Deaths Among Adult Patients with Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality.

Context:Patients with hypopituitarism have an increased standardized mortality rate. The basis for this has not been fully clarified.Objective:To investigate in detail the cause of death in a large cohort of patients with hypopituitarism subjected to long-term follow-up.Design and Methods:All-cause and cause-specific mortality in 1286 Swedish patients with hypopituitarism prospectively monitored in KIMS (Pfizer International Metabolic Database) 1995-2009 were compared to general population data in the Swedish National Cause of Death Registry. In addition, events reported in KIMS, medical records, and postmortem reports were reviewed.Main Outcome Measures:Standardized mortality ratios (SMR) were calculated, with stratification for gender, attained age, and calendar year during follow-up.Results:An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence interval: 1.18-1.70). Infections, brain cancer, and sudden death were associated with significantly increased SMRs (6.32, 9.40, and 4.10, respectively). Fifteen patients, all ACTH-deficient, died from infections. Eight of these patients were considered to be in a state of adrenal crisis in connection with death (medical reports and post-mortem examinations). Another 8 patients died from de novo malignant brain tumors, 6 of which had had a benign pituitary lesion at baseline. Six of these 8 subjects had received prior radiation therapy.Conclusion:Two important causes of excess mortality were identified: first, adrenal crisis in response to acute stress and intercurrent illness; second, increased risk of a late appearance of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these causes may be in part preventable by changes in the management of pituitary disease

A prospective case-control study on miRNA circulating levels in subjects born small for gestational age (SGA) evaluated from childhood into young adulthood

OBJECTIVE:microRNAs (miRNAs) associated with metabolic risk have never been extensively investigated in SGA subjects. The aim of the current study was to evaluate miRNAs in SGA and AGA subjects and their relationships with the metabolic status and growth. DESIGN AND METHODS:A prospective longitudinal case-control study was performed in 23 SGA with postnatal catch-up growth and 27 AGA subjects evaluated at the age of 9 and 21 years. Circulating levels of miR-122-5p, miR-16-5p, miR-126-3p, and miR-486-5p were assessed by qPCR. RESULTS:SGA subjects were shorter both at 9 and at 21 years. No significant differences in insulin like growth factors and metabolic profile were found with the exception of basal glycemia at 9 years. miRNA levels did not differ between SGA and AGA subjects, at 9 and 21 years. miR-16-5p and miR-126-3p levels were higher at 9 than at 21 years. In SGA subjects, miR-122-5p at 9 years was inversely related to adiponectin levels at 21 years and miR-486-5p at 9 years was inversely related to whole-body insulin sensitivity at 9 years and directly related to Hb1Ac at 21 years. Regression analyses showed no predictive value of miRNAs for growth parameters in neither SGA nor AGA subjects. CONCLUSIONS:SGA with postnatal catch-up growth did not show any difference in metabolic risk markers or miRNA circulating levels compared to AGA controls in childhood and young adulthood. miR-122-5p during childhood could identify SGA subjects at higher risk of developing insulin resistance and, eventually, type 2 diabetes in adulthood but further studies are needed to confirm it

Establishing a valid cohort of patients with acromegaly by combining the national patient register with the Swedish pituitary register

Purpose: The aim of this study was to establish a valid national cohort of patients diagnosed with acromegaly by combining data from the general National Patient Register (NPR) and the disease-specific Swedish Pituitary Register (SPR). Methods: Patients ≥ 18 years of age at diagnosis of acromegaly reported from 1991 to 2018 who were registered in the NPR and/or SPR were included. The diagnosis of acromegaly was considered correct for patients identified in both registers or confirmed through chart review. Medical records were reviewed in two of Sweden´s six health care regions if the patient was reported only in the NPR. An algorithm for the NPR, with criteria requiring multiple diagnosis registrations and tumour and/or surgery codes, was constructed to reduce the number of patients to review in the remaining four regions. Results: A total of 1866 patients were identified. Among these, 938 were reported in both registers. After application of the algorithm and chart review, the diagnosis was confirmed for 83 of the 906 patients found only in the NPR. Among 22 patients only registered in the SPR, a review of medical records confirmed acromegaly in 13. This resulted in a total of 1034 cases with acromegaly during the study period. The incidence rate of acromegaly in Sweden 1991–2018 was calculated to 4.0/million/year in the entire population and 5.1/million/year among subjects ≥ 18 years of age. Conclusion: The combination of the SPR and NPR established a valid cohort of patients diagnosed with acromegaly and increased the estimated incidence in Sweden

Tumoral MGMT content predicts survival in patients with aggressive pituitary tumors and pituitary carcinomas given treatment with temozolomide

Temozolomide (TMZ) has recently been recommended as the first line chemotherapy in patients with aggressive pituitary tumors (APT) and pituitary carcinomas (PC) not controlled by standard treatment, i.e., surgery, radiotherapy and/or medical therapy (dopamine agonists, somatostatin analogs) [1]. About 40% of patients respond initially to TMZ, complete tumor regression is observed in <10% of patients [2, 3]. The predictive value of the DNA repair protein O6 -methylguanine-DNA methyltransferase (MGMT) as a biomarker for response to TMZ has been debated. Here we present survival data after TMZ treatment in relation to tumoral MGMT content. […