Clinical Endocrinology最新文献

Objective: This study aimed to evaluate the long-term effects of hormone therapies on the body composition, adipokines and metabolic parameters of adult men with congenital hypogonadotropic hypogonadism (CHH).

Methods: Sixty-six patients with CHH and 21 healthy controls were recruited. Patients were divided into untreated (n = 33) and treated (n = 33) groups based on hormone therapy history. Body composition was assessed using dual-energy X-ray absorptiometry (DXA), and adipokines and metabolic parameters were measured in all participants.

Results: Compared to the healthy control group, patients in the treated group had lower serum testosterone levels (p < 0.001), increased body fat percentage (BFP) and visceral adipose tissue (VAT) volume, decreased lean soft tissue (LST) and bone mineral content (BMC) (p < 0.05), increased serum leptin levels accompanied by decreased adiponectin (ADP) (p < 0.05), higher HOMA-IR with lower QUICKI (p < 0.05). Compared to the untreated group, patients in the treated group (therapy duration 4.8 ± 2.3 years) had higher serum testosterone levels (p < 0.001), decreased BFP and VAT volume, increased LST and BMC (p < 0.05), decreased serum leptin levels (p < 0.001), and decreased HOMA-IR accompanied by increased QUICKI (p < 0.05). Among them, VAT volume, LST, BMC, HOMA-IR and QUICKI reached healthy control levels (p > 0.05). Multiple stepwise linear regression analysis showed serum testosterone levels were negatively correlated with BFP (β = -0.564, p < 0.001) and VAT volume (β = -0.260, p = 0.045), positively correlated with LST (β = 0.305, p = 0.018) and BMC (β = 0.423, p = 0.001). Serum testosterone levels were independently negatively correlated with leptin levels (β = -0.277, p = 0.004).

Conclusions: Patients with untreated CHH had impaired body composition, adipokines and metabolic parameters. While hormone therapies can improve body composition and glucolipid metabolism in patients with CHH, this imperfect treatment does not fully rescue body composition abnormalities when compared to healthy individuals. Abnormal metabolic parameters in patients with CHH are associated with increased fat mass and abnormal serum leptin level. Serum testosterone levels were independently negatively correlated with leptin levels.

Objective: Ghrelin is emerging as a promising therapeutic option for heart failure (HF) due to its potent inotropic, anabolic, and cardioprotective properties. This review aims to critically examine the available clinical evidence on ghrelin therapy in HF, while also incorporating key findings from preclinical studies that support its therapeutic potential.

Methods: A comprehensive search was conducted in PubMed and the Cochrane Library up to September 15, 2024, using the keywords "heart failure" and "ghrelin." From 247 identified records, four randomized controlled trials, one open-label trial, one observational study, and key preclinical studies were included. Two independent authors performed the screening and quality assessment, with any discrepancies resolved through consensus.

Results: Clinical trials investigating ghrelin's acute effects in HF patients have demonstrated significant improvements in cardiac output, ranging from 15% to 30%. Moreover, one study showed that a 3-week course of ghrelin therapy significantly increased maximal oxygen consumption, lean body mass, and grip strength in HF patients. Preclinical studies further support these clinical findings, highlighting additional benefits of ghrelin, including modulation of the autonomic nervous system, promotion of vasodilation, enhancement of endothelial function, prevention of myocardial remodeling, reduction of arrhythmogenic risk, and increased muscle mass in HF models.

Conclusions: Ghrelin is a promising therapeutic option for HF, particularly as an inotropic agent with multifaceted benefits, including autonomic nervous system modulation, anabolic effects, and metabolic regulation. However, further trials are required to confirm its long-term efficacy and safety and assess whether its benefits can translate into reductions in hard clinical endpoints.

Background: The International Medullary Thyroid Carcinoma Grading System (IMTCGS) was recently introduced in medullary thyroid carcinoma (MTC). This study aimed to assess the predictive value of the IMTCGS for disease response and survival, and compare its predictive ability with that of other traditional risk factors in a Chinese MTC cohort.

Methods: The data of 137 MTC patients undergoing initial surgery between January 2004 and June 2023 were included for analysis. Histologic features were reviewed by two pathologists. Kaplan-Meier survival analysis and Cox proportional hazard model were performed to analyse the association between risk factors (including IMTCGS high vs low grade) and progression-free survival (PFS) and disease-specific survival (DSS). ROC analysis and Delong's test were used to compare the predictive ability of IMTCGS with that of other risk factors.

Results: Local recurrence, distant metastasis, and disease-specific death were observed in 14/134 (10.45%), 3/134 (2.24%), and 6/137 (4.38%) MTC patients, respectively. IMTCGS, TNM stage, postoperative calcitonin, postoperative CEA, and vascular invasion were associated with PFS in Kaplan-Meier survival analysis (all p < 0.05). Postoperative calcitonin was the only independent predictor for PFS in multivariate analysis (HR = 1.002, p = 0.002). ROC analysis and Delong's test showed that postoperative calcitonin had superior predictive value for structural recurrence than IMTCGS (AUC 0.90 vs. 0.64, p = 0.002). IMTCGS, TNM stage, and vascular invasion were associated with DSS in Kaplan-Meier survival analysis (both p < 0.05). In multivariate analysis, IMTCGS was the only independent predictor for DSS (HR = 11.23, p = 0.05). The AUC of IMTCGS was 0.81 (p = 0.01) for disease-specific death.

Conclusion: In this Chinese MTC cohort, IMTCGS was a powerful predictor of disease-specific death, while postoperative calcitonin was a powerful predictor of structural recurrence.

Objective: Patients with mild autonomous cortisol secretion (MACS) are at increased risk of cardiometabolic outcomes, such as hyperglycemia, metabolic syndrome, and cardiovascular diseases. Nonalcoholic fatty liver disease (NAFLD) is also associated with increased cardiometabolic risk. We aimed to investigate the prevalence and predictors of NAFLD in metabolically healthy subjects with MACS.

Methods: Forty patients with MACS and 60 patients with nonfunctioning adrenal incidentaloma (NFAI) matched for age, gender, and body mass index were included. We excluded various diseases that may lead to NAFLD, such as diabetes, cardiovascular diseases, and liver disorders. Non-alcoholic fatty liver disease was evaluated with unenhanced abdominal computed tomography and noninvasive fatty liver indices.

Results: Patients with MACS had lower mean liver attenuation values (Hounsfield units, HU) than those with NFAI (p = 0.001). Visceral adiposity index, hepatic steatosis index, and fatty liver index were higher in the MACS group than in the NFAI group (p = 0.009, p = 0.002, p = 0.023, respectively). However, there was no significant association between the mean liver HU value and these indices. There was a significant association between serum cortisol level after the 1 mg dexamethasone suppression test (DST) and mean liver HU value independent of other traditional risk factors in various models performed in multivariable linear regression analysis.

Conclusions: Our findings suggest that MACS is associated with an increased risk of NAFLD, and serum cortisol level after 1 mg DST is an independent predictor of NAFLD in patients with MACS.

The management of hypoglycaemia is pivotal in the care of patients with insulinoma. Blood glucose monitoring and regulation needs careful attention pre- and peri-operatively for patients undergoing surgical resection and as part of the long-term management for patients with inoperable or metastatic disease. Hypoglycaemia symptoms are frequently pervasive and disabling, with many patients showing impaired hypoglycaemia awareness that can lead to life-threatening severe hypoglycaemia. Herein, we review the literature and describe our tertiary centre experience in the mutli-disciplinary management of hypoglycaemia for patients with proven insulinomas. We propose a stepwise algorithm for the management of hypoglycaemia, stratified by localised versus metastatic disease. We discuss our strategy for the nutritional management of hypoglycaemia, reviewing the evidence for the use of cornstarch products and artificial nutrition. We discuss pharmacological management including diazoxide, somatostatin receptor antagonists (SSAs), everolimus and glucocorticoids, in addition to other therapeutic interventions such as peptide receptor radionuclide therapy (PRRT) and endoscopic ablation.

Background: Osteocalcin is a metabolic active hormone, which correlates positively with bone formation and inversely with body mass index and waist circumference in adults.

Objectives: To investigate whether osteocalcin in infancy and early childhood were related to childhood growth or body composition.

Methods: A Swedish longitudinal birth cohort with blood samples from 551 children from birth until 5 years of age. Regular anthropometric measurements were carried out up to 8 years of age and dual-energy X-ray absorptiometry (DXA) scans were also performed at 8 years. The results included p-values and Spearman's rho (ρ).

Results: Osteocalcin at 4 months of age correlated inversely and consecutively with weight from 4 to 24 months and to waist circumference from 6 to 24 months in boys. The correlations for girls were limited to weight at 4 months and waist circumference at 6 and 18 months (ρ < 0.3, p = 0.001 to 0.048). The boys' osteocalcin levels at 5 years correlated positively with their height and weight at 5 and 6.5 years (ρ < 0.3, p < 0.01). Meanwhile, the girls' osteocalcin at 3 years showed positive correlations to all weight and height measurements until 8 years of age (ρ < 0.3, p = 0.003 to 0.023). DXA data showed that the boys' osteocalcin at 5 years correlated with the fat-free mass index (FFMI) (ρ 0.212, p = 0.026) but not the fat mass index (FMI) at 8 years. The opposite was seen for the girls' osteocalcin at 3 years, which correlated with FMI (ρ 0.222, p = 0.020) but not FFMI.

Conclusion: Early levels of osteocalcin showed inverse correlations with later weight, height and body composition in infancy and positive correlations during childhood. The weak but consistent correlations suggest that osteocalcin carries information about future growth. Girls with high osteocalcin at 3 and 5 years had a larger fat mass at 8 years, while boys, in contrast, had a larger lean mass. These sex differences need to be further explored.