.
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Affiliation(s)
- Esther Park
- Department of Pediatrics, Jeonbuk National University Hospital, Jeonju, Korea
| | - Min-Sun Kim
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eu Seon Noh
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji-Eun Lee
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, Korea
| | - Su Jin Kim
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, Korea
| | - Young Se Kwon
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon, Korea
| | - Sung Yoon Cho
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Li Y. Bilateral hypocalcaemic cataracts due to idiopathic parathyroid insufficiency: A case report. World J Clin Cases 2022; 10:9378-9383. [PMID: 36159405 PMCID: PMC9477687 DOI: 10.12998/wjcc.v10.i26.9378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 07/02/2022] [Accepted: 08/05/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Hypoparathyroidism is uncommon, and cataracts secondary to hypoparathyroidism are even rarer. Herein, we report a case of bilateral cataracts following hypoparathyroidism.
CASE SUMMARY A 27-year-old man presented to our hospital because of painless and progressive visual impairment of both eyes over two years. He was previously diagnosed with hypocalcemia but did not take calcium supplements regularly. He had no history of anterior neck thyroid surgery. After admission, the biochemical analysis indicated a serum calcium level of 1.21 mmol/L and an intact parathyroid hormone level of 0 pg/mL. Ocular examination revealed bilateral symmetrical opacity of the lens presenting as punctate opacity in the posterior subcapsular cortex together with radial opacity in the peripheral cortex (N1C2P3). Phacoemulsification with an intraocular lens was performed in both eyes sequentially. Postoperatively, the patient had a satisfactory recovery and greatly improved visual acuity.
CONCLUSION This patient had hypocalcemia owing to idiopathic parathyroid insufficiency. Hypoparathyroidism may go unnoticed for years but with some latent clinical manifestations, such as bilateral symmetrical posterior subcapsular cataracts. This case report highlights that the cause of hypocalcemia in particularly young patients should be further investigated. Clinicians should be aware of hypoparathyroidism as a cause of bilateral cataracts. Early identification of hypoparathyroidism can save patients from further complications.
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Affiliation(s)
- Yan Li
- Department of Ophthalmology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
- Medical School of Ophthalmology and Optometry, North Sichuan Medical College, Nanchong 637000, Sichuan Province, China
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31
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Hashimoto Encephalopathy—Still More Questions than Answers. Cells 2022; 11:cells11182873. [PMID: 36139446 PMCID: PMC9496753 DOI: 10.3390/cells11182873] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Revised: 09/05/2022] [Accepted: 09/12/2022] [Indexed: 12/03/2022] Open
Abstract
The normal function of the nervous system is conditioned by the undisturbed function of the thyroid gland and its hormones. Comprehensive clinical manifestations, including neurological disorders in Hashimoto’s thyroiditis, have long been understood and, in recent years, attention has been paid to neurological symptoms in euthyroid patients. Hashimoto encephalopathy is a controversial and poorly understood disease entity and the pathogenesis of the condition remains unclear. We still derive our understanding of this condition from case reports, but on the basis of these, a clear clinical picture of this entity can be proposed. Based on a review of the recent literature, the authors present the current view on the subject, discuss controversies and questions that still remain unanswered, as well as ongoing research in this area and the results of our own work in patients with Hashimoto’s thyroiditis.
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Kakleas K, Kossyva L, Korona A, Kafassi N, Karanasios S, Karavanaki K. Predictors of associated and multiple autoimmunity in children and adolescents with type 1 diabetes mellitus. Ann Pediatr Endocrinol Metab 2022; 27:192-200. [PMID: 34793669 PMCID: PMC9537678 DOI: 10.6065/apem.2142168.084] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 11/01/2021] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Type 1 diabetes mellitus (T1DM) is an autoimmune condition characterised by the presence of antipancreatic antibodies. The autoimmune process is also directed against other organs, most frequently against the thyroid gland, intestinal mucosa, and gastric parietal cells. METHODS Our investigation included 121 children with T1DM with a mean age±standard deviation of 11.99±4.63 years (range, 2.0-20.0 years). We explored the frequency of associated autoimmunity; the presence of predictive factors such as current age, sex, and severity at diabetes diagnosis; T1DM duration; and family history of autoimmunity. RESULTS Associated autoimmunity was present in 28.9% of T1DM patients. Children with associated autoimmunity were older at diabetes diagnosis (p=0.009) and had a longer diabetes duration compared to children without associated autoimmunity (p=0.044). Adolescents aged 12-20 years had a statistically significant higher chance of developing thyroid autoimmunity compared to children aged 1-5 years (p=0.019). Multiple autoimmunity (MA), T1DM, and 2 or more autoimmune diseases were present in 5.8% of the study population. All children with MA presented with ketoacidosis at diabetes diagnosis and had a higher percentage of familial autoimmunity (p=0.042). The familial autoimmunity of these patients most frequently affected ≥3 relatives (p=0.026) and was more frequently diagnosed before 5 years of age (p=not significant). CONCLUSION Associated autoimmunity was present in almost one-third of T1DM patients. Significant associations with associated autoimmunity were longer diabetes duration, female sex, older age at diabetes diagnosis, and glutamic acid decarboxylase positivity. Predictors of MA were age <5 years at T1DM diagnosis, the presence of diabetic ketoacidosis at diagnosis, and a significant family history of autoimmunity.
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Affiliation(s)
- Konstantinos Kakleas
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, 'P. & A. Kyriakou' Children's Hospital, Athens, Greece,Address for correspondence: Konstantinos Kakleas Athens General Children's Hospital "Pan. & Aglaia Kyriakou", Thivon kai Levadias, Athens P.C. 11527 Telephone: 0030-213 2009000
| | - Lydia Kossyva
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, 'P. & A. Kyriakou' Children's Hospital, Athens, Greece
| | - Anastasia Korona
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, 'P. & A. Kyriakou' Children's Hospital, Athens, Greece
| | | | - Spyridon Karanasios
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, 'P. & A. Kyriakou' Children's Hospital, Athens, Greece
| | - Kyriaki Karavanaki
- Diabetic Clinic, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, 'P. & A. Kyriakou' Children's Hospital, Athens, Greece
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Qi Y, Zhang R, Lu Y, Zou X, Yang W. Aire and Fezf2, two regulators in medullary thymic epithelial cells, control autoimmune diseases by regulating TSAs: Partner or complementer? Front Immunol 2022; 13:948259. [PMID: 36110862 PMCID: PMC9468217 DOI: 10.3389/fimmu.2022.948259] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
The expression of tissue-specific antigens (TSAs) in medullary thymic epithelial cells (mTECs) is believed to be responsible for the elimination of autoreactive T cells, a critical process in the maintenance of central immune tolerance. The transcription factor autoimmune regulator (Aire) and FEZ family zinc finger 2(Fezf2) play an essential role in driving the expression of TSAs in mTECs, while their deficiency in humans and mice causes a range of autoimmune manifestations, such as type 1 diabetes, Sjögren's syndrome and rheumatoid arthritis. However, because of their regulatory mechanisms, the expression profile of TSAs and their relationship with special autoimmune diseases are still in dispute. In this review, we compare the roles of Aire and Fezf2 in regulating TSAs, with an emphasis on their molecular mechanisms in autoimmune diseases, which provides the foundation for devising improved diagnostic and therapeutic approaches for patients.
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Affiliation(s)
| | | | | | - Xueyang Zou
- Department of Immunology, College of Basic Medical Sciences, School of Public Health, Jilin University, Changchun, China
| | - Wei Yang
- Department of Immunology, College of Basic Medical Sciences, School of Public Health, Jilin University, Changchun, China
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Ismaeel H, Tariq S, Akram Z. End-Stage Renal Disease in a Patient With Schmidt’s Syndrome: A Case Report. Cureus 2022; 14:e27342. [PMID: 36046305 PMCID: PMC9416904 DOI: 10.7759/cureus.27342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/27/2022] [Indexed: 12/02/2022] Open
Abstract
Schmidt's syndrome constitutes Addison's disease in conjunction with autoimmune hypothyroidism or type 1 diabetes mellitus. It has misleading symptomology and an unclear order of presentation of symptoms. This often results in missed and late diagnosis. Chronic kidney disease is a rarely reported phenomenon in Schmidt’s syndrome. Multiple factors may have the potential to cause renal failure, such as Addison's disease and/or hypothyroidism, the understanding of which is still evolving. A 45-year-old gentleman who is a known case of Schmidt's syndrome presented to us with fatigue, anorexia, and weight gain. Further evaluation revealed a picture of chronic kidney disease. We would like to alert fellow peers of this potential complication and the importance of screening as well as timely diagnosis.
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Graf S, Poeppelman RS, McVean J, Rayannavar A, Sunni M. An unusual presentation of primary adrenal insufficiency with new onset type 1 diabetes: case report and review of the literature. J Pediatr Endocrinol Metab 2022; 35:531-534. [PMID: 34821121 DOI: 10.1515/jpem-2021-0193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 10/25/2021] [Indexed: 11/15/2022]
Abstract
OBJECTIVES To describe an atypical presentation of primary adrenal insufficiency in conjunction with new onset type 1 diabetes. CASE PRESENTATION Here, we describe a case of new-onset type 1 diabetes (T1D) presenting simultaneously with an unusual presentation of primary adrenal insufficiency in a previously healthy 16-year-old. He was admitted for a typical presentation of diabetic ketoacidosis, but with extreme hyponatremia. An extensive workup revealed a low aldosterone level, appropriate cortisol level, and positive 21-hydroxylase antibodies. While the phenomenon of multiple autoimmune conditions developing in the same patient is well-described, this particular case has several atypical aspects. Our patient's case highlights the danger of relying on random serum cortisol in the setting of acute illness to rule out adrenal insufficiency. CONCLUSIONS Adrenal insufficiency can present as isolated hypoaldosteronism without hypocortisolemia and can manifest as severe hyponatremia in the context of diabetic ketoacidosis. Workup for an unusual presentation of T1D should include a 21-hydroxylase antibody, as well as thyroid and celiac disease studies.
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Affiliation(s)
- Shelby Graf
- PGY-3, University of Minnesota Pediatrics, 2450 Riverside Ave., Room M136, 1st Floor, East Building, Minneapolis, MN 55454, USA
| | - Rachel Stork Poeppelman
- Pediatric Critical Care, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA
| | - Jennifer McVean
- Pediatric Endocrinology and Diabetes, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA
| | - Arpana Rayannavar
- Department of Pediatrics, Division of Endocrinology and Diabetes, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA
| | - Muna Sunni
- Pediatric Endocrinology, University of Minnesota Masonic Children's Hospital, Minneapolis, MN, USA
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36
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Wang Z, Guo L, Chen S, Guan J, Powell M, Furmaniak J, Rees Smith B, Chen L. Characteristic phenotype of Chinese patients with adult-onset diabetes who are autoantibody positive by 3-Screen ICA™ ELISA. Acta Diabetol 2022; 59:189-196. [PMID: 34533636 PMCID: PMC8841311 DOI: 10.1007/s00592-021-01778-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 07/27/2021] [Indexed: 02/07/2023]
Abstract
AIMS To assess the prevalence of diabetes-associated autoantibodies in Chinese patients recently diagnosed with adult-onset diabetes and to evaluate the potential role of the autoantibody markers for characterization of disease phenotype in the patient population. METHODS The study included 1273 recent-onset adult patients with phenotypic type 2 diabetes mellitus (T2DM). Serum samples were tested using the 3-Screen ICA™ ELISA (3-Screen) designed for combined measurement of GADAb and/or IA-2Ab and/or ZnT8Ab. 3-Screen positive samples were then tested for individual diabetes-associated and other organ-specific autoantibodies. Clinical characteristics of patients positive and negative in 3-Screen were analysed. RESULTS Forty-four (3.5%) of the T2DM patients were positive in 3-Screen, and 38 (86%) of these were also positive for at least one of GADAb, IA-2Ab and ZnT8Ab in assays for the individual autoantibodies. 3-Screen positive patients had lower BMI, higher HbA1c, lower fasting insulin levels and lower fasting C-peptide levels compared to 3-Screen negative patients. Analysis using a homeostatic model assessment (HOMA2) indicated that HOMA2-β-cell function was significantly lower for the forty-four 3-Screen positive patients compared to 3-Screen negative patients. Twenty (45%) 3-Screen positive patients were also positive for at least one thyroid autoantibody. CONCLUSIONS The 3-Screen ELISA has been used successfully for the first time in China to detect diabetes autoantibodies in patients with phenotypic T2DM. 3-Screen positive patients presented with poorer β cell function.
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Affiliation(s)
- Zhida Wang
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
| | - Liang Guo
- FIRS Laboratories, RSR Ltd Parc Ty Glas, Llanishen, Cardiff, CF14 5DU, UK
| | - Shu Chen
- FIRS Laboratories, RSR Ltd Parc Ty Glas, Llanishen, Cardiff, CF14 5DU, UK
- RSR Tianjin Biotech Ltd, Haitai Green Area, Hi Huayuan Industrial Park, Tianjin, 300384, China
| | - Jun Guan
- RSR Tianjin Biotech Ltd, Haitai Green Area, Hi Huayuan Industrial Park, Tianjin, 300384, China
| | - Michael Powell
- FIRS Laboratories, RSR Ltd Parc Ty Glas, Llanishen, Cardiff, CF14 5DU, UK
| | - Jadwiga Furmaniak
- FIRS Laboratories, RSR Ltd Parc Ty Glas, Llanishen, Cardiff, CF14 5DU, UK
| | - Bernard Rees Smith
- FIRS Laboratories, RSR Ltd Parc Ty Glas, Llanishen, Cardiff, CF14 5DU, UK
- RSR Tianjin Biotech Ltd, Haitai Green Area, Hi Huayuan Industrial Park, Tianjin, 300384, China
| | - Liming Chen
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
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Vance SJ, Horsley JT, Welch MP, Muterspaugh RD, Pandey J. Educational Case: Adrenocortical insufficiency—Causes and pathogenesis. Acad Pathol 2022; 9:100019. [PMID: 35607601 PMCID: PMC9123195 DOI: 10.1016/j.acpath.2022.100019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 12/02/2021] [Accepted: 01/02/2022] [Indexed: 11/15/2022] Open
Affiliation(s)
| | | | | | | | - Jyotsna Pandey
- Corresponding author. Central Michigan University College of Medicine, 1280 East Campus Drive, Mount Pleasant, MI 48859, USA.
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Chera A, Stancu AL, Bucur O. Thyroid-related adverse events induced by immune checkpoint inhibitors. Front Endocrinol (Lausanne) 2022; 13:1010279. [PMID: 36204105 PMCID: PMC9530140 DOI: 10.3389/fendo.2022.1010279] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 08/29/2022] [Indexed: 11/24/2022] Open
Abstract
Immune checkpoint inhibitors, namely anti-CTLA-4, anti-PD-1 and anti-PD-L1 monoclonal antibodies, have emerged in the last decade as a novel form of cancer treatment, promoting increased survival in patients. As they tamper with the immune response in order to destroy malignant cells, a new type of adverse reactions has emerged, known as immune-related adverse events (irAEs), which frequently target the endocrine system, especially the thyroid and hypophysis. Thyroid irAEs include hyperthyroidism, thyrotoxicosis, hypothyroidism and a possibly life-threatening condition known as the "thyroid storm". Early prediction of occurrence and detection of the thyroid irAEs should be a priority for the clinician, in order to avoid critical situations. Moreover, they are recently considered both a prognostic marker and a means of overseeing treatment response, since they indicate an efficient activation of the immune system. Therefore, a multidisciplinary approach including both oncologists and endocrinologists is recommended when immune checkpoint inhibitors are used in the clinic.
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Affiliation(s)
- Alexandra Chera
- Victor Babes National Institute of Pathology, Bucharest, Romania
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Andreea Lucia Stancu
- Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, United States
| | - Octavian Bucur
- Victor Babes National Institute of Pathology, Bucharest, Romania
- Viron Molecular Medicine Institute, Boston, MA, United States
- *Correspondence: Octavian Bucur, ;;
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4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care in Diabetes-2022. Diabetes Care 2022; 45:S46-S59. [PMID: 34964869 PMCID: PMC8935396 DOI: 10.2337/dc22-s004] [Citation(s) in RCA: 84] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Li CW, Osman R, Menconi F, Faustino LC, Kim K, Clarke OB, Hou H, Tomer Y. Cepharanthine Blocks Presentation of Thyroid and Islet Peptides in a Novel Humanized Autoimmune Diabetes and Thyroiditis Mouse Model. Front Immunol 2021; 12:796552. [PMID: 34987519 PMCID: PMC8721038 DOI: 10.3389/fimmu.2021.796552] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Accepted: 12/03/2021] [Indexed: 11/13/2022] Open
Abstract
Autoimmune polyglandular syndrome type 3 variant (APS3v) refers to an autoimmune condition in which both type 1 diabetes (T1D) and autoimmune thyroiditis (AITD) develop in the same individual. HLA-DR3 confers the strongest susceptibility to APS3v. Previously we reported a unique amino acid signature pocket that predisposes to APS3v. We found that this pocket is flexible and can trigger APS3v by presenting both thyroid (Tg.1571, TPO.758) and islet (GAD.492) peptides to induce autoimmune response. We hypothesized that blocking the specific APS3v-HLA-DR3 pocket from presenting thyroid/islet antigens can block the autoimmune response in APS3v. To test this hypothesis we performed a virtual screen of small molecules blocking APS3v-HLA-DR3, and identified 11 small molecules hits that were predicted to block APS3v-HLA-DR3. Using the baculovirus-produced recombinant APS3v-HLA-DR3 protein we tested the 11 small molecules in an in vitro binding assay. We validated 4 small molecule hits, S9, S5, S53 and S15, that could block the APS3v-HLA-DR3 pocket in vitro. We then developed a novel humanized APS3v mouse model induced by co-immunizing a peptide mix of Tg.1571, TPO.758 and GAD.492. The immunized mice developed strong T-cell and antibody responses to the thyroid/islet peptides, as well as mouse thyroglobulin. In addition, the mice showed significantly lower free T4 levels compared to controls. Using the APS3v mouse model, we showed that one of the 4 small molecules, Cepharanthine (S53), blocked T-cell activation by thyroid/islet peptides ex vivo and in vivo. These findings suggested Cepharanthine may have a therapeutic potential in APS3v patients carrying the specific APS3v-HLA-DR3 pocket.
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MESH Headings
- Animals
- Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
- Antigen Presentation
- Autoantigens/immunology
- Benzylisoquinolines/therapeutic use
- Binding Sites/genetics
- Cells, Cultured
- Diabetes Mellitus, Type 1/drug therapy
- Diabetes Mellitus, Type 1/immunology
- Disease Models, Animal
- Genetic Predisposition to Disease
- Glutamate Decarboxylase/immunology
- HLA-DR3 Antigen/genetics
- HLA-DR3 Antigen/metabolism
- Humans
- Immunity, Humoral
- Immunization
- Iodide Peroxidase/immunology
- Iron-Binding Proteins/immunology
- Islets of Langerhans/immunology
- Lymphocyte Activation
- Mice
- Mice, SCID
- Peptide Fragments/genetics
- Peptide Fragments/immunology
- Polyendocrinopathies, Autoimmune/drug therapy
- Polyendocrinopathies, Autoimmune/immunology
- T-Lymphocytes/immunology
- Thyroglobulin/genetics
- Thyroglobulin/immunology
- Thyroiditis, Autoimmune/drug therapy
- Thyroiditis, Autoimmune/immunology
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Affiliation(s)
- Cheuk Wun Li
- The Fleischer Institute for Diabetes and Metabolism, Department of Medicine, Albert Einstein College of Medicine, New York, NY, United States
| | - Roman Osman
- Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | | | - Larissa C. Faustino
- The Fleischer Institute for Diabetes and Metabolism, Department of Medicine, Albert Einstein College of Medicine, New York, NY, United States
| | - Kookjoo Kim
- Department of Anesthesiology, Columbia University, New York, NY, United States
- Department of Physiology, Columbia University, New York, NY, United States
| | - Oliver B. Clarke
- Department of Anesthesiology, Columbia University, New York, NY, United States
- Department of Physiology, Columbia University, New York, NY, United States
| | - Hanxi Hou
- The Fleischer Institute for Diabetes and Metabolism, Department of Medicine, Albert Einstein College of Medicine, New York, NY, United States
| | - Yaron Tomer
- The Fleischer Institute for Diabetes and Metabolism, Department of Medicine, Albert Einstein College of Medicine, New York, NY, United States
- *Correspondence: Yaron Tomer,
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Sánchez J, Cohen M, Zapater JL, Eisenberg Y. Primary Adrenal Insufficiency After COVID-19 Infection. AACE Clin Case Rep 2021; 8:51-53. [PMID: 34805497 PMCID: PMC8590605 DOI: 10.1016/j.aace.2021.11.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 11/01/2021] [Accepted: 11/08/2021] [Indexed: 11/26/2022] Open
Abstract
Background/Objective The multisystemic effects of COVID-19 are becoming evident. In the adrenal gland, adrenal hemorrhage and infarction after COVID-19 infection have been reported. Our objective is to present a case of autoimmune adrenal insufficiency diagnosed after COVID-19 infection, without the evidence of a hemorrhage or an infarction. Case Report A 64-year-old woman with hypothyroidism and type 2 diabetes presented with a 1-week history of abdominal pain, nausea, and vomiting. She had experienced asymptomatic COVID-19 infection 5 months prior and reported an unintentional 30-lb weight loss. The home medications included enalapril, atorvastatin, and levothyroxine. A physical examination was notable for hypotension, epigastric tenderness, and mucocutaneous hyperpigmentation. Laboratory tests revealed a serum sodium level of 117 mmol/L (range, <20 mmol/L), thyroid-stimulating hormone level of 0.33 μIU/mL (range, 0.35-4.00 μIU/mL), free thyroxine level of 1.4 ng/dL (range, 0.6-1.7 ng/dL), serum osmoles of 253 mOsm/kg (range, 279-300 mOsm/kg), urine osmoles of 324 mOsm/kg (range, 300-900 mOsm/kg), and urine sodium level of 104 mmol/L. The morning cortisol level was 2.6 μg/dL (reference [ref], >18 μg/dL). This was followed by a high-dose, 250-μg adrenocorticotropic hormone (ACTH) stimulation test, which revealed that the cortisol level was 2.3, 2.9, and 2.6 μg/dL (ref, >18 μg/dL) at baseline, 30 minutes, and 60 minutes, respectively. The ACTH level was 1944 pg/mL (range, 7.2-63.3 pg/mL), the aldosterone level was <3.0 ng/dL (range, 4.0-31.0 ng/dL), and anti-21-hydroxylase antibody was present (ref, negative). A computed tomography scan of the adrenals was unremarkable. Hypotension and hyponatremia resolved after initiation of intravenous hydrocortisone, and she was discharged on hydrocortisone and fludrocortisone. Discussion The patient’s symptoms, elevated ACTH level, low cortisol level, and presence of 21-hydroxylase antibodies were consistent with Addison disease. COVID-19 might have contributed to rapid, clinically relevant disease progression after the infection. Conclusion The development of autoimmune Addison disease in the patient might be related to the prior COVID-19 infection.
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Affiliation(s)
- Julienne Sánchez
- Internal Medicine Residency, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 840 South Wood Street, Room 440 (M/C 718), Chicago, Illinois, USA, 60612
| | - Melissa Cohen
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 835 South Wolcott Avenue, Suite 625E (M/C 640), Chicago, IL, USA, 60612
| | - Joseph L Zapater
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 835 South Wolcott Avenue, Suite 625E (M/C 640), Chicago, IL, USA, 60612
| | - Yuval Eisenberg
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 835 South Wolcott Avenue, Suite 625E (M/C 640), Chicago, IL, USA, 60612
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Hodé AK, Dédjan H. Autoimmune thyroiditis - track towards autoimmune polyendocrinopathy type III. Arch Clin Cases 2021; 6:109-111. [PMID: 34754918 PMCID: PMC8565712 DOI: 10.22551/2019.25.0604.10163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Autoimmune polyendocrinopathies are rare diseases characterized by the coexistence of at least two endocrine diseases linked to an autoimmune mechanism, however sometimes are associated with non-endocrine autoimmune diseases. They are divided into two main subgroups: autoimmune polyendocrinopathy type I and polyendocrinopathies type II-IV. We report a case of a 53-year-old female patient followed for 2 years for Hashimoto's thyroiditis. On admission, she was complaining of polyuropolydipsic syndrome, asthenia, weight loss, abdominal pain and vomiting. The clinical examination noted a dehydrated patient in poor general condition, without fever, tachycardic at 104 beats/min, and polypneic at 24 cycles/min. Laboratory tests revealed hyperglycemia (4.7 g/l), glucosuria, acetonuria, anti-GAD>2000 UI/l antibody, normal TSH. The 8-hour cortisol level and anti-21 hydroxylase antibodies level were normal. In this context, the patient was diagnosed with diabetes type 1 associated with Hashimoto's thyroiditis (autoimmune polyendocrinopathy type III). In conclusion, the autoimmune polyendocrinopathy type III is a rare syndrome, predominantly affecting females. In our patient's case, the initial presentation of the disease was dominated by the autoimmune thyroiditis, which is the most frequent endocrine autoimmunity diagnosed in adults with polyglandular autoimmune syndrome. Therefore, the recommended treatment is based on hormonal substitution.
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Affiliation(s)
| | - Hubert Dédjan
- Department of Endocrinology, Metabolism and Nutrition, CNHU-HKM Cotonou, Bénin
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43
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Jiang Q, Wu T, Zhang Y, Wang S, Wang L, Su W, Lin M, Li X. Case Report: A Rare Case of Coexisting of Autoimmune Polyglandular Syndrome Type 3 and Isolated Gonadotropin-Releasing Hormone Deficiency. Front Immunol 2021; 12:734685. [PMID: 34594339 PMCID: PMC8476964 DOI: 10.3389/fimmu.2021.734685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 08/30/2021] [Indexed: 12/03/2022] Open
Abstract
APS (autoimmune polyglandular syndrome) is defined as the coexistence of at least two kinds of endocrine autoimmune diseases. APS type 3 comprises autoimmune thyroid diseases and other autoimmune diseases but does not involve autoimmune Addison’s disease. So far, APS-3 combined with isolated gonadotropin-releasing hormone (GnRH) reduction caused by the suspected autoimmune hypothalamic disease has not been reported. We recently received a 43-year-old woman with a one-year history of Graves’ disease (GD) and a four-month history of type 1 diabetes presented with hyperthyroidism and hyperglycemia. After the GnRH stimulation test, she was diagnosed with secondary amenorrhea attributed to suspected autoimmune Hypothalamitis and APS type 3 associated with Graves’ disease and Latent Autoimmune Diabetes (LADA). According to this case, the hypothalamus cannot be spared from the general autoimmune process. It is recommended to carry out the GnRH stimulation test when encountering APS patients combined with secondary amenorrhea.
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Affiliation(s)
- Qiuhui Jiang
- The School of Clinical of Medicine, Fujian Medical University, Fuzhou, Fujian, China
| | - Ting Wu
- The School of Clinical of Medicine, Fujian Medical University, Fuzhou, Fujian, China
| | - Yuxian Zhang
- Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Shunhua Wang
- Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Liying Wang
- Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Weijuan Su
- Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Mingzhu Lin
- Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Xuejun Li
- Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China
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44
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Fröhlich-Reiterer E. Komorbiditäten bei Typ-1-Diabetes im Kindes- und Jugendalter. Monatsschr Kinderheilkd 2021. [DOI: 10.1007/s00112-021-01249-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
ZusammenfassungTyp-1-Diabetes (T1D) ist eine der häufigsten Stoffwechselerkrankungen im Kindes- und Jugendalter. Komorbiditäten beim T1D können in physische und psychische unterteilt werden. Dieser Beitrag beschäftigt sich mit physischen/organspezifischen Komorbiditäten. Die Assoziation zwischen T1D und anderen Autoimmunerkrankungen ist gut bekannt. Die beiden häufigsten assoziierten Autoimmunerkrankungen bei Kindern und Jugendlichen mit T1D sind die Autoimmunthyreoiditis und die Zöliakie. Da diese oft asymptomatisch sind, sollen regelmäßige Screeninguntersuchungen auf eine assoziierte Autoimmunthyreoiditis und Zöliakie durchgeführt werden. Weitere Komorbiditäten können die Haut, das Gewicht und Längenwachstum sowie die Knochen und Gelenke betreffen. Regelmäßige Messungen von Körperlänge und -gewicht (Perzentilen), Blutdruck (Perzentilen), die Beurteilung der Pubertätsentwicklung (Tanner-Stadien) sowie die regelmäßige Überprüfung der Haut, hier v. a. die Injektions‑/Katheter- und Sensor-Stellen, sollen fixer Bestandteil der Langzeitbetreuung von Kindern und Jugendlichen mit T1D sein.
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45
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Gulden T, Yahyavi SK, Lodding IP, Jensen JEB, Blomberg Jensen M. Severe hypocalcemia due to hypoparathyroidism associated with HIV: A case report. Bone Rep 2021; 15:101119. [PMID: 34504905 PMCID: PMC8414048 DOI: 10.1016/j.bonr.2021.101119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 08/10/2021] [Accepted: 08/14/2021] [Indexed: 11/29/2022] Open
Abstract
Calcemia is not routinely determined among people living with human immunodeficiency virus (HIV). In people living with HIV, the most frequent electrolyte disturbance is hyponatremia and since symptoms of hypocalcemia often are unspecific, calcium is typically measured with some delay. Hypocalcemia in people living with HIV is mainly due to indirect causes such as vitamin D deficiency, renal failure, or drug related. However, in rare cases direct viral involvement of the parathyroid glands has been reported. We present a case of a 67-year-old male living with HIV who presented at an emergency department with symptomatic severe hypocalcemia, without any previous history of neck surgery, radiation therapy or large infections in the head and neck area. At the time of admission serum concentrations were for ionized calcium 0.98 mmol/L (ref. 1.18-1.32 mmol/L) and PTH 1.3 mmol/L (ref. 2.0-8.5 pmol/L). Vitamin D status was sufficient with 25OHD at 73 nmol/L to 112 nmol/L (ref. 60-160 nmol/L) from 2016 through 2019. The patient was diagnosed with primary hypoparathyroidism and was treated with Alphacalcidol 0,5 μg × 1/daily, calcium 500 mg × 4 the first day followed by 400 mg × 2 and magnesium 360 mg × 3, which induced rapid clinical recovery with dissolvement of muscular pain and biochemical improvement. This case study suggests that further studies are needed to investigate the added value of routine monitoring for hypocalcemia as part of clinical follow-up of people living with HIV.
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Affiliation(s)
- Taran Gulden
- Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, 2650 Hvidovre, Denmark
| | - Sam Kafai Yahyavi
- Group of Skeletal, Mineral, and Gonadal Endocrinology, Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark
| | - Isabelle Paula Lodding
- Department of Infectious Diseases, Hvidovre Hospital, University of Copenhagen, 2650 Hvidovre, Denmark
| | - Jens-Erik Beck Jensen
- Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, 2650 Hvidovre, Denmark.,Institute of Clinical Medicine, University of Copenhagen, Denmark
| | - Martin Blomberg Jensen
- Group of Skeletal, Mineral, and Gonadal Endocrinology, Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.,Division of Bone and Mineral Research, Harvard School of Dental Medicine/Harvard Medical School, Harvard University, Boston, MA 02108, United States
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46
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Rispoli MG, Ferri L, Ajdinaj P, Falzano V, Di Muzio A. Guillain-Barré syndrome and myasthenia gravis in the context of autoimmune polyendocrine syndrome type III. Neurol Sci 2021; 42:4789-4792. [PMID: 34331156 DOI: 10.1007/s10072-021-05517-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2021] [Accepted: 07/18/2021] [Indexed: 10/20/2022]
Affiliation(s)
- Marianna Gabriella Rispoli
- Department of Neuroscience, Imaging and Clinical Sciences, G. D'Annunzio University, SS Annunziata Hospital, Via dei Vestini, 66100, Chieti, Abruzzo, Italy. .,Center for Neuromuscular Diseases, "SS Annunziata" Hospital, Chieti, Abruzzo, Italy.
| | - Laura Ferri
- Department of Neuroscience, Imaging and Clinical Sciences, G. D'Annunzio University, SS Annunziata Hospital, Via dei Vestini, 66100, Chieti, Abruzzo, Italy.,Center for Neuromuscular Diseases, "SS Annunziata" Hospital, Chieti, Abruzzo, Italy
| | - Paola Ajdinaj
- Department of Neuroscience, Imaging and Clinical Sciences, G. D'Annunzio University, SS Annunziata Hospital, Via dei Vestini, 66100, Chieti, Abruzzo, Italy.,Center for Neuromuscular Diseases, "SS Annunziata" Hospital, Chieti, Abruzzo, Italy
| | - Valeriana Falzano
- Endocrinology Unit, "SS Annunziata" Hospital, Chieti, Abruzzo, Italy
| | - Antonio Di Muzio
- Center for Neuromuscular Diseases, "SS Annunziata" Hospital, Chieti, Abruzzo, Italy.,Department of Neurology, SS Annunziata Hospital, Chieti, Italy
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Cai Y, Yan J, Gu Y, Chen H, Chen Y, Xu X, Zhang M, Yu L, Zheng X, Yang T. Autoimmune thyroid disease correlates to islet autoimmunity on zinc transporter 8 autoantibody. Endocr Connect 2021; 10:534-542. [PMID: 33909592 PMCID: PMC8183620 DOI: 10.1530/ec-20-0650] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 04/28/2021] [Indexed: 11/27/2022]
Abstract
OBJECTIVE The most common coexisting organ-specific autoimmune disease in patients with type 1 diabetes mellitus (T1DM) is autoimmune thyroid disease (AITD). However, there have been few clinical reports based on a large population about the prevalence of zinc transporter 8 autoantibody (ZnT8A) and other islet autoantibodies in AITD patients. We aimed to explore the presence of islet autoantibodies, ZnT8A, glutamic acid decarboxylase autoantibodies (GADA) and insulinoma-associated antigen 2 autoantibodies (IA-2A) compared with thyroid autoantibodies, thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TGAb) and thyrotropin receptor autoantibodies (TRAb) in patients with Graves' disease (GD), Hashimoto's thyroiditis (HT) and T1DM patients with AITD. METHODS Totally, 389 patients with GD, 334 patients with HT, 108 T1DM patients with AITD and 115 healthy controls (HC) were recruited in the study. Islet autoantibodies (ZnT8A, GADA and IA-2A) were detected by radioligand binding assay. Thyroid autoantibodies, TPOAb and TGAb were detected by chemiluminescence assay, and TRAb was detected by RIA. RESULTS The prevalence of ZnT8A, GADA and IA-2A was higher in GD and HT patients than that of HC (ZnT8A: GD 8.48%, HT 10.8% vs HC 1.74%; GADA: GD 7.46%, HT 7.74% vs HC 0.870%; IA-2A: GD 4.88%, HT 3.59% vs HC 0%; All P < 0.05) but lower than that of T1DM subjects with AITD (ZnT8A: 42.6%; IA-2A: 44.4%; GADA: 74.1%; all P < 0.0001). CONCLUSIONS An increased prevalence of ZnT8A as well as GADA and IA-2A was found in both GD and HT patients, indicating that there is a potential link between thyroid autoimmunity and islet autoimmunity.
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Affiliation(s)
- Yun Cai
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jieni Yan
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yong Gu
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Heng Chen
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yang Chen
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xinyu Xu
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Mei Zhang
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Liping Yu
- Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Xuqin Zheng
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Correspondence should be addressed to X Zheng or T Yang: or
| | - Tao Yang
- Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Correspondence should be addressed to X Zheng or T Yang: or
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Htut TW, Thein KZ, Oo TH. Pernicious anemia: Pathophysiology and diagnostic difficulties. J Evid Based Med 2021; 14:161-169. [PMID: 34015185 DOI: 10.1111/jebm.12435] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 04/28/2021] [Indexed: 11/29/2022]
Abstract
Pernicious anemia (PA) is the most common cause of vitamin B12 (cobalamin) deficiency anemia in the world. It is an autoimmune disease, comprising of salient features of autoimmune chronic atrophic gastritis (CAG) and cobalamin deficiency (CD). Although the anemia was first described as pernicious, it may well be controlled with vitamin B12 replacement. The onset and progression of PA is often insidious. Alternatively, patients may have no anemic symptoms since they become acclimatized to the subtle nature of the disease. Oftentimes, there is a possibility that the underlying disease may be missed unless a full blood count (FBC) is investigated, leading to hindrance in the treatment journey. Diagnostic challenges remain tangible for many practicing clinicians, since there is lack of reliable cobalamin assays to diagnose CD as well as clinical mimics, which simulate many other hematological conditions, such as myelodysplastic syndrome, acute leukemia, sideroblastic anemias, bone marrow failure states, thrombotic microangiopathy, and thromboembolism. Moreover, prompt recognition of the symptoms of CD is also vital, because some neurologic sequalae may become irreversible despite replenishing cobalamin. Herein, we discuss a literature review on the pathophysiology, challenging clinical presentations and diagnostic difficulties of PA. Since the cobalamin replacement therapy for PA is straightforward, it will not be discussed in this review.
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Affiliation(s)
- Thura Win Htut
- Department of Hematology, Aberdeen Royal Infirmary Hospital, The University of Aberdeen, NHS Grampian, Scotland, UK
| | - Kyaw Zin Thein
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - Thein Hlaing Oo
- Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, USA
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Bosa L, Batura V, Colavito D, Fiedler K, Gaio P, Guo C, Li Q, Marzollo A, Mescoli C, Nambu R, Pan J, Perilongo G, Warner N, Zhang S, Kotlarz D, Klein C, Snapper SB, Walters TD, Leon A, Griffiths AM, Cananzi M, Muise AM. Novel CARMIL2 loss-of-function variants are associated with pediatric inflammatory bowel disease. Sci Rep 2021; 11:5945. [PMID: 33723309 PMCID: PMC7960730 DOI: 10.1038/s41598-021-85399-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Accepted: 03/01/2021] [Indexed: 01/31/2023] Open
Abstract
CARMIL2 is required for CD28-mediated co-stimulation of NF-κB signaling in T cells and its deficiency has been associated with primary immunodeficiency and, recently, very early onset inflammatory bowel disease (IBD). Here we describe the identification of novel biallelic CARMIL2 variants in three patients presenting with pediatric-onset IBD and in one with autoimmune polyendocrine syndrome (APS). None manifested overt clinical signs of immunodeficiency before their diagnosis. The first patient presented with very early onset IBD. His brother was found homozygous for the same CARMIL2 null variant and diagnosed with APS. Two other IBD patients were found homozygous for a nonsense and a missense CARMIL2 variant, respectively, and they both experienced a complicated postoperative course marked by severe infections. Immunostaining of bowel biopsies showed reduced CARMIL2 expression in all the three patients with IBD. Western blot and immunofluorescence of transfected cells revealed an altered expression pattern of the missense variant. Our work expands the genotypic and phenotypic spectrum of CARMIL2 deficiency, which can present with either IBD or APS, aside from classic immunodeficiency manifestations. CARMIL2 should be included in the diagnostic work-up of patients with suspected monogenic IBD.
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Affiliation(s)
- Luca Bosa
- Department of Woman's and Child's Health, University of Padova, 35128, Padua, Italy
| | - Vritika Batura
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada
| | - Davide Colavito
- Research & Innovation (R&I Genetics) Srl, C.so Stati Uniti 4, 35127, Padua, Italy
| | - Karoline Fiedler
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada
| | - Paola Gaio
- Department of Woman's and Child's Health, University of Padova, 35128, Padua, Italy
| | - Conghui Guo
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada
| | - Qi Li
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada
| | - Antonio Marzollo
- Pediatric Hematology, Oncology and Stem Cell Transplant Division, Padova University Hospital, 35128, Padua, Italy
- Fondazione Città della Speranza, Istituto di Ricerca Pediatrica, 35127, Padua, Italy
| | - Claudia Mescoli
- Department of Medicine, Padova University Hospital, 35128, Padua, Italy
| | - Ryusuke Nambu
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada
- Division of Gastroenterology and Hepatology, Saitama Children's Medical Center, 1-2 Shintoshin, Chuo-ku, Saitama, Saitama, 330-8777, Japan
| | - Jie Pan
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada
| | - Giorgio Perilongo
- Department of Woman's and Child's Health, University of Padova, 35128, Padua, Italy
| | - Neil Warner
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada
| | - Shiqi Zhang
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada
| | - Daniel Kotlarz
- Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Christoph Klein
- Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany
| | - Scott B Snapper
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA, USA
| | - Thomas D Walters
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada
- Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, M5G1X8, Canada
| | - Alberta Leon
- Research & Innovation (R&I Genetics) Srl, C.so Stati Uniti 4, 35127, Padua, Italy
| | - Anne M Griffiths
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada
- Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, M5G1X8, Canada
| | - Mara Cananzi
- Department of Woman's and Child's Health, University of Padova, 35128, Padua, Italy
| | - Aleixo M Muise
- SickKids Inflammatory Bowel Disease Centre, The Hospital for Sick Children, 555 University Ave, Toronto, ON, M5G 1X8, Canada.
- Department of Paediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON, M5G1X8, Canada.
- Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, ON, M5G0A4, Canada.
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Perniola R, Fierabracci A, Falorni A. Autoimmune Addison's Disease as Part of the Autoimmune Polyglandular Syndrome Type 1: Historical Overview and Current Evidence. Front Immunol 2021; 12:606860. [PMID: 33717087 PMCID: PMC7953157 DOI: 10.3389/fimmu.2021.606860] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 01/25/2021] [Indexed: 12/11/2022] Open
Abstract
The autoimmune polyglandular syndrome type 1 (APS1) is caused by pathogenic variants of the autoimmune regulator (AIRE) gene, located in the chromosomal region 21q22.3. The related protein, AIRE, enhances thymic self-representation and immune self-tolerance by localization to chromatin and anchorage to multimolecular complexes involved in the initiation and post-initiation events of tissue-specific antigen-encoding gene transcription. Once synthesized, the self-antigens are presented to, and cause deletion of, the self-reactive thymocyte clones. The clinical diagnosis of APS1 is based on the classic triad idiopathic hypoparathyroidism (HPT)—chronic mucocutaneous candidiasis—autoimmune Addison's disease (AAD), though new criteria based on early non-endocrine manifestations have been proposed. HPT is in most cases the first endocrine component of the syndrome; however, APS1-associated AAD has received the most accurate biochemical, clinical, and immunological characterization. Here is a comprehensive review of the studies on APS1-associated AAD from initial case reports to the most recent scientific findings.
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Affiliation(s)
- Roberto Perniola
- Department of Pediatrics-Neonatal Intensive Care, V. Fazzi Hospital, ASL LE, Lecce, Italy
| | - Alessandra Fierabracci
- Infectivology and Clinical Trials Research Department, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Alberto Falorni
- Section of Internal Medicine and Endocrinological and Metabolic Sciences, Department of Medicine, University of Perugia, Perugia, Italy
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