Disorders of pubertal onset and progression are a common cause for referral to paediatric endocrinologists, with delayed puberty in males being particularly frequent. Pubertal development depends on the hypothalamic-pituitary-testicular (HPT) axis, which is established during fetal life and undergoes distinct phases: fetal androgen production, postnatal "minipuberty", and reactivation during adolescence. Key regulators include GnRH neurons, Sertoli and Leydig cells, and biomarkers such as AMH, inhibin B, testosterone and INSL3. Puberty is marked clinically by testicular enlargement beyond 4 mL, usually at a median age of 11.5 years. Delayed puberty is defined as absence of testicular enlargement by age 14. The most common cause is self-limited delayed puberty (SLDP), often familial and benign. Functional hypogonadotropic hypogonadism due to chronic illness, and permanent central hypogonadism (congenital or acquired), account for additional cases. Congenital hypogonadotropic hypogonadism (CHH), including Kallmann syndrome, is frequently genetic, with variants in genes such as FGFR1, ANOS1 and GNRHR. Clinical assessment includes family history, growth patterns, and red flags such as micropenis, cryptorchidism or anosmia.

Resistance to thyroid hormone syndrome (RTHS) is a rare disorder caused by mutations in the thyroid hormone receptor beta (THRB) gene, resulting in impaired action of thyroid hormones on target tissues and organs. We report a case of a 57-year-old Chinese male who presented with palpitations and hand tremors. Laboratory tests revealed elevated serum thyroid hormone levels, while serum thyroid-stimulating hormone (TSH) levels remained within the normal range. Enhanced magnetic resonance imaging of the pituitary gland showed no abnormalities. Through genetic testing, we identified a rare heterozygous point mutation in the THRB gene, specifically c.938T>C: p.M313T. To the best of our knowledge, this mutation site has not been previously reported in the literature. Clinically, RTHS is often misdiagnosed as hyperthyroidism, leading to inappropriate treatment and potential exacerbation of thyroid hormone resistance. Therefore, accurate diagnosis of this condition is crucial. Given the rarity of RTHS, we hope that this case report will enhance the understanding of its clinical manifestations and management, particularly in patients with THRB gene mutations.

Mahvash disease is a rare autosomal recessive condition caused by biallelic inactivating variants in the GCGR gene, impairing glucagon signaling and leading to alpha-cell hyperplasia and pancreatic neuroendocrine tumors (PNETs). Fewer than 20 cases have been reported, and the clinical impact of heterozygous variants remains unclear. Case Presentation: We report a family with a novel GCGR splice-site variant (c.1176+1_1176+7delGTGCCCG). The index case, a 61-year-old woman, presented with extensive pancreatic cystic disease and was found to be homozygous for the variant. She developed well-differentiated PNETs and underwent total pancreatectomy. Her sister, also homozygous, had similar clinical features and surgical history. In contrast, the heterozygous brother and two sons showed mild biochemical changes, such as elevated glucagon levels and small pancreatic cysts, without overt disease. The two homozygous sisters required pancreatic surgery followed by insulin and enzyme replacement therapy, whereas heterozygous carriers are currently being managed with biochemical and imaging surveillance. This family's phenotype suggests a broader spectrum of GCGR-related disease. While homozygous individuals displayed classic Mahvash disease, heterozygotes exhibited subtle biochemical and structural pancreatic changes, indicating possible semidominant expression. These findings are consistent with emerging evidence that monoallelic receptor pathway mutations may produce mild or subclinical phenotypes. This case challenges the classical recessive model of Mahvash disease and highlights the potential for disease expression in heterozygous carriers. These findings suggest that heterozygosity is not entirely silent and underline the need to reconsider surveillance recommendations for GCGR heterozygotes.

Substantial evidence highlights the pervasive nature of weight stigma, reported by people of all ages and backgrounds. Weight stigma is experienced across the life course and in many settings across society. These harmful experiences may include verbal and physical behaviours, with long-lasting effects on mental and physical health. They may also impact the patient-practitioner when weight stigma is experienced in a healthcare setting, as well as reducing health seeking behaviour and avoidance of healthcare. It is therefore essential that weight stigma in healthcare is addressed given the important implications of these experiences in this setting, Interventions need to be longer term and given the widespread nature of weight stigma, change is needed throughout society from policy to practice. Thus, a whole system approach to weight stigma is needed to address the entrenched and often robust nature of weight stigma attitudes.

Over the past year, three new key guidelines have been published in the area of female hypogonadism, one from the Society for Endocrinology covering the full spectrum of causes of female hypogonadism in adult life, which will form the core of this review; another solely covering premature ovarian insufficiency from a consortium comprising the International Menopause Society (IMS), the European Society of Human Reproduction & Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) that updates the 2016 ESHRE guidance, and a third covering Turner syndrome across all stages of life from the International Turner Syndrome Consensus Group. In this review, we aim to synthesize the key elements from all of these documents, providing a timely update for clinicians managing affected women.

To evaluate the diagnostic performance and determine the optimal cutoff values of the triglyceride-to-high-density lipoprotein cholesterol ratio and lipid accumulation product index as predictors of metabolic syndrome among adults with obesity in Indonesia. This cross-sectional study analyzed secondary data from the 2023 Indonesia Health Survey, which included 3,988 samples (2,958 women). Descriptive statistics were used to characterize the sample. Receiver Operating Characteristic curve analysis and the Youden index were employed to assess diagnostic performance and determine the optimal cutoff values of the triglyceride-to-high-density lipoprotein cholesterol ratio and lipid accumulation product index. The associations between both predictors and the presence of metabolic syndrome were examined using multivariable logistic regression. The lipid accumulation product index exhibited greater predictive accuracy than the triglyceride-to-high-density lipoprotein cholesterol ratio, particularly among men. This result indicated the superior utility of the lipid accumulation product index as a clinical screening tool for metabolic syndrome, with area under the curve values of 0.842 (95% CI 0.817-0.866) for men and 0.737 (95% CI 0.720-0.755) for women, compared to that of the triglyceride-to-high-density lipoprotein cholesterol ratio, with area under the curve values of 0.810 (95% CI 0.784-0.837) for men and 0.728 (95% CI 0.710-0.746) for women. The optimal cutoff values of the triglyceride-to-high-density lipoprotein cholesterol ratio and lipid accumulation product index were 4.456 (sensitivity 64.8%, specificity 81.4%) and 45.752 (sensitivity 75.5%, specificity 81.2%) for men and 2.792 (sensitivity 59.2%, specificity 76.8%) and 41.285 (sensitivity 58.6%, specificity 75.8%) for women, respectively. The lipid accumulation product index demonstrated superior accuracy in predicting metabolic syndrome among adults with obesity, particularly among men. Sex-specific cutoff values enhance its reliability and practicality for early screening and intervention to prevent metabolic complications.

Accurate assessment of metastatic status is crucial for determining radioactive iodine (RAI) dosing in postoperative papillary thyroid carcinoma (PTC) patients. This study aimed to identify unbiased biomarkers in metastatic PTC patients after surgery by applying a metabolomics workflow in saliva samples. Saliva samples from 70 postoperative PTC patients (35 metastatic PTC patients in metastasis group and 35 non-metastatic PTC patients in control group) were analyzed using liquid chromatography - mass spectrometry. Orthogonal partial least-squares-discriminant analysis was applied to identify differential metabolites and significant pathways were examined within these metabolites. Receiver operating characteristic curve (ROC) analysis was utilized to further evaluate the diagnostic performance of candidate metabolites. A total of 119 differential metabolites were identified, with 108 upregulated and 11 downregulated. Pathway analysis revealed 13 significantly dysregulated metabolic pathways in metastatic PTC, including necroptosis, choline metabolism in cancer, sphingolipid signaling, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and pantothenate and CoA biosynthesis. ROC analysis demonstrated six discriminating biomarkers (5 lipids, 1 amine) that effectively distinguished metastatic from non-metastatic PTC, with all area under the curve values exceeding 0.8. Notably, these metabolites maintained diagnostic performance even in the thyroglobulin antibody-positive subgroup (≥ 4.11 IU/mL) for metastatic screening. This study demonstrates the potential of salivary biomarkers as a non-invasive diagnostic approach for metastatic PTC to aid the appropriate dosing for RAI therapy. It also offers new insights into the mechanisms of PTC metastasis and potential targets for adjuvant therapy.

Familial non-medullary thyroid cancer (FNMTC) is defined as non-medullary thyroid cancer occurring in two or more first-degree relatives, without features of known hereditary syndromes. Although familial predisposition is well established, its clinical behavior remains debated. This study aimed at characterizing familial cases compared to sporadic non-medullary thyroid cancer (SNMTC). FNMTC and SNMTC patients were recruited from the Endocrine Division (SEMPR) of the Federal University of Paraná, Brazil, and private endocrine clinics in Curitiba, Paraná, Brazil (2000-2019). Baseline, histopathological, and clinical data were analyzed using SPSS Statistics 26.0. Statistical comparisons employed chi-square, Student's t test, and Mann-Whitney U test, as appropriate. Post hoc power analysis was performed using G*Power 3.1.9.7, and R 2025.05.0. We analyzed 39 FNMTC and 119 SNMTC patients. Papillary thyroid carcinoma was the predominant histological type in both groups. FNMTC patients were diagnosed at a younger age (38.5 ± 14.2 vs. 46.6 ± 13.8 years, p = 0.003) and more frequently presented with lymph node metastases at diagnosis (46.2% vs. 21.8%, p = 0.007), with a 4.57-fold increased risk. Despite these differences, long-term outcomes did not differ significantly between groups. An earlier disease onset in subsequent generation suggests a possible anticipation phenomenon. These findings suggest that FNMTC patients may present with earlier onset and higher rates of lymph node involvement, underscoring the need for thorough preoperative lateral neck evaluation. In view of a possible anticipation phenomenon, cervical ultrasound screening might be considered starting in adolescence.

ObjectiveThis study aimed to evaluate the expression of miR-29a-3p and miR-192-5p inpatients with type 1 diabetes mellitus (T1DM) with diabetic kidney disease(DKD) compared to those without DKD.Subjects and methodsThis study included 29 patients with T1DM, comprising 13 without DKD (non-DKDgroup) and 16 with DKD, who were further subdivided into nine patients withmoderate DKD and seven with severe DKD. MiR-29a-3p and miR-192-5p expressionlevels were measured in urine samples using qPCR and are presented asmedians (25-75th percentiles).ResultsmiR-29a-3p levels were higher in patients with DKD compared to the non-DKDgroup [1.24 (0.97-1.74) versus 0.83 (0.72-0.99); P = 0.008]. Its expressionshowed a negative correlation with estimated glomerular filtration rate(eGFR) (P = 0.007) and a positive correlation with creatinine levels (P =0.004). MiR-192-5p levels were higher in patients with moderate DKD comparedto the non-DKD group [2.15 (1.45-4.21) versus vs. 1.42 (0.98-2.45); P =0.015], showing a negative correlation with eGFR (P = 0.003) and a positivecorrelation with creatinine (P = 0.006).ConclusionThe differential expression of miR-29a-3p and miR-192-5p in DKD highlightstheir potential as promising biomarkers for this complication.

To determine the frequency and types of breast calcif ication, the distribution of breast imaging-reporting and data system (BI-RADS) scores, and the association between calcif ication and biochemical/clinical findings in patients with primary hyperparathyroidism (PHPT). We recruited ≥ 40-year-old female patients with PHPT (n = 104) and age-matched healthy women (n = 107) as controls. Mammography was performed on all participants. Calcif ication, calcif ication type, and BI-RADS scores were recorded, and patients were divided into two groups based on PHPT duration and presence/absence of calcification. BI-RADS score distribution was indifferent between groups. The frequency of calcification and distribution of calcification types showed no difference between groups. Likewise, mammography findings were consistent among PHPT patients regardless of disease duration. There was no cutoff for disease duration that could predict the presence of calcification. Breast calcification was negatively correlated with parathyroid hormone (r = -0.220, p = 0.025) and 24-hour urine calcium levels (r = -0.195, p = 0.048), and positively correlated with age (r = 0.219, p = 0.025) in PHPT patients. Of the six patients who underwent cytological examination, one was found to be malignant (PHPT group). Female patients with PHPT do not have an increased incidence of breast calcification or higher BI-RADS scores compared to healthy women, and the calcification rates were unaffected by the duration of the disease. The presence of calcification does not appear to be associated with an increased risk of breast cancer in PHPT patients. Nonetheless, given the frequency of breast cancer and that the only patient with breast cancer was part of the PHPT group, it would be appropriate to screen these patients for breast cancer carefully.