Clinical Endocrinology最新文献

Context: Sheehan's syndrome (SS) is a rare cause of hypopituitarism. Data on skeletal health in patients with this condition is limited and predictors of low bone mineral density (BMD) are not well elucidated. We aimed to explore hormonal profile and BMD in a large multicentric cohort of treated SS patients.

Design and patients: The study recruited patients with SS on stable hormone replacement (n = 110) and healthy female controls (n = 102). The hormonal profile (cortisol, DHEAS, T4, TSH, prolactin, IGF1) was analyzed. Bone turnover markers (P1NP, β-CTX) were estimated by electrochemiluminescence assay. BMD was evaluated using DXA. Prevalence and predictors of low BMD were assessed.

Results: The cohort comprised 110 patients with SS with a mean age of 45.3 ± 10.5 years and a delay of 7.9 ± 6.3 years from disease onset to diagnosis. Patients were on glucocorticoid (94.6%) and levothyroxine (90.5%) replacement, with prior exposure to estrogen-progestin (66.7%). Bone turnover markers were not significantly different between the two groups. Low BMD (osteopenia/osteoporosis) was prevalent in a significantly greater proportion of the cases as compared to controls at the lumbar spine (94% vs 47%) and femoral neck (80% vs 36%). The most important predictor of low BMD at the lumbar spine was the length of delay prior to diagnosis (OR 1.48 (95% CI 1.002-2.206), p = 0.04).

Conclusion: SS is characterized by a high prevalence of multiple pituitary hormone deficiencies, including hypoprolactinaemia. Low BMD is highly prevalent in SS compared to age, and BMI-matched controls. Despite adequate relevant hormone replacement therapy, a longer delay in diagnosing is the major determinant of low BMD in patients with SS.

Objective: Virilizing ovarian tumors (VOT) are rare in the paediatric population. The literature regarding their clinical spectrum, hormonal profile, imaging characteristics, histology, and outcomes is limited. Here, we perform a systematic review on the characteristics of paediatric VOT.

Design and methods: A systematic review was conducted in accordance with PRISMA guidelines. Databases including PubMed and Google Scholar were searched to identify English-language reports of paediatric (< 20 years) VOT with biochemical evidence of hyperandrogenemia and histological confirmation of an ovarian neoplasm. Data on demographics, clinical features, hormone profiles, imaging, tumor histology, management and outcomes were extracted and analysed.

Results: A total of 117 paediatric patients (median age: 15 years) with VOT were included. The most common symptoms were hirsutism (73.5%), clitoromegaly (68.4%), menstrual irregularity (n = 79), and voice change (60.7%). Children < 8 years had shorter diagnostic latency with less frequent hyperandrogenic manifestations. Baseline 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosteroe sulfate (DHEAS) were elevated in 70% and 18.3% of patients, respectively. Median tumor size was 6.6 cm, whereas tumors were bilateral in eight patients. Juvenile granulosa cell tumors and Sertoli-Leydig cell tumors were most common in the < 8 years and > 13 years groups, respectively. Recurrence was rare over a median follow-up of 1 year.

Conclusion: Hyperandrogenic manifestations are less frequent in children < 8 years with VOT. Elevated 17-OHP and/or DHEAS should not exclude the possibility of VOT. Etiological spectrum of paediatric VOT is relatively age-specific. Larger multicenter studies with longer follow-up are warranted to better delineate prognosis and management strategies.

Objective: Polycystic ovary syndrome (PCOS) is associated with an increased risk of cerebrovascular disease, but the effects on cerebrovascular function are unknown. In this pilot study, we sought to compare cerebrovascular perfusion, pulsatility, reactivity and metabolism between women with PCOS and healthy volunteers using MRI, and investigated the influence of testosterone and insulin resistance on these parameters.

Design: Case-control pilot study.

Patients: Fifteen patients with PCOS (age: 32.0 ± 7.4 years; body mass index [BMI]: 31.8 ± 5.7 kg/m²) and 12 healthy controls (HC) (age: 30.7 ± 6.4 years; BMI: 30.2 ± 5.8 kg/m²).

Measurements: We used 3T magnetic resonance imaging (MRI) to assess several aspects of cerebrovascular function: (1) perfusion (cerebral blood flow [CBF] and arterial arrival time [AAT]; PCOS N = 15; HC N = 12), (2) pulsatility index (PCOS N = 15; HC N = 12), (3) breath-hold induced cerebrovascular reactivity (CVR; PCOS N = 15; HC N = 10), and (4) global oxygen metabolism (oxygen extraction fraction [OEF] and cerebral metabolic rate of oxygen [CMRO₂]; PCOS N = 9; HC N = 8). Linear regression models investigated the contribution of PCOS status, serum testosterone and Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR). Regional analysis underwent false discovery rate (FDR) correction for multiple comparisons.

Results: Overall baseline CBF was not statistically different in PCOS patients compared to controls after adjustment for other variables (χ²(1) = 3.29; p = 0.07) but did show evidence for regional reduction with PCOS status in the transverse temporal gyrus (χ²(84) = 110.31; p = 0.03; -29.05 mL/100 g/min ± 7.26 [standard error; SE]). Similarly, while PCOS status was not associated with overall CVR (χ²(1) = 0.78; p = 0.38), there was evidence of a regional interaction (χ²(84) = 154.25; p < 0.001) in the parahippocampus (1.37% signal change ± 0.27 [SE]) and pericalcarine cortex (1.04% signal change ± 0.26 [SE]). Neither testosterone nor HOMA2-IR was associated with any outcome measure.

Conclusions: We observed regional reduction in cerebral blood flow and regional increase in cerebrovascular reactivity in women with PCOS compared to healthy controls. However, due to the limited statistical power and unclear menstrual timing in this pilot study, these results require further replication.

Purpose: To analyze the dexamethasone bioavailability in the 1mg-dexamethasone suppression test (DST) in patients with adrenal incidentalomas (AIs) to assess the reliability of the DST for the diagnosis of mild autonomous cortisol secretion (MACS).

Methods: A prospective cross-sectional study of 140 consecutive patients with AIs who underwent simultaneous testing of serum dexamethasone and cortisol levels after the DST. MACS diagnosis was based on a DST value > 1.8 µg/dL in absence of specific clinical data of Cushing's syndrome, and nonfunctioning adrenal incidentaloma (NFAIs) diagnosis was established when cortisol post-DST was ≤ 1.8 µg/dL and no evidence of other adrenal hormonal hypersecretion. Serum dexamethasone was measured with liquid chromatography coupled to mass spectrometry (LC-MS/MS).

Results: We enrolled 89 patients with MACS and 51 patients with NFAIs. Patients with MACS had higher late-nigh salivary cortisol and cortisol post-DST levels and lower DHEAS and ACTH values than NFAIs. In addition, they were older, had a higher prevalence of hypertension, diabetes and bilateral and larger adrenal tumors than NFAIs. Considering the 3.3 nmol/L serum dexamethasone threshold, we found that only 3.6% (n = 5) of the patients who underwent DST did not achieve proper serum dexamethasone levels during the DST. A weak positive correlation between age and serum dexamethasone levels (r = 0.191, p = 0.024) was observed. In addition, patients with MACS, hypertension and dyslipidemia reached higher serum dexamethasone levels after DST than those without these comorbidities.

Conclusion: Up to 4% of the patients with MACS diagnosis based on a DST > 1.8 µg/dl do not achieve enough dexamethasone levels to suppress the hypothalamic pituitary adrenal axis, suggesting that the positive results in the DST were not related with autonomous cortisol secretion.

Background: Fibromyalgia (FM) is a chronic pain syndrome increasingly linked to immune and endocrine dysfunction. This study aimed to evaluate the prevalence of endocrine comorbidities in FM patients compared to matched controls using a large healthcare database.

Methods: A population-based case-control study was conducted using data from Leumit Health Services, Israel. The cohort included 9,232 adults diagnosed with FM according to ACR criteria, matched by age and sex to 46,160 control subjects. Endocrine disorders were identified via ICD-9 codes. Statistical analyses included Student's t-test or Mann-Whitney U test for continuous variables, Pearson's chi-squared or Fisher's exact test for categorical variables, and multivariable logistic regression adjusting for age, sex, and BMI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Both statistical significance and effect sizes are reported to facilitate assessment of clinical relevance.

Results: FM patients showed a significantly higher prevalence of endocrine comorbidities compared to controls. Thyroid disorders, including Hashimoto's thyroiditis (13.3% vs. 10.0%; OR = 1.38, p < 0.001) and Graves' disease (4.1% vs. 3.0%; OR = 1.38, p < 0.001), were more common. Diabetes mellitus type 1 (0.9% vs. 0.3%; OR = 3.64, p < 0.001) and type 2 (23.5% vs. 18.6%; OR = 1.34, p < 0.001), adrenal disorders such as Cushing's syndrome (OR = 5.01, p < 0.001), prolactinoma (OR = 1.81, p = 0.014), osteoporosis (19.1% vs. 11.6%; OR = 1.80, p < 0.001), and vitamin D deficiency (39.9% vs. 30.3%; OR = 1.53, p < 0.001) were also significantly associated. Less common conditions (e.g., thyroiditis subtypes and thyroid malignancy) also appeared more frequent among FM patients, though effect sizes varied and some associations did not reach robust significance.

Conclusion: This is among the largest datasets to date to systematically examine a comprehensive spectrum of endocrine comorbidities in FM. Our findings suggest that FM and endocrine disorders may share overlapping pathophysiological mechanisms. Future studies should clarify causal pathways and assess the clinical utility of routine endocrine screening in FM patients.

Context: Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is widely used in malignancy diagnosis and surveillance. However, benign conditions also increase avidity. Distinguishing between benign and pathological uptake is critical. Rising PET-CT utilisation has led to increased detection of incidental pituitary FDG uptake. Referral pathways and secondary imaging remain inconsistent, and no UK guidelines exist. This study aims to review our current practice and assess the potential role of SUVmax to differentiate physiological from pathological uptake in the pituitary gland.

Design: A retrospective single-centre cohort study was conducted at a UK tertiary hospital.

Patients: Among 15824 PET-CT scans between 01/01/2017-30/06/2024, 70 patients (mean age 72.1 ± 1.3 years, 25.7% female) were included.

Measurements: Demographics, primary pathology, oncological treatment, SUVmax on initial PET-CT, secondary imaging findings, endocrine referral, and pituitary biochemistry were collected.

Results: 48 patients (68.6%) underwent secondary imaging; 70.8% (n = 34) were normal. Pathological findings included macroadenomas (n = 6), microadenomas (n = 3), and other lesions (n = 5). Mean SUVmax was significantly higher in patients with pituitary pathology (pituitary adenomas- 20.62 ± 4.82; all pathology- 16.74 ± 3.80) versus normal imaging- 4.66 ± 0.26 (p < 0.001). A SUVmax threshold of 4.75 yielded 100% sensitivity and 53.9% specificity for detecting pituitary pathology (ROC curve; 95% CI: 69%-100%).

Conclusions: Our review highlights significant variation in referral patterns for secondary imaging and to the Endocrine department. We suggest potential use of SUVmax threshold to distinguish physiological from pathological pituitary FDG uptake. Further validation in larger cohorts is warranted before routine clinical application.