Daily Endocrinology Research Analysis

BACKGROUND: Recurrence after successful pituitary surgery remains a challenge in the management of patients with Cushing's disease, with no reliable predictors of long-term outcome. Pathogenic somatic USP8 variants are found in one third of cases and their association with recurrence is unclear. The aim of this study was to determine the association between USP8 status and postoperative outcome. METHODS: This international, retrospective, longitudinal study was done in eight tertiary centres in east Asia, Europe, and North America. We reviewed clinical records and genetic information of patients with clinically diagnosed and pathologically confirmed Cushing's disease who underwent first pituitary surgery in any of the participating centres between Jan 1, 1989, and April 1, 2024. Inclusion criteria were postoperative follow-up of at least 3 months after first pituitary surgery, known postsurgical outcome, and tissue availability or known USP8 status. The primary outcomes were recurrence and time to recurrence after first surgery. We assessed recurrence-free intervals and recurrence risk using survival analysis, multivariate logistic regression, and Cox proportional hazards models. FINDINGS: We retrospectively retrieved and examined clinical records from 558 patients, 123 of whom were excluded. 360 (83%) of 435 patients were female and 75 (17%) were male. We detected USP8 variants in 195 (45%) cases. Recurrence was recorded in 66 (18%) of 371 patients in immediate remission. Risk of recurrence depended on USP8 status and tumour size. Patients with USP8-variant microadenomas and USP8-variant macroadenomas had similar cumulative hazards for recurrence, so they were considered as a single risk group. 10-year recurrence rate was higher for USP8-variant tumours (36·8%, 95% CI 23·7-47·7) than for wildtype microadenomas (15·0%, 4·9-24·0; adjusted p=0·016) but was lower than for wildtype macroadenomas (44·5%, 26·2-58·2; adjusted p=0·025). Patients with USP8-variant tumours (hazard ratio 2·41, 95% CI 1·19-4·87; p=0·014) or wildtype macroadenomas (4·48, 2·11-9·52; p<0·0001) had significantly higher risk of recurrence than patients with wildtype microadenomas, even after adjusting for age, postoperative nadir serum cortisol, tumour invasion, and ethnicity or centre. INTERPRETATION: Combined USP8 genotype-tumour size identified patients at increased risk of recurrence, particularly in largely heterogeneous groups of patients with non-invasive tumours or low postoperative serum cortisol not considered high risk in standard care. Implementing this combined genetic-clinical stratification could provide more accurate risk assessment, indicate those at higher risk of recurrence, and ultimately personalise long-term follow-up in patients with Cushing's disease. FUNDING: Deutsche Forschungsgemeinschaft, National Natural Science Funds of China, and CAMS Innovation Fund for Medical Sciences.

BACKGROUND: Evidence on the individual risks of type 1 and type 2 diabetes following gestational diabetes mellitus (GDM) exposure, particularly in large Asian populations, remains limited. We examined whether maternal GDM increases the risk of type 1 and type 2 diabetes in offspring in a Korean nationwide cohort. METHODS: After excluding mothers with preexisting diabetes, we analyzed a nationwide Korean birth cohort of 3,491,680 mother-child pairs from 2009 to 2018, followed for up to 14 years. Type 1 diabetes was defined as International Classification of Diseases, 10th Revision (ICD-10) E10 with insulin prescription; type 2 diabetes as ICD-10 E11-E14 with antidiabetic medication use. Cox proportional hazards models were used to estimate hazard ratios (HRs) across three groups, offspring born to mothers without GDM (reference), with GDM but not treated with insulin, and with GDM treated with insulin, adjusting for maternal and neonatal covariates. RESULTS: Of the total cohort, 424,185 (12.1%) pregnancies were complicated by GDM, among which 30,003 (7.1%) required insulin therapy during pregnancy. GDM without insulin therapy was not associated with type 1 diabetes in offspring (HR, 0.857 [95% confidence interval, 0.696-1.054]). However, offspring of GDM mothers requiring insulin during pregnancy had a higher risk of type 1 diabetes (HR, 1.936 [1.228-3.052]). For offspring type 2 diabetes, GDM without insulin during pregnancy was significantly associated with increased risk (HR, 1.281 [1.146-1.433]), with a greater risk among insulin-treated GDM pregnancies (HR, 4.329 [3.555-5.270]). CONCLUSIONS: Maternal GDM without insulin therapy is associated with an increased risk of type 2 diabetes, but not type 1 diabetes, in offspring, whereas insulin treatment for GDM during pregnancy is associated with increased risk for both type 1 and type 2 diabetes. These findings underscore the need for individualized postnatal monitoring for offspring of mothers with GDM, with heightened attention for those whose mothers required insulin therapy during pregnancy.

BACKGROUND: Adrenal venous sampling (AVS) plays a pivotal role in treatment optimization for primary aldosteronism (PA) to minimize the cardiovascular risks. However, technical difficulties often hinder accurate cannulation to the adrenal veins (AVs). This study aimed to explore the distribution of partial pressure of oxygen (pO2) in the adrenal and neighboring veins, inspired by our awareness of lighter red color of adrenal venous blood than the others. METHODS: We enrolled 179 PA patients who underwent AVS from 2021 to 2024. During AVS, we collected residual blood samples from bilateral adrenal, hepatic, inferior phrenic and external iliac veins for blood gas analysis. Statistical analysis was conducted to evaluate pO2 distributions and its associations with clinical parameters. RESULTS: Among 179 patients examined, 168 received oxygen supplementation during AVS and in those cases, the pO2 levels were significantly higher in the bilateral AVs than in the hepatic and inferior phrenic veins at baseline, whereas the levels of partial pressure of carbon dioxide were lower. Following cosyntropin stimulation, the pO2 levels in the AVs decreased but distribution patterns across the examined veins remained similar. The pO2 evaluation provided highly accurate identification of AVs both before and after cosyntropin stimulation. CONCLUSION: This is the first study to examine the pO2 dynamics in the human adrenal and non-adrenal veins, demonstrating its potential to improve AVS cannulation success rates. Our findings also presented the oxygen consumption in the adrenal glands for steroidogenesis. The pO2 measurement is a faster, easier and less-expensive tool enhancing AVS techniques.