Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association最新文献

Endogenous Cushing's syndrome (CS) is a rare disease characterized by a glucocorticoid excess. If inadequately treated, hypercortisolism can lead to increased morbidity and mortality. Surgical removal of the underlying tumor is the first-line treatment but is sometimes not feasible or even contraindicated. Additionally, in cases with severe CS, rapid control of hypercortisolism may be required. In these scenarios, steroidogenesis inhibitors represent a therapeutic alternative to surgery. Over the last years, the knowledge of the broad therapeutic effects of steroidogenesis inhibitors per se and the number of available drugs have increased. However, large comparative studies are still lacking. Accordingly, the decision on which drug to be used in a certain patient or clinical setting may be difficult. This review aims to summarize the main characteristics of steroidogenesis inhibitors.

The genetic landscape of corticotroph tumours of the pituitary gland has dramatically changed over the last 10 years. Somatic changes in the USP8 gene account for the most common genetic defect in corticotrophinomas, especially in females, while variants in TP53 or ATRX are associated with a subset of aggressive tumours. Germline defects have also been identified in patients with Cushing's disease: some are well-established (MEN1, CDKN1B, DICER1), while others are rare and could represent coincidences. In this review, we summarise the current knowledge on the genetic drivers of corticotroph tumorigenesis, their molecular consequences, and their impact on the clinical presentation and prognosis.

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: KDM1A inactivation by germline heterozygous pathogenic variants is constantly associated with a loss-of-heterozygosity of the short arm of chromosome 1, containing the KDM1A locus. This causes biallelic inactivation of KDM1A, resulting in the GIPR overexpression in the adrenal cortex. These new insights allow us to propose the KDM1A 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 KDM1A variant carriers. Given that KDM1A 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.

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.

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.

Objective: 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).

Methods: 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.

Results: 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).

Conclusion: 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.

Introduction: 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.

Methods: The potential modulatory effects of DHM on high glucose-induced dopaminergic neuronal damage and its mechanism were studied.

Results: 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.

Discussion: DHM ameliorates high glucose-induced dopaminergic neuronal damage by activating the AMPK-autophagy pathway.

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.

Aims: 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.

Methods: 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.

Results: 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).

Conclusion: 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.