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Allen ME, Beck RT, Zwagerman NT, Coss D, Fisco A, Ioachimescu AG. Isolated IgG4-related Infundibulo-hypophysitis. JCEM CASE REPORTS 2024; 2:luae182. [PMID: 39416274 PMCID: PMC11482006 DOI: 10.1210/jcemcr/luae182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Indexed: 10/19/2024]
Abstract
A 72-year-old man presented with several months of weakness, poor appetite, and depressed moods. Laboratory tests indicated central hypocortisolism, hypothyroidism and hypogonadism, and mild hyperprolactinemia. Imaging indicated a homogenously enhancing solid suprasellar mass inseparable from the hypothalamus and contiguous with a thickened proximal infundibulum. Neuro-ophthalmological evaluation was normal. Symptoms improved with hydrocortisone, levothyroxine, and testosterone replacement. After 6 months, transsphenoidal biopsy was performed due to mass enlargement and revealed fibrosis, lymphoplasmacytic infiltration, and CD138 and IgG4 staining. The levels of serum IgG4, complement, inflammatory markers, protein electrophoresis, amylase, and lipase and imaging of the chest, abdomen, and thyroid were unremarkable. After 1 month of prednisone therapy (starting dose 40 mg/day), the mass significantly involuted and remained stable afterward. Prednisone was gradually tapered to 5 mg daily over 10 weeks. During 22 months of follow-up, no systemic IgG4 disease was detected. Glucocorticoid, thyroid, and testosterone replacement was continued. This case of isolated IgG4-related hypophysitis illustrates the variable presentation that may not entail vasopressin deficiency or clinical mass effect. This entity should be considered in the differential diagnosis of suprasellar masses even in the absence of IgG4 systemic disease or characteristic serology. Management entails multidisciplinary collaboration and long-term follow-up.
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Affiliation(s)
| | - Ryan T Beck
- Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226 USA
| | - Nathan T Zwagerman
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226 USA
| | - Dylan Coss
- Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI 53226 USA
| | - Amy Fisco
- Department of Medicine, Division of Endocrinology, Ascension All Saints Hospital, Racine, WI, USA
| | - Adriana G Ioachimescu
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226 USA
- Department of Medicine, Division of Endocrinology, Medical College of Wisconsin, Milwaukee, WI 53226 USA
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2
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Zhang SF, Deng J, Xiao J, Wu BH. Mikulicz's disease combined with IgG4-related hypophysitis: a case report. BMC Geriatr 2024; 24:522. [PMID: 38880897 PMCID: PMC11181676 DOI: 10.1186/s12877-024-05142-7] [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: 11/21/2023] [Accepted: 06/11/2024] [Indexed: 06/18/2024] Open
Abstract
BACKGROUND IgG4-related diseases are very uncommon, and its diagnosis and treatment are complicated as it encompasses multiple disciplines. CASE PRESENTATION A 77-year-old woman was admitted with a jaw mass and nausea and vomiting. Laboratory tests showed elevated serum IgG4, pituitary MRI suggested thickening of the pituitary stalk, and head and neck CT suggested orbital and mandibular masses. Patients with mandibular mass were diagnosed with Mikulicz's disease with IgG4-related hypophysitis. We found no other evidence of causing thickening of the pituitary stalk. She was given oral prednisolone 30 mg daily, and her nausea and vomiting improved significantly, and the mandibular and ocular masses decreased in size. CONCLUSION Mikulicz's disease combined with IgG4-related hypophysitis is a rare case of IgG4-RD in elderly women. IgG4-RD is one of the causes of head and neck exocrine gland mass and pituitary stalk thickening in the elderly.
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Affiliation(s)
- Shu-Fan Zhang
- Department of Geriatrics, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, China
| | - Jing Deng
- Department of Geriatrics, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, China
| | - Jie Xiao
- Department of Geriatrics, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, China
| | - Bi-Hua Wu
- Department of Geriatrics, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, China.
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Tahara S, Osamura RY, Hattori Y, Ishisaka E, Inomoto C, Sugihara H, Teramoto A, Morita A. Concurrent IgG4-related hypophysitis and clinically nonfunctioning gonadotroph pituitary neuroendocrine tumor. BMC Endocr Disord 2023; 23:96. [PMID: 37143052 PMCID: PMC10158217 DOI: 10.1186/s12902-023-01353-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 04/25/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND Some patients develop immunoglobulin G4 (IgG4)-related hypophysitis associated with systemic diseases. More than 30 cases of IgG4-related hypophysitis have been reported. However, biopsy has rarely been performed in these patients, and none have had an associated pituitary neuroendocrine tumor (PitNET). We present a case of concurrent IgG4-related hypophysitis and PitNET. CASE PRESENTATION A 56-year-old Japanese man arrived at the hospital with visual impairment, bitemporal hemianopia, and right abducens nerve palsy. Magnetic resonance imaging revealed pituitary body and stalk swelling as well as a small poorly enhanced right anterior lobe mass. Laboratory and loading test results suggested hypopituitarism. Because IgG4 level was elevated, a systemic examination was performed; multiple nodules were found in both lung fields. The diagnosis was based on an endoscopic transnasal biopsy of the pituitary gland. A histopathological examination revealed a marked infiltration of plasma cells into the pituitary gland, which was strongly positive for IgG4. The histological features of the resected tumor were consistent with those of gonadotroph PitNET, which was immunohistochemically positive for follicle-stimulating hormone-β and steroidogenic factor-1, and no plasma cell infiltration was observed. Based on the histopathological examination results, steroid therapy was initiated, which reduced pituitary gland size and serum IgG4 levels. DISCUSSION AND CONCLUSIONS This is the first reported case of IgG4-related hypophysitis with PitNET. Although no pathological findings indicating a relationship between the two conditions were found, we were able to preoperatively differentiate multiple lesions via detailed diagnostic imaging.
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Affiliation(s)
- Shigeyuki Tahara
- Department of Neurological Surgery, Graduate School of Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan.
| | | | - Yujiro Hattori
- Department of Neurological Surgery, Graduate School of Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan
- Department of Anatomy and Neurobiology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Eitaro Ishisaka
- Department of Neurological Surgery, Graduate School of Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan
| | - Chie Inomoto
- Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan
| | - Hitoshi Sugihara
- Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Nippon Medical School, Tokyo, Japan
| | | | - Akio Morita
- Department of Neurological Surgery, Graduate School of Medicine, Nippon Medical School, 1-1-5Bunkyo-Ku, SendagiTokyo, 113-8603, Japan
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Iwamoto Y, Mori S, Tatsumi F, Sugisaki T, Dan K, Katakura Y, Kimura T, Shimoda M, Nakanishi S, Mune T, Kaneto H. Central Diabetes Insipidus Due to IgG4-related Hypophysitis That Required over One Year to Reach the Final Diagnosis Due to Symptoms Being Masked by Sialadenitis. Intern Med 2022; 61:3541-3545. [PMID: 35569983 PMCID: PMC9790782 DOI: 10.2169/internalmedicine.9365-22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Pituitary inflammation due to IgG4-related disease is a rare condition and is sometimes accompanied by central diabetes insipidus. Central diabetes insipidus produces a strong thirst sensation, which may be difficult to distinguish when complicated by salivary insufficiency. A 45-year-old man was admitted to our department for a thorough examination of his thirst and polyuria. He had suddenly developed these symptoms more than one year earlier and visited an oral surgeon. Swelling of the left submandibular gland, right parotid gland, and cervical lymph nodes had been observed. Since his IgG4 level was relatively high at 792 mg/dL and a lip biopsy showed high plasmacytoid infiltration around the gland ducts, he had been diagnosed with IgG4-related disease. He had started taking 0.4 mg/kg/day of prednisolone, and his chief complaint temporarily improved. However, since the symptom recurred, he was referred to our institution. After admission, to examine the cause of his thirst and polyuria, we performed a water restriction test, vasopressin loading test, hypertonic saline loading test and pituitary magnetic resonance imaging. Based on the findings, we diagnosed him with central diabetes insipidus due to IgG4-related hypophysitis. We increased the dose of prednisolone to 0.6 mg/kg/day and started 10 μg/day of intranasal desmopressin. His symptoms were subsequently alleviated, and his serum IgG4 level finally normalized. We should remember that IgG4-related disease can be accompanied by hypophysitis and that central diabetes insipidus is brought about by IgG4-related hypophysitis. This case report should remind physicians of the fact that pituitary inflammation due to IgG4-related disease is very rare and can be masked by symptoms due to salivary gland inflammation, which can lead to pitfalls in the diagnosis in clinical practice.
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Affiliation(s)
- Yuichiro Iwamoto
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
| | - Shigehito Mori
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
| | - Fuminori Tatsumi
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
| | - Toshitomo Sugisaki
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
| | - Kazunori Dan
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
| | - Yukino Katakura
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
| | - Tomohiko Kimura
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
| | - Masashi Shimoda
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
| | - Shuhei Nakanishi
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
| | - Tomoatsu Mune
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
| | - Hideaki Kaneto
- Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Japan
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Chen K, Yao Y, Mao X, You H, Wang L, Duan L, Deng K, Zhang W, Lian X, Zhu H. Sellar germinoma mimicking IgG4-related hypophysitis: a case report. BMC Endocr Disord 2022; 22:23. [PMID: 35033046 PMCID: PMC8760830 DOI: 10.1186/s12902-021-00930-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 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: 06/08/2021] [Accepted: 12/30/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar germinoma is usually infiltrated by lymphocytes or plasma cells, and may be confused with hypophysitis. CASE PRESENTATION A 36-year-old man with diabetes insipidus, elevated serum IgG4 level (336 mg/dl), and sellar mass was suspected to have IgG4-related hypophysitis, and no other lesion of IgG4-related disease was detected. After treated by prednisone and mycophenolate mofetil, the serum IgG4 decreased to 214 mg/dl. However, after withdrawal of the drugs, the IgG4 level increased to 308 mg/dl. Endocrine assessments revealed panhypopituitarism, and the sellar mass enlarged. Transsphenoidal sellar exploration and biopsy was conducted. Pathological examination showed that the lesion was germinoma with lymphocytes and plasma cells infiltration, and IgG4-staining was positive (70/HPF, IgG4/IgG ratio = 10%). The patient was then treated by cisplatin and etoposide. After four cycles of chemotherapy, the serum IgG4 was 201 mg/dl, and the sellar mass was invisible. CONCLUSION Sellar germinoma can mimic the clinical characteristics of IgG4-related hypophysitis. Poor response to glucocorticoids can be used as an exclusion criterion in the clinical diagnosis of IgG4-related hypophysitis.
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Affiliation(s)
- Kang Chen
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China
| | - Yong Yao
- Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xinxin Mao
- Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Hui You
- Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Linjie Wang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China
| | - Lian Duan
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China
| | - Kan Deng
- Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Wen Zhang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xin Lian
- Department of Radiation Oncology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Huijuan Zhu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China.
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6
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Gersey ZC, Rajjoub KR, Pearce TM, Segel SA, Gardner PA, Snyderman CH, Wang EW, Zenonos GA. Immunoglobulin G4 hypophysitis in a 63-year-old woman with no autoimmune history: a case report. J Med Case Rep 2021; 15:446. [PMID: 34481512 PMCID: PMC8418724 DOI: 10.1186/s13256-021-03018-7] [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: 10/03/2020] [Accepted: 07/20/2021] [Indexed: 11/10/2022] Open
Abstract
Background Immunoglobulin-G4-related hypophysitis is a rare inflammatory disease that can present as a tumefactive pituitary lesion mimicking hypophyseal neoplasms such as pituitary adenoma or craniopharyngioma. The literature on this entity is sparse, with fewer than 100 cases reported across 19 publications; a recent review found only 24 cases published from 2007 to 2018. Previous reports have described demographic differences, with immunoglobulin-G4-related hypophysitis in females tending to present in the second and third decades in association with other autoimmune disease, while males tend to present in the fifth and sixth decades of life without an autoimmune history. Case presentation In contrast to the reported demographic trends, here we describe a unique case of immunoglobulin-G4-related hypophysitis in a 63-year-old white female with no history of autoimmune disease who presented with a rapidly enlarging sellar and hypothalamic mass causing headaches and cranial nerve palsies, prompting biopsy for diagnosis. The patient experienced rapid response to treatment with high-dose steroids and rituximab. Conclusion The case contributes to the growing clinicopathologic description of immunoglobulin-G4-related hypophysitis and illustrates that this diagnosis should be a consideration even outside the conventional demographic setting.
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Affiliation(s)
- Zachary C Gersey
- Department of Neurological Surgery, University of Pittsburgh Medical Center, 200 Lothrop St Suite B-400, Pittsburgh, PA, 15213, USA.
| | - Kenan R Rajjoub
- Department of Neurological Surgery, The George Washington University School of Medicine, Washington, District of Columbia, USA
| | - Thomas M Pearce
- Division of Anatomic Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Scott A Segel
- Department of Endocrinology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Paul A Gardner
- Department of Neurological Surgery, University of Pittsburgh Medical Center, 200 Lothrop St Suite B-400, Pittsburgh, PA, 15213, USA
| | - Carl H Snyderman
- Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Eric W Wang
- Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Georgios A Zenonos
- Department of Neurological Surgery, University of Pittsburgh Medical Center, 200 Lothrop St Suite B-400, Pittsburgh, PA, 15213, USA.
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7
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Amirbaigloo A, Esfahanian F, Mouodi M, Rakhshani N, Zeinalizadeh M. IgG4-related hypophysitis. Endocrine 2021; 73:270-291. [PMID: 33837927 DOI: 10.1007/s12020-021-02714-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 03/23/2021] [Indexed: 12/13/2022]
Abstract
Hypophysitis is a rare pituitary inflammatory disorder classified in different ways. Immunoglobulin G4-related disease (IgG4-RD), also a rare disease is a systemic fibro-inflammatory condition characterized by infiltration of tissue with IgG4-positive plasma cells; however prevalence of both of them probably is underestimated. In this paper, we present an Iranian patient with biopsy-proven IgG4-related hypophysitis and then review the clinical characteristics, laboratory, imaging, pathologic findings and therapeutic management as well as prognosis of 115 published cases of hypophysitis secondary to IgG4-related disease.
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Affiliation(s)
| | - Fatemeh Esfahanian
- Department of Endocrinology and Metabolism, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
| | - Marjan Mouodi
- Department of Endocrinology and Metabolism, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasser Rakhshani
- Department of Pathology, Firoozgar Hospital, Iran University of medical sciences, Tehran, Iran
| | - Mehdi Zeinalizadeh
- Department of Neurological Surgery, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
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8
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Autoimmune Hypophysitis with Late Renal Involvement: A Case Report. ENDOCRINES 2021. [DOI: 10.3390/endocrines2020016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We report a case of a 50-year-old male admitted to the Endocrinology Unit because of persistent headaches, nausea, feeling tired, sudden weight loss, cold intolerance, decreased appetite, and lack of sex interest. Diagnostic workup showed a 6-millimeter pituitary tumor without signs of compression, and a condition of progressive panhypopituitarism. After 12 months of hormone replacement therapy, the patient was hospitalized because of sudden weight gain, periorbital-peripheral edema, severe dyslipidemia, hypertension, and proteinuria. Corticosteroid therapy was shifted from oral to continuous intravenous infusion, and once the diagnosis of “immune complex-mediated glomerulonephritis with mesangial deposits suggestive for membranoproliferative glomerulonephritis type IIIIgG4-positive” was made, the immunosuppressant mycophenolate (1500 mg/day) was started. After a 6-month follow-up, the complete resolution of renal symptoms was accompanied by the disappearance of a pituitary lesion and the patient was back to prior hormone replacement therapy. Autoimmune hypophysitis (AH) is a rare autoimmune inflammatory disease of the pituitary gland that can impair hormone secretion and function. IgG4-hypophysitis is rare and is usually associated with other IgG4-related diseases. Herein, we describe a rare case of AH associated with late renal disease, and without any other organ involvement.
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9
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Saitakis G, Chwalisz BK. The neurology of IGG4-related disease. J Neurol Sci 2021; 424:117420. [PMID: 33845982 DOI: 10.1016/j.jns.2021.117420] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 10/29/2020] [Accepted: 03/24/2021] [Indexed: 12/26/2022]
Abstract
PURPOSE OF REVIEW IgG4-related disease (IgG4-RD) is emerging as a fibro-inflammatory entity affecting multiple organs, including manifold neurologic manifestations. This review discusses general characteristics of IgG4-RD neurologic disease including epidemiology, histology, clinical picture and treatment approaches. RECENT FINDINGS IgG4-RD is increasingly recognized as an important underlying pathophysiology in multiple disorders of neurologic interest, including orbital inflammation, infundibulo-hypophysitis, hypertrophic pachymeningitis, and even in rare cases CNS parenchymal disease and cranial vascular involvement. These were previously considered idiopathic and unrelated to any systemic disease but now known to share a common histopathology. New knowledge regarding the pathogenesis, clinical features and epidemiology of IgG4 is emerging, and new neurological manifestations continue to be described. Diagnostic progress includes CT-PET imaging, the use of flow cytometry for plasmablast quantification, and the use of reverse passive latex agglutination aiming to overcome the prozone phenomenon. Histopathologic confirmation of IgG4-RD remains the gold standard method of diagnosis but new diagnostic criteria for systemic and organ-specific disease are being proposed. Though glucorticoids remain the mainstay of therapy, relapses and incomplete recovery are frequent. Rituximab is a promising treatment in IgG4-RD that is severe, refractory or glucocorticoid dependent. Initiation of immunosuppression at an early stage of disease should be considered in order to avoid development of refractory fibrosis. SUMMARY The current review emphasizes the neurologic manifestations of IgG4-RD.
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Affiliation(s)
- G Saitakis
- Division of Neuro-Ophthalmology, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary/Harvard Medical School, Boston, MA, USA
| | - B K Chwalisz
- Division of Neuro-Ophthalmology, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary/Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
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10
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Arya VB, El-Gasim SA, Das S, Reisz Z, Zebian B, D'Cruz D, King A, Hampton T, Aylwin SJB, Kapoor RR, Buchanan CR. IgG4-related hypophysitis in adolescence. J Pediatr Endocrinol Metab 2021; 34:395-399. [PMID: 33675204 DOI: 10.1515/jpem-2020-0535] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 11/05/2020] [Indexed: 12/14/2022]
Abstract
OBJECTIVES IgG4-related hypophysitis is a novel clinical disease entity, which is typically seen in the sixth decade of life and is typically complicated by hypopituitarism. We describe an adolescent female with IgG4-related hypophysitis with normal pituitary function and summarize the relevant literature. CASE PRESENTATION A 11.8-year-old girl presented with headache and left VI cranial nerve palsy. MRI brain identified an enlarged pituitary gland. Endocrine investigations revealed normal pituitary function. She underwent a transsphenoidal biopsy of the pituitary gland, and histological examination confirmed the diagnosis of IgG4-related hypophysitis. Serum IgG4 concentrations were normal and no evidence of other organ involvement was found. Although the patient tested strongly positive for TB on an interferon gamma release assay, pituitary biopsy was negative for granuloma formation and acid-fast bacilli (Ziehl-Neelson staining). IgG4-related hypophysitis was treated with oral prednisolone and mycophenolate-mofetil with a good response. CONCLUSIONS We describe to the best of our knowledge, the youngest patient in the published literature with IgG4-related hypophysitis presenting without pituitary insufficiency. A literature review identified only five cases of IgG4-related hypophysitis in adolescence. Serum IgG4 concentrations were normal in all, except one of the adolescent patients reported so far, and appear unhelpful in diagnosis in this age group.
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Affiliation(s)
- Ved Bhushan Arya
- Department of Paediatric Endocrinology, Variety Children Hospital, King's College Hospital NHS Foundation Trust, London, UK
| | - Sarra Abu El-Gasim
- Department of Paediatric Endocrinology, Variety Children Hospital, King's College Hospital NHS Foundation Trust, London, UK
| | - Sreena Das
- Department of Paediatrics, Variety Children Hospital, King's College Hospital NHS Foundation Trust, London, UK
| | - Zita Reisz
- Department of Neuropathology, King's College Hospital NHS Foundation Trust, London, UK
| | - Bassel Zebian
- Department of Neurosurgery, King's College Hospital NHS Foundation Trust, London, UK
| | - David D'Cruz
- Louise Coote Unit, Guy's and St Thomas NHS Foundation Trust, London, UK.,Division of Immunology, Infection and Inflammatory Diseases, King's College London, London, UK
| | - Andrew King
- Department of Neuropathology, King's College Hospital NHS Foundation Trust, London, UK
| | - Tim Hampton
- Department of Neuroradiology, King's College Hospital NHS Foundation Trust, London, UK
| | - Simon J B Aylwin
- Department of Endocrinology, King's College Hospital NHS Foundation Trust, London, UK
| | - Ritika R Kapoor
- Department of Paediatric Endocrinology, Variety Children Hospital, King's College Hospital NHS Foundation Trust, London, UK.,Faculty of Medicine and Life Science, King's College London, London, UK
| | - Charles R Buchanan
- Department of Paediatric Endocrinology, Variety Children Hospital, King's College Hospital NHS Foundation Trust, London, UK
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11
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Vasaitis L, Wikström J, Ahlström S, Gudjonsson O, Kumlien E, Edén Engström B, Casar-Borota O. Histopathological findings in the landscape of IgG4-related pathology in patients with pituitary dysfunction: Review of six cases. J Neuroendocrinol 2021; 33:e12942. [PMID: 33615590 DOI: 10.1111/jne.12942] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 01/05/2021] [Accepted: 01/19/2021] [Indexed: 12/18/2022]
Abstract
IgG4-related hypophysitis (IgG4-RH) is increasingly being reported as an isolated entity or, less frequently, as a manifestation of a multiorgan IgG4-related disease (IgG4-RD), in which typical histopathology is a cornerstone for the diagnosis. We aimed to describe the histopathological changes in the surgical specimens from patients with clinical signs of pituitary disease that fulfilled the current diagnostic criteria for IgG4-RH. Histopathological features were correlated with clinical and radiological findings. Of 19 patients with pituitary dysfunction and inflammatory changes in the surgical pituitary specimen operated on during 2011-2019, we identified five patients with typical IgG4-related pathology (lymphoplasmacytic infiltration with more than 10 IgG4-positive plasma cells per one high power microscopic field, representing at least 40% of all plasma cells and at least focal storiform fibrosis). One patient with diabetes insipidus and pachymeningitis with IgG4-related changes in a biopsy from the dura was also included. Additional histopathological changes that typically are not part of the IgG4-RH were observed: Rathke's cleft cyst in four and granulomatous changes in two patients. One patient had an elevated serum IgG4 level and systemic manifestations that could be associated with the systemic IgG4-RD. Our findings indicate that pure IgG4-RH is uncommon. All patients with pituitary dysfunction, beyond typical IgG4-related pathology, had other pathological findings that could trigger the secondary IgG4-response. Both primary pathology and secondary IgG4-related features should be reported in patients with pituitary dysfunction because their co-occurrence may cause atypical clinical and imaging features, and unexpected response to surgical and pharmacological treatment. The current criteria for the diagnosis of IgG4-RH can lead to overdiagnosis of IgG4-RH if additional pathological changes are not taken into consideration. The classification criteria of IgG4-RD proposed by the American College of Rheumatology/European League Against Rheumatism could help classify patients more properly as IgG4-RH if applied to the pituitary gland.
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Affiliation(s)
- Lilian Vasaitis
- Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden
| | - Johan Wikström
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Sengul Ahlström
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden
| | | | - Eva Kumlien
- Department of Neuroscience, Uppsala University, Uppsala, Sweden
| | - Britt Edén Engström
- Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden
| | - Olivera Casar-Borota
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden
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12
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Hajsadeghi S, Pakbaz M, Hassanzadeh M, Sadeghipour A. A challenging case report of IgG4-related systemic disease involving the heart and retroperitoneum with a literature review of similar heart lesions. Echocardiography 2020; 37:1478-1484. [PMID: 32841427 DOI: 10.1111/echo.14828] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2020] [Revised: 07/09/2020] [Accepted: 07/27/2020] [Indexed: 12/13/2022] Open
Abstract
The IgG4-related disease is a distinct, steroid-responsive fibro-inflammatory disorder of unknown etiology. This multiorgan disease is characterized by tumefactive lesions that contain rich infiltrations of IgG4-positive plasma cells, with the pancreas, and the salivary and lacrimal glands being the main involved. The more common cardiovascular involvements include inflammatory peri-aortitis, coronary arteritis, and pericarditis. Intra-cardiac tumefactive lesions are rarely reported. Herein, we describe a challenging case of IgG4-related disease with a long-time lag between initiation of symptoms to proper diagnosis with biopsy-proven cardiac and retroperitoneal and possible pituitary gland involvement. Concerning the rarity of the cardiac lesion in our case, we conducted a literature review of similar case reports.
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Affiliation(s)
- Shokoufeh Hajsadeghi
- Research Center for Prevention of Cardiovascular Disease, Institute of Endocrinology & Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Marziyeh Pakbaz
- Department of Cardiovascular Disease, Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Morteza Hassanzadeh
- Department of Internal Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Sadeghipour
- Department of Pathology and Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
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13
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Ogasawara N, Imamura T, Koyama R, Inoshita N, Nakayama A, Hattori D, Ito Y, Sato Y, Tamura T, Hashimoto M. Pancreatic ductal adenocarcinoma with mismatch repair deficiency resected after long-term observation. Clin J Gastroenterol 2020; 13:959-968. [PMID: 32424776 DOI: 10.1007/s12328-020-01128-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Accepted: 04/14/2020] [Indexed: 10/24/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) with mismatch repair (MMR) deficiency is a rare subtype, clinicopathological features of which have not been fully understood. A 70-year-old woman was admitted for the investigation of a 20-mm pancreatic tumor in the pancreatic head, detected during the cause scrutiny of exacerbation of diabetes mellitus and panhypopituitarism. The tumor decreased in size after administration of hydrocortisone for panhypopituitarism. Autoimmune pancreatitis, complicated with hypophysitis, was suspected, and prednisolone treatment was administered. The tumor did not show enlargement for 3 years during which a dose of prednisolone was maintained. However, 1.5 years after the cessation of prednisolone administration, the tumor size increased again. On endoscopic ultrasonography, the tumor was found to be a 25.2-mm mass lesion with almost uniformly low echogenicity and blood flow signal, and anisonucleosis on cytodiagnosis was revealed. Pancreatoduodenectomy was performed, and on histological analysis, moderately differentiated tubular adenocarcinoma with massive lymphocytic infiltration was observed. Immunohistochemistry revealed a concomitant loss of MSH2 and MSH6 in the tumor cells, which implicated mutant MSH2 gene. She has remained well with no recurrence for 2.9 years since her surgery. We herein report a case of PDAC with MMR deficiency, resected after long-term observation.
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Affiliation(s)
- Nobuhiko Ogasawara
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan
| | - Tsunao Imamura
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan.
| | - Rikako Koyama
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan
| | - Naoko Inoshita
- Department of Pathology, Toranomon Hospital, Tokyo, Japan
| | | | - Daisuke Hattori
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan
| | - Yasuo Ito
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan
| | - Yoshiki Sato
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan
| | - Tetsuo Tamura
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan
| | - Masaji Hashimoto
- Department of Gastrointestinal Surgery, Toranomon Hospital, Tokyo, Japan
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14
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Takahashi M, Fujinaga Y, Notohara K, Koyama T, Inoue D, Irie H, Gabata T, Kadoya M, Kawa S, Okazaki K. Diagnostic imaging guide for autoimmune pancreatitis. Jpn J Radiol 2020; 38:591-612. [PMID: 32297064 DOI: 10.1007/s11604-020-00971-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 04/01/2020] [Indexed: 02/07/2023]
Abstract
The International Consensus Diagnosis Criteria for autoimmune pancreatitis (AIP) has been published internationally for the diagnosis of AIP. However, since the revisions in 2006 and 2011, the Clinical Diagnostic Criteria for Autoimmune Pancreatitis 2018 have been published. The criteria were revised based the Clinical Diagnostic Criteria 2011, and included descriptions of characteristic imaging findings such as (1) pancreatic enlargement and (2) distinctive narrowing of the main pancreatic duct. In addition, pancreatic duct images obtained by magnetic resonance cholangiopancreatography as well as conventional endoscopic retrograde pancreatography were newly adopted. The guideline explains some characteristic imaging findings, but does not contain descriptions of the imaging methods, such as detailed imaging parameters and optimal timings of dynamic contrast-enhanced computed tomography/magnetic resonance imaging. It is a matter of concern that imaging methods can vary from hospital to hospital. Although other characteristic findings have been reported, these findings were not described in the guideline. The present paper describes the imaging methods for obtaining optimal images and the characteristic imaging findings with the aim of standardizing image quality and improving diagnostic accuracy when radiologists diagnose AIP in actual clinical settings.
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Affiliation(s)
- Masaaki Takahashi
- Department of Radiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Yasunari Fujinaga
- Department of Radiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Okayama, Japan
| | - Takashi Koyama
- Department of Diagnostic Radiology, Kurashiki Central Hospital, Kurashiki, Okayama, Japan
| | - Dai Inoue
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Hiroyuki Irie
- Department of Radiology, Faculty of Medicine, Saga University, Saga, Japan
| | - Toshifumi Gabata
- Department of Radiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
| | - Masumi Kadoya
- Department of Radiology, Hohseikai Marunouchi Hospital, Matsumoto, Japan
| | - Shigeyuki Kawa
- Department of Internal Medicine, Matsumoto Dental University, Shiojiri, Japan
| | - Kazuichi Okazaki
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
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15
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Lojou M, Bonneville JF, Ebbo M, Schleinitz N, Castinetti F. IgG4 hypophysitis: Diagnosis and management. Presse Med 2020; 49:104016. [PMID: 32234384 DOI: 10.1016/j.lpm.2020.104016] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Accepted: 02/13/2019] [Indexed: 02/06/2023] Open
Abstract
IgG4-related hypophysitis is a rare disease, due to a lymphoplasmocytic IgG4 positive infiltration of the pituitary. Literature data are scarce, even though the description of cases has drastically increased over the last years. The aim of this review is to better characterize the natural history, the diagnosis and the management of IgG4-related hypophysitis, based on a clinical case, an exhaustive Pubmed research, and a reappraisal of the criteria for diagnosis. We will specifically focus on the differences with other etiologies of hypophysitis, in the aim of improving the diagnostic procedures for all the physicians who could have to take care of such patients.
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Affiliation(s)
- M Lojou
- Inserm, U1251, CRMR HYPO, department of endocrinology, Aix-Marseille université, La Conception hospital, AP-HM, 147, boulevard Baille, Marseille, France
| | - J F Bonneville
- Departments of endocrinology and medical imaging, centre hospitalier universitaire de Liège, Liège, Belgium
| | - M Ebbo
- Département de médecine interne, Timone, Aix-Marseille université, AP-HM, 13005 Marseille, France
| | - N Schleinitz
- Département de médecine interne, Timone, Aix-Marseille université, AP-HM, 13005 Marseille, France
| | - F Castinetti
- Inserm, U1251, CRMR HYPO, department of endocrinology, Aix-Marseille université, La Conception hospital, AP-HM, 147, boulevard Baille, Marseille, France.
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16
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Gubbi S, Hannah-Shmouni F, Verbalis JG, Koch CA. Hypophysitis: An update on the novel forms, diagnosis and management of disorders of pituitary inflammation. Best Pract Res Clin Endocrinol Metab 2019; 33:101371. [PMID: 31866206 PMCID: PMC7078033 DOI: 10.1016/j.beem.2019.101371] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hypophysitis is a heterogeneous condition that leads to inflammation of the sella and/or suprasellar region, potentially resulting in hormonal deficiencies and/or mass effects. A preponderance of hypophysitis subtypes have an underlying autoimmune aetiology. The overall incidence and prevalence of hypophysitis has dramatically increased over the past decade, mainly due to increased awareness of the condition in the medical community, improvements in imaging techniques, and a rise in the occurrence of certain forms of hypophysitis such as IgG4 hypophysitis (IgG4Hy) and immune checkpoint inhibitor induced hypophysitis (ICIHy). The clinical presentation varies from an asymptomatic condition to a fatal disease often as a result of electrolyte abnormalities due to glucocorticoid deficiency in the context of adrenal crisis from central adrenal insufficiency. Milder forms of hypophysitis are treated with replacement of deficient hormones while more acute presentations with mass effects require glucocorticoid therapy, immunosuppressive therapy or surgery. Timely diagnosis and interventions are keys to prevention of the lethal complications of this disease. In this review, we provide an update on the recent advances in the field of pituitary autoimmunity, with an emphasis on autoimmune hypophysitis and novel forms of hypophysitis such as anti-PIT1 hypophysitis, IgG4Hy and ICIHy.
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Affiliation(s)
- Sriram Gubbi
- Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
| | - Fady Hannah-Shmouni
- Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
| | - Joseph G Verbalis
- Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University Medical Center, Washington, DC, 20007, USA.
| | - Christian A Koch
- The University of Tennessee Health Science Center, Memphis, TN, 38163, USA; Fox Chase Cancer Center, Philadelphia, PA, USA.
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17
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Wehbeh L, Alreddawi S, Salvatori R. Hypophysitis in the era of immune checkpoint inhibitors and immunoglobulin G4-related disease. Expert Rev Endocrinol Metab 2019; 14:167-178. [PMID: 30939947 DOI: 10.1080/17446651.2019.1598260] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Accepted: 03/19/2019] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Hypophysitis is a rare disorder, defined as inflammation of the pituitary gland that may result in pituitary enlargement and varying anterior and posterior pituitary hormonal deficits. It involves different histopathological subtypes and variable etiologies, with considerable overlap between classification systems. Histopathology is the gold standard diagnostic approach. AREAS COVERED In this article, we will review the major histopathological subtypes of hypophysitis with a special focus on immunoglobulin G4 (IgG4)-related hypophysitis and immune checkpoint inhibitor-induced hypophysitis, given their recent appearance and increasing incidence. We will summarize the similarities and differences between the different subtypes as it relates to epidemiology, pathogenesis, presentation, diagnosis, and management. EXPERT OPINION Hypophysitis is a heterogeneous and wide term used to describe different, possibly distinct diseases often with poorly understood pathogenesis. It involves a wide range of subtypes with certain differences in incidence rates, pathogenesis, and management. Management usually focuses on relieving the mass effect symptoms and replacing the deficient pituitary hormones. Spontaneous recovery is possible but recurrence is not uncommon.
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Affiliation(s)
- Leen Wehbeh
- a Division of Endocrinology, Diabetes and Metabolism, and Pituitary Center , The Johns Hopkins University Hospital , Baltimore , MD , USA
| | - Sama Alreddawi
- b Medstar Health Internal Medicine Residency Program, Department of Medicine , Union Memorial Hospital , Baltimore , MD , USA
| | - Roberto Salvatori
- a Division of Endocrinology, Diabetes and Metabolism, and Pituitary Center , The Johns Hopkins University Hospital , Baltimore , MD , USA
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18
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Disease heterogeneity in IgG4-related hypophysitis: report of two histopathologically proven cases and review of the literature. Virchows Arch 2019; 475:373-381. [PMID: 30911814 DOI: 10.1007/s00428-019-02564-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 03/14/2019] [Accepted: 03/17/2019] [Indexed: 12/20/2022]
Abstract
IgG4-related hypophysitis (IgG4-RH) is a rare disease, which can occur singularly or as manifestation of a systemic IgG4-related disease (IgG4-RD). Less than one hundred cases have been reported in the literature, very few of which were histopathologically documented. We analyzed the clinical, radiological, and histopathological features of two cases of IgG4-RH, the former observed in a 66-year-old man in the context of an IgG4-RD, and the latter affecting a 21-year-old woman, as an isolated lesion. In addition, we performed a comprehensive review of the previously published histopathologically documented cases of IgG4-RH. Pituitary samples from both patients showed dense lymphoplasmacytic infiltration, interstitial and storiform fibrosis, and high numbers of IgG4-positive plasma cells, consistent with IgG4-RH. From the literature review, we retrieved 18 papers reporting a total of 22 cases of histopathologically documented IgG4-RH. The revision of these cases, also including the two reported herein, showed an equal distribution of IgG4-RH in the two sexes, albeit significant clinico-pathological variation was found between cases arisen in female and male patients, respectively. In detail, IgG4-RH females were affected in their second-third decade of life, with a solitary pituitary lesion, low IgG4 serum level, and frequent association with autoimmune disorders. By contrast, IgG4-RH in men was a disease of the elderly, often in the context of a systemic IgG4-RD, with high IgG4 serum levels. Our study shows that IgG4-RH, as currently defined, is a clinically heterogenous disease, with different features in the two sexes. Indeed, cases diagnosed in young women, as our case 2, mostly do not present other evidence of IgG4-RD and might be better classified as lymphocytic hypophysitis with abundant IgG4+ plasma cells. For this reason, the histopathological examination of the pituitary lesion, particularly in female patients, may still be useful for a correct differential diagnosis with other variants of primary hypophysitis.
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19
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Kanie K, Bando H, Iguchi G, Shiomi H, Masuda A, Fukuoka H, Nishizawa H, Fujita Y, Sakai A, Kobayashi T, Shiomi Y, Yoshida K, Matsumoto R, Suda K, Kodama Y, Ogawa W, Takahashi Y. IgG4-related hypophysitis in patients with autoimmune pancreatitis. Pituitary 2019; 22:54-61. [PMID: 30607745 DOI: 10.1007/s11102-018-00930-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
PURPOSE IgG4-related disease involves various organs including the pituitary and pancreas. The prevalence of IgG4-related hypophysitis is relatively rare compared with IgG4-related pancreatitis (autoimmune pancreatitis). Although several cases demonstrating both autoimmune pancreatitis and hypophysitis have been reported, the prevalence of IgG4-related hypophysitis in patients with autoimmune pancreatitis remains unknown. This study aimed at screening for IgG4-related hypophysitis to accurately determine its prevalence in patients with autoimmune pancreatitis. METHODS In this cohort study, we screened IgG4-related hypophysitis via pituitary magnetic resonance imaging (MRI) and endocrinological examination in 27 patients who were undergoing follow-up for autoimmune pancreatitis at Kobe University Hospital between 2014 and 2018. RESULTS Among 27 patients with autoimmune pancreatitis, 5 patients exhibited morphological abnormalities in the pituitary (18.5%). Among them, one patient (3.7%) met the criteria for hypophysitis with an enlarged pituitary and stalk concomitant with hypopituitarism. After glucocorticoid treatment, the enlarged pituitary shrank and became empty sella during the clinical course. Four patients (14.8%) revealed empty sella without obvious pituitary dysfunction. Four of 5 patients with morphological pituitary abnormalities showed multiple organ involvement in addition to pancreatic and pituitary involvement. Accordingly, multiple organ involvement was more prevalent in patients with morphological pituitary abnormalities (80%) compared to those without (48%). CONCLUSIONS Although a large-scale study is necessary to validate these results, these data suggest that the prevalence of hypophysitis in patients with autoimmune pancreatitis may be underestimated. Based on our findings, we recommend screening for hypophysitis, especially in patients with multiple organ involvement.
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Affiliation(s)
- Keitaro Kanie
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Hironori Bando
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Genzo Iguchi
- Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan
| | - Hideyuki Shiomi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Atsuhiro Masuda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hidenori Fukuoka
- Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan
| | - Hitoshi Nishizawa
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Yasunori Fujita
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Arata Sakai
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuuki Shiomi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kenichi Yoshida
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Ryusaku Matsumoto
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Kentaro Suda
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Wataru Ogawa
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Yutaka Takahashi
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
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20
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Rzepecka A, Babińska A, Sworczak K. IgG4-related disease in endocrine practice. Arch Med Sci 2019; 15:55-64. [PMID: 30697253 PMCID: PMC6348348 DOI: 10.5114/aoms.2017.70889] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 09/28/2017] [Indexed: 12/24/2022] Open
Abstract
IgG4-related disease is a set of symptoms resulting from a chronic, usually multiple organ inflammatory condition which affects various organs. It consists of lymphoplasmacytic infiltrations with attendant fibrosis and deep vein thrombosis. Frequently observed tissue lesions are accompanied by elevated IgG4 levels in serum. The etiopathogenesis of the lesions is of multifactor character and the clinical manifestation of the disease is highly diverse. The diagnostic process is based on the patient's medical history, clinical examination and additional tests, including a histopathological examination of the infected organ's tissues. Almost forty different locations of the disease have been reported, including disorders of the endocrine system. IgG4-related endocrinopathies are quite rare. However, it is likely that the diagnosis is under-reported due to lack of awareness of this clinical entity. Despite increasing interest in the subject, there are not enough reliable studies evaluating the link between IgG4-RD and endocrine disorders.
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Affiliation(s)
- Agata Rzepecka
- Department of Endocrinology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland
| | - Anna Babińska
- Department of Endocrinology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland
| | - Krzysztof Sworczak
- Department of Endocrinology and Internal Medicine, Medical University of Gdansk, Gdansk, Poland
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21
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Li Y, Gao H, Li Z, Zhang X, Ding Y, Li F. Clinical Characteristics of 76 Patients with IgG4-Related Hypophysitis: A Systematic Literature Review. Int J Endocrinol 2019; 2019:5382640. [PMID: 31929792 PMCID: PMC6935800 DOI: 10.1155/2019/5382640] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 10/20/2019] [Accepted: 11/19/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND IgG4-related hypophysitis (IgG4-RH) is a rare disease, and its prevalence remains unclear. In recent years, an increasing number of cases have been reported because of the increasing recognition of this disease. We aimed to summarize case reports of IgG4-RH and outline the clinical features and outcomes. METHODS We performed PubMed search of articles using the search terms "hypophysitis [AND] IgG4." Consequently, only 54 English articles (76 cases) met Leporati's diagnostic criteria. RESULTS Of the 76 cases, the ratio of men to women was 1.5 : 1, and the age at diagnosis was 54.1 ± 17.8 years. The median IgG4 concentration was 405.0 mg/dl. Anterior hypopituitarism, isolated central diabetes insipidus, and panhypopituitarism were observed in 14 (18.4%), 12 (15.8%), and 44 (57.9%) cases, respectively. The sequence of anterior hormone deficiency was as follows: gonadotropin (68.4%), ACTH (63.2%), TSH (59.2%), GH (48.7%), and prolactin (42.1%). The median number of involved organs was 1.5, and the lung (18.4%), retroperitoneum (17.1%), kidney (15.8%), submandibular glands (14.5%), and pancreas (13.2%) were the common involved organs. Elevated IgG4 concentration and normal IgG4 level were in 42 (76.4%) and 13 (23.6%) cases, respectively. Patients with elevated serum IgG4 concentration were older (60.9 ± 14.3 vs 45.6 ± 17.4, p=0.001) and male-prone (78.6% vs 40.4%, p=0.003) and had a susceptibility of multiple organ involvement (78.6% vs 35.0%, p=0.001) compared to those with normal serum IgG4 levels. Males were older at disease onset (61.5 ± 12.6 vs 42.9 ± 18.8, p < 0.001) and had a higher IgG4 concentration (425.0 vs 152.5, p=0.029) and a greater number of involved organs (2.0 vs 0.0, p=0.001), while isolated hypophysitis was more prominent in female (63.3% vs 26.1%, p=0.001). CONCLUSION In this review, we found that there were different characteristics between different genders. Patients with elevated serum IgG4 level in terms of some clinical features were also different from those with normal serum IgG4 level. However, the data in this review were limited by bias and confounding. Further clinical studies with larger sample sizes are warranted.
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Affiliation(s)
- Yujuan Li
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Hua Gao
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhen Li
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Xinxin Zhang
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Yizhi Ding
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Fengao Li
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
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22
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Kuranari Y, Tamura R, Mikami S, Ohara K, Toda M, Yoshida K. Severe headache in a patient with meningioma showing extensive dural tail correlates with IgG4-positive plasma cells and eosinophils: A case report and review of literature. Surg Neurol Int 2018; 9:202. [PMID: 30386672 PMCID: PMC6194731 DOI: 10.4103/sni.sni_231_18] [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: 07/07/2018] [Accepted: 08/17/2018] [Indexed: 11/04/2022] Open
Abstract
Background Meningiomas originate from meningothelial cells of the arachnoid membrane. Few cases of meningioma with infiltration of inflammatory cells, such as lymphocytes and plasma cells, have been reported, and the mechanisms underlying meningioma-induced inflammatory reactions have not been fully elucidated. Case Description In this study, we report an extremely rare case of meningioma with infiltration of both IgG4-positive plasma cells and eosinophils showing extensive dural tail and reactive inflammation of the surrounding arachnoid tissue. The main clinical manifestation was a severe headache, which was improved by surgical excision of the tumor. Conclusion Only 8 cases of meningioma with IgG4-positive plasma cells have been reported, and only one case exhibited eosinophil infiltration. IgG4-related inflammatory response might mediate inflammation in surrounding tissue, resulting in thickening of the dura adjacent to a meningioma and severe headache. The mechanisms underlying inflammation by meningiomas require further investigation.
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Affiliation(s)
- Yuki Kuranari
- Department of Neurosurgery, Keio University School of Medicine, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Ryota Tamura
- Department of Neurosurgery, Keio University School of Medicine, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Shuji Mikami
- Division of Diagnostic Pathology, Keio University School of Medicine, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Kentaro Ohara
- Division of Diagnostic Pathology, Keio University School of Medicine, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Masahiro Toda
- Department of Neurosurgery, Keio University School of Medicine, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Kazunari Yoshida
- Department of Neurosurgery, Keio University School of Medicine, Shinjuku-Ku, Tokyo, 160-8582, Japan
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Joshi MN, Whitelaw BC, Carroll PV. MECHANISMS IN ENDOCRINOLOGY: Hypophysitis: diagnosis and treatment. Eur J Endocrinol 2018; 179:R151-R163. [PMID: 29880706 DOI: 10.1530/eje-17-0009] [Citation(s) in RCA: 79] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 06/06/2018] [Indexed: 12/19/2022]
Abstract
Hypophysitis is a rare condition characterised by inflammation of the pituitary gland, usually resulting in hypopituitarism and pituitary enlargement. Pituitary inflammation can occur as a primary hypophysitis (most commonly lymphocytic, granulomatous or xanthomatous disease) or as secondary hypophysitis (as a result of systemic diseases, immunotherapy or alternative sella-based pathologies). Hypophysitis can be classified using anatomical, histopathological and aetiological criteria. Non-invasive diagnosis of hypophysitis remains elusive, and the use of currently available serum anti-pituitary antibodies are limited by low sensitivity and specificity. Newer serum markers such as anti-rabphilin 3A are yet to show consistent diagnostic value and are not yet commercially available. Traditionally considered a very rare condition, the recent recognition of IgG4-related disease and hypophysitis as a consequence of use of immune modulatory therapy has resulted in increased understanding of the pathophysiology of hypophysitis. Modern imaging techniques, histological classification and immune profiling are improving the accuracy of the diagnosis of the patient with hypophysitis. The objective of this review is to bring readers up-to-date with current understanding of conditions presenting as hypophysitis, focussing on recent advances and areas for future development. We describe the presenting features, investigation and diagnostic approach of the patient with likely hypophysitis, including existing conventional techniques and those in the research/development arena. Hypophysitis usually results in acute and persistent pituitary hormone deficiency requiring long-term replacement. Management of hypophysitis includes control of the inflammatory pituitary mass using a variety of treatment strategies including surgery and medical therapy. Glucocorticoids remain the mainstay of medical treatment but other immunosuppressive agents (e.g. azathioprine, rituximab) show benefit in some cases, but there is a need for controlled studies to inform practice.
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Affiliation(s)
- Mamta N Joshi
- Department of Endocrinology, Guy's & St. Thomas' NHS Foundation Trust, London, UK
| | - Benjamin C Whitelaw
- Department of Endocrinology, Kings College Hospital NHS Foundation Trust, London, UK
- Faculty of Life Sciences & Medicine, King's College Hospital London, London, UK
| | - Paul V Carroll
- Department of Endocrinology, Guy's & St. Thomas' NHS Foundation Trust, London, UK
- Faculty of Life Sciences & Medicine, King's College Hospital London, London, UK
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24
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Koide H, Shiga A, Komai E, Yamato A, Fujimoto M, Tamura A, Kono T, Nakayama A, Takiguchi T, Higuchi S, Sakuma I, Nagano H, Hashimoto N, Suzuki S, Takeda Y, Shibuya M, Nishioka H, Yamada S, Inoshita N, Ishiwatari N, Horiguchi K, Yokote K, Tanaka T. Prednisolone-responsive Postpartum IgG4-related Hypophysitis. Intern Med 2018; 57:367-375. [PMID: 29093382 PMCID: PMC5827318 DOI: 10.2169/internalmedicine.8446-16] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
We herein report the case of a 25-year-old woman who presented with severe headache and visual field defects after childbirth. Magnetic resonance imaging revealed marked swelling of the pituitary gland, and an endocrinological examination revealed panhypopituitarism and diabetes insipidus. An immunohistological analysis of a transsphenoidal biopsy sample of the pituitary gland showed the significant accumulation of an immunogloblin G4 (IgG4)-positive population, leading to the diagnosis of IgG4-related hypophysitis. The patient was treated with prednisolone, which markedly reduced the swelling of the pituitary gland, in association with recovery of the pituitary function. This is a rare case of biopsy-proven IgG4-related hypophysitis with a postpartum onset.
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Affiliation(s)
- Hisashi Koide
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Akina Shiga
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Eri Komai
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Azusa Yamato
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Masanori Fujimoto
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Ai Tamura
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Takashi Kono
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Akitoshi Nakayama
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Tomoko Takiguchi
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Seiichiro Higuchi
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Department of Molecular Diagnosis, Chiba University Graduate School of Medicine, Japan
| | - Ikki Sakuma
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Hidekazu Nagano
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Naoko Hashimoto
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Sawako Suzuki
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Yasuaki Takeda
- Department of Neurosurgery, Tokyo Yamate Medical Center, Japan
| | - Makoto Shibuya
- Central Laboratory, Hachioji Medical Center, Tokyo Medical University, Japan
| | - Hiroshi Nishioka
- Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Japan
| | - Shozo Yamada
- Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Japan
| | | | - Norio Ishiwatari
- Department of Neurological Surgery, Chiba University Hospital, Japan
| | - Kentaro Horiguchi
- Department of Neurological Surgery, Chiba University Hospital, Japan
| | - Koutaro Yokote
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine, Japan
| | - Tomoaki Tanaka
- Department of Medicine, Division of Diabetes, Metabolism and Endocrinology, Chiba University Hospital, Japan
- Department of Molecular Diagnosis, Chiba University Graduate School of Medicine, Japan
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25
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Rotondo F, Qaddoura A, Syro LV, Karamchandani J, Munoz DG, Arroyave MJ, Ospina WP, Cusimano MD, Kovacs K. Immunoglobulin G4 (IgG4)-Related Hypophysitis. Endocr Pathol 2017; 28:308-314. [PMID: 28084610 DOI: 10.1007/s12022-016-9464-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
We report two different cases of IgG4-related hypophysitis. In the first case, a pituitary lesion was accompanied by lymphocytic meningitis possibly mimicking tuberculous meningitis. The second case was unassociated with involvement of other organs. No histologic differences were noted between the two cases indicating that the morphologic features of the hypophysial lesion do not depend on the presence of other lesions. The pathogenesis of IgG4 hypophysitis is not known, and further study is necessary to explore the cause, progression, and influencing factors of this disease.
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Affiliation(s)
- Fabio Rotondo
- Department of Laboratory Medicine, Division of Pathology, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B1W8, Canada.
- Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada.
| | - Amro Qaddoura
- Department of Surgery, Division of Neurosurgery, St. Michael's Hospital, Toronto, ON, Canada
- Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada
| | - Luis V Syro
- Department of Neurosurgery, Hospital Pablo Tobon Uribe and Clinica Medellin, Medellin, Colombia
| | - Jason Karamchandani
- Department of Pathology, Montreal Neurological Hospital, McGill University, Montreal, QC, Canada
| | - David G Munoz
- Department of Laboratory Medicine, Division of Pathology, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B1W8, Canada
- Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada
| | - Mariam J Arroyave
- Department of Pathology, Laboratorio de Patologia y Citología Rodrigo Restrepo, Clinica Medellin, Medellin, Colombia
| | - William P Ospina
- Department of Internal Medicine, Infectious diseases, Clinica Medellin, Medellin, Colombia
| | - Michael D Cusimano
- Department of Surgery, Division of Neurosurgery, St. Michael's Hospital, Toronto, ON, Canada
- Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada
| | - Kalman Kovacs
- Department of Laboratory Medicine, Division of Pathology, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B1W8, Canada
- Keenan Research Centre for Biomedical Science at the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada
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Hadjigeorgiou GF, Lund EL, Poulsgaard L, Feldt-Rasmussen U, Rasmussen ÅK, Wegener M, Fugleholm K. Intrachiasmatic abscess caused by IgG4-related hypophysitis. Acta Neurochir (Wien) 2017; 159:2229-2233. [PMID: 28799078 DOI: 10.1007/s00701-017-3288-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Accepted: 07/26/2017] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Autoimmune hypophysitis is a rare disease of the pituitary, which may affect vision by inflammation and compression of the optic chiasm. However, intrachiasmatic abscess formation has not been previously reported. METHODS In this study, we report a case of a 29-year-old female with bitemporal hemianopia due to a cystic intrasellar tumor. The patient underwent surgical decompression of the lesion, which was found to be an intrachiasmatic abscess. RESULTS The histologic findings were consistent with IgG4 hypophysitis. CONCLUSION This rare clinical presentation suggests that in case of a disproportionate degree of visual impairment in relation to the size of the lesion, suspicion should lead to an intrachiasmatic lesion.
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Affiliation(s)
- Georgios F Hadjigeorgiou
- Department of Neurosurgery, Academic Hospital Munich-Bogenhausen, Technical University of Munich, Munich, Germany.
| | - Eva Løbner Lund
- Department of Pathology, University Hospital of Copenhagen, Copenhagen, Denmark
| | - Lars Poulsgaard
- Department of Neurosurgery, University Hospital of Copenhagen, Copenhagen, Denmark
| | - Ulla Feldt-Rasmussen
- Department of Endocrinology, University Hospital of Copenhagen, Copenhagen, Denmark
| | - Åse Krogh Rasmussen
- Department of Endocrinology, University Hospital of Copenhagen, Copenhagen, Denmark
| | - Marianne Wegener
- Department of Neuro-opthalmology, University Hospital of Copenhagen, Copenhagen, Denmark
| | - Kåre Fugleholm
- Department of Neurosurgery, University Hospital of Copenhagen, Copenhagen, Denmark
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Gu WJ, Zhang Q, Zhu J, Li J, Wei SH, Mu YM. Rituximab was used to treat recurrent IgG4-related hypophysitis with ophthalmopathy as the initial presentation: A case report and literature review. Medicine (Baltimore) 2017; 96:e6934. [PMID: 28614220 PMCID: PMC5478305 DOI: 10.1097/md.0000000000006934] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
RATIONALE Immunoglobulin G4 (IgG4)-related hypophysitis is a type of IgG4-related disease (IgG4-RD), which is characterized by plasma cells infiltration in the pituitary causing functional changes and (or) space-occupying effect in the pituitary. IgG4-related hypophysitis is sensitive to hormone therapy in most patients, but recurrence is very likely. PATIENT CONCERNS Here, we report a 57-year-old male patient with bilateral eye redness as the initial presentation. He later presented with pituitary hypofunction that involved multiple organs, including eyes, lacrimal gland, pituitary, lung, gall bladder, and intestine. There was an elevation of C-reactive protein and blood sedimentation, but the IgG and IgG4 levels of the serum and the cerebrospinal fluid did not increase obviously following irregular glucocorticoid therapy. Magnetic resonance imaging revealed enlarged pituitary and obviously thickened pituitary stalk. IgG4-related hypophysitis was confirmed by biopsy of the pituitary. DIAGNOSES The patient was diagnosis of IgG4-related hypophysitis with ophthalmopathy by pathological and molecular tests. INTERVENTIONS The patient responded to methylprednisolone pulse therapy but relapsed during the maintenance therapy using small-dose hormones combined with azathioprine. Methylprednisolone pulse therapy was given for 3 days followed by rituximab injection for 4 weeks. OUTCOMES After use methylprednisolone pulse therapy with rituximab the patient achieved complete remission. LESSONS Rituximab achieved good effect for recurrent IgG4-related hypophysitis after glucocorticoid therapy combined with immunosuppressant in this case. Moreover, comparative analysis was carried out with other reported cases of IgG4-related hypophysitis in terms of clinical features, treatment, and follow-up.
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Affiliation(s)
- Wei-Jun Gu
- Department of Endocrinology, Chinese PLA General Hospital
| | - Qian Zhang
- Department of Endocrinology, Chinese PLA General Hospital
- Department of Endocrinology, PLA Army General Hospital, Nanmencang
| | | | | | - Shi-Hui Wei
- Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China
| | - Yi-Ming Mu
- Department of Endocrinology, Chinese PLA General Hospital
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28
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Abstract
PURPOSE IgG4-related hypophysitis is a rare disease, with only 34 cases published in English (2015). Available short reviews may not present complete details of IgG4-related hypophysitis. We aimed to survey case reports of IgG4-related hypophysitis, including abstracts of scientific meetings, in English and Japanese. METHODS We searched for information about IgG4-related hypophysitis in PubMed and Igakuchuozasshi (Japan Medical Abstracts Society). Among 104 case reports found, we reviewed 84 fulfilling Leporati's diagnostic criteria. RESULTS The mean ± SD age of onset was 64.2 ± 13.9, 67.5 ± 9.8, and 56.4 ± 18.6 years for all subjects, men, and women, respectively. Men:women was 2.4:1. On magnetic resonance imaging, pituitary, stalk, and pituitary-stalk mass were observed at frequencies of 14.3, 21.4, and 64.3%, respectively. Manifestations were anterior hypopituitarism in 26.2% (22 cases), central diabetes insipidus in 17.9% (15 cases), and panhypopituitarism in 52.4% (44 cases). The median level of serum IgG4 was 264.5 mg/dL for all subjects, 405 mg/dL for men, and 226 mg/dL for women. The mean number of IgG4-related systemic diseases was 2.7 ± 1.5 in all subjects, 3.0 ± 1.5 in men, and 1.8 ± 1.1 in women. Among the IgG4-related diseases, retroperitoneal fibrosis was the most frequent (26.2%), followed by salivary gland diseases (25%). Glucocorticoid therapy was generally effective, except for two cases that received replacement doses. There were significant differences between sexes in terms of age, serum IgG4 levels, and number of IgG4-related diseases. CONCLUSION IgG4-related hypophysitis may have different clinical characteristics between genders. This survey may lack some information because the Japanese abstracts did not contain certain details.
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Affiliation(s)
- Junpei Shikuma
- Department of Diabetology, Metabolism, and Endocrinology, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Kenshi Kan
- Department of Diabetology, Metabolism, and Endocrinology, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Rokuro Ito
- Department of Diabetology, Metabolism, and Endocrinology, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Kazuo Hara
- Department of Diabetology, Metabolism, and Endocrinology, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Hiroyuki Sakai
- Department of Diabetology, Metabolism, and Endocrinology, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Takashi Miwa
- Department of Diabetology, Metabolism, and Endocrinology, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Akira Kanazawa
- Department of Diabetology, Metabolism, and Endocrinology, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan
| | - Masato Odawara
- Department of Diabetology, Metabolism, and Endocrinology, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, 160-0023, Japan.
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Bernreuther C, Illies C, Flitsch J, Buchfelder M, Buslei R, Glatzel M, Saeger W. IgG4-related hypophysitis is highly prevalent among cases of histologically confirmed hypophysitis. Brain Pathol 2017; 27:839-845. [PMID: 27864854 DOI: 10.1111/bpa.12459] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2016] [Accepted: 11/17/2016] [Indexed: 12/24/2022] Open
Abstract
IgG4-related disease is an immune-mediated disease with manifestations in most organ systems among them the pituitary gland. To date, few cases of histologically confirmed cases of IgG-related hypophysitis have been reported. The aim of this study was to retrospectively determine the prevalence of IgG4-related hypophysitis among cases previously diagnosed as primary hypophysitis (lymphocytic hypophysitis, granulomatous hypophysitis and hypophysitis not otherwise specified). Histological and immunohistochemical analysis revealed that 12 of 29 cases (41.4%) previously diagnosed as primary hypophysitis fulfilled the criteria for IgG4-related disease and, thus, IgG4-related hypophysitis should always be considered in the differential diagnosis of primary hypophysitis. All cases of IgG4-related hypophysitis showed a dense lymphoplasmacytic infiltrate with more than 10 IgG4-positive cells per high power field and a ratio of IgG4/IgG-positive cells of more than 40%, whereas storiform fibrosis was an inconsistent histological feature and was also seen in few cases of non-IgG-related hypophysitis, thus lacking sensitivity and specificity. Obliterative phlebitis was not seen in any case. Thus, histological criteria defined for IgG4-related disease in other organs should be modified for IgG4-related hypophysitis, accordingly.
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Affiliation(s)
- Christian Bernreuther
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christopher Illies
- Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden
| | - Jörg Flitsch
- Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Michael Buchfelder
- Department of Neurosurgery, University of Erlangen-Nürnberg, Erlangen, Germany
| | - Rolf Buslei
- Institute of Neuropathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Markus Glatzel
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Wolfgang Saeger
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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30
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Decker L, Crawford AM, Lorenzo G, Stippler M, Konstantinov KN, SantaCruz K. IgG4-Related Hypophysitis: Case Report and Literature Review. Cureus 2016; 8:e907. [PMID: 28083451 PMCID: PMC5208633 DOI: 10.7759/cureus.907] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
IgG4-related hypophysitis is a rare, inflammatory process of the pituitary that mimics more commonly seen pituitary tumors. We report a case of IgG4-related hypophysitis in a 16-year-old female with diabetes insipidus who was found to have IgG4-related hypophysitis based on tissue diagnosis. This entity has not been previously described in a pediatric patient. Recognition of certain inflammatory processes of the pituitary may lead to alternative means of diagnosis and medical management without a biopsy.
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Affiliation(s)
- Lauren Decker
- Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico
| | | | - Gamaliel Lorenzo
- Department of Radiology, University of New Mexico School of Medicine, Albuquerque, New Mexico
| | | | | | - Karen SantaCruz
- Pathology, University of New Mexico School of Medicine, Albuquerque, New Mexico
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31
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Caturegli P, Di Dalmazi G, Lombardi M, Grosso F, Larman HB, Larman T, Taverna G, Cosottini M, Lupi I. Hypophysitis Secondary to Cytotoxic T-Lymphocyte-Associated Protein 4 Blockade: Insights into Pathogenesis from an Autopsy Series. THE AMERICAN JOURNAL OF PATHOLOGY 2016; 186:3225-3235. [PMID: 27750046 PMCID: PMC5225294 DOI: 10.1016/j.ajpath.2016.08.020] [Citation(s) in RCA: 259] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 08/08/2016] [Accepted: 08/10/2016] [Indexed: 12/19/2022]
Abstract
Hypophysitis that develops in cancer patients treated with monoclonal antibodies blocking cytotoxic T-lymphocyte-associated protein 4 (CTLA-4; an inhibitory molecule classically expressed on T cells) is now reported at an incidence of approximately 10%. Its pathogenesis is unknown, in part because no pathologic examination of the pituitary gland has been reported to date. We analyzed at autopsy the pituitary glands of six cancer patients treated with CTLA-4 blockade, one with clinical and pathologic evidence of hypophysitis, one with mild lymphocytic infiltration in the pituitary gland but no clinical signs of hypophysitis, and four with normal pituitary structure and function. CTLA-4 antigen was expressed by pituitary endocrine cells in all patients but at different levels. The highest levels were found in the patient who had clinical and pathologic evidence of severe hypophysitis. This high pituitary CTLA-4 expression was associated with T-cell infiltration and IgG-dependent complement fixation and phagocytosis, immune reactions that induced an extensive destruction of the adenohypophyseal architecture. Pituitary CTLA-4 expression was confirmed in a validation group of 37 surgical pituitary adenomas and 11 normal pituitary glands. The study suggests that administration of CTLA-4 blocking antibodies to patients who express high levels of CTLA-4 antigen in the pituitary can cause an aggressive (necrotizing) form of hypophysitis through type IV (T-cell dependent) and type II (IgG dependent) immune mechanisms.
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Affiliation(s)
- Patrizio Caturegli
- Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland.
| | - Giulia Di Dalmazi
- Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland; Department of Medicine, G. D'Annunzio University of Chieti, Chieti, Italy
| | - Martina Lombardi
- Endocrinology Unit, Saints Anthony and Biagio, and Cesare Arrigo Hospital, Alessandria, Italy; Oncology Center, Saints Anthony and Biagio, and Cesare Arrigo Hospital, Alessandria, Italy
| | - Federica Grosso
- Oncology Center, Saints Anthony and Biagio, and Cesare Arrigo Hospital, Alessandria, Italy
| | - H Benjamin Larman
- Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Tatianna Larman
- Division of Immunology, Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland
| | - Giacomo Taverna
- Department of Radiology, Mesothelioma Unit, Saint Spirit Hospital, Casale Monferrato, Italy
| | - Mirco Cosottini
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Isabella Lupi
- Department of Endocrinology, University of Pisa, Pisa, Italy
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Bellastella G, Maiorino MI, Bizzarro A, Giugliano D, Esposito K, Bellastella A, De Bellis A. Revisitation of autoimmune hypophysitis: knowledge and uncertainties on pathophysiological and clinical aspects. Pituitary 2016; 19:625-642. [PMID: 27503372 PMCID: PMC7088540 DOI: 10.1007/s11102-016-0736-z] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE This publication reviews the accepted knowledges and the findings still discussed on several features of autoimmune hypophysitis, including the most recently described forms, such as IgG4 and cancer immunotherapy- related hypophysitis. METHODS The most characteristic findings and the pending controversies were derived from a literature review and previous personal experiences. A single paragraph focused on some atypical examples of the disease presenting under confounding pretences. RESULTS Headache, visual field alterations and impaired pituitary secretion are the most frequent clinical findings of the disease. Pituitary biopsy, still considered the gold diagnostic standard, does not always receive consent from the patients. The role of magnetic resonance imaging is limited, as this disease may generate images similar to those of other diseases. The role of antipituitary and antihypothalamus antibodies is still discussed owing to methodological difficulties and also because the findings on the true pituitary antigen(s) are still debated. However, the low sensitivity and specificity of immunofluorescence, one of the more widely employed methods to detect these antibodies, may be improved, considering a predetermined cut-off titre and a particular kind of immunostaining. CONCLUSION Autoimmune hypophysitis is a multifaceted disease, which may certainly be diagnosed by pituitary biopsy. However, the possible different clinical, laboratory and imaging features must be considered by the physician to avoid a misdiagnosis when examining a possibly affected patient. Therapeutic choice has to be made taking into account the clinical conditions and the degree of hypothalamic-pituitary involvement, but also considering that spontaneous remissions can occur.
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Affiliation(s)
- Giuseppe Bellastella
- Endocrinology and Metabolic Diseases Unit, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy
| | - Maria Ida Maiorino
- Endocrinology and Metabolic Diseases Unit, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy
| | - Antonio Bizzarro
- Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy
| | - Dario Giugliano
- Endocrinology and Metabolic Diseases Unit, Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy
| | - Katherine Esposito
- Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy
| | - Antonio Bellastella
- Endocrinology and Metabolic Diseases Unit, Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Piazza L. Miraglia 2, 80138, Naples, Italy.
| | - Annamaria De Bellis
- Endocrinology and Metabolic Diseases Unit, Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Piazza L. Miraglia 2, 80138, Naples, Italy
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Abstract
Hypophysitis is the acute or chronic inflammation of the pituitary gland. The spectrum of hypophysitis has expanded in recent years with the addition of two histologic subtypes and recognition as a complication of treatment with immune checkpoint inhibitors. Despite the increased number of published cases, the pathogenesis of hypophysitis is poorly understood, and treatment strategies are diverse and controversial. The diagnosis of hypophysitis generally requires histopathologic confirmation. The presentation and clinical course of hypophysitis varies. Hypophysitis can resolve spontaneously, relapse may occur, and some cases can be refractory to treatment.
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Affiliation(s)
- Alexander Faje
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114 USA
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Ngaosuwan K, Trongwongsa T, Shuangshoti S. Clinical course of IgG4-related hypophysitis presenting with focal seizure and relapsing lymphocytic hypophysitis. BMC Endocr Disord 2015; 15:64. [PMID: 26510826 PMCID: PMC4625849 DOI: 10.1186/s12902-015-0062-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 10/23/2015] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND This is the first case report of focal seizure as a manifestation of Immunoglobulin G4 (IgG4)-related hypophysitis. IgG4-related hypophysitis is a novel category of hypophysitis. The clinical presentations, imaging studies and initial pathology studies can mimic lymphocytic hypophysitis. Here we report additional clinical clues in differentiating these two conditions. CASE PRESENTATION A 43-year-old Thai male presented with focal seizure, headache, and anterior pituitary hypofunction. His MRI study showed typical hypophysitis lesion with abnormal cerebral parenchymal signal intensity at right frontal lobe. The pituitary biopsied was obtained and the patient was initially diagnosed with lymphocytic hypophysitis. Following initial low-dose steroid therapy, his seizure and headache resolved but his anterior pituitary hormones remained deficient. However, during steroid tapering, he developed new onset acute visual loss. Upon rigorous pathologic review, his diagnosis of IgG4-related hypophysitis with suspected CNS involvement was established. He was subsequently treated with high-dose steroid and rapidly regained his sight. CONCLUSION This case report highlights the important distinguishing features of IgG4-related hypophysitis from lymphocytic hypophysitis. These include the relapsing clinical course of hypophysitis after steroid decrement and concomitant pachymeningitis particularly in middle-aged to elderly Asian male who presented with hypophysitis. With appropriate dosage of steroids, medical treatment is usually sufficient to control the disease and surgical interventions are usually not required.
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Affiliation(s)
- Kanchana Ngaosuwan
- Department of Internal Medicine, Faculty of Medicine, Srinakharinwirot University, Ongkarak, Nakhon Nayok, Thailand.
| | - Therdkiat Trongwongsa
- Department of Pathology, Faculty of Medicine, Srinakharinwirot University, Ongkarak, Nakhon Nayok, Thailand.
| | - Shanop Shuangshoti
- Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
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Allix I, Rohmer V. Hypophysitis in 2014. ANNALES D'ENDOCRINOLOGIE 2015; 76:585-94. [DOI: 10.1016/j.ando.2015.08.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Revised: 07/07/2015] [Accepted: 08/04/2015] [Indexed: 12/24/2022]
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Abstract
PURPOSE The authors review their treatment experience and summarize clinical outcomes for patients with hypophysitis over the past 15 years. METHODS A retrospective analysis was conducted on patients with lymphocytic, granulomatous or IgG4-related hypophysitis treated from 1997 to 2014 at a single academic center. Patients' medical records were reviewed and binary logistic regression analysis was used to assess whether various clinical parameters were associated with improved outcomes including endocrine function, radiographic appearance and disease recurrence. RESULTS Twenty-one patients (13 women and 8 men) were identified with a median diagnosis age of 37.4 years. All but two patients (90%) were diagnosed histopathologically and the remaining two were diagnosed clinically with lymphocytic hypophysitis. 16 patients (76%) had lymphocytic hypophysitis, 3 (14%) had granulomatous hypophysitis, 1 (5%) had IgG4-related hypophysitis and 1 (5%) had mixed lymphocytic-granulomatous. Patients presented with various symptoms of expanding sellar mass with most common signs including headache (57%), polyuria/polydipsia (52%), vision changes (52%) and amenorrhea or decreased libido (48%). Pre-treatment endocrine evaluation revealed that 12 (57%) patients had complete anterior hypopituitarism, 11 patients (52%) had diabetes insipidus, ten patients (48%) had mild hyperprolactinemia and three patients (14%) had isolated endocrine axis deficiencies with partial gland function. We observed a broad diversity in pre-treatment imaging with common findings including uniform contrast enhancement (62%), thickened infundibulum (57%) and loss of hypophysis bright spot on T1 imaging (43%). Patients were treated with steroids and hormone supplementation as needed. 16 patients (76%) had recorded post-treatment MRI scans which revealed that half had radiographic improvement and half had stable or worsened post-treatment imaging. Only female gender was found to significantly predict improved odds of post-steroid radiographic improvement. For post-treatment endocrine evaluation, six patients (29%) did not have an evaluation on record, four patients (19%) had some improvement in at least one axis, seven patients (33%) had stable but non-worsened endocrine function and four patients (19%) had worsened endocrine function post-steroids. CONCLUSIONS Hypophysitis is an increasingly recognized diagnosis that can present with a broad array of radiographic and clinical features. Surgical biopsy can be helpful to make definitive diagnosis and may guide treatment decision-making.
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Affiliation(s)
- Brandon S Imber
- Department of Neurological Surgery, University of California at San Francisco, 505 Parnassus Ave. Room M779, San Francisco, CA, 94143, USA
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Abstract
IgG4-related disease (IgG4-RD) is a recently recognized systemic disease characterized by tumefactive lesions in various organ systems. The list of organs that can be involved continues to expand, and recently computed tomography (CT) descriptions of the pulmonary lesions found in the disease have been described. The clinical symptoms are nonspecific and may include cough, dyspnea, chest pain, and fever. The appropriate clinical presentation along with elevated serum IgG4 concentrations and pathologic evidence of lymphoplasmacytic infiltrates with abundant IgG4-positive plasma cells and storiform fibrosis is consistent with the disease. Steroids are used to treat this disease in addition to immunosupressives such as cyclosporine or rituxumab for steroid refractory disease. The pulmonary manifestations and imaging features can often mimic malignancy, and as such knowledge of the diagnostic, clinicopathologic, and radiographic features of the disease is required in order to provide appropriate diagnostic workup and treatment.
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McKinnon T, Randazzo WT, Kim BD, Biddinger P, Forseen S. IgG4-Related Disease Presenting as a Solitary Neck Mass. J Radiol Case Rep 2015; 9:1-8. [PMID: 25926922 DOI: 10.3941/jrcr.v9i2.1993] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
IgG4-related disease is a newly recognized entity associated with autoimmune conditions involving almost every organ system. It is characterized by elevated serum IgG4 as well as mass like tissue infiltration by IgG4-positive plasma cells. Imaging findings are nonspecific, vary depending on the site of disease, and include mass like enlargement of the salivary or lacrimal glands and enlarged lymph nodes. Radiographic findings often mimic malignancy, necessitating tissue sampling to confirm the diagnosis. Distinguishing IgG4-related disease from malignancy is important as IgG4 responds well to steroids and conservative management.
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Affiliation(s)
- Tyler McKinnon
- Department of Radiology, Georgia Regents University, Augusta, GA, USA
| | | | - Brian D Kim
- Department of Pathology, Georgia Regents University, Augusta, GA, USA
| | - Paul Biddinger
- Department of Pathology, Georgia Regents University, Augusta, GA, USA
| | - Scott Forseen
- Department of Radiology, Georgia Regents University, Augusta, GA, USA
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Batista RL, Ramos LS, Cescato VA, Musolino NRC, Borba CG, Silva GO, Moreno LH, Cunha Neto MBC. Thickened Pituitary Stalk Associated with a Mass in the Sphenoidal Sinus: An Alarm to Suspect Hypophysitis by Immunoglobulin G4? Int Arch Otorhinolaryngol 2015; 19:273-6. [PMID: 26157505 PMCID: PMC4490927 DOI: 10.1055/s-0034-1397333] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Accepted: 11/24/2014] [Indexed: 12/24/2022] Open
Abstract
Introduction Hypophysitis is a chronic inflammation of the pituitary gland of complex and still incompletely defined pathogenesis. It belongs to the group of non-hormone-secreting sellar masses, sharing with them comparable clinical presentation and radiographic appearance. Objectives Describe the case of immunoglobulin G4 (IgG4)-related hypophysitis presenting as a mass in the sphenoid sinus. Resumed Report A 40-year-old Brazilian man had a diagnosis of central diabetes insipidus since 2001 associated with pituitary insufficiency. Pituitary magnetic resonance imaging revealed a centered pituitary stalk with focal nodular thickening and the presence of heterogeneous materials inside the sphenoid sinus. The patient was treated with testosterone replacement therapy. Laboratory results revealed increased IgG4 serum. Conclusion IgG4-related hypophysitis should be considered in patients with pituitary insufficiency associated with sellar mass and/or thickened pituitary stalk. IgG4 serum measurement for early diagnosis of IgG4-related hypophysitis should be performed.
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Mulay K, Aggarwal E, Honavar SG. Clinicopathologic features of orbital immunoglobulin G4-related disease (IgG4-RD): a case series and literature review. Graefes Arch Clin Exp Ophthalmol 2015; 253:803-9. [PMID: 25572352 DOI: 10.1007/s00417-014-2905-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2014] [Revised: 12/10/2014] [Accepted: 12/15/2014] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Involvement of orbital structures by immunoglobulin G4-related disease (IgG4-RD) is not uncommon. We conducted this study to evaluate the clinicopathologic features of orbital IgG4-RD. MATERIAL/METHODS This was a retrospective, clinicopathologic study. Clinical records, light microscopic features, results of immunostaining with IgG & IgG4 and laboratory findings were reviewed in 16 patients diagnosed with orbital IgG4-RD. RESULTS Eleven patients had a bilateral disease, and the lacrimal gland was involved in 14. Dense sclerosis, plasma cell aggregates and dense lymphoplasmacytic infiltrate were seen in all patients. Serum IgG4 titre was elevated in 12 patients. Nine patients responded completely to glucocorticoid treatment. Five patients had a relapse on discontinuation of treatment. CONCLUSION Orbital IgG4-RD is a distinct clinicopathologic entity requiring increased awareness and needs to be differentiated from other orbital lymphoproliferative lesions.
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Affiliation(s)
- Kaustubh Mulay
- National Reporting Centre for Ophthalmic Pathology (NRCOP), Centre For Sight, Ashoka Capitol Building, Banjara Hills, Road No.2, Hyderabad, 500034, India,
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Quoi de neuf dans les hypophysites ? Rev Med Interne 2014; 35:815-22. [DOI: 10.1016/j.revmed.2014.05.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Revised: 05/14/2014] [Accepted: 05/26/2014] [Indexed: 12/24/2022]
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Sosa GA, Bell S, Christiansen SB, Pietrani M, Glerean M, Loto M, Lovazzano S, Carrizo A, Ajler P, Fainstein Day P. Histologically confirmed isolated IgG4-related hypophysitis: two case reports in young women. Endocrinol Diabetes Metab Case Rep 2014; 2014:140062. [PMID: 25298883 PMCID: PMC4174594 DOI: 10.1530/edm-14-0062] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Accepted: 08/29/2014] [Indexed: 12/17/2022] Open
Abstract
UNLABELLED IgG4-related hypophysitis is a recently described entity belonging to the group of IgG4-related diseases. Many other organs can also be affected, and it is more common in older men. To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy and the majority affecting multiple organs. The aim of this report is to present two cases of biopsy-proven IgG4-related hypophysitis occurring in two young female patients with no evidence of involvement of other organs at the time of diagnosis. LEARNING POINTS IgG4-related hypophysitis belongs to the group of IgG4-related diseases, and is a fibro-inflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells and storiform fibrosis.It is more common in older men, but young women may also present this type of hypophysitis.Although involvement of other organs is frequent, isolated pituitary disease is possible.Frequent clinical manifestations include anterior hypopituitarism and/or diabetes insipidus.THE DIAGNOSIS MAY BE CONFIRMED WITH ANY OF THE FOLLOWING CRITERIA: a pituitary biopsy with lymphoplasmacytic infiltrates, with more than ten IgG4-positive cells; a sellar mass and/or thickened pituitary stalk and a biopsy-proven involvement of another organ; a sellar mass and/or thickened pituitary stalk and IgG4 serum levels >140 mg/dl and sellar mass reduction and symptom improvement after corticosteroid treatment.Glucocorticoids are recommended as first-line therapy.
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Affiliation(s)
- Gabriela Alejandra Sosa
- Department of Endocrinology, Metabolism and Nuclear Medicine, Hospital Italiano , Perón 41901202, Buenos Aires , Argentina
| | - Soledad Bell
- Department of Endocrinology, Metabolism and Nuclear Medicine, Hospital Italiano , Perón 41901202, Buenos Aires , Argentina
| | | | - Marcelo Pietrani
- Department of Radiology, Hospital Italiano , Perón 41901202, Buenos Aires , Argentina
| | - Mariela Glerean
- Department of Endocrinology, Metabolism and Nuclear Medicine, Hospital Italiano , Perón 41901202, Buenos Aires , Argentina
| | - Monica Loto
- Department of Endocrinology, Metabolism and Nuclear Medicine, Hospital Italiano , Perón 41901202, Buenos Aires , Argentina
| | - Soledad Lovazzano
- Department of Endocrinology, Metabolism and Nuclear Medicine, Hospital Italiano , Perón 41901202, Buenos Aires , Argentina
| | - Antonio Carrizo
- Department of Neurosurgery, Hospital Italiano , Perón 41901202, Buenos Aires , Argentina
| | - Pablo Ajler
- Department of Neurosurgery, Hospital Italiano , Perón 41901202, Buenos Aires , Argentina
| | - Patricia Fainstein Day
- Department of Endocrinology, Metabolism and Nuclear Medicine, Hospital Italiano , Perón 41901202, Buenos Aires , Argentina
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De Bellis A, Bellastella G, Colella C, Bizzarro A, Bellastella A, Esposito K. Use of serum pituitary antibodies to improve the diagnosis of hypophysitis. Expert Rev Endocrinol Metab 2014; 9:465-476. [PMID: 30736209 DOI: 10.1586/17446651.2014.932689] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Lymphocytic hypophysitis is characterized by an extensive infiltration of lymphocytic cells. Pituitary biopsy is the gold diagnostic standard for lymphocytic hypophysitis but the disease occurs with moderate or without pituitary enlargement. The role of antipituitary antibodies (APA) in autoimmune hypophysitis is still discussed due to various methodological difficulties. Indirect immunofluorescence, a widely employed method to detect APA at this time produces highly variable results due to the use of human or animal pituitary substrates. For many years the authors have conducted a re-evaluation of APA by immunofluorescence in patients with other autoimmune diseases and in patients with apparently idiopathic hypopituitarism, using pituitary from young baboons as substrate but considering a predetermined cut-off of the titer and immunofluorescence pattern. This procedure allowed us to find out those with autoimmune pituitary impairment and to foresee the kind of future hypopituitarism in those with pituitary function still normal. Moreover, in APA positive patients, the use of a second step of a double immunofluorescence method allowed identification of the pituitary cells targeted by APA, verifying the correspondence with the kind of hypopituitarism, also when present in subclinical stage. However, to carry out an international workshop comparing the detection of APA by immunofluorescence using different substrates could contribute to verify the best choice to improve the sensitivity and specificity of this method.
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Affiliation(s)
- Annamaria De Bellis
- a Chair of Endocrinology and Metabolism, Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
- c Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy
| | - Giuseppe Bellastella
- a Chair of Endocrinology and Metabolism, Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
- c Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy
| | - Caterina Colella
- a Chair of Endocrinology and Metabolism, Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
- c Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy
| | - Antonio Bizzarro
- b Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy
- c Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy
| | - Antonio Bellastella
- a Chair of Endocrinology and Metabolism, Department of Cardiothoracic and Respiratory Sciences, Second University of Naples, Naples, Italy
- c Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy
| | - Katherine Esposito
- b Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy
- c Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy
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Caputo C, Bazargan A, McKelvie PA, Sutherland T, Su CS, Inder WJ. Hypophysitis due to IgG4-related disease responding to treatment with azathioprine: an alternative to corticosteroid therapy. Pituitary 2014; 17:251-6. [PMID: 23794123 DOI: 10.1007/s11102-013-0498-9] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE Fifteen cases of lymphocytic hypophysitis due to IgG4-related disease have been reported demonstrating marked improvement with corticosteroid therapy. This is the first case of IgG4-related hypophysitis demonstrating improvement with azathioprine, where corticosteroids were initially tried but ceased due to concern regarding enlargement of the pituitary infiltrate. METHODS Case description and review of 15 cases reported in the literature. A 40 year old male was diagnosed with IgG-4 related disease based on pituitary and lacrimal gland biopsies associated with raised serum concentration of IgG4. The patient was commenced on prednisolone 30 mg/day, as rapid response to prednisolone treatment has been described in the literature for other cases of IgG4-related hypophysitis. Over the next 3 months, prednisolone treatment resulted in a reduction of serum IgG4 levels, but repeat MRI scan showed an enlarging pituitary mass with new optic nerve compression. Azathioprine 75 mg twice daily was commenced and in the subsequent 3 months, IgG4 levels normalised (0.58 g/L) and MRI scan showed 50% shrinkage of the pituitary mass. After 10 months of azathioprine treatment the MRI showed a normal sized pituitary but persistence of the infraorbital nerve thickening. CONCLUSIONS Hypophysitis due to IgG4-related disease usually demonstrates prompt response to corticosteroids. This case highlights the need to image promptly after starting treatment to exclude an enlarging pituitary mass despite corticosteroid treatment. Alternative therapy with azathioprine can result in marked improvement. It should be remembered that IgG-4 related hypophysitis is part of a multi-organ disease.
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Affiliation(s)
- Carmela Caputo
- Department of Endocrinology, St Vincent's Hospital, 4th Floor Daly Wing, 35 Victoria Parade Fitzroy, Melbourne, 3065, Australia,
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O’Reilly DA, Malde DJ, Duncan T, Rao M, Filobbos R. Review of the diagnosis, classification and management of autoimmune pancreatitis. World J Gastrointest Pathophysiol 2014; 5:71-81. [PMID: 24891978 PMCID: PMC4025075 DOI: 10.4291/wjgp.v5.i2.71] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 04/17/2014] [Indexed: 02/06/2023] Open
Abstract
Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, with as yet undetermined incidence and prevalence in the general population. Our understanding of it continues to evolve. In the last few years, 2 separate subtypes have been identified: type 1 AIP has been recognised as the pancreatic manifestation of a multiorgan disease, named immunoglobulin G4 (IgG4)-related disease while type 2 AIP is a pancreas specific disorder not associated with IgG4. International criteria for the diagnosis of AIP have been defined: the HISORt criteria from the Mayo clinic, the Japan consensus criteria and, most recently, the international association of pancreatology “International Consensus Diagnostic Criteria”. Despite this, in clinical practice it can still be very difficult to confirm the diagnosis and differentiate AIP from a pancreatic cancer. There are no large studies into the long-term prognosis and management of relapses of AIP, and there is even less information at present regarding the Type 2 AIP subtype. Further studies are necessary to clarify the pathogenesis, treatment and long-term outcomes of this disease. Critically for clinicians, making the correct diagnosis and differentiating the disease from pancreatic cancer is of the utmost importance and the greatest challenge.
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Amendment of the Japanese Consensus Guidelines for Autoimmune Pancreatitis, 2013 II. Extrapancreatic lesions, differential diagnosis. J Gastroenterol 2014; 49:765-84. [PMID: 24664402 DOI: 10.1007/s00535-014-0944-0] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Accepted: 02/06/2014] [Indexed: 02/04/2023]
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Bando H, Iguchi G, Fukuoka H, Taniguchi M, Yamamoto M, Matsumoto R, Suda K, Nishizawa H, Takahashi M, Kohmura E, Takahashi Y. The prevalence of IgG4-related hypophysitis in 170 consecutive patients with hypopituitarism and/or central diabetes insipidus and review of the literature. Eur J Endocrinol 2014; 170:161-72. [PMID: 24165017 DOI: 10.1530/eje-13-0642] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The prevalence and clinical characteristics of IgG4-related hypophysitis remain unclear due to the limited number of case reports. Therefore, in this study, we screened consecutive outpatients with hypopituitarism and/or diabetes insipidus (DI) to estimate its prevalence. METHODS A total of 170 consecutive outpatients with hypopituitarism and/or central DI were screened at Kobe University Hospital for detecting IgG4-related hypophysitis by pituitary magnetic resonance imaging, measuring serum IgG4 concentrations, assessing the involvement of other organs, and carrying out an immunohistochemical analysis to detect IgG4-positive cell infiltration. RESULTS Among the screened cases, 116 cases were excluded due to diagnosis of other causes such as tumors and congenital abnormalities. Additionally, 22 cases with isolated ACTH deficiency were analyzed and were found not to meet the criteria of IgG4-related hypophysitis. The remaining 32 cases were screened and seven were diagnosed with IgG4-related hypophysitis, of which three cases were diagnosed by analyzing pituitary specimens. IgG4-related hypophysitis was detected in 30% (seven of 23 patients) of hypophysitis cases and 4% of all hypopituitarism/DI cases. The mean age at the onset of IgG4-related hypophysitis was 61.8±8.8 years, and the serum IgG4 concentration was 191.1±78.3 mg/dl (normal values 5-105 mg/dl and values in IgG4-related disease (RD) ≥135 mg/dl). Pituitary gland and/or stalk swelling was observed in six patients, and an empty sella was observed in one patient. Multiple co-existing organ involvement was observed in four of the seven patients prior to the onset of IgG4-related hypophysitis. CONCLUSION These data suggest that the prevalence of IgG4-related hypophysitis has been underestimated. We should also consider the possibility of the development of hypopituitarism/DI caused by IgG4-related hypophysitis during the clinical course of other IgG4-RDs.
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Affiliation(s)
- Hironori Bando
- Division of Diabetes and Endocrinology, Department of Internal Medicine
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Mulay K, Aggarwal E, Jariwala M, Honavar SG. Orbital immunoglobulin-G4-related disease: case series and literature review. Clin Exp Ophthalmol 2014; 42:682-7. [PMID: 24330202 DOI: 10.1111/ceo.12284] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Accepted: 12/05/2013] [Indexed: 12/19/2022]
Abstract
Immunoglobulin-G4-related disease (IgG4-RD) is a distinct group of diseases characterized by elevated serum IgG4 titres and infiltration of affected organs by IgG4-positive plasma cells. IgG4-RD can involve any ocular adnexal tissue. They have a distinct prognosis and pattern of tissue involvement and hence need to be differentiated from orbital lesions with similar clinicopathological features. We report three cases of IgG4-RD and review the literature extensively discussing various aspects of this novel entity.
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Affiliation(s)
- Kaustubh Mulay
- National Reporting Centre for Ophthalmic Pathology (NRCOP), Centre for Sight, Hyderabad, India; Ophthalmic Pathology Service, L.V. Prasad Eye Institute, Hyderabad, India
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