Endocrine Connections最新文献

Introduction: Cardiovascular disease is the commonest cause of death in Turner syndrome (TS) for which, arterial hypertension has a direct influence and is a key modifiable risk factor.

Objective: To investigate the prevalence and patterns of hypertension diagnosis and management in adult patients with TS who are registered in a large international multicentre database (TS-HTN study).

Methods: Retrospective multi-centre observational study of patients aged ≥18 years, included in the I-TS (International-TS) registry (2020-2022) utilising registry and participating centre collected data.

Results: Twelve international centres participated, including 182 patients with the median age of 28 years (IQR 23,37.2). Arterial hypertension was recorded in 13.2% (n=24). The median age at hypertension diagnosis was 27 years (range 10,56), with 92% aged less than 50 years at the diagnosis. The majority (75%) were classified as primary hypertension (n=18). In binomial regression analysis, higher body-mass-index (BMI) was the only parameter significantly associated with the occurrence of hypertension (B=1.487, p=0.004). Among patients with aortic disease (n=9), 50% had Systolic BP ≥130 mmHg, and 66.6% had Diastolic BP ≥ 80 mmHg during the last clinic review. Angiotensin converting enzyme inhibitors (ACEi) were the commonest (n=16) medication prescribed, followed by Angiotensin receptor blockers (n=6), beta blockers (n=6), and calcium channel blockers (n=6).

Conclusions: Arterial hypertension is common in TS and occurs form a young age. Overweight/obesity was a notable risk factors for hypertension. The frequency of sub-optimal BP control among high-risk patients highlights the importance of increased awareness and TS-specific consensus guidance on management.

Background: Prostate cancer therapy with surgical or chemical castration with GnRH agonists has been linked to elevated FSH levels, which may contribute to secondary health disorders, including atherosclerosis and diabetes. Although recent findings suggest a role for FSH beyond the reproductive system, its metabolic impact remains unclear and difficult to disentangle from that of androgens. In this study, we examined the metabolic changes induced by FSH and distinguished them from those caused by testosterone.

Methods: Plasma samples from temporarily medically castrated young men (n=33) treated with FSH and/or testosterone were characterized by proteomics and metabolomics approaches. All subjects received GnRH antagonists. Sixteen men were randomized to recombinant FSH (rFSH, 300 IU 3 times/week) for 5 weeks, while seventeen men served as controls. After 3 weeks, all men received 1000 mg testosterone undecanoate intramuscular. Blood samples were collected at the start, after 3 weeks, and after 5 weeks. The proteome and metabolome signatures were characterized in all samples.

Results: FSH significantly upregulates key proteins involved in the modulation of inflammatory response and innate immune system (p≤0.03) and dysregulates lipid metabolism, evidenced by downregulation of multiple apolipoproteins (p≤0.04) and increased levels of cholesterol and glycerophospholipids (p≤0.03). Additionally, low FSH levels were correlated with a reduction in the active form of vitamin D (p<0.02). These results highlight the short-term metabolic impacts of FSH in males.

Conclusions and clinical implications: Our findings underlined the FSH effect on extra-gonadal systems and its connection to metabolic disorders often seen as secondary effects of prostate cancer treatment.

Metabolic syndrome (MetS) is associated with osteogenic transdifferentiation of vascular smooth muscle cells (VSMC) and accumulation of arterial calcifications (AC). Metformin (MET) inhibits this transdifferentiation in vitro. Here, we evaluate the in vivo efficacy of oral MET to reduce AC in a model of MetS. 20 young male Wistar rats were divided into 2 groups: one received water, the other water plus 20% fructose to induce MetS. After 14 days, and for another 4 weeks, MET (100 mg/kg/day) was added to half of each group's drinking source, thus: C (water), F (fructose), M (MET) and FM (fructose+MET). Serum and adipose tissue were collected. Aortas were dissected for histomorphometric and immunohistochemical analysis; ex vivo calcification studies; and to isolate VSMC to measure their alkaline phosphatase activity (ALP), collagen production, extracellular mineralization, gene expression of RUNX2 and RAGE (receptor for AGEs), and elastic fiber production. F group showed parameters compatible with MetS. Aortic tunica media from F showed decreased elastic-to-muscular ratio, increased collagen content and increased levels of the AGEs carboxymethyl-lysine. Aortic arches from F presented a tendency for higher ex vivo calcification. VSMC from F showed increased ALP, collagen secretion, mineralization and expression of RUNX2 and RAGE; and decreased elastic fiber production. All these effects were reverted by MET co-treatment (FM group). In vitro, AGEs-BSA upregulated RAGE expression of control VSMC, and this was prevented by MET in an AMPK-dependent manner. Thus, experimental MetS induces RAGE upregulation and osteogenic transdifferentiation of aortic VSMC, that is curbed by oral treatment with MET.

Objective: To evaluate whether a person-centered care practice following surgery for pituitary tumors increased psychological well-being. Secondary aims were to study whether person-centered care would lead to better health status, less fatigue, and better self-efficacy.

Design and methods: The study is a prospective, single center study using a quasi-experimental design to evaluate the effect of a 12-month person-centered practice by means of a name-given nurse care manager, an interdisciplinary team, and peer-support against usual care. All patients (≥ 18 years) with a benign pituitary tumor and planned for endoscopic transsphenoidal surgery were consecutively invited to participate. Psychological well-being, self-reported health, fatigue, and self-efficacy were assessed before surgery, at discharge, and at 3-6 and 12 months after surgery.

Results: In total, 82 patients in the intervention group and 66 patients in the control group were included. Psychological well-being improved 12 months following surgery in both groups to comparable levels. The intervention group had greater improvement in anxiety compared to the control group (P = 0.02). No differences were seen between groups in self-reported health status, fatigue, or self-efficacy. Patients in the intervention group with other types of pituitary tumors than non-functioning pituitary adenomas showed greater improvement in psychological well-being than the control group.

Conclusions: The intervention did not result in major advantages in terms of health or psychological well-being. The study does, however, suggest that the intervention may reduce anxiety 12 months after surgery and that certain subgroups of patients may benefit more from a structured person-centered practice following pituitary surgery.

Anti-Müllerian hormone (AMH), a biomarker secreted by Sertoli cells in the testes, has emerged as a critical indicator of male reproductive function with significant clinical application potential. AMH reflects Sertoli cell activity and plays a pivotal role across different stages of male gonadal function. Firstly, in prepubertal males, AMH levels are crucial for assessing testicular development and the progression of puberty, with delayed or insufficient AMH secretion often being associated with disorders like delayed puberty. Secondly, in reproductive-age males, AMH serves as an important biomarker for evaluating spermatogenic capacity, particularly in cases of idiopathic non-obstructive azoospermia. In these patients, AMH levels can help predict the success of testicular sperm extraction, thereby influencing fertility treatment strategies. This review explores the physiological mechanisms of AMH and its diagnostic and prognostic significance in both delayed puberty and fertility disorders in reproductive-age males. While AMH shows great promise in the management of hypogonadism, further research is needed to validate its clinical utility and refine treatment protocols for optimizing patient outcomes.

Objective: To assess whether individual diagnosis of low urinary iodine concentration (UIC) in pregnant women is associated with adverse maternal and neonatal outcomes.

Methods: Studies that compared pregnant women with UIC <150 μg/L and those with UIC 150-249 μg/L were systematically reviewed. MEDLINE, EMBASE, LILACS, and CENTRAL were our source databases. Selection of studies, risk of bias assessment, and data extraction were performed in pairs and independently. Relative risk (RR) with 95% confidence interval (CI) were calculated as an estimate of the effect of iodine <150 μg/L. Stata software was used to perform meta-analyses. The quality of evidence was determined according to the Grading of Recommendations Assessment, Development, and Evaluation.

Results: In total, 7,000 studies were identified, of which 63 were included. With low or very certainty of the evidence, no difference in the incidence of miscarriage (RR: 0.87, 95% CI: 0.64-1.18, 6 studies, 4,855 participants), maternal hypothyroidism (RR: 1.05, 95% CI: 0.68-1.60, 10 studies, 11,773 participants), preterm birth (RR: 1.20, 95% CI: 0.97-1.48, 13 studies, 15,644 participants), stillbirths (RR: 0.79, 95% CI: 0.34-1.82, 6 studies, 3,406 participants), low birth weight (RR: 1.25, 95% CI: 0.88-1.78, 10 studies, 10,775 participants), and small for gestational age (RR: 1.11, 95% CI: 0.90-1.37, 5 studies, 4,266 participants) was observed between the two groups.

Conclusion: In pregnant women, individual diagnosis of UIC <150 μg/L was not associated with adverse maternal and neonatal outcomes, emphasizing UIC concentration as a limited method to assess individual iodine status during pregnancy.

Background: Arterial hypertension and left ventricular hypertrophy and remodeling are independent cardiovascular risk factors in patients with Cushing's syndrome. Changes in the renin-angiotensin system and in the mineralocorticoid axis activity could be involved as potential mechanisms in their pathogenesis, in addition to cortisol excess.

Methods: In this ancillary study of our previous study prospectively investigating patients with ACTH-dependent Cushing's syndrome by cardiac magnetic resonance imaging (NCT02202902), 11 patients without any interfering medication were cross-sectionally compared to 20 control subjects matched for age, sex and body mass index. Angiotensin metabolites and adrenal steroids were measured by liquid chromatography tandem mass spectrometry and their relation to blood pressure and cardiac structure was evaluated.

Results: Concentrations of angiotensin I and angiotensin II were comparable, but the angiotensin-converting enzyme activity was significantly lower (2.19 (1.67;3.08) vs 4.07 (3.1;5.6); p<0.001) in patients compared to controls. Aldosterone concentrations were significantly lower (6.9 (6.9;124.1) vs 239.9 (181.4;321.9) pmol/l; p<0.001) in the group of patients, but adrenal aldosterone precursor metabolites were comparable between patients and controls. Inverse correlations were observed for 24h urinary free cortisol and aldosterone with the ratio of left ventricular mass to end-diastolic volume (r=0.470, p=0.012 and r= -0.367, p=0.046, respectively).

Conclusions: We describe a disease specific profile of angiotensin metabolites in patients with ACTH dependent Cushing's syndrome. Low levels of aldosterone in the presence of unchanged precursor metabolites indicate a direct inhibitory action of cortisol excess on the aldosterone synthase. Further, glucocorticoid excess per se drives cardiac muscle remodeling.

Subacute thyroiditis (SAT) is an inflammatory thyroid disease characterized by neck pain, tenderness, general symptoms, and thyroid dysfunction. Despite gaining new insights into the epidemiology, pathogenesis, and treatment of SAT in recent years, the exact pathogenesis and determinants of its clinical progression remain unclear. Here, we profiled thyroid in situ protein alterations in fine needle aspiration biopsy samples from SAT patients using proteomic analysis and uncovered 57 differentially abundant proteins. Gene Ontology and KEGG enrichment analyses identified that these proteins were enriched in processes involving infection, inflammatory response, and cell adhesion and junction, which likely contribute to the pathogenesis. Moreover, the top three high-abundance proteins (NNMT, FTL, and TYMP) were further validated in the plasma from a larger SAT cohort using an enzyme-linked immunosorbent assay. After adjusting for sex, Spearman correlation analysis showed that NNMT, FTL, and TYMP levels were positively correlated with FT3, FT4, T3, T4, Tg, and ESR and negatively correlated with TSH. Furthermore, binary logistic regression analyses revealed that NNMT, FTL, and TYMP were independent factors of SAT. We also conducted a receiver operating characteristic (ROC) curve analysis to assess the diagnostic accuracy of NNMT, FTL, and TYMP for SAT. The results revealed that each factor demonstrated an area under the curve (AUC) score above 0.8. Thus, these high-abundance proteins can potentially serve as biomarkers for SAT diagnosis and outcome prediction. Our findings provide valuable insights into SAT biomarkers, and shed light on the potential pathogenesis and therapeutic targets of SAT.

Objective: Hypercalcemia is often considered as an emergency because of a potential risk life-threatening arrhythmias or coma. However, there is little evidence, apart from case studies, that hypercalcemia can be immediately life-threatening. The aim of our study was to assess prospectively, if hypercalcemia (Ca ≥ 3 mmol/L) was associated with immediately life-threatening complications.

Design and methods: We conducted a prospective observational study aiming to include the first one hundred patients aged ≥ 18, who had a calcium concentration ≥ 3 mmol/L, admitted to the Emergency Department. The primary outcome was the number of life-threatening cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, sinus arrest and 2nd or 3rd degree atrioventricular blocks) or neurological complications defined by a Coma Glasgow Score < 9 during the stay on the ED. The secondary outcomes were correlation between calcium concentrations and ECG QTc intervals, Coma Glasgow Scores and mortality at 7 days and 12 months.

Results: Median calcium concentration was 3.3 mmol/L (3.1-3.7). Cancer was the first cause of hypercalcemia. No patient presented a life-threatening cardiac arrhythmia during stay on the ED. Three patients presented a life-threatening neurological complication. There was no correlation between calcemia and QTc intervals or Coma Glasgow Score. Prognosis was poor, 43 patients died during the 12 months.

Conclusions: We found no cases of immediately life-threatening cardiac arrhythmias. Three patients had indeed a life-threatening neurological complication but always had at least one other major factor which could severely alter mental status such as profound metabolic acidosis.

Objective: Androgen insensitivity syndrome (AIS) due to androgen receptor (AR) mutations creates a spectrum of clinical presentations based on residual AR function with the mildest impairment creating mild AIS (MAIS) whose undefined molecular mechanism and subtle clinical features leave it less understood and underdiagnosed.

Design: In silico modeling and in vitro androgen bioassay of the mutated AR are used to identify its structural and physiological mechanism. Clinical features and responses to high-dose testosterone treatment of three cases of MAIS across a six-generation family pedigree are described.

Methods: Structural and dynamic in silico molecular modeling and in vitro yeast-based androgen bioassays of the mutant AR are employed. Three cases of MAIS with consistent (gynecomastia and micropenis) and variable (infertility) clinical features across generations are reported, and the effects of high-dose testosterone treatment are studied.

Results: The missense AR exon 8 mutation (nucleotide aga → gga, p.R872G arginine to glycine), known to cause an increased ligand dissociation rate in mutant AR in binding assays, was analyzed. Modeling shows that the mutation weakens the closure energy of the 'lid' of the ligand-binding pocket, allowing easier ligand dissociation from the binding site but with unimpaired in vitro androgen bioactivity. High-dose testosterone treatment for 3 years in one young man caused increased virilization and height growth but was ineffective for treating micropenis. Genetic counseling allowed effective prediction of MAIS risks in progeny for carrier and noncarrier sisters.

Conclusions: The differential diagnosis and clinical management of MAIS is reviewed. The novel molecular mechanism of an AR ligand-binding domain mutation in MAIS may be present in other cases of MAIS.