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Brue T, Rahabi H, Barry A, Barlier A, Bertherat J, Borson-Chazot F, Castinetti F, Cazabat L, Chabre O, Chevalier N, Christin-Maitre S, Cortet C, Drui D, Kamenicky P, Lançon C, Lioté F, Pellegrini I, Reynaud R, Salenave S, Tauveron I, Touraine P, Vantyghem MC, Vergès B, Vezzosi D, Villa C, Raverot G, Coutant R, Chanson P, Albarel F. Position statement on the diagnosis and management of acromegaly: The French National Diagnosis and Treatment Protocol (NDTP). ANNALES D'ENDOCRINOLOGIE 2023; 84:697-710. [PMID: 37579837 DOI: 10.1016/j.ando.2023.08.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Abstract
Acromegaly is a rare disease with prevalence of approximately 60 cases per million, slight female predominance and peak onset in adults in the fourth decade. Clinical diagnosis is often delayed by several years due to the slowly progressive onset of symptoms. There are multiple clinical criteria that define acromegaly: dysmorphic syndrome of insidious onset, symptoms related to the pituitary tumor (headaches, visual disorders), general signs (sweating, carpal tunnel syndrome, joint pain, etc.), complications of the disease (musculoskeletal, cardiovascular, pneumological, dental, metabolic comorbidities, thyroid nodules, colonic polyps, etc.) or sometimes clinical signs of associated prolactin hypersecretion (erectile dysfunction in men or cycle disorder in women) or concomitant mass-induced hypopituitarism (fatigue and other symptoms related to pituitary hormone deficiencies). Biological confirmation is based initially on elevated IGF-I and lack of GH suppression on oral glucose tolerance test or an elevated mean GH on repeated measurements. In confirmed cases, imaging by pituitary MRI identifies the causal tumor, to best determine management. In a minority of cases, acromegaly can be linked to a genetic predisposition, especially when it occurs at a young age or in a familial context. The first-line treatment is most often surgical removal of the somatotroph pituitary tumor, either immediately or after transient medical treatment. Medical treatments are most often proposed in patients not controlled by surgical removal. Conformal or stereotactic radiotherapy may be discussed on a case-by-case basis, especially in case of drug inefficacy or poor tolerance. Acromegaly should be managed by a multidisciplinary team, preferably within an expert center such as a reference or skill center for rare pituitary diseases.
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Affiliation(s)
- Thierry Brue
- Service d'endocrinologie, centre de référence des maladies rares de l'hypophyse HYPO, assistance publique-hôpitaux de Marseille (AP-HM), hôpital de la Conception, 147, boulevard Baille, 13005 Marseille, France; Aix Marseille université, INSERM, MMG, Marseille Medical Genetics, Marseille, France.
| | - Haïfa Rahabi
- Service d'endocrinologie, centre de référence des maladies rares de l'hypophyse HYPO, assistance publique-hôpitaux de Marseille (AP-HM), hôpital de la Conception, 147, boulevard Baille, 13005 Marseille, France
| | - Abdoulaye Barry
- Service d'endocrinologie, centre de référence des maladies rares de l'hypophyse HYPO, assistance publique-hôpitaux de Marseille (AP-HM), hôpital de la Conception, 147, boulevard Baille, 13005 Marseille, France
| | - Anne Barlier
- Service d'endocrinologie, centre de référence des maladies rares de l'hypophyse HYPO, assistance publique-hôpitaux de Marseille (AP-HM), hôpital de la Conception, 147, boulevard Baille, 13005 Marseille, France; Aix Marseille université, INSERM, MMG, Marseille Medical Genetics, Marseille, France
| | - Jérôme Bertherat
- Service d'endocrinologie, hôpital Cochin, AP-HP centre université Paris Cité, France
| | - Françoise Borson-Chazot
- Service d'endocrinologie, centre de référence des maladies rares de l'hypophyse HYPO « groupement hospitalier Est » hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron, France
| | - Frédéric Castinetti
- Service d'endocrinologie, centre de référence des maladies rares de l'hypophyse HYPO, assistance publique-hôpitaux de Marseille (AP-HM), hôpital de la Conception, 147, boulevard Baille, 13005 Marseille, France; Aix Marseille université, INSERM, MMG, Marseille Medical Genetics, Marseille, France
| | - Laure Cazabat
- Hôpital Foch, service de neurochirurgie, UMR 1198 BREED, UFR Simone Veil Santé, UVSQ-Paris Saclay, 40, rue Worth, 92150 Suresnes, France
| | - Olivier Chabre
- University Grenoble Alpes, UMR 1292 Inserm-CEA-UGA, endocrinologie CHU de Grenoble Alpes, 38000 Grenoble, France
| | - Nicolas Chevalier
- Université Côte d'Azur, CHU, Inserm U1065, C3M, équipe 5, Nice, France
| | - Sophie Christin-Maitre
- Service d'endocrinologie, diabétologie et médecine de la reproduction, centre de référence des maladies endocriniennes rares de la croissance et du développement (CMERC) Centre de compétence HYPO, Sorbonne université, hôpital Saint-Antoine, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg Saint-Antoine, 75012 Paris, France
| | - Christine Cortet
- Service d'endocrinologie, diabétologie et maladies métaboliques, CHRU de Lille, rue Polonowski, Lille cedex, France
| | - Delphine Drui
- Service d'endocrinologie, l'institut du thorax, centre hospitalier universitaire de Nantes, boulevard Jacques-Monod, 44093 Nantes cedex, France
| | - Peter Kamenicky
- Service d'endocrinologie et des maladies de la reproduction, centre de référence des maladies rares de l'hypophyse, université Paris-Saclay, Inserm, physiologie et physiopathologie endocriniennes, AP-HP, hôpital BicêtreLe Kremlin-Bicêtre, France
| | - Catherine Lançon
- « Acromégales, pas seulement… », association nationale de l'acromégalie reconnue d'intérêt général, 59234 Villers-Au-Tertre, France
| | - Frédéric Lioté
- Centre Viggo Petersen, faculté de santé, université Paris Cité, Inserm UMR 1132 Bioscar et service de rhumatologie, DMU Locomotion, AP-HP, hôpital Lariboisière, 75475 Paris cedex 10, France
| | - Isabelle Pellegrini
- Service d'endocrinologie, centre de référence des maladies rares de l'hypophyse HYPO, assistance publique-hôpitaux de Marseille (AP-HM), hôpital de la Conception, 147, boulevard Baille, 13005 Marseille, France
| | - Rachel Reynaud
- Aix Marseille université, INSERM, MMG, Marseille Medical Genetics, Marseille, France; Service de pédiatrie multidisciplinaire, centre de référence des maladies rares de l'hypophyse HYPO, Assistance publique-Hôpitaux de Marseille (AP-HM), hôpital de la Timone enfants, 13005 Marseille, France
| | - Sylvie Salenave
- Service d'endocrinologie et des maladies de la reproduction, centre de référence des maladies rares de l'hypophyse, université Paris-Saclay, Inserm, physiologie et physiopathologie endocriniennes, AP-HP, hôpital BicêtreLe Kremlin-Bicêtre, France
| | - Igor Tauveron
- Service d'endocrinologie diabétologie, institut génétique, reproduction & développement (iGReD), CHU de Clermont-Ferrand, CNRS, Inserm, université Clermont-Auvergne, Clermont-Ferrand, France
| | - Philippe Touraine
- Service d'endocrinologie et médecine de la reproduction, centre de maladies endocrinennes rares de la croissance et du développement, Sorbonne université médecine, hôpital Pitié Salpêtrière, Paris, France
| | - Marie-Christine Vantyghem
- Service d'endocrinologie, diabétologie et maladies métaboliques, CHRU de Lille, rue Polonowski, Lille cedex, France; Service d'endocrinologie, l'institut du thorax, centre hospitalier universitaire de Nantes, boulevard Jacques-Monod, 44093 Nantes cedex, France
| | - Bruno Vergès
- Service d'endocrinologie, CHU de Dijon, centre Inserm LNC-UMR1231, 14, rue Gaffarel, 21000 Dijon, France
| | - Delphine Vezzosi
- Service d'endocrinologie, hôpital Larrey, CHU Toulouse, 24 chemin de Pouvourville, TSA 30030, université Paul Sabatier, 21059 Toulouse cedex 9, France
| | - Chiara Villa
- Département de neuropathologie de la Pitié Salpêtrière, hôpital de la Pitié-Salpêtrière - AP-HP, Sorbonne université, 47-83, boulevard de l'Hôpital, 75651 Paris cedex 13, France
| | - Gérald Raverot
- Service d'endocrinologie, centre de référence des maladies rares de l'hypophyse HYPO « groupement hospitalier Est » hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron, France
| | - Régis Coutant
- Service d'endocrinologie-diabétologie-nutrition, centre de référence des maladies rares de l'hypophyse, université d'Angers, CHU d'Angers, Angers, France
| | - Philippe Chanson
- Service d'endocrinologie et des maladies de la reproduction, centre de référence des maladies rares de l'hypophyse, université Paris-Saclay, Inserm, physiologie et physiopathologie endocriniennes, AP-HP, hôpital BicêtreLe Kremlin-Bicêtre, France
| | - Frédérique Albarel
- Service d'endocrinologie, centre de référence des maladies rares de l'hypophyse HYPO, assistance publique-hôpitaux de Marseille (AP-HM), hôpital de la Conception, 147, boulevard Baille, 13005 Marseille, France
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Ji X, Fu J, Li X, Yuan K, Sun X, Yao Q. Serum biomarkers of colonic polyps in patients with acromegaly: a meta-analysis and systematic review. Pituitary 2023; 26:1-8. [PMID: 36542278 DOI: 10.1007/s11102-022-01287-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/24/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE In the past few decades, acromegaly and colonic polyps have been associated with an increased risk of colorectal cancer. Previous studies highlighted the importance of serum biomarkers of colonic polyps in patients with acromegaly. METHODS We reviewed studies on serum biomarkers of colonic polyps in patients with acromegaly, published on PubMed, Embase, Cochrane Library, Medline, and Chinese databases from January 1, 1966, to May 8, 2022. Meta-analysis and systematic review were conducted using Stata MP 14.0. RESULTS Eight articles were included in this study. The mean (standard deviation) concentrations of serum biomarkers for acromegaly with and without colorectal polyps were extracted from these studies. Meta-analysis results showed that, compared to patients without colonic polyps, the levels of insulin-like growth factor-1 × upper limit of normal range (IGF-1 × ULN) and fasting insulin were significantly increased; while the levels of growth hormone (GH) were significantly decreased in patients with acromegaly and colonic polyps (IGF-1 × ULN: SMD 0.23; 95% CI 0.03-0.42, p < 0.05) (fasting insulin: SMD 0.95; 9 5% CI 0.11-1.8, p < 0.05) (GH: SMD - 0.25; 95% CI - 0.41 to - 0.08, p < 0.05). IGF-1 and FPG levels did not differ significantly (IGF-1: SMD -0.03; 95% CI - 0.22 to 0.17, p > 0.05) (FPG: SMD 0.14; 95% CI - 0.23 to 0.52, p > 0.05). The systematic review results suggest no significant differences in hemoglobin A1C, TSH, free thyroxine, FT4, T3, PRL, total cholesterol, HDL, LDL, fibrinogen, clathrate antigen, serum antigen 19-9, and α-fetoprotein levels, but serum Klotho levels. CONCLUSION We present the first meta-analysis and systematic review of serum biomarkers in patients with acromegaly or colonic polyps. The prevalence of colonic lesion polyps, is associated with higher IGF-1 × ULN levels, higher insulin levels in acromegaly. Further research is required to confirm GH and serum soluble Klotho levels as biomarkers of colonic polyps. When IGF-1 × ULN, fasting insulin levels change in patients with acromegaly, the occurrence of colonic polyps should be monitored. Early detection may reduce the possibility of developing malignant colon neoplasms.
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Affiliation(s)
- Xiaoyu Ji
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Jiajia Fu
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiaozhe Li
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Kun Yuan
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China
| | - Xuebo Sun
- Department of Neurosurgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, Jiangsu, China.
| | - Qiaoling Yao
- Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
- National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Molecular Cancer Epidemiology, Tianjin Medical University, Tianjin, China.
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Palui R, Sridharan K, Kamalanathan S, Sahoo J, Naik D. Growth hormone and gastrointestinal malignancy: An intriguing link. World J Gastrointest Pathophysiol 2023; 14:1-11. [PMID: 36743656 PMCID: PMC9896462 DOI: 10.4291/wjgp.v14.i1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 12/25/2022] [Accepted: 01/17/2023] [Indexed: 01/20/2023] Open
Abstract
Growth hormone (GH) excess is associated with several systemic complications, one of which is the increased risk of neoplastic processes particularly of the gastrointestinal (GI) tract. Among the GI neoplasms, the most reported association is with benign and malignant neoplasms of the colon. In the majority of published literature, an increased incidence of GI neoplasms, both colonic adenomas as well as colorectal carcinoma is reported. However, the studies on colon cancer-specific mortality rate are conflicting with recent studies reporting similar cancer-specific mortality rates in comparison to controls. Many studies have reported an association of colorectal neoplasms with GH levels. Pathogenic mechanisms put forward to explain this association of GH excess and GI neoplasms primarily involve the increased GH-insulin-like growth factor 1 (IGF-1) signaling. Both GH and IGF-1 have proliferative, anti-apoptotic, and angiogenic effects on the systemic tissues leading to cellular proliferation. Other contributing factors to the increased risk of GI neoplasms include slow intestinal transit with a redundant large bowel, altered bile acids, deranged local immune response, shared genetic susceptibility factors and hyperinsulinemia. In view of the increased risk association, most guidelines for the care of acromegaly patients recommend an initial screening colonoscopy. Recommendations for further follow-up colonoscopy differ but broadly, the guidelines agree that it depends on the findings at first colonoscopy and state of remission of GH excess. Regarding the concern about the risk of colorectal cancers in patients receiving recombinant GH therapy, most cohort studies do not show an increased risk.
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Affiliation(s)
- Rajan Palui
- Department of Endocrinology, The Mission Hospital, Durgapur 713212, West Bengal, India
| | - Kalyani Sridharan
- Department of Endocrinology, All India Institute of Medical Science, Rishikesh 249203, Uttarakhand, India
| | - Sadishkumar Kamalanathan
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Jayaprakash Sahoo
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Dukhabandhu Naik
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
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Peng G, Li X, Zhou Y, Bai J, Hong P, Li W, Zhang Y, Zhang L, Liao Q, Liao M, Zhou L, Sun Z, Shen R, Zheng H, Long M. Clinical Characteristics and Associated Factors of Colonic Polyps in Acromegaly. Exp Clin Endocrinol Diabetes 2022; 130:714-722. [PMID: 36075228 DOI: 10.1055/a-1913-7900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
PURPOSE To investigate the clinical characteristics and associated factors of colonic polyps in patients with acromegaly. METHODS Clinical characteristics and colonoscopy findings of 86 acromegaly patients who received treatment were retrospectively reviewed, and colonoscopy findings and the correlation with growth hormone (GH)-secreting pituitary adenoma (GHPA) volume and hormonal/metabolic levels were analyzed. RESULTS The prevalence of colonic polyps in acromegaly patients was 40.7% and increased significantly with advanced age, especially in those ≥50 years. Multiple polyps (62.8%) and colonic polyps in the left colon (54.2%) were detected more frequently. Compared to acromegaly patients without polyps, those with polyps displayed higher insulin-like growth factor-1 × upper limit of normal (IGF-1×ULN) levels (P=0.03). IGF-1 levels and GHPA volumes in patients with polyps showed increasing trends, although the differences were not significant. GH levels were higher in patients with polyps of diameter ≤5 mm than those with polyps of diameter >5 mm (P=0.031). The univariate and multivariate logistic regression analysis revealed that GHPA volumes (OR: 1.09, 95% CI: 1.01-1.20; P=0.039) and IGF-1×ULN Q2 levels (OR: 6.51, 95% CI: 1.20-44.60; P=0.038) were independent factors for predicting the risk of colonic polyp occurrence in acromegaly patients. A nomogram was prepared to evaluate the risk of colonic polyps in acromegaly patients. CONCLUSION The acromegalic patients are a population with a high prevalence of colonic polyps. GHPA volumes and IGF-1×ULN levels may be predictors of colonic polyp occurrence.
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Affiliation(s)
- Guiliang Peng
- Department of Endocrinology, Translational Research Key Laboratory for Diabetes, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Xing Li
- Department of Endocrinology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Yuanyuan Zhou
- Department of Gastroenterology, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Jianying Bai
- Department of Gastroenterology, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Pian Hong
- Department of Endocrinology, Translational Research Key Laboratory for Diabetes, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Weixing Li
- Department of Endocrinology, Translational Research Key Laboratory for Diabetes, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Yuling Zhang
- Department of Endocrinology, Translational Research Key Laboratory for Diabetes, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Lei Zhang
- Department of Radiology, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Qian Liao
- Department of Endocrinology, Translational Research Key Laboratory for Diabetes, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Mingyu Liao
- Department of Endocrinology, Translational Research Key Laboratory for Diabetes, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Ling Zhou
- Department of Endocrinology, Translational Research Key Laboratory for Diabetes, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Zheng Sun
- Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, Texas, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
| | - Rufei Shen
- Department of Endocrinology, Translational Research Key Laboratory for Diabetes, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Hongting Zheng
- Department of Endocrinology, Translational Research Key Laboratory for Diabetes, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
| | - Min Long
- Department of Endocrinology, Translational Research Key Laboratory for Diabetes, The Second Affiliated Hospital (Xinqiao Hospital), Army Medical University, Chongqing, China
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Kasuki L, Maia B, Gadelha MR. Acromegaly and Colorectal Neoplasm: An Update. Front Endocrinol (Lausanne) 2022; 13:924952. [PMID: 35795151 PMCID: PMC9251006 DOI: 10.3389/fendo.2022.924952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 05/18/2022] [Indexed: 12/20/2022] Open
Abstract
Acromegaly is a systemic disease caused by excessive inappropriate secretion of GH and IGF-I levels, resulting in many systemic complications, including cardiovascular, respiratory, metabolic diseases, and a possible increased risk of some neoplasias. Although many studies on acromegaly and cancer remain uncertain, most data indicate that colorectal cancer (CRC) incidence is increased in this population. The exact mechanism involved in the role of GH-IGF-I axis in CRC has not been fully explained, yet it is associated with local and circulating effects of GH and IGF-I on the colon, promoting angiogenesis, cell proliferation, risk of mutation, inhibition of tumor-suppressor genes and apoptosis, thus facilitating a tumor microenvironment. Nevertheless, population-based studies present controversial findings on CRC incidence and mortality. All worldwide guidelines and expert consensuses agree with the need for colonoscopic screening and surveillance in acromegaly, although there is no consensus regarding the best period to do this. This review aims to analyze the existing data on CRC and acromegaly, exploring its pathophysiology, epidemiological studies and their limitations, colonic polyp characteristics, overall cancer and CRC incidences and mortality, risk factors for colon cancer pathophysiology, and recommendation guideline aspects.
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Affiliation(s)
- Leandro Kasuki
- Endocrine Unit and Neuroendocrinology Research Center, Medical School and Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Neuroendocrine Unit - Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
- *Correspondence: Leandro Kasuki,
| | - Bernardo Maia
- Endocrine Unit and Neuroendocrinology Research Center, Medical School and Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Mônica R. Gadelha
- Endocrine Unit and Neuroendocrinology Research Center, Medical School and Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Neuroendocrine Unit - Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
- Neuropathology and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
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Pekic S, Stojanovic M, Popovic V. Pituitary tumors and the risk of other malignancies: is the relationship coincidental or causal? ENDOCRINE ONCOLOGY (BRISTOL, ENGLAND) 2022; 2:R1-R13. [PMID: 37435457 PMCID: PMC10259320 DOI: 10.1530/eo-21-0033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 12/21/2021] [Indexed: 07/13/2023]
Abstract
Pituitary adenomas are benign neoplasms of the pituitary. The most prevalent are prolactinomas and non-functioning pituitary adenomas, followed by growth hormone- and ACTH-secreting adenomas. Most pituitary adenomas seem to be sporadic and their persistent growth is very atypical. No molecular markers predict their behavior. The occurrence of pituitary adenomas and malignancies in the same patient can be either pure coincidence or caused by shared underlying genetic susceptibility involved in tumorigenesis. Detailed family history on cancers/tumors in the first, second and third generation of family members on each side of the family has been reported in a few studies. They found an association of pituitary tumors with positive family history for breast, lung and colorectal cancer. We have reported that in about 50% of patients with pituitary adenomas, an association with positive family history for cancer has been found independent of secretory phenotype (acromegaly, prolactinoma, Cushing's disease or non-functioning pituitary adenomas). We also found earlier onset of pituitary tumors (younger age at diagnosis of pituitary tumors) in patients with a strong family history of cancer. In our recent unpublished series of 1300 patients with pituitary adenomas, 6.8% of patients were diagnosed with malignancy. The latency period between the diagnosis of pituitary adenoma and cancer was variable, and in 33% of patients, it was longer than 5 years. Besides the inherited trophic mechanisms (shared underlying genetic variants), the potential influence of shared complex epigenetic influences (environmental and behavioral factors - obesity, smoking, alcohol intake and insulin resistance) is discussed. Further studies are needed to better understand if patients with pituitary adenomas are at increased risk for cancer.
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Affiliation(s)
- Sandra Pekic
- School of Medicine, University of Belgrade, Belgrade, Serbia
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center Belgrade, Belgrade, Serbia
| | - Marko Stojanovic
- School of Medicine, University of Belgrade, Belgrade, Serbia
- Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center Belgrade, Belgrade, Serbia
| | - Vera Popovic
- School of Medicine, University of Belgrade, Belgrade, Serbia
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Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer. Int J Mol Sci 2021; 22:ijms22126434. [PMID: 34208601 PMCID: PMC8234711 DOI: 10.3390/ijms22126434] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 06/04/2021] [Accepted: 06/14/2021] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.
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Battistone MF, Miragaya K, Rogozinski A, Agüero M, Alfieri A, Ballarino MC, Boero L, Danilowicz K, Diez S, Donoso M, Fainstein-Day P, Furioso A, Garcia-Basavilbaso N, Glerean M, Katz D, Loto M, Mallea-Gil S, Martinez M, Sabate MI, Servidio M, Slavinsky P, Stalldecker G, Sosa S, Szuman G, Tkatch J, Caldo I, Lubieniecki D, Guitelman M. Increased risk of preneoplastic colonic lesions and colorectal carcinoma in acromegaly: multicenter case-control study. Pituitary 2021; 24:96-103. [PMID: 33057946 DOI: 10.1007/s11102-020-01090-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/28/2020] [Indexed: 12/11/2022]
Abstract
PURPOSE Current international guidelines recommend colonoscopy in patients with acromegaly at the time of diagnosis, even though the risk of developing colorectal neoplasm is still controversial. The main objective of this Argentine multicenter study was to analyze through screening colonoscopy the presence of advanced neoplastic lesions considered as precancerous, in patients with acromegaly compared to a control group. METHODS This is a case-control retrospective study. Full length colonoscopy of 70 acromegalic patients and 128 control subjects were studied. Polyps were classified into non pre-cancerous lesions and advance neoplastic lesions which included advanced adenomas (preneoplastic) and colorectal carcinomas. RESULTS Thirty three out of 70 acromegalic patients and 32 out of 128 subjects controls presented polyps in the colonoscopy [47.1% vs 25%, p = 0.002, OR 2.68]. Non precancerous polyps were found in 11 (15.7%) and 23 (17.9%) (p = 0.690), while advanced neoplastic lesions were found in 22 (31.4%) and 9 (7.0%) (p = 0,0001 - OR: 6.06) patients and controls respectively. Advanced adenomas and colorectal carcinomas were found in 18 (27.3%) and 9 (7.0%) (p = 0,0006-OR: 4,57), and 4 (5.7%) and 0 (0.0%) p = 0.0063) of patients and controls respectively. The presence of insulin resistance was the only statistically significant associated factor among acromegalic patients with and without colonic polyps. CONCLUSIONS Our findings show an increased risk of preneoplastic colonic lesions and colorectal carcinoma in patients with chronic and sustained GH excess compared to a control group. This supports the recommendation to perform screening colonoscopy at diagnosis of acromegaly.
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Affiliation(s)
| | - Karina Miragaya
- Servicio de Endocrinología, Sanatorio Güemes, Buenos Aires, Argentina
| | - Amelia Rogozinski
- División Endocrinología, Hospital Ramos Mejía, Buenos Aires, Argentina
| | - Monica Agüero
- Grupo de trabajo Endocrinología, Hospital Tornú, Buenos Aires, Argentina
| | - Analia Alfieri
- Servicio de Endocrinología, Hospital Nacional Profesor A. Posadas, El Palomar, Buenos Aires, Argentina
| | | | - Laura Boero
- División Endocrinología, Hospital de Clínicas José de San Martin UBA, Buenos Aires, Argentina
| | - Karina Danilowicz
- División Endocrinología, Hospital de Clínicas José de San Martin UBA, Buenos Aires, Argentina
| | - Sabrina Diez
- Servicio de Endocrinología, Hospital General de Agudos Dr. Ignacio Pirovano,, Buenos Aires, Argentina
| | - Marina Donoso
- Servicio de Endocrinología, Hospital Nacional Profesor A. Posadas, El Palomar, Buenos Aires, Argentina
| | | | - Alejandra Furioso
- División Endocrinología, Hospital Ramos Mejía, Buenos Aires, Argentina
| | | | - Mariela Glerean
- Servicio de Endocrinología, Hospital Italiano, Buenos Aires, Argentina
| | - Debora Katz
- Sección Neuroendocrinología, FLENI, Buenos Aires, Argentina
| | - Monica Loto
- Servicio de Endocrinología, Hospital Británico, Buenos Aires, Argentina
| | - Susana Mallea-Gil
- Servicio de Endocrinología, Hospital Militar Central, Buenos Aires, Argentina
| | - Marcela Martinez
- Servicio de Endocrinología, Hospital C. Milstein, Buenos Aires, Argentina
| | - Maria Isabel Sabate
- Servicio de Endocrinología, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - Marisa Servidio
- Unidad de Endocrinología, Hospital Teodoro Alvarez, Buenos Aires, Argentina
| | | | - Graciela Stalldecker
- Servicio de Endocrinología, Hospital General de Agudos Dr. Ignacio Pirovano,, Buenos Aires, Argentina
| | - Soledad Sosa
- División Endocrinología, Hospital de Clínicas José de San Martin UBA, Buenos Aires, Argentina
| | - Grabriela Szuman
- Servicio de Endocrinología, Sanatorio Municipal Dr. J. Mendez, Buenos Aires, Argentina
| | - Julieta Tkatch
- División Endocrinología, Hospital Carlos G. Durand, Buenos Aires, Argentina
| | - Ignacio Caldo
- Unidad de Gastroenterología, Hospital Carlos G. Durand, Buenos Aires, Argentina
| | - Daniela Lubieniecki
- Unidad de Gastroenterología, Hospital Carlos G. Durand, Buenos Aires, Argentina
| | - Mirtha Guitelman
- División Endocrinología, Hospital Carlos G. Durand, Buenos Aires, Argentina
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Ucan B, Kizilgul M, Karci AC, Duger H, Erkam Sencar M, Imga NN, Demirci T, Berker D, Erman Cakal. THE PREVALENCE OF CANCER AND ITS RELATION TO DISEASE ACTIVITY IN PATIENTS WITH ACROMEGALY: TWO CENTERS' EXPERIENCE. Endocr Pract 2021; 27:51-55. [PMID: 33475501 DOI: 10.4158/ep-2020-0398] [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] [Indexed: 11/15/2022]
Abstract
OBJECTIVE Acromegaly is characterized by increased serum concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Although animal studies have demonstrated a relationship between these hormones and cancer risk, the results of human studies evaluating cancer prevalence in acromegaly are inconsistent. We aimed to investigate the prevalence of malignant neoplasms in patients with acromegaly. METHODS Cancer risk was evaluated in a cohort of 280 patients (male/female: 120/160; mean age: 50.93 ± 12.07 years) with acromegaly. Patients were categorized into 2 groups according to the presence or absence of cancer. Standard incidence ratios were calculated as compared to the general population. RESULTS From 280 patients, cancer was diagnosed in 19 (6.8%) patients; 9 (47%) of them had thyroid cancer, which was the most common cancer type. Standard incidence ratios of all cancers were 0.8 (95% CI, 0.5-1.1) and 1.0 (95% CI, 0.8-1.3) in men and women, respectively. Compared to patients without cancer, the current age was higher in patients with cancer (59 [49-65] to 51 [42-59], P = .027). In contrast, the age at diagnosis was similar in both groups. Not only was the time to diagnosis and disease duration similar in both groups but also the basal and current GH and IGF-1 levels. The prevalence of active disease was also similar between the groups (32% to 23%, P = .394). CONCLUSION Our findings were not consistent with the studies suggesting that patients with acromegaly encounter an increased cancer risk. Furthermore, there were similar basal and current GH and IGF-1 levels in patients with acromegaly, both with and without cancer.
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Affiliation(s)
- Bekir Ucan
- Department of Endocrinology and Metabolism, University of Health Sciences, Dıskapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Muhammed Kizilgul
- Department of Endocrinology and Metabolism, University of Health Sciences, Dıskapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey.
| | - Alper Cagri Karci
- Department of Endocrinology and Metabolism, University of Health Sciences, Numune Training and Research Hospital, Ankara, Turkey
| | - Hakan Duger
- Department of Endocrinology and Metabolism, University of Health Sciences, Dıskapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Muhammed Erkam Sencar
- Department of Endocrinology and Metabolism, University of Health Sciences, Dıskapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Narin Nasiroglu Imga
- Department of Endocrinology and Metabolism, University of Health Sciences, Numune Training and Research Hospital, Ankara, Turkey
| | - Taner Demirci
- Department of Endocrinology and Metabolism, University of Health Sciences, Dıskapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
| | - Dilek Berker
- Department of Endocrinology and Metabolism, University of Health Sciences, Numune Training and Research Hospital, Ankara, Turkey
| | - Erman Cakal
- Department of Endocrinology and Metabolism, University of Health Sciences, Dıskapı Yıldırım Beyazıt Training and Research Hospital, Ankara, Turkey
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de Pablos-Velasco P, Venegas EM, Álvarez Escolá C, Fajardo C, de Miguel P, González N, Bernabéu I, Valdés N, Paja M, Díez JJ, Biagetti B. Diagnosis, treatment and follow-up of patients with acromegaly in a clinical practice setting in Spain: the ACROPRAXIS program Delphi survey. Pituitary 2020; 23:129-139. [PMID: 31823249 PMCID: PMC7066268 DOI: 10.1007/s11102-019-01012-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
AIM The ACROPRAXIS program aims to describe the management of acromegaly in Spain and provide guidance. METHODS Ninety-three endocrinologists were organized into 13 panels to discuss the practical issues in managing acromegaly. Based on the key learnings, an online Delphi survey with 62 statements was performed, so those statements achieving consensus could be used as guidance. Statements were rated on a 9-point scale (9, full agreement; consensus > 66.6% of response in the same tertile). RESULTS Ninety-two endocrinologists (98.8%) answered two rounds of the survey (mean age 47.6 years; 59.8% women; median 18.5 years of experience). Consensus was achieved for 49 (79%) statements. DIAGNOSIS The levels of insulin-like growth factor I (IGFI) is the preferred screening test. If IGFI levels 1-1.3 ULN, the test is repeated and growth hormone (GH) after oral glucose tolerance test (OGTT) is assessed. A pituitary magnetic resonance is performed after biochemical diagnosis. TREATMENT Surgery is the first treatment choice for patients with microadenoma or macroadenoma with/without optical pathway compression. Pre-surgical somatostatin analogues (SSA) are indicated when surgery is delayed and/or to reduce anaesthesia-associated risks. After unsuccessful surgery, reintervention is performed if the residual tumor is resectable, while if non-resectable, SSA are administered. Follow-up First biochemical and clinical controls are performed 1-3 months after surgery. Disease remission is considered if random GH levels are < 1 µg/L or OGTT is < 1 or ≤ 0.4 µg/L, depending on the assay's sensitivity. CONCLUSION Current clinical management for acromegaly is homogeneous across Spain and generally follows clinical guidelines.
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Affiliation(s)
- Pedro de Pablos-Velasco
- Endocrinology Service, Hospital Universitario de Gran Canaria Dr. Negrín, C/Barranco de la Ballena, s/n, 35010, Las Palmas de Gran Canaria, Spain.
| | - Eva María Venegas
- Endocrinology Service, Hospital Universitario Virgen del Rocío, Seville, Spain
| | | | - Carmen Fajardo
- Endocrinology Service, Hospital Universitario de La Ribera, Valencia, Spain
| | - Paz de Miguel
- Endocrinology Service, Hospital Universitario Clínico San Carlos, Madrid, Spain
| | - Natividad González
- Endocrinology Service, Hospital Universitario Virgen Macarena, Seville, Spain
| | - Ignacio Bernabéu
- Endocrinology Service, Hospital Clínico Universitario Santiago de Compostela, Santiago de Compostela, Spain
| | - Nuria Valdés
- Endocrinology Service, Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Miguel Paja
- Endocrinology Service, Hospital Universitario de Basurto, Bilbao, Spain
| | - Juan José Díez
- Endocrinology Service, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain
| | - Betina Biagetti
- Endocrinology Service, Hospital Universitario Vall d'Hebrón, Barcelona, Spain
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Gadelha MR, Kasuki L, Lim DST, Fleseriu M. Systemic Complications of Acromegaly and the Impact of the Current Treatment Landscape: An Update. Endocr Rev 2019; 40:268-332. [PMID: 30184064 DOI: 10.1210/er.2018-00115] [Citation(s) in RCA: 206] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Accepted: 07/26/2018] [Indexed: 12/19/2022]
Abstract
Acromegaly is a chronic systemic disease with many complications and is associated with increased mortality when not adequately treated. Substantial advances in acromegaly treatment, as well as in the treatment of many of its complications, mainly diabetes mellitus, heart failure, and arterial hypertension, were achieved in the last decades. These developments allowed change in both prevalence and severity of some acromegaly complications and furthermore resulted in a reduction of mortality. Currently, mortality seems to be similar to the general population in adequately treated patients with acromegaly. In this review, we update the knowledge in complications of acromegaly and detail the effects of different acromegaly treatment options on these complications. Incidence of mortality, its correlation with GH (cumulative exposure vs last value), and IGF-I levels and the shift in the main cause of mortality in patients with acromegaly are also addressed.
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Affiliation(s)
- Mônica R Gadelha
- Neuroendocrinology Research Center/Endocrine Section and Medical School, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.,Neuroendocrine Section, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde do Rio de Janeiro, Rio de Janeiro, Brazil.,Neuropathology and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil
| | - Leandro Kasuki
- Neuroendocrinology Research Center/Endocrine Section and Medical School, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.,Neuroendocrine Section, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde do Rio de Janeiro, Rio de Janeiro, Brazil.,Endocrine Unit, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil
| | - Dawn S T Lim
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Maria Fleseriu
- Department of Endocrinology, Diabetes and Metabolism, Oregon Health and Science University, Portland, Oregon.,Department of Neurological Surgery, Oregon Health and Science University, Portland, Oregon.,Northwest Pituitary Center, Oregon Health and Science University, Portland, Oregon
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