Horm. Metab. Res. [JOURNAL]
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200 papers
An Evaluation of Immature Granulocytes as Predictors of Malignancy in Patients with Atypia of Undetermined Significance Thyroid Nodules.
Tüfekçi D, Gucer H
Horm Metab Res · 2026 Jun · PMID 41839205 · Full text
This retrospective study aimed to evaluate hematological and inflammatory markers as predictors of thyroid cancer in patients with atypia of undetermined significance thyroid nodules. A total of 174 patients with atypia...
This retrospective study aimed to evaluate hematological and inflammatory markers as predictors of thyroid cancer in patients with atypia of undetermined significance thyroid nodules. A total of 174 patients with atypia of undetermined significance who underwent thyroidectomy were included. Pre- and postoperative immature granulocyte counts, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were analyzed after achieving euthyroid status. Propensity score matching for age and gender resulted in a final cohort of 128 patients (64 benign and 64 malignant). Static preoperative and postoperative immature granulocyte values did not differ significantly between the benign and malignant groups; however, the delta immature granulocyte value, defined as the change between pre- and postoperative measurements, was significantly lower in malignant cases (=0.007). Receiver operating characteristic analysis demonstrated an area under the curve of 0.651 at a cut-off value of≤- 0.01, with a sensitivity of 46.2% and a specificity of 79.2%. Univariate logistic regression revealed that delta immature granulocytes independently predicted malignancy in the overall cohort (odds ratio=3.273 and =0.007) and in patients younger than 55 years (odds ratio=5.082 and =0.007), whereas this association was not observed in patients aged 55 years and older. The neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios were not significant predictors. These findings suggest that dynamic changes in immature granulocyte levels between the pre- and postoperative periods, rather than single-time-point measurements, may serve as a cost-effective and accessible complementary tool for malignancy prediction in atypia of undetermined significance thyroid nodules.
Association between Hyperparathyroidism and the Risk of Cerebrovascular Disease in the General Population.
Yin GH, Ayeni FE, Eslick GD … +1 more , Edirimanne S
Horm Metab Res · 2026 May · PMID 41825458 · Publisher ↗
Hyperparathyroidism has been associated with an increased risk of stroke in several previous studies; but the findings have not been consistent, which prompts further investigation. This study aimed to elucidate the asso...
Hyperparathyroidism has been associated with an increased risk of stroke in several previous studies; but the findings have not been consistent, which prompts further investigation. This study aimed to elucidate the association between high serum parathyroid hormone levels and stroke through a systematic review and meta-analysis. PubMed, Embase, Scopus and Google Scholar were systematically searched up to May 2025 for relevant and original observational studies. Pooled odds ratios and hazard ratios were calculated with corresponding 95% confidence intervals, along with heterogeneity and publication bias. The combined search yielded 2,063 unique articles, and 14 studies were included in statistical analysis. Two associations were analysed: nine studies focused on comparing the risk of stroke between populations with normal and high parathyroid hormone levels and the remaining five studies focused on comparing the rate of hyperparathyroidism between populations with stroke and normal population. In the first group, subgroup analyses of studies reported that both hazard ratios and odds ratios demonstrated stroke to be more likely in groups with hyperparathyroidism (odds ratio: 1.49 and 95% confidence interval: 1.38-1.61; hazard ratio: 1.38 and 95% confidence interval: 1.09-1.75). In the second group, analysis demonstrated that groups with stroke are more likely to have higher level of parathyroid hormone (mean difference of parathyroid hormone levels: 10.30 pg/mL and 95% confidence interval: 1.60-19.00). There were no significant publication biases in any of the analyses (> 0.05). This review is supportive of the association between hyperparathyroidism and stroke but does not establish a conclusive causal relationship.
Five-Year Fracture Outcomes with Zoledronate in Postmenopausal Osteoporotic Women with and without Diabetes.
Giri S, Ramkumar G, Sahoo J … +8 more , Kamalanathan S, Naik D, Reddy SVB, Merugu C, Durgia H, Venkatesh S, Suryadevara V, Mondal SA
Horm Metab Res · 2026 Mar · PMID 41780541 · Publisher ↗
Zoledronate is most effective when bone turnover is elevated, as in postmenopausal women. Individuals with type 2 diabetes mellitus show lesser bone mineral density gains compared to non-diabetes mellitus individuals wit...
Zoledronate is most effective when bone turnover is elevated, as in postmenopausal women. Individuals with type 2 diabetes mellitus show lesser bone mineral density gains compared to non-diabetes mellitus individuals with zoledronate, and fractures often occur despite preserved bone mineral density. It is unclear whether zoledronate reduces fracture risks in type 2 diabetes mellitus. This study aimed to evaluate skeletal outcomes, including fracture incidence, over 5 years in postmenopausal osteoporotic women with and without type 2 diabetes mellitus. This prospective cohort included postmenopausal women with bone mineral density -scores of≤-2.5 at the lumbar spine, femoral neck, or hip. Participants were classified as type 2 diabetes mellitus or non-diabetes mellitus. All received annual zoledronate (4 mg), daily calcium (1000 mg), and cholecalciferol (500 IU), with standardized fall-prevention measures. Fracture history was recorded at follow-up visits, and annual spine radiographs were performed to detect morphometric vertebral fractures. Women completing≥5 years of follow up were included in the final analysis. The primary end point was fracture incidence; secondary end points were changes in bone mineral density and bone turnover markers. Of 221 women enrolled, 150 completed 5 years (63 type 2 diabetes mellitus and 87 non-diabetic mellitus; median age 59 y). The baseline bone mineral density was similar, but bone turnover markers were lower in type 2 diabetes mellitus. At a minimum of 60 months follow up, 20 new fractures occurred in 15 women: 8 (12.7%) with type 2 diabetes mellitus and 7 (8.0%) without. The relative risk (RR) was 1.58 (95% confidence interval: 0.60-4.13; =0.2). Both groups showed comparable bone mineral density improvements. Despite differences in baseline bone turnover, fracture incidence did not differ significantly between postmenopausal women with and without type 2 diabetes mellitus treated with annual zoledronate over a 5-year follow-up. However, the low number of fracture events and wide confidence intervals limit definitive inference.
Unraveling the Origins of Thyroid Nodules: Inflammation, Hormones, Toxins, and Micronutrient Interactions.
Mazza AD
Horm Metab Res · 2026 Apr · PMID 41776945 · Publisher ↗
Thyroid nodules are among the most frequently encountered endocrine abnormalities, affecting up to two-thirds of adults in iodine-sufficient regions. Although thyroid-stimulating hormone and genetic mutations have long b...
Thyroid nodules are among the most frequently encountered endocrine abnormalities, affecting up to two-thirds of adults in iodine-sufficient regions. Although thyroid-stimulating hormone and genetic mutations have long been implicated in their pathogenesis, emerging evidence reveals a multifactorial interplay among inflammatory, hormonal, toxic, and micronutrient influences that extends beyond the classical model. This narrative review examines the converging biological pathways that contribute to thyroid nodule formation, emphasizing the integrative roles of inflammation, estrogen signaling, environmental endocrine disruptors, and micronutrient imbalance in altering thyroid cellular homeostasis. Chronic low-grade inflammation and oxidative stress create a permissive microenvironment for thyrocyte proliferation and clonal expansion. Estrogen receptor activation-amplified by insulin and insulin-like growth factor 1 signaling-enhances vascular and proliferative responses within thyroid tissue, contributing to the female predominance of nodular disease. Exposure to heavy metals and xenoestrogens disrupts thyroid peroxidase activity, deiodinase regulation, and immune tolerance, while deviations in iodine, selenium, zinc, and vitamin D status further impair redox balance and DNA repair mechanisms. Together, these factors promote a spectrum of structural changes ranging from microscopic hyperplasia to clinically significant nodules. Thyroid nodules represent a visible manifestation of intersecting metabolic and environmental stressors rather than a single endocrine defect. Integrating insights from molecular endocrinology, environmental toxicology, and nutritional science may advance early detection and preventive strategies targeting the inflammatory-hormonal-toxic axis of thyroid disease.
Prevalence, Incidence, and Remission of Erectile Dysfunction in Newly Diagnosed and Uncomplicated Type 2 Diabetic Men: The Role of Testosterone, Hyperuricemia, and Patient Education.
Coppola A, Gallotti P, Pujia C … +3 more , Montalcini T, Falcone C, Gazzaruso C
Horm Metab Res · 2026 Mar · PMID 41771288 · Publisher ↗
In type 2 diabetes mellitus, the prevalence at diagnosis, incidence, and remission of erectile dysfunction are unknown. We evaluated the prevalence, incidence, remission, and predictors of erectile dysfunction in newly d...
In type 2 diabetes mellitus, the prevalence at diagnosis, incidence, and remission of erectile dysfunction are unknown. We evaluated the prevalence, incidence, remission, and predictors of erectile dysfunction in newly diagnosed and uncomplicated type 2 diabetic men. We consecutively enrolled 549 diabetic men without complications. Erectile dysfunction was diagnosed using the International Index for Erectile Function 5 questionnaire. Patients were followed up for 64.2±22.1 months. At baseline, 133 patients had erectile dysfunction and 416 patients did not. The prevalence of erectile dysfunction was 24.2%. Among the 416 patients without erectile dysfunction at baseline, 67 (16.1%) patients developed erectile dysfunction at follow-up, with an erectile dysfunction incidence of 2.3%/y. Among the 133 patients with erectile dysfunction at baseline, 27 (20.3%) patients had remission at follow-up, with an erectile dysfunction remission rate of 0.9%/y. Multivariate analysis showed that age>60 years, total testosterone levels of<2.8 ng/mL and uric acid levels of>6 mg/dL were predictors of erectile dysfunction at diagnosis. Predictors of erectile dysfunction incidence were age>60 years, smoking and low total testosterone levels, whereas total testosterone levels of>2.8 ng/mL predicted erectile dysfunction remission. No significant association between therapeutic patient education and erectile dysfunction was observed. In conclusion, one quarter of men with newly diagnosed and uncomplicated type 2 diabetes has erectile dysfunction at diagnosis. The incidence of erectile dysfunction was 2.3%/y, while remission was 0.9%/y. Older age, low total testosterone levels, and hyperuricemia were associated with erectile dysfunction at diabetes diagnosis, while older age, smoking, and total testosterone levels were the longitudinal predictors of erectile dysfunction.
The Fate of Normocalcemic Hyperparathyroidism: Insights from a 3-Year Multicenter Follow-Up.
Tuna MM, Ayçiçek B, Engin İ … +18 more , Gökçay Canpolat A, Kır Y, Tufan C, Köroğlu EY, Sakar K, Görgel A, Kılınç Candemır D, Konak YYU, Aydemır M, Şahın M, Gülçelık NE, Karakiliç E, Çakır B, Akbaba G, Baldane S, Kilinç F, Bılgıner C, Sari R
Horm Metab Res · 2026 May · PMID 41748079 · Publisher ↗
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...
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 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.
Clinical Evaluation of a New Automated Bridge Assay for the Detection of Thyroid-Stimulating Hormone Receptor Autoantibodies.
Schott-Ohly P, Albeiruty S, Muchalla M … +9 more , Doetter U, Hommen J, Eberwein T, Vogkou C, Hermsen D, Timm J, MacKenzie C, Giesel F, Schott M
Horm Metab Res · 2026 Feb · PMID 41730272 · Publisher ↗
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...
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.
Correction: Exploring the Therapeutic Potential of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis in Patients with Type 2 Diabetes: A Narrative Review.
Al Rashid S, Suriyan A, Bilal Azam M … +4 more , Balasubramanian R, Pakkir Maideen NM, Chidambaram K, Amirthalingam P
Horm Metab Res · 2026 Feb · PMID 41702547 · Publisher ↗
Abstract loading — click title to view on PubMed.
Lactate, Capnia, and Fat Oxidation as Therapeutic Axes for SARS-CoV-2 Spike Protein-Induced Sequelae.
Gracidas C, Levy R, Varon J … +1 more , Halma M
Horm Metab Res · 2026 Mar · PMID 41672424 · Publisher ↗
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 trium...
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 CO), 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.
Exploring the Therapeutic Potential of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis in Patients with Type 2 Diabetes: A Narrative Review.
Al Rashid S, Suriyan A, Bilal Azam M … +4 more , Balasubramanian R, Pakkir Maideen NM, Chidambaram K, Amirthalingam P
Horm Metab Res · 2026 Mar · PMID 41643685 · Publisher ↗
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...
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.
Procalcitonin as a Tumour Marker in Medullary Thyroid Carcinoma: A Comparative Study with Calcitonin and Carcinoembryonic Antigen.
Kopanos S, Khalil AH, Scheel SN … +2 more , Wehmeier M, Feldkamp J
Horm Metab Res · 2026 Feb · PMID 41643684 · Publisher ↗
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 dysf...
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 (=0.874 and <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.
A Meta-Analysis of the Effects of Homocysteine-Lowering Therapy on Chronic Kidney Disease.
Lin H, Liu Y, Geng S … +4 more , Sun Y, Li X, Li B, Liu Y
Horm Metab Res · 2026 Jan · PMID 41617174 · Publisher ↗
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...
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 (²=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; = 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; =0.008) and in non-White populations (relative risk=0.89 and 95% confidence interval=0.81-0.97; =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.
Does POLG2 Play a Role in Cerebellar Ataxia and Hypogonadotropic Hypogonadism?
Koch CA, Tüttelmann F, Vedanarayanan V
Horm Metab Res · 2026 Jan · PMID 41617173 · Publisher ↗
Abstract loading — click title to view on PubMed.
Papillary Thyroid Carcinoma and Hashimoto's Thyroiditis: New Insights into the Immunological Link.
Schott-Ohly P, Schott M
Horm Metab Res · 2026 Feb · PMID 41461175 · Publisher ↗
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 i...
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.
Venous Thromboembolism and Testosterone Therapy in Klinefelter Syndrome.
Ferguson R, Alarayedh A, Clark C … +17 more , Elnabarawy R, Shanmugathasan K, Samy I, Melling F, Birch S, Tomlinson C, Elshirif A, Frodsham L, Briggs K, Gad M, Arshad S, Allchorne P, Foran N, Prezzi D, Hunt B, Carroll P, Yap T
Horm Metab Res · 2026 Jan · PMID 41412196 · Publisher ↗
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 incre...
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 (=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.
Factors Associated with Hypoparathyroidism and Vocal Cord Paralysis Following Thyroid Surgery: A Multicenter Cross-Sectional Analysis of 3,365 Cases.
Kirchner C, Krieg S, Schott M … +2 more , Krieg A, Kostev K
Horm Metab Res · 2026 Feb · PMID 41365329 · Publisher ↗
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 multi...
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.
Adrenal Cortical Steroidogenic Enzyme Expression is Associated with Hypertension, Obesity and Corticosteroid Use: A Tissue Microarray Study of Human Adrenal Tissue.
Oppliger A, Kirschfink A, Benning L … +9 more , Schwarz EI, Weber A, Maccio U, Perakakis N, Steenblock C, Kanczkowski W, Bornstein SR, Beuschlein F, Varga Z
Horm Metab Res · 2025 Dec · PMID 41360104 · Publisher ↗
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...
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 (<0.001 and =0.0149), higher body mass index (=0.026 and =0.001), and the administration of corticosteroids (=0.0012, =0.001, and =0.002). CYP11B2 showed reduced expression in the zona glomerulosa only in the non-COVID-19 hypertension group (=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.
Delay in Diagnosis of Thyroid-Stimulating Hormone-Secreting Pituitary Adenomas: Clinical and Endocrinological Profiles from a Retrospective Cohort Study.
Kopanos S, Knappe UJ, Moeller AS … +2 more , Scheel SN, Feldkamp J
Horm Metab Res · 2026 Jan · PMID 41338539 · Publisher ↗
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, biochemica...
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; =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.
Extracellular Matrix-Guided Islet Cell Transplantation Results in Improved Glycemic Control in a NOD-SCID Mouse Model.
Korol R, Even-Ram S, Molakandov K … +12 more , Puchinsky D, Hemed M, Mizrahi N, Toledo I, Lazar D, Chebath J, Tritel M, Ofir R, Ludwig B, Revel M, Shapiro AMJ, Bornstein SR
Horm Metab Res · 2025 Dec · PMID 41297833 · Publisher ↗
Current insulin therapy fails to fully restore physiological glucose homeostasis in type 1 diabetes mellitus, with 75% of patients unable to achieve the desired management targets. While stem cell-derived islets offer pr...
Current insulin therapy fails to fully restore physiological glucose homeostasis in type 1 diabetes mellitus, with 75% of patients unable to achieve the desired management targets. While stem cell-derived islets offer promising therapy, they require an enhanced extracellular matrix support for optimal transplantation outcomes. To address this challenge, we developed biofunctional endocrine micro-pancreata using decellularized porcine lung scaffolds seeded with embryonic stem cell-derived islets. In vivo efficacy was evaluated following subcutaneous or intraperitoneal transplantation into NOD-SCID mice, followed by streptozotocin induction of diabetes, with the comprehensive assessment of human insulin secretion, glucose homeostasis, and graft integration over 3 months. Our results demonstrated that endocrine micro-pancreata exhibited 1.4-fold-increased glucose-stimulated insulin secretion in vitro compared to non-responsive free islets. In vivo, endocrine micro-pancreas recipients maintained significantly lower glucose levels than controls throughout the experiment. Subcutaneous endocrine micro-pancreata showed superior performance, with 46% improved glucose tolerance versus 31% improvement for intraperitoneal delivery. Extensive CD31-positive neovascularization as well as insulin staining confirmed successful graft integration and sustained insulin production. Endocrine micro-pancreata provide a scalable platform for diabetes cell therapy, demonstrating sustained insulin secretion and improved glycemic control. The preserved extracellular matrix microenvironment supports islet function and vascularization, offering significant potential for clinical translation.
Retrospective Analysis of Nivolumab-Induced Isolated Adrenocorticotropin Deficiency.
Wen W, He Y, Fan Z
Horm Metab Res · 2025 Dec · PMID 41285381 · Publisher ↗
To investigate the clinical features of nivolumab-induced isolated adrenocorticotropin deficiency and to provide a reference for the diagnosis, treatment and rational use of nivolumab, clinical reports of nivolumab induc...
To investigate the clinical features of nivolumab-induced isolated adrenocorticotropin deficiency and to provide a reference for the diagnosis, treatment and rational use of nivolumab, clinical reports of nivolumab induced isolated adrenocorticotropin deficiency were collected by searching the database until August 31, 2025. Clinical data were collected and retrospectively analyzed. Seventy-one patients were enrolled, with a median age of 66 years (range: 26-87), and 73.2% of whom were male and 67.6% from Japan. Melanoma (36.6%) was the main indication for nivolumab. The median time from initiation of nivolumab to the onset of isolated adrenocorticotropin deficiency was 24 weeks (range: 3-60) and the median was 8 cycles (range: 2-33). Fatigue (76.1%), anorexia (66.2%) and nausea (23.9%) were the most common symptoms of isolated adrenocorticotropin deficiency. Laboratory tests revealed hyponatremia (50.7%) and eosinophilia (28.2%). Pituitary magnetic resonance imaging showed no abnormality in most patients (71.8%). Thyroid dysfunction (26.8%) often coexists with isolated adrenocorticotropin deficiency. These patients had a good prognosis after receiving a physiological dose of hydrocortisone. Nivolumab-induced isolated adrenocorticotropin deficiency is a rare disorder with possible racial differences. The possibility of isolated adrenocorticotropin deficiency should be considered in patients with fatigue and fatigue during treatment. Serum sodium and eosinophil ratios should also be closely monitored. The prognosis is good after hydrocortisone replacement therapy.
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