Hormone and Metabolic Research最新文献

Normocalcemic primary hyperparathyroidism is thought to be an early form of hypercalcemic primary hyperparathyroidism. However, some studies have shown progression to hypercalcemia, hypercalciuria or kidney stones, bone loss and fractures in a proportion of patients over time, whereas other studies have not observed such outcomes. The aim of this study was to investigate the clinicopathological features and natural history of the disease in a large patient population and to provide clinicians with strong evidence-based recommendations. This is a nationwide, multicenter, observational, retrospective cohort study. Tertiary healthcare endocrinology departments were the setting for this study. Data from different regions of Turkey, including 527 patients, were included in this study. A total of 123 patients were not eligible for inclusion, and the remaining 404 patients were included in the final analysis. All laboratory assessments, dual-energy X-ray absorptiometry and renal ultrasound were performed locally at each center at baseline and several times during follow-up. The mean age was 54.63±11.41 years. As expected, there was a female predominance of 362 (89.4%). A total of 376 patients were followed up for 1 year and 252 patients for 3 years. Forty-seven out of 404 patients (11.6%) developed hypercalcemia within 3 years. Twenty-eight patients became hypercalcemic within the 1^st year, and 19 patients became hypercalcemic within 3 years. Among the 47 patients, only four patients had a calcium level above 11 mg/dL during the follow-up. Nephrolithiasis was detected in 50 patients (12.6%). There was no significant difference in calcium, parathyroid hormone, 25-hydroxyvitamin D, or urinary calcium levels or the presence of nephrolithiasis. Bone mineral density assessments revealed that only 90 patients (28.5%) had normal bone mineral density. A total of 135 (42.7%) patients had osteopenia, and 91 (28.8%) patients had osteoporosis at least one site at presentation. This study revealed that patients with normocalcemic primary hyperparathyroidism have significant adverse skeletal outcomes, a slight increase in kidney stones. Only a small proportion of patients develop hypercalcemia, and the risk of developing significant hypercalcemia that would alter the patient's treatment management is much lower.

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.

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.

Graves' disease is an autoimmune disease caused by autoantibodies to the thyroid-stimulating hormone receptor, which usually leads to hyperthyroidism in these patients. The aim of the present study was to evaluate a new automated bridge chemiluminescence thyroid-stimulating hormone receptor autoantibody assay for the diagnosis and in the follow-up of Graves' disease patients and to compare this assay with another established competition assay. Altogether, 132 Graves' disease, 39 autoimmune thyroiditis, 28 non-autoimmune nodular goiter and 27 thyroid cancer patients were included in this study. Receiver-operating characteristic plot analysis based on above mentioned samples revealed an area under the curve of 0.9994 (95% confidence interval: 0.9980-1.001), indicating high sensitivity and specificity of the assay. The optimal sensitivity (99.22%; 95% confidence interval: 95.7-99.8%) and specificity (98.98%; 95% confidence interval: 94.4%-99.8%) were seen at a cut-off level of 0.550 IU/L. The corresponding positive predictive value was 99.22%, whereas the negative predictive value was estimated to be 98.98%. A detailed comparison of the two assay systems used revealed a slightly different thyroid-stimulating hormone receptor autoantibody distribution with the new bridge assay detecting more thyroid-stimulating hormone receptor autoantibody-positive follow-up patients with active Graves' disease compared with the competition assay. The measurement of thyroid-stimulating hormone receptor autoantibodies revealed a steady decline over the time of follow-up. In summary, our results demonstrate that the new automated bridge assay for detecting thyroid-stimulating hormone receptor autoantibodies has high sensitivity and specificity for diagnosing Graves' disease and to discriminate from other thyroid diseases, respectively.

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.

Thyroid hormones, primarily triiodothyronine (T3) and thyroxine (T4), are critical regulators of metabolic rate, mitochondrial function, and cellular repair mechanisms. Emerging evidence suggests that thyroid status may significantly influence aging trajectories and longevity through modulation of key cellular pathways. This review explores the role of thyroid hormones in aging biology, with a focus on their interaction with longevity-associated signaling pathways and the hallmarks of aging. Both physiological and subclinical thyroid states in the context of healthspan, cognitive preservation, metabolic resilience, and mitochondrial integrity are explored. A narrative synthesis of human and animal studies was conducted, including mechanistic, epidemiologic, and clinical data, to evaluate how thyroid hormone levels affect aging pathways such as mechanistic target of rapamycin, AMP-activated protein kinase, IGF-1, sirtuins, FOXO transcription factors, and mitochondrial biogenesis. Thyroid hormones modulate several hallmarks of aging, including mitochondrial dysfunction, genomic instability, epigenetic drift, and deregulated nutrient sensing. T3 enhances mitochondrial respiration and autophagy while interacting with mechanistic target of rapamycin and AMP-activated protein kinase to regulate energy balance. Altered thyroid function-particularly subclinical hypothyroidism-has been paradoxically associated with increased longevity in some centenarian cohorts, possibly due to reduced oxidative metabolism. However, overt thyroid dysfunction is linked to increased metabolic risk in aging populations. Thyroid hormones serve as metabolic gatekeepers that influence both cellular aging and organismal longevity. A deeper understanding of their role in aging pathways may inform novel strategies for promoting healthy aging, including thyroid hormone modulation and personalized endocrine optimization.

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.