Hormone and Metabolic Research最新文献

{"title":"Endocrine Regulation of Appetite: Interactions between Gut Microbiota, Microbial Metabolites, and Appetite-related Hormones.","authors":"Seval Arvas, Oguz Ozcelik, Yunus E Beyhan, Sermin Algul","doi":"10.1055/a-2851-0224","DOIUrl":"https://doi.org/10.1055/a-2851-0224","url":null,"abstract":"<p><strong>Abstract: </strong>The gut microbiota has emerged as a key endocrine modulator that shapes host appetite regulation through its metabolites and their interactions with enteroendocrine and central neuroendocrine pathways. Microbial metabolites-including short-chain fatty acids, bile acid derivatives, indole compounds, and tryptophan-derived serotonin-activate receptors such as G-protein-coupled receptor 41/43, Takeda G protein-coupled receptor 5, and Toll-like receptor 4 on enteroendocrine cells, influence the secretion of appetite-related hormones including ghrelin, leptin, glucagon-like peptide-1, peptide YY, nesfatin-1, and cholecystokinin. These hormones subsequently modulate hypothalamic circuits, particularly the NPY/AgRP and POMC/CART pathways, establishing a mechanistic link between microbial signaling and central appetite control. Ghrelin serves as the primary orexigenic hormone, whereas leptin, glucagon-like peptide-1, peptide YY, nesfatin-1, and cholecystokinin collectively exert anorexigenic effects that promote satiety and energy homeostasis. Dysbiosis disrupts receptor-mediated endocrine signaling, alters hormonal secretion, and contributes to leptin resistance, impaired glucagon-like peptide-1 responsiveness, and dysregulated appetite-key features in obesity, insulin resistance, and metabolic syndrome. This review synthesizes current mechanistic insights into the microbiota-hormone axis and highlights how microbial modulation influences endocrine appetite regulation. Understanding these interactions provides a translational framework for developing microbiota-targeted endocrine therapies aimed at restoring metabolic balance and preventing obesity and related metabolic disorders.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parathyroid Cancer in the United Kingdom: A Systematic Review and Meta-analysis of 10-year Post-surgical Recurrence.","authors":"Taoreed Adegoke Azeez, Rishi Harith Nagamangala Sathisha, Babatunde Ayodeji","doi":"10.1055/a-2835-0669","DOIUrl":"10.1055/a-2835-0669","url":null,"abstract":"<p><strong>Abstract: </strong>Parathyroid cancer is an uncommon malignant condition that usually presents with symptoms of hypercalcaemia. The standard treatment involves surgery, which has a broad spectrum of post-operative recurrence rates. This meta-analysis aimed to identify the clinical characteristics and the 10-year recurrence rate of parathyroid cancer in the UK. This study was a systematic review carried out in strict compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The meta-analysis was performed utilizing MetaXL version 5.3, applying the DerSimonian Laird random effects model. A total of five studies, encompassing 115 participants, fulfilled the eligibility requirements. The mean age of the subject was 53.8 years. The ratio of women to men was roughly equal. Additionally, 10.5% of the patients presented with metastatic disease. Hypercalcaemia was noted in every case. The combined 10-year post-operative recurrence rate for parathyroid cancer in the UK stands at 9.0% (95% confidence interval: 4.0-15.0). The recurrence rate after surgery for parathyroid cancer is significantly elevated; therefore, it is highly recommended to establish long-term, and possibly lifetime, monitoring. The high occurrence of synchronous metastases in parathyroid indicates a necessity for sensitive biomarkers to facilitate early detection.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"171-176"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Endothelial Responses in Individuals With Primary Hyperparathyroidism.","authors":"Thiago Siqueira Chagas, Karynne Grutter Lopes, João Antonio Gonçalves Bastos Torres, Bárbara Gehrke, Lia Roque Assumpção, Maria Cristina Araujo Maya, Eliete Bouskela, Luiz Guilherme Kraemer-Aguiar, Maria Caroline Alves Coelho","doi":"10.1055/a-2841-7309","DOIUrl":"10.1055/a-2841-7309","url":null,"abstract":"<p><strong>Abstract: </strong>Primary hyperparathyroidism is a prevalent endocrine disorder marked by excessive parathyroid hormone secretion. Beyond its classical biochemical features, accumulating evidence suggests that primary hyperparathyroidism may adversely affect cardiovascular homeostasis. In this context, we aimed to evaluate whether patients with primary hyperparathyroidism exhibit impaired vascular function and heightened systemic inflammation compared with matched healthy controls. This cross-sectional study initially recruited 39 patients with primary hyperparathyroidism. After predefined exclusion criteria were applied, 30 patients with primary hyperparathyroidism were included and compared with 45 age-, sex-, and body mass index-matched healthy controls. Endothelium dependent and independent vasodilation were assessed using venous occlusion plethysmography. High-sensitivity C-reactive protein levels were measured. Endothelium-independent vasodilation was reduced in primary hyperparathyroidism compared to controls (-15.5%; <i>p</i>=0.01), indicating vascular smooth muscle dysfunction. High-sensitivity C-reactive protein levels were significantly higher in primary hyperparathyroidism (905.7%; <i>p</i><0.001). The mean arterial pressure was elevated (~12.2%; <i>p</i><0.001), with a higher prevalence of hypertension (60% vs. 35.6%; <i>p</i>=0.03). These findings suggest that primary hyperparathyroidism is associated with impaired vascular function and systemic inflammation, even in patients without overt cardiovascular disease. This highlights a possible subclinical cardiovascular risk in primary hyperparathyroidism and supports the need for further longitudinal studies to confirm these associations and their clinical relevance.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"193-198"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Fate of Normocalcemic Hyperparathyroidism: Insights from a 3-Year Multicenter Follow-Up.","authors":"Mazhar Müslüm Tuna, Berçem Ayçiçek, İsmail Engin, Asena Gökçay Canpolat, Yusuf Kır, Ceren Tufan, Ekin Yiğit Köroğlu, Kenan Sakar, Ahmet Görgel, Dılek Kılınç Candemır, Yudum Yaprak Usda Konak, Mustafa Aydemır, Mustafa Şahın, Neşe Ersöz Gülçelık, Ersen Karakiliç, Bekır Çakır, Gülhan Akbaba, Süleyman Baldane, Faruk Kilinç, Cüneyt Bılgıner, Ramazan Sari","doi":"10.1055/a-2812-1864","DOIUrl":"10.1055/a-2812-1864","url":null,"abstract":"<p><strong>Abstract: </strong>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.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"163-170"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary Hyperparathyroidism in Africa: A Systematic Review and Meta-Analysis of Clinical Manifestations.","authors":"Taoreed Adegoke Azeez, Oyindamola Awofisoye, Olapeju Oluwafunmilayo Adeyemi","doi":"10.1055/a-2820-3666","DOIUrl":"10.1055/a-2820-3666","url":null,"abstract":"<p><strong>Abstract: </strong>Primary hyperparathyroidism is an endocrine disorder characterized by chronic hypercalcaemia resulting from the unregulated excessive production of parathyroid hormone. This study aimed mainly to determine the clinical manifestations of primary hyperparathyroidism within the African population. This study was a systematic review carried out in strict compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The meta-analysis was executed utilizing Meta XL version 5.3, applying the DerSimonian Laird random-effects model. A total of 52 studies met the eligibility criteria, resulting in an overall sample size of 2,807 patients. The average age was 55.1 years. Seventy-nine percentage of the patients were women. Asymptomatic individuals represented 26% of the population. The most common symptoms include bone pain, lethargy, and features related to renal stones. Familial primary hyperparathyroidism is observed in 6% of patients. The majority of individuals diagnosed with primary hyperparathyroidism are women in their sixth decade. In contrast to developed countries, a considerable number of Africans suffering from primary hyperparathyroidism have already shown symptoms, which are frequently non-specific or have encountered complications before obtaining a diagnosis.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"199-209"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between Hyperparathyroidism and the Risk of Cerebrovascular Disease in the General Population.","authors":"Grace H Yin, Femi E Ayeni, Guy D Eslick, Senarath Edirimanne","doi":"10.1055/a-2818-9158","DOIUrl":"10.1055/a-2818-9158","url":null,"abstract":"<p><strong>Abstract: </strong>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 (<i>p</i>> 0.05). This review is supportive of the association between hyperparathyroidism and stroke but does not establish a conclusive causal relationship.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"177-185"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contemporary Trends in Calcium Levels and Related Clinical Conditions: A Two Decade Analysis of U.S. National Health and Nutritional Examination Survey Data.","authors":"Ethan Frank, Eric Adjei Boakye, Brendan C Stack","doi":"10.1055/a-2854-1289","DOIUrl":"10.1055/a-2854-1289","url":null,"abstract":"<p><strong>Abstract: </strong>Ambulatory hypercalcemia is a proxy for primary hyperparathyroidism. Reports of an increased incidence of hypercalcemia and undiagnosed primary hyperparathyroidism in several electronic medical record studies have prompted a population-based trend analysis of serum calcium. Data from the 2000-2020 U.S. National Health and Nutritional Examination Survey were used to study the trend of serum calcium and related factors. The NHANES has contemporary insight into the ambulatory state of health in the large and diverse U.S. population. Joinpoint regression estimated yearly changes of serum calcium and related factors using annual percentage changes. Serum calcium levels increased by an average of 0.65 mg/dL/y from 2000 to 2004 and then decreased on average by 0.12 mg/dL annually from 2004 to 2020. Among women, serum calcium levels increased by an average of 0.69 mg/dL/y from 2000 to 2004 but then decreased on average by 0.13 mg/dL annually from 2004 to 2020. Among men, serum calcium levels increased by an average of 0.61 mg/dL/y from 2000 to 2004 and then remained stable. Trends of body mass index increased by an average of 0.49/y from 2014 to 2020. Ambulatory hypercalcemia is a proxy for primary hyperparathyroidism. Over 20 years in the U.S. National Health and Nutritional Examination Survey (2000-2020), calcium levels have been decreasing slightly since 2004 after an increase while body mass index has been increasing since 2014. These data conflict with reported observations of the undiagnosed and increased incidence of primary hyperparathyroidism. These data may ultimately serve to refine primary hyperparathyroidism data phenotype for machine learning deployed within an electronic medical record.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":"186-192"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of 12 Weeks of Endurance Physical Training Associated with the Administration of Melatonin on Bone Parameters of Rats under Hypoestrogenism.","authors":"Taciane M M Pejon, Milena R Castro, Alinson E Cipriano, Wladimir R Beck","doi":"10.1055/a-2852-1389","DOIUrl":"https://doi.org/10.1055/a-2852-1389","url":null,"abstract":"<p><strong>Abstract: </strong>Hypoestrogenism causes an imbalance in bone homeostasis, which can affect bone microarchitecture and result in loss of tissue strength and increased risk of fractures. Physical training and melatonin can act on bone formation; however, in a state of hypoestrogenism, the potential effect of the combination of both interventions is not understood. The aim of this study was to investigate the effect of 12 weeks of swimming physical training associated with melatonin administration on the mineral content and biomechanical parameters in bone tissue under hypoestrogenism conditions. The animals (Wistar rats) performed an incremental swimming test to determine the individual anaerobic lactacidemic threshold and underwent bilateral ovariectomy. The interventions consisted of physical training (30 min, 5 d/wk, 90% of individual anaerobic lactacidemic threshold) and melatonin administration (10 mg/kg/d via gavage). After 12 weeks, the femur was collected for the analysis of calcium and phosphorus contents and the three-point flexion test to obtain biomechanical parameters. Data were expressed as mean±standard deviation, subjected to factorial analysis of variance and the Newman-Keuls post hoc test (a significance level of 5%). The association of endurance physical training with melatonin administration resulted in a significant increase in calcium and phosphorus contents, while presenting a significant increase in the capacity to support a greater maximum load and promote rigidity to bone tissue. Considering the detrimental impact of hypoestrogenism on bone tissue, both interventions, endurance physical training and melatonin administration, were able to generate beneficial results regarding the bone mineral content, influencing the improvement of biomechanical parameters that determine tissue strength, which can prevent bone fracture.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thyroid Hormone Excess in Sudden Death: A Clinicopathological Spectrum in an Autopsy Study.","authors":"Yukiko Hata, Yu Saito, Keiichi Hirono, Shojiro Ichimata, Naoki Nishida","doi":"10.1055/a-2851-8963","DOIUrl":"https://doi.org/10.1055/a-2851-8963","url":null,"abstract":"<p><p>Thyrotoxicosis is associated with heightened adrenergic activity, arrhythmogenic susceptibility, and procoagulant alterations; yet, its contribution to sudden death outside overt thyroid storm remains incompletely understood. We retrospectively screened 975 consecutive autopsies and identified 7 cases with biochemical evidence of thyroid hormone excess defined by elevated free T3 and/or free T4 levels. Clinical background, medication exposure, thyroid-related biomarkers, including thyroglobulin, thyroid autoantibodies, and interleukin-6, together with detailed histopathological examination of the thyroid gland and the cardiovascular system, were integrated to assess the potential contribution of thyroid hormone excess to the fatal outcome. Targeted genetic analysis was additionally performed in selected cases. Two cases fulfilled clinicopathological criteria for thyroid storm and showed markedly elevated IL-6 concentrations, suggesting severe systemic decompensation. In the remaining cases, death was attributed to structural cardiovascular or cerebrovascular pathology, including intracerebral hemorrhage, acute coronary thrombosis with plaque rupture, hydrocephalus, or presumed arrhythmic mechanisms. Biochemical thyrotoxicosis was observed even in the absence of thyroid-stimulating hormone suppression, and exogenous or treatment-associated thyrotoxicosis was sometimes accompanied by thyroid atrophy rather than hyperplasia. These findings indicate that thyroid hormone excess detected at autopsy represents a clinicopathological spectrum ranging from primary thyroid-driven death to contexts in which thyrotoxicosis functions as a physiological modifier that lowers the threshold for fatal cardiovascular events. Integrative interpretation of biochemical, pathological, and clinical findings may improve the understanding of thyroid hormone-mediated vulnerability in sudden death.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cushing's Shadow: An Overlooked Diagnosis in Endocrinology.","authors":"Lala Soltanova, Serdar Sahin, Yucel Erbilgin, Banu Betul Kocaman, Ilkin Muradov, Seda Duman, Muge Sayitoglu, Pinar Kadioglu","doi":"10.1055/a-2848-7602","DOIUrl":"https://doi.org/10.1055/a-2848-7602","url":null,"abstract":"<p><p>The purpose of this study was to describe a novel heterozygous missense variant in the nuclear receptor subfamily 3 group C member 1 ligand-binding domain causing primary generalized glucocorticoid resistance and highlight diagnostic pitfalls that can mimic Cushing's disease.A 22-year-old woman was evaluated for suspected Cushing's disease after elevated cortisol levels and pituitary imaging findings. She underwent three transsphenoidal surgeries, but hypercortisolism and clinical symptoms including hirsutism, acne, menstrual irregularities, and weight gain persisted. The absence of classical Cushing's stigmata prompted genetic evaluation, which led to the diagnosis of primary generalized glucocorticoid resistance.Whole-exome sequencing was performed in the index case. The identified variant was validated by Sanger sequencing and segregation analysis was carried out in her sister. A novel heterozygous, likely pathogenic missense variant (NM_000176.3:c.1940T>C, p.(Leu647Pro)) in the <i>nuclear receptor subfamily 3 group C member 1</i> gene was detected in two siblings. We describe a novel <i>nuclear receptor subfamily 3 group C member 1</i> variant associated with primary generalized glucocorticoid resistance, expanding the mutational spectrum of glucocorticoid receptor defects. This case underscores the importance of considering primary generalized glucocorticoid resistance in patients with adrenocorticotropic hormone-dependent hypercortisolism lacking typical Cushing's features to prevent unnecessary invasive procedures and guide appropriate genetic counseling.</p>","PeriodicalId":12999,"journal":{"name":"Hormone and Metabolic Research","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}