Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association最新文献

Purpose: Primary hyperparathyroidism (PHPT) has been associated with subclinical neuromuscular dysfunction; however, the clinical correlates of muscle strength and morphology in PHPT remain undercharacterized. We hypothesized that muscle dysfunction in PHPT is reversible after parathyroidectomy and that the reduction in serum calcium predicts early postoperative improvement.

Design: A prospective observational study conducted at a tertiary care center Methods: Fifty-three PHPT patients and 53 age-, sex-, and BMI-matched healthy controls were assessed using handgrip strength tests (HGS), 4-meter walking speed (4MGS), the timed-up-and-go (TUG) test, and the 5-time sit-to-stand test (5XSTS). Muscle thickness was measured via ultrasonography and body composition by bioelectrical impedance analysis (BIA). Surgical indications were based on international guidelines for classical PHPT and on clinical judgment in selected normocalcemic cases. Thirty-four patients underwent PTX and were re-evaluated three months postoperatively. Generalized Linear Mixed Models (GLMM) were used to identify predictors of changes in muscle function.

Results: At baseline, patients with PHPT demonstrated significantly reduced HGS, prolonged durations in the TUG and 5XSTS tests, and decreased gastrocnemius muscle (GM) thickness compared to healthy controls (p < 0.05). Following PTX, both GM thickness and lower limb functional performance (TUG, 5XSTS) improved significantly. GLMM analysis identified reductions in serum calcium as independent predictors of functional improvement. Vitamin D status was standardized across all participants to minimize confounding and enhance internal validity.

Conclusion: Parathyroidectomy in PHPT patients leads to early improvements in muscle thickness and lower extremity function, suggesting a multimodal recovery process; whether assessment enhances surgical decision-making and patient selection needs to be explored in further studies.

Background:  Neuropathic pain is a frequent and disabling complication of type 2 diabetes mellitus. Although poor glycemic control is known to contribute to diabetic neuropathy, its specific relationship with painful manifestations remains incompletely characterized.

Objective:  The aim of this study was to evaluate the association between hemoglobin A1c levels and the presence of neuropathic pain in patients with type 2 diabetes mellitus.

Methods:  A cross-sectional analytical study was conducted in 172 adults with type 2 diabetes mellitus attending outpatient clinics at a tertiary hospital in northern Peru. Neuropathic pain was assessed using the validated Spanish version of the Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs questionnaire. Glycemic control was evaluated using hemoglobin A1c, analyzed both as a continuous variable and a dichotomous variable at 7%. Clinical, metabolic, and demographic variables were compared between patients with and without neuropathic pain. Associations were examined using Poisson regression with robust variance and logistic regression, estimating crude and adjusted effect measures with 95% confidence intervals.

Results:  Neuropathic pain was identified in 50% of participants. Patients with neuropathic pain showed higher hemoglobin A1c values and a greater proportion of values equal to or above 7%. In adjusted models, elevated hemoglobin A1c levels remained independently associated with neuropathic pain, when analyzed both as a dichotomous variable and as a continuous variable. Dyslipidemia and hypertension also showed independent associations.

Conclusions:  Higher hemoglobin A1c levels are independently associated with neuropathic pain in patients with type 2 diabetes mellitus, underscoring the importance of sustained glycemic control.

Ulnar compression neuropathy is the second most frequent entrapment neuropathy of the upper extremity and is observed with increased prevalence among diabetes mellitus patients. The metabolic burden of diabetes mellitus, including chronic hyperglycaemia, microvascular dysfunction, and systemic inflammation, promotes nerve susceptibility to mechanical compression. This review summarises current evidence on the association between diabetes mellitus and ulnar compression neuropathy, highlighting epidemiological data, metabolic contributors, clinical manifestations, diagnostic tools, and management strategies. Diagnostic evaluation in diabetes mellitus patients may be challenging due to coexisting polyneuropathy, necessitating a multimodal and individualized approach. Management strategies include both conservative measures and surgical decompression, with early intervention being critical to prevent permanent deficits. Clinicians should maintain high suspicion of ulnar compression neuropathy in diabetes mellitus patients to ensure timely diagnosis and improve functional outcomes in this high-risk population.

First-degree relatives of patients with type 2 diabetes mellitus may exhibit metabolic abnormalities and subclinical myocardial dysfunction before the onset of overt disease. Left Ventricular Speckle-tracking echocardiography (LV-STE) enables early detection of left ventricular impairment, while osteogenic biomarkers such as osteoprotegerin, osteocalcin, and osteopontin have been linked to cardiometabolic risk. This study aimed to evaluate myocardial strain parameters and serum osteogenic biomarkers in normoglycemic first-degree relatives of patients with type 2 diabetes mellitus.We enrolled 160 normoglycemic participants, comprising 80 individuals with at least one first-degree relative diagnosed with type 2 diabetes mellitus and 80 controls without such a family history. Serum osteocalcin, osteopontin, and osteoprotegerin levels were measured by ELISA. LV-STE was used to assess global longitudinal and circumferential strain from apical four-chamber (A4C), two-chamber (A2C), three-chamber (A3C), and short-axis basal/mid/apical views.Compared with the control group, the study group presented significantly lower mean short-axis basal/mid/apical and A4C/A2C/A3C strain values. The serum osteocalcin level was significantly lower and weakly negatively correlated with the fasting plasma glucose level. osteoprotegerin was positively correlated with LDL-C. No significant associations were found between strain parameters and biomarkers.Normoglycemic first-degree relatives of type 2 diabetes mellitus patients exhibit early myocardial impairment detectable by LV-STE and reduced osteocalcin levels. LV-STE may enhance early risk stratification in this population. Longitudinal studies are needed to determine the prognostic value of osteogenic biomarkers in the progression to type 2 diabetes mellitus and cardiovascular disease.

Guidelines recommend GLP-1 receptor agonists (GLP-1-RA) and SGLT2-inhibitors (SGLT2i) for individuals with type 2 diabetes (T2D) at high risk of atherosclerotic cardiovascular disease (ASCVD). In the context of precision medicine, we evaluated a personalized treatment algorithm to guide the initial decision between these therapies.Using data from the observational Diabetes Prospective Follow-up registry (Germany/Austria) we studied individuals with T2D who initiated GLP-1-RA (n=1433) or SGLT2i (n=2547) in a multicenter, real-world setting. Baseline characteristics included age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), HbA1c, diabetes duration, and history of ASCVD. Non-fatal ASCVD events (myocardial infarction, angina, revascularization, stroke, transient ischemic attack, and peripheral artery disease) were analyzed using dynamic weighted survival modeling to predict the optimal treatment for each individual.The algorithm predicted 48% of individuals to have better ASCVD outcomes with GLP-1-RA and 52% with SGLT2i. GLP-1-RA-optimal individuals had on average a higher BMI (37 vs 31 kg/m²), lower eGFR (71 vs 93 ml/min per 1.73 m²) and less history of ASCVD (9 vs 18%) compared to SGLT2i-optimal individuals. However, an internal model validation showed that the predicted optimal treatment did not statistically significantly prolong the average time to a non-fatal ASCVD event compared to the suboptimal treatment (AFT parameter: 1.13; 95% CI: 0.83-1.56; HR: 0.88; 95% CI: 0.64-1.21).The personalized treatment algorithm for GLP-1-RA and SGLT2i did not result in clear individual ASCVD benefits on either drug, a finding consistent with the clinical equipoise reflected in current T2D treatment guidelines.

Succinate dehydrogenase (SDH) gene variants are the most common cause of the neuroendocrine tumour hereditary paraganglioma, which is associated with an over 20% metastasis risk as well as significant morbidity. There are currently no relevant human tumour cell lines or mouse models, and molecular understanding of downstream tumourigenic pathways is still rudimentary despite over two decades of concerted effort worldwide. These tumours generally show extremely slow in vivo doubling times (4-12 years), presumably existing in a primarily semi-quiescent state with little cell cycling or DNA replication. This characteristic makes deriving a useful tumour cell line impractical. A better alternative would be a cell line in which cell proliferation can be turned on and off at will, allowing expansion to generate sufficient cell numbers and experimentation once tumour cells have returned to their natural semi-quiescent state. The closest models currently available, highly-proliferating rat and mouse adrenal paraganglioma cell lines, are molecularly unrelated to SDH tumours. In this pilot study, we investigated whether primary SDH-derived paraganglioma tumour cells can be made to proliferate in vitro. We successfully transduced primary paraganglioma tumour cells with a lentiviral construct, using the proven strategy of c-MYC¬T58A (c-MYC) controlled by a Tet-On doxycycline-inducible expression system. We present the first evidence that primary paraganglioma chromaffin cells can be induced to proliferate in vitro, even in later passage cultures. Without any prior selection for chromaffin tumour cells, passaged cultures were obtained with over 80% synaptophysin-expressing chromaffin tumour cells, suggesting that this highly promising strategy deserves further exploration.

Primary hyperparathyroidism (PHPT) is a prevalent endocrine disorder characterized by disrupted calcium-phosphorus homeostasis. Accurate biochemical assessment, including albumin-corrected calcium, and preoperative localization of parathyroid adenomas are essential for optimal management. This study aimed to evaluate temporal changes in imaging detectability, biochemical markers, and adenoma size, and to assess novel biochemical indices in patients with asymptomatic PHPT (aPHPT).In this multicenter retrospective study, 416 aPHPT patients underwent clinical, biochemical, and radiological evaluation at three time points. Biochemical parameters included albumin-corrected calcium, phosphorus, parathyroid hormone (PTH), 25-hydroxyvitamin D, alkaline phosphatase (ALP), and 24-hour urinary calcium. Novel indices-calcium/phosphorus (Ca/P), PTH/phosphorus (PTH/P), and calcium×chloride/phosphorus (Ca×Cl/P)-were calculated to evaluate diagnostic and predictive value. Imaging included high-resolution neck ultrasonography, 99mTc-sestamibi SPECT/CT, and four-dimensional CT to assess adenoma detectability and size changes. Statistical analyses included repeated-measures ANOVA or Friedman tests for temporal comparisons, correlation analyses, logistic regression for predictors of adenoma detection, and ROC curves to evaluate diagnostic accuracy. A p-value<0.05 was considered significant.Among 416 patients (87% female), ultrasound-detected adenomas decreased over time due to surgery of clearly visible lesions. CT and SPECT/CT initially improved localization, with later decline in CT but continued gains in SPECT/CT. Adenoma size increased, and the PTH/phosphorus ratio changed significantly. Baseline albumin-corrected calcium, phosphorus, and adenoma size predicted radiological detectability, with ROC AUCs of 0.78 for adenoma size and 0.72 for phosphorus. Surgically treated patients exhibited more pronounced biochemical abnormalities and superior CT-based localization.Following imaging and biochemical assessments, including albumin-corrected calcium, improve detection, monitoring, and management of aPHPT. Novel indices such as PTH/phosphorus and Ca/P ratios provide practical, low-cost tools for early disease identification and risk stratification. Integrating dynamic biochemical markers with imaging supports individualized, evidence-based clinical decision-making.

Ectopic Cushing's syndrome is a severe endocrine disorder with high morbidity and mortality, making timely diagnosis and effective cortisol control crucial. The aim of this study was to assess the 12-year experience at a tertiary centre.We retrospectively analyzed clinical, biochemical, imaging, treatment, and outcome data in this single-center, non-interventional cohort of patients treated from 2012 to 2024 at the University Hospital Centre Zagreb.Twelve patients were included (10/12 female, 83.3%; median age 43.5 years, range 22-74). Primary tumors were predominantly neuroendocrine (8/12, 66.7%), and 9/12 (75.0%) had metastatic disease at diagnosis. Common features were fat redistribution in 10/12 (83.3%), facial plethora in 8/12 (66.7%), hypertension in 8/12 (66.7%), and peripheral edema in 7/12 (58.3%). Frequent biochemical alterations were hypokalemia in 11/12 (91.7%) and hyperglycemia or new-onset/worsening diabetes in 10/12 (83.3%). Median 24-hour urinary free cortisol was 5,594 nmol/24 h (range: 196-72,954), and ACTH 52.4 pmol/L (range: 8-498). A urinary free cortisol level≥50×the upper limit of normal identified a high-risk group with shorter survival (Spearman ρ=-0.50). Biochemical remission was achieved in 1/12 (8.3%) patient through tumor resection, while the majority required bilateral adrenalectomy (8/12, 66.7%) due to inadequate response to medical therapy or as first-line treatment. At the time of last follow-up, 8/12 (66.7%) patients had died due to disease progression, with a median time to death of 12 months (range: 1-51). The median overall survival was 20 months (range: 1-154).Most patients presented with metabolic disturbances and limited response to medical therapy, leading to bilateral adrenalectomy. Early mortality was driven by uncontrolled hypercortisolism rather than tumor burden, and higher urinary free cortisol was associated with shorter survival. These findings highlight the prognostic relevance of cortisol burden and the importance of prompt cortisol control.

The existing literature on the effects of semaglutide in people with HIV (PWH) and diabetes mellitus remains limited. In this study, the effects of semaglutide on weight control and inflammation in PWH were evaluated.This is a prospective observational study that included PWH with type 2 diabetes mellitus monitored at the HIV Unit of the University General Hospital of Alexandroupolis and a matched control group of non-HIV individuals. Demographic, anthropometric, and clinical characteristics, including HIV-related data and comorbidities, were reported. All participants received semaglutide with a gradual dose increase to 1 mg once weekly. Body Mass Index (BMI), glycosylated haemoglobin (HbA1c), and inflammatory markers (IL-6, TNF, hsCRP, sCD14, CD4/CD8 ratio) were recorded at baseline and at 6, 12, 18, and 24 months.Fifty participants (PWH: n=25; non-HIV: n=25) were included. At baseline, the mean BMI was 35.2±8.0 kg/m² for PWH and 36.1±6.0 kg/m² for non-HIV controls. Semaglutide treatment resulted in significant and sustained weight loss in both groups (p<0.001). At 24 months, the median weight loss was -14.6 kg in the PWH group and -18.8 kg in the non-HIV group for those with a baseline BMI>35 kg/m². Glycemic control also improved significantly, with mean HbA1c decreasing from 7.7%±1.23 to 5.2%±1.02 in PWH (p<0.001), and from 7.9%±1.16 to 5.6%±1.21 in non-HIV controls (p<0.001). Significant reductions were observed in hsCRP and sCD14 levels in both cohorts. A unique finding was the significant increase in the CD4/CD8 ratio in the PWH group, from a mean baseline of 0.54±0.12 to 0.83±0.14 at 24 months (p<0.001), a change not seen in the non-HIV controls.Semaglutide appears to be an effective and safe option for weight reduction and inflammation control in PWHIV. Further studies with a larger number of patients are necessary to substantiate these findings.

The human KISS1 gene encodes the hypothalamic Kisspeptin, which is released in a pulsatile manner and binds the KISS1 receptor, that is located on gonadotropin releasing hormone neurons. This interaction ensures pulsatile gonadotropin releasing hormone secretion leading to induction of the hypothalamic-pituitary-gonadal axis and by this controls puberty onset. Disruption of this process is associated with hypogonadotropic hypogonadism. We identified a novel heterozygous KISS1 variant c.-7C>T in two brothers diagnosed with hypogonadotropic hypogonadism. The mutation affects the Kozak consensus sequence of the KISS1 gene and potentially interferes with KISS1 gene expression. Consequently, this affects the hypothalamic-pituitary-gonadal axis resulting in hypogonadotropic hypogonadism. In both patients, complete development of primary and secondary male sex characteristics and stabilization of serum sex steroid hormone levels was achieved by testosterone therapy. Additionally, human chorionic gonadotropin and follicle stimulating hormone combination therapy in the older brother (patient 1) induced spermatogenesis and enabled fatherhood. Apart from this, we identified the heterozygous CHD7 variant c.2690G>A in the younger brother (patient 2). However, the contribution of this variant to the pathogenesis of hypogonadotropic hypogonadism remains elusive.