Endocrine Connections最新文献

Background: Alcohol consumption was shown to increase endogenous fibroblast growth factor 21 (FGF21), but knowledge about the effect of alcohol cessation on FGF21 is limited. The effects of cigarette smoking and cessation on FGF21 levels are unknown. The objective of this study was to investigate moderate alcohol and cigarette consumption and their cessation on FGF21 levels.

Methods: This is a secondary analysis of two prospective intervention studies. Study 1: ten healthy men undergoing a beer or water intervention with blood sampling over 720 min. Differences in FGF21 levels between alcohol and water intake were assessed using a mixed-effect model. Study 2: 144 alcohol-drinking men or women undergoing a 12-week intervention of glucagon-like peptide 1 (GLP-1) receptor agonist dulaglutide vs placebo on smoking and alcohol cessation. Differences in FGF21 levels after 12 weeks of treatment with GLP-1 in persistent drinkers/smokers compared to those who had stopped drinking/smoking, were assessed using mixed-effect models.

Results: Study 1: FGF21 levels at 240 min following beer intake were higher compared to water intake (1.386.0 pg/mL (95% CI: 934.55; 1,837.44), P < 0.001). Study 2: participants who stopped drinking alcohol had lower FGF21 levels compared to persistent drinkers (-228.65 pg/mL (95% CI: -440.4; -14.6), P = 0.03). Smoking cessation had no effect on FGF21 levels (P = 0.13).

Conclusion: Our findings demonstrate a dynamic response in FGF21 levels, with acute moderate alcohol consumption inducing elevated FGF21 levels, and cessation of drinking lowering FGF21 levels, indicative of potential liver recovery. No effect of cigarette smoking cessation on plasma FGF21 levels was observed.

Abstract: Childhood-onset growth-hormone deficiency (GHD) requires growth-hormone therapy (GHT) to optimize final height. GHT may also have benefits after final height is achieved, notably on bone. The objective of this retrospective single-center observational cohort study of patients who had persistent GHD after achieving their final height was to assess bone parameters at the transition to adult care and then more than 6 months later (6.08 (3.33-10.25) years). Bone mineral density (BMD) and Z-score at the lumbar spine and hip were determined. Of 162 patients transitioned to adult care in 1994-2021, 105 received GHT for longer than 6 months (GHT group) and 57 received either no GHT or GHT for less than 6 months (no-GHT group); however, BMD and Z-score data from both evaluations were available for only a minority of patients. Lumbar-spine BMD was significantly higher at the second evaluation in the GHT group than in the no-GHT group (P = 0.034). The lumbar-spine Z-scores at the first and second evaluations were -1.61 and -1.32 in the no-GHT group vs -1.09 and -0.61 in the GHT group (P = 0.047 for the difference in median change over time between groups). Changes in BMD at the lumbar spine and in BMD and Z-score at the femoral neck were not significantly different between the two groups. These results suggest beneficial effects of continued GHT in patients with persistent GHD after final height attainment, adding evidence to continue GH therapy during and after the transition period.

Plain language summary: Children with insufficient growth-hormone levels are given growth-hormone injections to allow them to gain height. Once the final height is achieved, the treatment is often stopped. However, further treatment during the transition to adulthood may have benefits, notably on bone.

Insulin resistance (IR) is a pathogenic mechanism for type 2 diabetes mellitus (T2DM), and receptor-interacting serine-threonine kinase 2 (RIPK2) participates in mediating IR. To investigate the specific role of RIPK2 in IR, this study utilized bovine serum albumin-conjugated palmitic acid (0.5 mmol/L) to create an IR model in rat L6 myotubes, followed by transfection with/without short hairpin RNA against RIPK2 (shRIPK2)/RIPK2 overexpression plasmid, and X-linked inhibitor of apoptosis (XIAP) overexpression plasmids. The expressions of RIPK2 and XIAP were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Oxidative stress markers superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were quantified. Western blot was performed to detect the levels of phosphorylation of extracellular signal-regulated kinases 1/2 (p-ERK1/2)/ERK1/2, p-p38/p38, and p-serine/threonine kinase (p-AKT)/AKT, as well as the influence of XIAP on RIPK2 ubiquitination. Glucose absorption was quantified using fluorescent probes (2-NBDG). In the IR model, RIPK2 expression was significantly increased, whereas XIAP expression was reduced. RIPK2 overexpression diminished SOD levels, CAT levels, and GPx levels and elevated MDA levels, accompanied by increased p-ERK1/2/ERK1/2 and p-p38/p38 ratios. Overexpression of RIPK2 lowered glucose absorption and the p-AKT/AKT ratio. RIPK2 was ubiquitinated by XIAP in the IR model. RIPK2 overexpression offset the impact of XIAP overexpression on SOD levels, CAT levels, GPx levels, and MDA levels, p-ERK1/2/ERK1/2 ratios, and p-p38/p38 ratios. XIAP overexpression enhanced glucose absorption and the p-AKT/AKT ratio. Our results demonstrate that XIAP deficiency reduces RIPK2 ubiquitination, thereby mediating IR in T2DM.

Background: Ipilimumab, a CTLA-4 targeting monoclonal antibody, enhances T-cell activation and improves outcomes in various malignancies. However, it is associated with Immune Related Adverse Events (IRAEs), including hypophysitis- a rare but potentially life-threatening condition. This review characterizes the clinical features, diagnostic approaches, and therapeutic strategies for ipilimumab-induced hypophysitis, and explores its underlying pathophysiology through a case report and literature synthesis.

Methodology: We conducted a systematic review of published cases of ipilimumab-induced hypophysitis, extracting data on demographics, comorbidities, cancer types, treatment regimens, imaging findings, endocrine dysfunctions, and therapeutic outcomes. Additionally, we present a detailed case report of a 60-year-old male with renal cell carcinoma who developed hypophysitis following ipilimumab-nivolumab combination immunotherapy.

Results: The literature review included 92 patients (mean age 57, 68% male), most commonly treated for melanoma. MRI revealed pituitary abnormalities in 46 patients. The most frequent symptoms were headache and fatigue, with panhypopituitarism and secondary adrenal insufficiency being the most common endocrine manifestations. Glucocorticoids were administered in 86 patients, and 62 required hormone replacement. Only 15/92 patients had full pituitary function recovery. Our case report mirrored these findings, with symptom onset after the third immunotherapy cycle and partial hormonal recovery following steroids.

Conclusions: Ipilimumab-induced hypophysitis is a significant IRAE with a variable clinical course and often irreversible endocrine dysfunction. Early recognition and management with glucocorticoids are critical, though long-term hormone replacement is frequently required. The autoimmune pathogenesis, linked to CTLA-4 expression in pituitary cells, underscores the need for further research into predictive markers and preventive strategies.

Objective: The impact of telomerase reverse transcriptase (TERT) promoter mutations on short-term prognosis in papillary thyroid carcinoma (PTC) remains unclear. Clarifying this association may improve early risk stratification and guide timely management. This study aimed to evaluate the influence of TERT promoter mutations on short-term clinical outcomes in PTC and propose an enhanced risk stratification model incorporating TERT status.

Methods: This study analyzed 3,078 patients who underwent thyroidectomy for PTC at a tertiary referral center in South Korea from 2019 to 2021. Among these, 57 had TERT promoter mutations. Using propensity score matching (4:1) by age and sex, 227 patients with wild-type TERT promoter were selected. Short-term outcomes were categorized as no evidence of disease (NED), biochemical incomplete, or structural incomplete response. A novel classification system (risk stratification system-TERT (RSS-T)) integrating TERT status into the 2015 American Thyroid Association (ATA) risk stratification system was developed to improve risk prediction.

Results: Patients with TERT promoter mutations showed more aggressive disease and received more intensive treatments. Mutation carriers had poorer short-term outcomes, with lower NED rates and higher structural incomplete response rates. Among intermediate- and high-risk groups, TERT promoter mutations were associated with significantly worse outcomes. The RSS-T system demonstrated superior predictive performance over the ATA system.

Conclusion: TERT promoter mutations are associated with poor short-term outcomes in PTC, especially among intermediate- and high-risk patients. Incorporating TERT status into risk stratification can refine initial risk stratification and facilitate the efficient allocation of medical resources for follow-up care after primary treatment.

Context: Primary aldosteronism (PA), the most common and potentially curable cause of secondary hypertension, remains under-investigated in the low- and middle-income countries (LMIC) of South Asia. Given the high population density in South Asia, including Bangladesh, the burden of PA is likely substantial. However, data on its prevalence are scarce.

Objective: To determine the prevalence of PA among hypertensive patients attending an endocrine hypertension clinic at a tertiary hospital in Bangladesh.

Methods: In this cross-sectional observational study, consecutive hypertensive patients with a plasma aldosterone-to-renin ratio (ARR) > 50 pmol/mIU underwent a seated saline suppression test (SST). PA was defined as a 4 h post-saline plasma aldosterone concentration (PAC) > 170 pmol/L. Participants with post-saline PAC ≤ 170 pmol/L were classified as non-PA. In the absence of adrenal vein sampling, subtyping was based on adrenal CT.

Results: Of 365 screened patients (mean age 41.6 ± 12.8 years; 70.7% female), 218 (59.7%) had an ARR > 50 pmol/mIU. Of these, 207 completed the SST, with 114 (31.2% overall) meeting biochemical criteria for PA. Most participants with PA and non-PA were normokalemic, although hypokalemia was significantly more frequent in those with PA (27.7 vs 9.5%; P < 0.001). The majority of patients with PA had controlled office blood pressure on standard antihypertensive medications or stage 1 hypertension; 5.3% had resistant hypertension.

Conclusion: PA appears highly prevalent among hypertensive patients in Bangladesh and often presents without classic features such as hypokalemia or resistant hypertension. These findings support recent guideline recommendations for broader PA screening in all individuals with hypertension to improve detection and cardiovascular outcomes.

Differentiated thyroid carcinoma includes papillary (PTC) and follicular thyroid carcinomas (FTC). The biological characteristics and prognostic factors of these two carcinomas differ significantly. PTC is generally diagnosed by cytology; large tumor size, clinical node metastasis, and gross extrathyroidal and extranodal tumor invasion are significant prognostic factors for disease recurrence-free survival (DFS) and cause-specific survival (CSS). Age is a very important prognostic factor. Young age affects only DFS, whereas old age is related to both DFS and CSS. Aggressive variants, such as tall cell and hobnail variants, high Ki-67 labeling index, and TERT promoter gene mutations, are pathological and molecular prognostic factors. FTC is generally diagnosed based on postoperative pathology. Old age and large tumor size are associated with poor prognosis. Importantly, FTC is classified as minimally invasive, encapsulated angioinvasive, and widely invasive, which are closely related to the prognosis. Recent studies have demonstrated that the grade of vascular invasion is an important prognostic factor, whereas capsular invasion is not, because widely invasive FTC with no vascular invasion has an excellent prognosis. Dynamic markers, such as thyroglobulin doubling rate, metastatic tumor volume-doubling rate, and immunological indicators, such as the neutrophil-to-lymphocyte ratio, are useful for predicting the prognosis and evaluating the effectiveness of treatments, such as radioactive iodine therapy and molecular targeted therapy for recurrent lesions. Clinicians should accurately evaluate the prognostic markers of PTC and FTC in the pre-, intra-, and postoperative phases.

Background: This systematic review seeks to employ a meta-analysis to evaluate the differential impacts of exercise interventions with high adherence versus those with low or uncertain adherence, following the American College of Sports Medicine (ACSM) guidelines, on factors such as glucose regulation and insulin sensitivity in prediabetic patients.

Methods: A thorough search was executed across databases such as PubMed, Embase, Web of Science, and the Cochrane Library from inception to September 1, 2025. We carried out a meta-analysis concentrating on exercise interventions among prediabetic patients. Only randomized controlled trials were included in our study. The meta-analyses determined WMDs for parameters such as fasting blood glucose (FBG), 2-hour plasma glucose (2hPG), glycated haemoglobin A1c (HbA1c), and homoeostasis model assessment of insulin resistance (HOMA-IR).

Results: There were 24 studies with a total of 1,480 participants. Compliance with the ACSM recommendations was categorised as 'high' in 9 studies and 'low or uncertain' in 15 studies. In the subgroup analysis comparing high compliance with ACSM recommendations to low or uncertain compliance, the results were as follows: FBG: -0.55 (95% CI: -1.01, -0.09) vs -0.42 (95% CI: -0.62, -0.21), 2hPG: -0.97 (95% CI: -1.48, -0.45) vs -0.70 (95% CI: -1.15, -0.25), HOMA-IR: -0.47 (95% CI: -0.81, -0.14) vs -0.50 (95% CI: -1.09, 0.08), HbA1c:-0.20 (95% CI: -0.50, 0.10) vs -0.29 (95% CI: -0.46, -0.12).

Conclusion: Subgroup analyses were conducted to evaluate whether intervention adherence modifies the metabolic benefits of exercise. Mean reductions in FBG, 2hPG, and HOMA-IR were numerically larger in participants with high, compared with low or uncertain, adherence, suggesting a possible dose-response relationship between adherence and glycaemic improvement. Conversely, HbA1c displayed a marginally greater reduction in the low-adherence stratum - an observation that contrasts with the pattern seen for the other glucose/insulin indices. This discrepancy may reflect greater analytical variability of HbA1c, differences in intervention duration, baseline imbalance, or heterogeneity in programme content and individual responsivity across adherence categories. Large-scale, long-term trials that standardise the measurement of adherence and the delivery of exercise interventions are needed to definitively clarify the association between adherence and metabolic outcome.

Background: Bariatric surgery affects multiple physiological systems, including the regulation of des-acyl ghrelin (DAG). DAG has been negatively associated with excess adiposity and insulin resistance.

Objectives: To assess the relationship between serum DAG concentrations and short-term weight loss following bariatric surgery.

Setting: Prospective multicenter cohort study across three bariatric surgery centers in Latvia.

Methods: Fasting blood samples for DAG measurement were collected 1 day preoperatively, 2 days postoperatively, and at 3 months post-surgery. Anthropometric and laboratory assessments were performed at the same time points.

Results: A total of 62 patients were included; 64.5% (n = 40) underwent Roux-en-Y gastric bypass (RYGB), and 35.5% (n = 22) sleeve gastrectomy (SG). The cohort was predominantly female (67.7%). Median baseline weight and BMI were 129 kg (IQR 106-150) and 45.1 kg/m2, respectively. Median excess weight loss at 3 months was 40.2% (IQR 32.2-54.3%). DAG concentrations showed significant inverse correlations with preoperative weight (r = -0.371), BMI (r = -0.311), and excess weight (r = -0.355; all P < 0.05). These associations persisted across all sampling points in the RYGB group, whereas in SG patients, they were largely confined to postoperative day 2. No significant relationships were observed between DAG and relative weight-loss metrics. DAG levels were higher in females; age showed no association with DAG changes.

Conclusion: DAG levels are inversely associated with absolute measures of adiposity, particularly among RYGB patients. These findings support DAG's potential relevance as a marker of total fat burden and early postoperative metabolic response.

Objective: Hepatocyte growth factor (HGF)/c-MET signaling regulates glucose metabolism and tissue remodeling, but its role in gestational diabetes mellitus (GDM) remains unclear. We aimed to investigate maternal serum HGF and soluble c-MET (sc-MET) levels, their tissue expression in placenta and maternal visceral adipose tissue, and their associations with obstetric and perinatal outcomes in GDM.

Methods: In this retrospective observational, cross-sectional study, 76 pregnant women (32 GDM, 44 normal glucose tolerance) were enrolled. Serum HGF and sc-MET were measured by ELISA; placental and visceral-fat HGF/c-MET expression was analyzed by RT-PCR and western blot. Clinical variables, including umbilical-cord blood gas and glucose values, were evaluated.

Results: Maternal sc-MET levels were significantly higher, and cord-blood HGF levels significantly lower, in the GDM group. HGF protein expression was increased in maternal visceral fat but unchanged in placenta. Maternal HGF correlated negatively with cord base excess and positively with lactic acid levels, while cord HGF correlated positively with neonatal glucose.

Conclusions: These findings indicate tissue-specific dysregulation of HGF/c-MET signaling in GDM, potentially linking maternal insulin resistance with fetal metabolic stress through visceral-fat-derived HGF. The associations between maternal HGF and neonatal lactic acid levels suggest an endocrine interaction influencing fetal adaptation. Further studies are needed to clarify underlying mechanisms across heterogeneous GDM phenotypes.

Plain language summary: GDM is a condition that develops during pregnancy and affects how the body regulates sugar. This study explored how two proteins, HGF and its receptor c-MET, may influence metabolism in mothers with GDM and their babies. Blood, placenta, and visceral fat samples were analyzed from women with and without GDM. Mothers with GDM had higher blood levels of soluble c-MET and lower HGF levels in cord blood. HGF activity was increased in visceral fat, suggesting altered fat metabolism may contribute to insulin resistance. These changes were linked to higher lactic acid levels in newborns, a sign of metabolic stress. The findings suggest that HGF/c-MET signaling helps coordinate hormonal communication between mother and fetus during pregnancy and could serve as a potential biomarker for maternal insulin resistance and fetal metabolic health in GDM.