{"title":"From the First Case Reports to KDM1A Identification: 35 Years of Food (GIP)-Dependent Cushing's Syndrome.","authors":"Lucas Bouys, Jérôme Bertherat","doi":"10.1055/a-2359-8051","DOIUrl":"10.1055/a-2359-8051","url":null,"abstract":"<p><p>Food-dependent Cushing's syndrome (FDCS) is a rare presentation of hypercortisolism from adrenal origin, mostly observed in primary bilateral macronodular adrenal hyperplasia (PBMAH) but also in some cases of unilateral adrenocortical adenoma. FDCS is mediated by the aberrant expression of glucose-dependent insulinotropic peptide (GIP) receptor (GIPR) in adrenocortical cells. GIP, secreted by duodenal K cells after food intake, binds to its ectopic adrenal receptor, and stimulates cortisol synthesis following meals. FDCS was first described more than 35 years ago, and its genetic cause in PBMAH has been recently elucidated: <i>KDM1A</i> inactivation by germline heterozygous pathogenic variants is constantly associated with a loss-of-heterozygosity of the short arm of chromosome 1, containing the <i>KDM1A</i> locus. This causes biallelic inactivation of <i>KDM1A</i>, resulting in the GIPR overexpression in the adrenal cortex. These new insights allow us to propose the <i>KDM1A</i> genetic screening to all PBMAH patients with signs of FDCS (low fasting cortisol that increases after a mixed meal or oral glucose load) and to all first-degree relatives of <i>KDM1A</i> variant carriers. Given that <i>KDM1A</i> is a tumor suppressor gene that has also been associated with monoclonal gammopathy of uncertain significance and multiple myeloma, the investigation of FDCS in the diagnostic management of patients with PBMAH and further genetic testing and screening for malignancies should be encouraged.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"697-704"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141768318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cushing's Syndrome in the Elderly.","authors":"Aleksandra Zdrojowy-Wełna, Elena Valassi","doi":"10.1055/a-2317-8821","DOIUrl":"10.1055/a-2317-8821","url":null,"abstract":"<p><p>Management of Cushing's syndrome (CS) can be particularly challenging in older patients, compared with younger individuals, due to the lack of several clinical features associated with cortisol excess along with a greater burden of associated comorbidities. Moreover, the interpretation of diagnostic tests could be influenced by age-related physiological changes in cortisol secretion. While mortality is higher and quality of life is more impaired in the elderly with CS as compared with the younger, there is currently no agreement on the most effective therapeutic options in aged individuals, and safety data concerning medical treatment are scanty. In this review, we summarize the current knowledge about age-related differences in CS etiology, clinical presentation, treatment, and outcomes and describe the potential underlying mechanisms.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"705-711"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial for Special Issue \"Improving Outcome of Cushing's Syndrome-4\" (IMPROCUSH-4).","authors":"Martin Reincke","doi":"10.1055/a-2462-6525","DOIUrl":"https://doi.org/10.1055/a-2462-6525","url":null,"abstract":"","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":"132 12","pages":"657-658"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Landscape of Androgens in Cushing's Syndrome.","authors":"Hanna F Nowotny, Leah Braun, Nicole Reisch","doi":"10.1055/a-2333-1907","DOIUrl":"10.1055/a-2333-1907","url":null,"abstract":"<p><p>Hyperandrogenemia in patients with Cushing's syndrome (CS) presents a diagnostic pitfall due to its rare occurrence and overlapping symptoms with more common conditions like polycystic ovary syndrome (PCOS). This review explores the significance of androgen dysregulation in CS, focusing on both classical and 11-oxygenated androgens. While classical androgens contribute to hyperandrogenism in CS, their levels alone do not fully account for clinical symptoms. Recent research highlights the overlooked role of 11oxC19 androgens, particularly 11OHA4 and 11KT, in driving hyperandrogenic manifestations across all CS subtypes. These adrenal-specific and highly potent androgens offer stable expression throughout the lifespan of a woman, serving as valuable diagnostic biomarkers. Understanding their prominence not only aids in subtype differentiation but also provides insights into the complex nature of androgen dysregulation in CS. Recognizing the diagnostic potential of 11oxC19 androgens promises to refine diagnostic approaches and improve clinical management strategies for patients with CS.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"670-677"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evaluating the Diagnostic Role of ACR-TIRADS and Bethesda Classifications in Thyroid Nodules Highlighted by Cyto-Histopathological Studies.","authors":"Marwa S Eissa, Rania M Sabry, Mona S Abdellateif","doi":"10.1055/a-2380-3674","DOIUrl":"10.1055/a-2380-3674","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the accuracy of thyroid imaging reporting and data system (ACR-TIRADS) and the Bethesda system for reporting cytopathology (TBSRCP) classifications for identifying or ruling out thyroid malignancy in relation to the gold standard (post-surgical pathology).</p><p><strong>Methods: </strong>This cross-sectional study included 573 patients with single or multiple thyroid nodules. Patients were evaluated using the TIRADS and the TBSRCP classification. The data from a cohort of patients who underwent surgery (77/573, 13.4%) were correlated with post-operative pathology and the relevant clinical features of the patients.</p><p><strong>Results: </strong>Of 573 patients, 545 (95.1%) were euthyroid, 24 (4.1%) were hypothyroid, and 4 (0.8%) were hyperthyroid; 419 (73.1%) had benign nodules (Bethesda II), 115 (20.1%) had intermediate (Bethesda III, IV), and 39 (6.8%) had Bethesda V and VI nodules. Four-hundred twenty (73.3%) patients were categorized as TIRADS 2,3, and 153 (26.7%) were categorized as TIRADS 4,5. The Bethesda and TIRADS classifications concorded significantly in thyroid nodule diagnosis (K=14.9%, P<0.001).Thyroid malignancy was significantly associated with microcalcification and interrupted halo, while benign nodules were significantly associated with macrocalcification and complete halo type (P=0.041, P=0.005, respectively). The TBSRCP could significantly detect malignant thyroid nodules with a sensitivity, specificity, PPV, and NPV of 64.1%, 98.1%, 85.0%, and 94.1%, respectively (K=88.2%, P<0.001), while the respective values for the TIRADS classification were 63.5%, 76.0%, 84.6%, and 50.0% (K=34.8%, P=0.001).</p><p><strong>Conclusion: </strong>The TIRADS and TBSRCP are essential primary steps for evaluating thyroid nodules and both are complimentary. Hence, each patient with thyroid nodules should be evaluated by both approaches before opting for surgery. Highly suspicious TIRADS categories TR4 and TR5 need further evaluation by fine needle aspiration cytology.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"596-606"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141895013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dihydromyricetin Improves High Glucose-Induced Dopaminergic Neuronal Damage by Activating AMPK-Autophagy Signaling Pathway.","authors":"Qi Li, Zhenjiang Song, Liting Peng, Shuidong Feng, Kebin Zhan, Hongyan Ling","doi":"10.1055/a-2399-1174","DOIUrl":"10.1055/a-2399-1174","url":null,"abstract":"<p><strong>Introduction: </strong>In recent years, a growing number of clinical and biological studies have shown that patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing Parkinson's disease (PD). Prolonged exposure to hyperglycemia results in abnormal glucose metabolism, which in turn causes pathological changes similar to PD, leading to selective loss of dopaminergic neurons in the compact part of the substantia nigra. Dihydromyricetin (DHM) is a naturally occurring flavonoid with various biological activities including antioxidant and hepatoprotective properties. In this study, the effect of DHM on high glucose-induced dopaminergic neuronal damage was investigated.</p><p><strong>Methods: </strong>The potential modulatory effects of DHM on high glucose-induced dopaminergic neuronal damage and its mechanism were studied.</p><p><strong>Results: </strong>DHM ameliorated high glucose-induced dopaminergic neuronal damage and autophagy injury. Inhibition of autophagy by 3-methyladenine abrogated the beneficial effects of DHM on high glucose-induced dopaminergic neuronal damage. In addition, DHM increased levels of p-AMP-activated protein kinase (AMPK) and phosphorylated UNC51-like kinase 1. The AMPK inhibitor compound C eliminated DHM-induced autophagy and subsequently inhibited the ameliorative effects of DHM on high glucose-induced dopaminergic neuronal damage.</p><p><strong>Discussion: </strong>DHM ameliorates high glucose-induced dopaminergic neuronal damage by activating the AMPK-autophagy pathway.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"631-641"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy of Thyroid Hormone Replacement Therapy in Nasopharyngeal Carcinoma Patients with Radiation-Induced Subclinical Hypothyroidism.","authors":"Chen-Lu Lian, Gui-Ping Chen, Rui Zhou, Yi-Feng Yu, Ping Zhou, Qin Lin, San-Gang Wu","doi":"10.1055/a-2373-0030","DOIUrl":"10.1055/a-2373-0030","url":null,"abstract":"<p><strong>Aims: </strong>Hypothyroidism is a common side effect of radiotherapy for nasopharyngeal carcinoma. However, the impact of thyroid hormone replacement therapy on patients with radiation-induced subclinical hypothyroidism has not been extensively explored. This study aimed to analyze the efficacy of thyroid hormone replacement therapy in nasopharyngeal carcinoma patients with subclinical hypothyroidism.</p><p><strong>Methods: </strong>Patients diagnosed with nasopharyngeal carcinoma who developed subclinical hypothyroidism after definitive radiotherapy between September 2019 and December 2020 were selected for inclusion in this study. Prior to thyroid hormone replacement therapy and after maintaining euthyroidism for 6-12 months through thyroid hormone replacement therapy, assessments using the SF36 Brief Health Status Scale and the Hypothyroidism-related Symptom Questionnaire were conducted via trained questionnaires. Lipid profiles were assessed at baseline and after 6-12 months of thyroid hormone replacement therapy. Statistical analyses were performed using matched samples T-test or Mann-Whitney U test.</p><p><strong>Results: </strong>The median follow-up period was 14.5 months. The median score of hypothyroid symptoms was 5.5 out of 19 points, with the most common symptoms being chills (65.0%), fatigue (50.0%), weight gain (45.0%), and limb numbness (40.0%). Thyroid hormone replacement therapy did not significantly improve the quality of life, hypothyroidism-related symptoms, or blood lipid profile in patients. However, there was an observed downward trend in serum cholesterol levels following treatment (P=0.052).</p><p><strong>Conclusion: </strong>Thyroid hormone replacement therapy did not have a significant impact on alleviating hypothyroid symptoms, improving quality of life, or enhancing lipid profiles in patients with radiation-induced subclinical hypothyroidism. Nevertheless, a potential decrease in serum cholesterol levels was noted after thyroid hormone replacement therapy.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"614-621"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Eleftheriou, Aikaterini Rokou, Evangelia Nena, Nikolaos Papanas
{"title":"Diabetes Mellitus and its Association with Work Patterns and Characteristics: A Narrative Review.","authors":"Anna Eleftheriou, Aikaterini Rokou, Evangelia Nena, Nikolaos Papanas","doi":"10.1055/a-2384-6275","DOIUrl":"10.1055/a-2384-6275","url":null,"abstract":"<p><p>Diabetes mellitus is a leading cause of disability with adverse effects on the quality of life. It also affects occupational health by impacting several work-related parameters. This review discusses the relationship between diabetes and absenteeism, presenteeism, work impairment and unemployment. The association between work and diabetic complications such as neuropathic pain, diabetic foot, psychological issues and hypoglycemia due to treatment is also examined. Evidence points to a relationship between diabetes and absenteeism, reduced work productivity, and, thus, overall work impairment. A stronger negative impact on work performance is mediated by painful diabetic neuropathy and diabetic foot. In addition, psychological distress has been positively correlated with total workdays lost and frequency of absence. Depression in the diabetic population has also been linked with increased absenteeism, presenteeism, and work disability. Moreover, hypoglycaemia induced by antidiabetic medication may affect work attendance and performance. Finally, diabetes has been associated with inequality in the work environment, lower job satisfaction and higher unemployment rates, mainly because of its complications.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"642-649"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Schenaarts, Floris K Hendriks, Cas J Fuchs, Wendy Em Sluijsmans, Tim Snijders, Luc Jc van Loon
{"title":"A Single Sauna Session Does Not Improve Postprandial Blood Glucose Handling in Individuals with Type 2 Diabetes Mellitus: A Cross-Over, Randomized, Controlled Trial.","authors":"Laura Schenaarts, Floris K Hendriks, Cas J Fuchs, Wendy Em Sluijsmans, Tim Snijders, Luc Jc van Loon","doi":"10.1055/a-2406-4491","DOIUrl":"10.1055/a-2406-4491","url":null,"abstract":"<p><strong>Introduction: </strong>Passive heat treatment has been suggested to improve glycemic control in individuals with type 2 diabetes mellitus (T2DM). Previous studies have focused predominantly on hot water immersion and traditional sauna bathing, as opposed to the more novel method of infrared-based sauna bathing. Here, the impact of a single infrared sauna session on post-prandial glycemic control was assessed in older individuals with T2DM.</p><p><strong>Methods: </strong>In this randomized controlled crossover trial, 12 participants with T2DM (male/female: 10/2, age: 69±7 y, BMI: 27.5±2.9 kg/m<sup>2</sup>) rested in an infrared sauna twice: once in a heated (60°C) and once in a thermoneutral (21°C) condition for 40 min, immediately followed by a 2-h oral glucose tolerance test (OGTT). Venous blood samples were obtained to assess plasma glucose and insulin concentrations and to determine the whole-body composite insulin sensitivity index.</p><p><strong>Results: </strong>Body core and leg skin temperature were higher following the heated condition compared to the thermoneutral condition (38.0±0.3 vs. 36.6±0.2°C and 39.4±0.8 vs. 31.3±0.8°C, respectively; P<0.001 for both). The incremental area under the curve (iAUC) of plasma glucose concentrations during the OGTT was higher after the heated condition compared to the thermoneutral condition (17.7±3.1 vs. 14.8±2.8 mmol/L/120 min; P<0.001). No differences were observed in plasma insulin concentrations (heated: 380±194 vs. thermoneutral: 376±210 pmol/L/120 min; P=0.93) or whole-body composite insulin sensitivity indexes (4.5±2.8 vs. 4.5±2.1; P=0.67).</p><p><strong>Conclusions: </strong>A single infrared sauna session does not improve postprandial blood glucose handling in individuals with T2DM. Future studies should assess the effect of more prolonged application of infrared sauna bathing on daily glycemic control.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"622-630"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142116446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Bessiène, Chiara Villa, Xavier Bertagna, Bertrand Baussart, Guillaume Assié
{"title":"From Nelson's Syndrome to Corticotroph Tumor Progression Speed: An Update.","authors":"Laura Bessiène, Chiara Villa, Xavier Bertagna, Bertrand Baussart, Guillaume Assié","doi":"10.1055/a-2359-8649","DOIUrl":"10.1055/a-2359-8649","url":null,"abstract":"<p><p>Since the first description of Nelson syndrome 60 years ago, the way to consider corticotroph pituitary neuroendocrine tumors (PitNETs) after bilateral adrenalectomy has evolved. Today, it is globally acknowledged that only a subset of corticotroph PitNETs is aggressive.After adrenalectomy, corticotroph tumor progression (CTP) occurs in about 30 to 40% of patients during a median follow-up of 10 years. When CTP occurs, various CTP speeds (CTPS) can be observed. Using simple metrics in patients with CTP, CTPS was reported to vary from a few millimeters to up to 40 mm per year. Rapid CTPS/ Nelson's syndrome was associated with more severe Cushing's disease, higher adrenocorticotropic hormone (ACTH) in the year following adrenalectomy, and higher Ki67 on pituitary pathology. Complications such as apoplexy, cavernous syndrome, and visual defects were associated with higher CTPS. During follow-up, early morning ACTH, absolute variations properly reflected CTPS. Finally, CTPS was not higher after than before adrenalectomy, suggesting that cortisol deprivation after adrenalectomy does not impact CTPS in a majority of patients.Taken together, rapid CTPS/ Nelson's syndrome probably reflects the intrinsic aggressiveness of some corticotroph PitNETs. The precise molecular mechanisms related to corticotroph PitNET aggressiveness remain to be deciphered. Regular MRIs combined with intermediate morning ACTH measurements probably provide a reliable way to detect early and manage fast-growing tumors and, therefore, limit the complications.</p>","PeriodicalId":94001,"journal":{"name":"Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association","volume":" ","pages":"581-590"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}