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- Casar Borota, Olivera, et al.
(författare)
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Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:4, s. 1183-1194
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Tidskriftsartikel (refereegranskat)abstract
- Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.
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| 2. |
- Burman, Pia, et al.
(författare)
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Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality
- 2013
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:4, s. 1466-1475
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Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for Objective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism Design and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with Main Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for Results: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence Conclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response
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| 3. |
- Johansson, H.-E., et al.
(författare)
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Gastric bypass alters the dynamics and metabolic effects of insulin and proinsulin secretion
- 2007
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 24:11, s. 1213-1220
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Tidskriftsartikel (refereegranskat)abstract
- Aims Hyperproinsulinaemia is associated with obesity and is a risk factor for Type 2 diabetes. We explored the dynamics of proinsulin and insulin and postprandial effects on glucose and lipids in subjects who had undergone gastric bypass (GBP) surgery compared with morbidly obese (MO) subjects and normal weight control subjects (NW). Methods Subjects free from diabetes were recruited: 10 previously MO subjects [body mass index (BMI) ± SD, 34.8 ± 6.2 kg/m2] who had undergone GBP surgery, 10 MO subjects (BMI 44 ± 3.1 kg/m2) and 12 NW control subjects (BMI 23.2 ± 2.4 kg/m2). After an overnight fast, a standard meal (2400 kJ) was ingested and glucose, proinsulin, insulin free fatty acids and triglycerides were determined up to 180 min. Results Fasting proinsulin was similar in the GBP group and NW control subjects, but threefold increased in MO subjects (P < 0.05). Postprandial AUC for glucose was similar in the three groups and AUC for proinsulin was high in MO, intermediate in the GBP group and lowest in NW control subjects (P for trend = 0.020). Postprandial proinsulin at 60 min was similar in the GBP group and MO subjects and twofold higher than in NW control subjects. Postprandial proinsulin at 180 min was normal in the GBP group, but fivefold increased in MO subjects (P = 0.008). Insulin increased rapidly at 30 min in the GBP group and was normal at 90 min, whereas insulin was still increased at 90-180 min in the MO subjects (P < 0.001). Conclusions MO subjects, free from diabetes, have elevated proinsulin concentrations in the fasting as well as the postprandial phase. After GBP surgery markedly lower fasting and postprandial proinsulin concentrations were observed, although BMI was higher compared with NW control subjects.
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| 4. |
- Papakokkinou, Eleni, et al.
(författare)
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Prevalence of Nelson's syndrome after bilateral adrenalectomy in patients with cushing's disease: a systematic review and meta-analysis
- 2021
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Bilateral adrenalectomy (BA) still plays an important role in the management of Cushing's disease (CD). Nelson's syndrome (NS) is a severe complication of BA, but conflicting data on its prevalence and predicting factors have been reported. The aim of this study was to determine the prevalence of NS, and identify factors associated with its development. Data sources Systematic literature search in four databases. Study Selection Observational studies reporting the prevalence of NS after BA in adult patients with CD. Data extraction Data extraction and risk of bias assessment were performed by three independent investigators. Data synthesis Thirty-six studies, with a total of 1316 CD patients treated with BA, were included for the primary outcome. Pooled prevalence of NS was 26% (95% CI 22-31%), with moderate to high heterogeneity (I-2 67%, P < 0.01). The time from BA to NS varied from 2 months to 39 years. The prevalence of NS in the most recently published studies, where magnet resonance imaging was used, was 38% (95% CI 27-50%). The prevalence of treatment for NS was 21% (95% CI 18-26%). Relative risk for NS was not significantly affected by prior pituitary radiotherapy [0.9 (95% CI 0.5-1.6)] or pituitary surgery [0.6 (95% CI 0.4-1.0)]. Conclusions Every fourth patient with CD treated with BA develops NS, and every fifth patient requires pituitary-specific treatment. The risk of NS may persist for up to four decades after BA. Life-long follow-up is essential for early detection and adequate treatment of NS.
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