Hormone and Metabolic Research最新文献

Metabolic alterations characterize a large subset of those with post-acute COVID-19 syndrome, and similar symptoms affect those with post-acute COVID-19 vaccination syndrome. These symptoms are characterized by the triumvirate of post-acute COVID-19 (vaccination) syndrome symptoms: post-exertional malaise, fatigue, and cognitive impairment, commonly referred to as brain fog. These symptoms can be recreated through perturbations that disrupt mitochondria, and spike protein has been observed to disrupt mitochondria in vitro, providing mechanistic support for this relationship. Post-acute COVID-19 (vaccination) syndrome patients suffer from a severely decreased lactate threshold and can experience symptoms of overexertion even at low power output. Furthermore, biopsies have revealed disrupted mitochondria, and energetics and physiological studies have shown that lipid oxidation constitutes a significantly reduced fraction of total energy production/consumption in post-acute COVID-19 (vaccination) syndrome patients. This review explores the therapeutic axes of lactate, carbon dioxide, and fatty acid oxidation for resolving the energy production challenges in post-acute COVID-19 (vaccination) syndrome, suggesting interventions that increase the lactate threshold, increase tissue oxygenation (paradoxically through increasing partial pressure of CO₂), and increase the rates at which lipids are oxidized relative to carbohydrates. Analogies from the world of exercise science are introduced, comparing post-acute COVID-19 (vaccination) syndrome to an overabundance of fast-twitch muscle fibers, with oxygenation similar to that experienced at high altitude, and presenting as an inverse 'fat adaptation' phenomenon, as observed in endurance athletes, especially those adopting low-carbohydrate diets.

Metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis are increasingly concerning health issues, especially in people with type 2 diabetes mellitus, where metabolic problems drive liver disease progression. While lifestyle changes remain essential, new drug strategies-particularly sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists-have gained growing interest for their potential to protect the liver. This review examines how sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists might help treat metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis, focusing on their mechanisms of action, study evidence, and results from meta-analyses. A thorough search of the literature found studies on how these drugs affect insulin sensitivity, liver fat, and inflammation. Preclinical models show that they can lower liver fat, reduce oxidative stress, and decrease fibrosis markers. Clinical trials and meta-analyses support their potential to improve liver enzyme levels, decrease liver fat, and slow fibrosis growth. Overall, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists appear promising in the management of metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis, especially in type 2 diabetes mellitus patients. Still, more long-term research studies are needed to confirm how well they work, how safe they are, and the best way to use them, either alone or in combination with other treatments. These drugs may represent important advances in the treatment of liver diseases linked to metabolic problems.

Medullary thyroid carcinoma is a rare neuroendocrine tumor of parafollicular C-cells. Calcitonin is the primary tumor marker but presents several limitations, including assay variability and false positives in renal dysfunction, proton pump inhibitor use and smoking. Procalcitonin may offer advantages in stability and specificity. To evaluate the diagnostic performance of procalcitonin compared to calcitonin and carcinoembryonic antigen in patients with medullary thyroid carcinoma, we conducted a retrospective study of 60 patients with histologically confirmed medullary thyroid carcinoma at a single endocrine center. Calcitonin, procalcitonin, and carcinoembryonic antigen levels were analyzed pre- and postoperatively over a 4-year period (2015-2019). Statistical analyses included Spearman's correlation and receiver operating characteristic curve analysis. Subgroup analyses examined the effects of renal dysfunction, proton pump inhibitors, and smoking. Calcitonin and procalcitonin showed a strong correlation (r=0.874 and p<0.001). Procalcitonin maintained high specificity and sensitivity (area under the curve>0.95 across all years) and remained unaffected by the proton pump inhibitor use or renal impairment. Carcinoembryonic antigen correlated with tumor progression but lacked sufficient specificity alone. The combined use of calcitonin and procalcitonin improved diagnostic accuracy. In all patients with detectable tumor burden, procalcitonin was positive. False-positive calcitonin results were observed in patients without evidence of active diseases but with renal dysfunction or proton pump inhibitor use; procalcitonin remained negative in these cases. Procalcitonin is a reliable tumor marker for medullary thyroid carcinoma, especially in postoperative surveillance. Its stability and independence from common confounders make it a valuable complement to calcitonin. The combined assessment of calcitonin and procalcitonin enhances diagnostic performance and should be considered in routine clinical practice.

Klinefelter syndrome is the most common genetic cause of male infertility, affecting approximately 1 in 660 men. It is characterized by the presence of one or more extra X chromosomes. Literature studies suggest an increased risk of venous thromboembolic events in Klinefelter syndrome. Testosterone replacement therapies are commonly used in Klinefelter syndrome to improve well-being, body composition and sexual function. However, testosterone replacement therapies may influence the risk of venous thromboembolic events. Our objective was to assess the rate of venous thromboembolic events, and its association with testosterone replacement therapies, in a cohort of Klinefelter syndrome patients. Data on venous thromboembolic events, testosterone replacement therapy usage, and demographics were obtained from a hospital-based Klinefelter syndrome clinical database. One hundred seventy-nine patients were included. The median age was 35 years (interquartile range: 29-42 y). One hundred eighteen patients (66%) had received testosterone replacement therapies prior to the review in clinics. Eleven patients (6.1%) had at least one venous thromboembolic event. The median age of the first venous thromboembolic event was 35 years (range: 19-73 y). The incidence of a venous thromboembolic event was 17.0 (95% confidence interval: 8.5-30.3) events per 10,000 person-years. Five of the 11 patients had received testosterone replacement therapies prior to venous thromboembolic events. There was no significant association between receiving testosterone replacement therapy and suffering a venous thromboembolic event (p=0.1). The incidence rate of the venous thromboembolic event in Klinefelter syndrome patients observed here is approximately four-fold higher than in the general adult male population. This is consistent with previous studies that have showed an increase rate ratio of between 2.1 and 12.1, dependent on the age. This study did not show a statistically significant difference in venous thromboembolic event incidence based on the use of testosterone replacement therapies.

Thyrotropin (thyroid-stimulating hormone)-secreting pituitary adenomas are a rare cause of hyperthyroidism that frequently presents diagnostic and therapeutic challenges. This study characterizes the clinical, biochemical, radiological, and histopathological features of thyrotropin-secreting pituitary adenomas, evaluates long-term outcomes, and identifies factors influencing remission and recurrence. We retrospectively analysed 12 patients with thyrotropin-secreting pituitary adenomas treated between January 2003 and February 2025 at a tertiary endocrine referral centre. Clinical presentation, hormonal profiles, imaging characteristics, histopathology, management, and follow-up were reviewed. Diagnostic criteria included inappropriately normal or elevated thyroid-stimulating hormone levels with increased free thyroid hormones and pituitary imaging confirming an adenoma. Remission was defined as clinical and biochemical normalization without ongoing therapy. Subgroup analysis examined the impact of diagnostic delay on tumour size, invasiveness, and outcome. The cohort comprised nine men (75%) and three women (25%) with a mean age at diagnosis of 47.8±17.2 years. Excluding one multiple endocrine neoplasia type 1 case with early detection, the mean diagnostic delay was 42.5 months (range: 4-156). Magnetic resonance imaging revealed macroadenomas in 75% of patients and Knosp grade 3-4 invasion in 41.7%. Longer diagnostic delay was correlated with significantly larger tumours (17.9±3.6 mm vs 9.8±1.0 mm; p=0.004). All patients underwent surgery; 50% achieved remission, while 33.3% required additional therapy (somatostatin analogues and/or radiotherapy). At a median 7.8-year follow-up, 66.7% remained in sustained remission. No patient experienced thyroid storm; transient postoperative hypothyroidism occurred in 25%. Thyrotropin-secreting pituitary adenomas often present with heterogeneous and misleading biochemical profiles leading to diagnostic delay, larger and more invasive tumours, and a greater need for multimodal therapy. Early recognition of discordant thyroid function tests-elevated free T3/T4 with non-suppressed thyroid-stimulating hormone-is critical to avoid unnecessary thyroid ablation and improve surgical outcomes.

Hyperhomocysteinemia is common in chronic kidney disease; however, whether homocysteine-lowering therapy slows chronic kidney disease progression remains uncertain. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guideline, we systematically searched PubMed and Web of Science (inception to January 2025) for randomized controlled trials evaluating folic acid alone or combined with vitamin B versus placebo/usual care/low-dose regimens in populations across the chronic kidney disease spectrum. The primary end point was composite kidney outcomes (all-cause mortality, cardiovascular events, and kidney disease progression). Relative risks with 95% confidence intervals were pooled using fixed- or random-effect models according to heterogeneity. Nine trials comprising 23,638 participants met inclusion criteria. Overall heterogeneity for the primary outcome was low (I²=27%), and homocysteine-lowering therapy was associated with a marginal reduction in composite kidney outcomes (relative risk=0.96 and 95% confidence interval=0.92-1.00; p = 0.04). Subgroup analyses suggested a greater benefit in participants with normal to moderate chronic kidney disease (relative risk=0.89 and 95% confidence interval=0.81-0.97; p=0.008) and in non-White populations (relative risk=0.89 and 95% confidence interval=0.81-0.97; p=0.008). No significant effects were observed for cardiovascular events (relative risk=0.94 and 95% confidence interval=0.84-1.06) or all-cause mortality (relative risk=0.99 and 95% confidence interval 0.87-1.11). In conclusion, homocysteine-lowering therapy yields, at most, a small reduction in composite kidney outcomes with limited clinical significance and provides no detectable benefits for cardiovascular events or mortality.

Hashimoto's thyroiditis is the most common autoimmune disease, which is characterized by a cellular immune response with lymphatic infiltration of the thyroid gland mainly by T cells and B cells as well as by a humoral immune response leading to specific antibody production. Papillary thyroid carcinoma, the most common endocrine malignancy, is also characterized by broad immune cell infiltration. In recent years, a growing body of evidence has suggested a close connection between papillary thyroid carcinoma and Hashimoto's thyroiditis. The mechanisms underlying the relationship between Hashimoto's thyroiditis and papillary thyroid carcinoma, however, remain incompletely understood. One hallmark in the understanding of the immunological link between both diseases was the description of identical epitope-specific cytotoxic T cells as clear evidence for a close connection between Hashimoto's thyroiditis und papillary thyroid carcinoma. In this review, we describe the role of Hashimoto's thyroiditis in the development and prognosis of papillary thyroid cancer, the role of thyroid-specific antibodies in the diagnosis and outcome prediction of papillary thyroid carcinoma and the potential implication of this knowledge for cancer immunotherapy in general.

Postoperative hypocalcemia caused by hypoparathyroidism and vocal cord paralysis remain common complications following thyroid surgery. Sex and metabolic comorbidities may influence their occurrence. We conducted a multicenter cross-sectional analysis using anonymized data from 3,365 patients (1,517 hemithyroidectomies and 1,848 thyroidectomies) treated at 27 German hospitals between 2019 and 2024. Primary outcomes were postprocedural hypoparathyroidism and vocal cord paralysis, identified via ICD-10 codes. Associations with age, sex, obesity, diabetes, thyroid pathology, and surgical extent were analyzed using multivariable logistic regression. Postoperative hypoparathyroidism was more frequent after thyroidectomy (3.6%) than hemithyroidectomy (0.3%). Female sex was positively associated with postoperative hypoparathyroidism (odds ratio: 2.30; 95% confidence interval: 1.11-4.77), while obesity was inversely associated with postoperative hypoparathyroidism (odds ratio: 0.15; 95% confidence interval: 0.04-0.63). Vocal cord paralysis was observed in 1.7% of hemithyroidectomy and 1.0% of thyroidectomy cases. Factors significantly or tendentially associated with vocal cord paralysis included malignant neoplasm (odds ratio: 4.00; 95% confidence interval: 1.37-11.64), diffuse goiter (odds ratio: 4.94; 95 % confidence interval: 0.86-28.37), parathyroidectomy (odds ratio: 3.47; 95% confidence: 1.04-11.59), and diabetes mellitus (odds ratio: 3.09; 95% confidence: 0.98-9.74). Individual risk profiling and intraoperative neuromonitoring are critical to improving outcomes after thyroid surgery.

Steroidogenesis in the human adrenal cortex follows a distinct anatomical and functional zonation, which is essential for maintaining electrolyte balance, stress response, and metabolic homeostasis. Dysregulation of this tightly controlled system leads to endocrine disorders causing hypertension, such as primary aldosteronism and glucocorticoid excess. The aim of this study was to analyze the zonal distribution and expression levels of enzymes involved in steroidogenesis and correlate these findings with hypertension, body mass index and previous administration of corticosteroids while correcting severe acute respiratory syndrome coronavirus 2 infection as a potential confounder. Tissue microarrays were constructed from 99 formalin-fixed paraffin-embedded adrenal glands obtained from adult human autopsies, with clinical information on hypertension status. As controls, 14 normal adrenal glands derived from surgical specimens were included. Protein expression of CYP11B2, CYP11B1, CYP17, HSD3B1, and HSD3B2 was assessed semi-quantitatively and evaluated with respect to their localization within specific adrenal cortical zones using immunohistochemistry. The expression of CYP17, CYP11B1, CYP11B2, and HSD3B2 was inversely correlated with the presence of hypertension (p<0.001 and p=0.0149), higher body mass index (p=0.026 and p=0.001), and the administration of corticosteroids (p=0.0012, p=0.001, and p=0.002). CYP11B2 showed reduced expression in the zona glomerulosa only in the non-COVID-19 hypertension group (p=0.031). Tissue microarray-based tissue analysis is a reliable method in a research setting to detect consistent downregulation of CYP11B1, CYP11B2, and CYP17 in patients with hypertension, independent of concomitant underlying infections. The positive correlation between the body mass index and CYP11B1 expression, and the negative correlation between glucocorticoid administration and CYP11B1, may reflect clinical factors such as obesity-associated hypertension and altered aldosterone production and its relationship with metabolic syndrome.