Clinical Endocrinology最新文献

Objective: There is limited information on population-specific norms of trabecular-bone-score (TBS) and its associated factors. Here, we provide norms of TBS in Asian-Indians and its relationship with serum 25-hydroxyvitamin D [25(OH)D] and intact-parathyroid hormone (iPTH).

Participants and measurements: TBS, bone-mineral-density (BMD), and vertebral-fractures (VFs) were assessed using dual-energy X-ray absorptiometry in 923 healthy Asian-Indians (aged 20-60 years). Serum 25(OH)D, iPTH, T4/TSH,, glycosylated-haemoglobin (HbA1c) were measured and associations with TBS assessed using multivariable linear regression. Subjects with BMD Z-score ≤ -2.0 or ≥2.0 at any sites, VFs, TSH > 10.0 or <0.05 µIU/ml, blood-glucose >11.1 mmol/L or HbA1c > 8.0% were excluded for generating Asian-Indian norms.

Results: TBS norms were generated in 744 healthy Asian-Indians (M:F,389:385). The cut-offs generated for 'normal', 'partially-degraded', and 'degraded' TBS were >1.305, 1.204-1.305 and <1.204, respectively. Mean TBS was lower in females than males (p < .001). There was 75% congruency in TBS categories between Asian-Indian and existing norms. Specificity (97.8 vs. 77.9%, p < .001) and diagnostic-accuracy (97.8% vs. 78.4%, p < .001) of TBS to detect osteoporosis were higher with Asian-Indian norms. The sensitivity of 'partially-degraded' TBS to diagnose osteopenia was also higher with Asian-Indian norms. In multivariable regression, gender, body-mass-index (BMI), BMD-L₁-L₄, serum PTH, daily dietary-calorie intake and calcium intake were associated with TBS. Though 25(OH)D inversely correlated with PTH, 25(OH)D was not associated with TBS.

Conclusion: This study provides norms for TBS in Asian-Indians with gender-specific differences. Increasing age and higher BMI were associated with lower TBS. Associations of TBS with circulating PTH and/or 25(OH)D need confirmation in further studies.

Objective: Optic nerve hypoplasia (ONH), the congenital underdevelopment of the optic nerve, is an increasing cause of visual impairment and is associated with pituitary dysfunction. Past studies have focused on the relationship between ONH, pituitary deficiencies, and brain imaging. However, recent studies have demonstrated the true risk for hypopituitarism lies with the presence or absence of ONH, irrespective of midline brain findings. This study reviewed the relationship between the health of the optic nerve (visual acuity) and pituitary gland (number and age of development of pituitary deficiencies) as a way to stratify risk, regardless of imaging findings.

Design, patients and measurements: Retrospective chart review of 197 patients seen at a single center from 2013 to 2022. Visual assessment was defined by distance acuity, and the presence of nystagmus or afferent pupillary defect. Pituitary deficiencies were diagnosed per Endocrine Society guidelines.

Results: In children with bilateral ONH (bONH), profound visual impairment was associated with more pituitary deficiencies between 0 and 15 years of age. The odds of having any pituitary deficiency were 4.9 times higher (95% confidence interval [95% CI]: 2.4-10.1) for patients with bONH versus unilateral ONH (uONH). Central hypothyroidism was the most common first presenting pituitary deficiency followed by growth hormone across all patients.

Conclusion: This study shows a significant association between severity of visual impairment and increased probability of pituitary deficiencies in children with bONH versus uONH. Children with ONH require urgent endocrine evaluation due to risk of pituitary deficiencies, but risk stratification may also be based on severity of visual impairment.

The spectrum of thyroid disorders presenting to paediatricians is different to that seen by adult physicians. Referrals reflect cases detected by the neonatal screening programme for congenital hypothyroidism and many of the inherited defects of thyroid hormone generation or action will be manifest in early life. Autoimmune thyroid disease can be particularly challenging to manage in the young and the potential impact of thyroid status on neurodevelopment and schooling are key considerations throughout childhood and adolescence.

Objective: ¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) allows noninvasive assessment of glucose metabolism and radiodensity in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). We aimed to address the effects of ageing and metabolic factors on abdominal adipose tissue.

Design, patients and measurements: We retrospectively analyzed data from 435 healthy men (mean 42.8 years) who underwent a health check-up programme twice, at baseline and the 5-year follow-up. The mean standardized uptake value (SUV) was measured using SAT and VAT and divided by the liver SUV. The mean Hounsfield units (HU) of the SAT and VAT were measured from the CT scans. The effects of clinical variable clusters on SUVR were investigated using Bayesian hierarchical modelling; metabolic cluster (BMI, waist-to-hip ratio, fat percentage, muscle percentage*-1, HOMA-IR), blood pressure (systolic, diastolic), glucose (fasting plasma glucose level, HbA1c) and C-reactive protein.

Results: All the clinical variables changed during the 5-year follow-up period. The SUVR and HU of the VAT increased during follow-up; however, those of the SAT did not change. SUVR and HU were positively correlated with both VAT and SAT. SAT and VAT SUVR were negatively associated with metabolic clusters.

Conclusions: Ageing led to increased glucose metabolism and radiodensity in VAT, but not in SAT. VAT may reflect the ageing process more directly than SAT. Glucose metabolism was higher and radiodensity was lower in VAT than in SAT, probably owing to differences in gene expression and lipid density. Both glucose metabolism and radiodensity of VAT and SAT reflect metabolic status.

Objectives: There is relatively scarce data regarding the association between primary hyperparathyroidism (PHPT) and incident diabetes in large population-based longitudinal studies. We aimed to evaluate the risk of incident diabetes in individuals with and without PHPT and investigate the association between serum calcium concentrations and the risk of incident diabetes in patients with PHPT.

Methods: We included 2749 PHPT patients and 13,745 age, sex and index year matched non-PHPT individuals during 2000-2019. We used Cox regression models to compare the risk of incident diabetes in individuals with and without PHPT, and the risk of incident diabetes in PHPT patients with serum calcium concentration above and below the median value. The association between serum calcium concentrations and the risk of incident diabetes was examined by restricted cubic spline analyses in patients with PHPT.

Results: During a median follow-up time of 5.17 years (IQR 2.17, 9.58), 433 patients (15.75%) with PHPT and 2110 individuals (15.35%) without PHPT developed diabetes, respectively. Patients with PHPT had a higher incidence rate of diabetes compared to non-PHPT individuals (27.60 [95% CI 25.00, 30.30] vs. 23.90 [95% CI 22.80, 24.90] per 1000 person-years, log-rank test p = .007]. Crude Cox regression model showed PHPT was associated with a 15% higher risk of incident diabetes (HR 1.15, 95%CI 1.04, 1.28). In patients with PHPT, a 44% higher risk of incident diabetes was found in patients with serum calcium concentrations above the median value (2.63 mmol/L), compared to those below the median value (HR 1.44, 95%CI 1.08, 1.90). Restricted cubic spline analyses confirmed a positive linear association between serum calcium concentrations and the risk of incident diabetes in those with PHPT (p-value for nonlinear = .751) CONCLUSIONS: Patients with PHPT had a higher risk of incident diabetes compared to non-PHPT individuals. A positive linear association was found between serum calcium concentrations and the risk of incident diabetes in patients with PHPT.

Hypophosphatasia (HPP) is a rare, inherited, and systemic disorder characterized by impaired skeletal mineralization and low tissue nonspecific serum alkaline phosphatase (TNSALP) activity. It is caused by either autosomal recessive or dominant-negative mutations in the gene that encodes TNSALP. The phenotype of HPP is very broad including abnormal bone mineralization, disturbances of calcium and phosphate metabolism, pain, recurrent fracture, short stature, respiratory impairment, developmental delay, tooth loss, seizures, and premature death. Other than supportive care, there has been no disease-specific treatment available for those with HPP. Asfotase alfa is a fully humanized, recombinant enzyme replacement therapy for the management of HPP. It is available in several countries for the treatment of the more severe forms of HPP, namely perinatal and infantile HPP. This review will summarize the preclinical data on asfotase alfa and highlight the data from clinical trials and case reports. These data show the transformative nature of asfotase alfa when administered as part of an interdisciplinary treatment model.