Clinical Endocrinology最新文献

Objective: Low testosterone is common in men with type 2 diabetes and is associated with adverse metabolic outcomes. Our objective was to identify factors associated with low total and calculated free testosterone (CFT) in men with type 2 diabetes, with a focus on relative estrogen excess and subcutaneous adipose aromatase expression.

Design: Cross-sectional study.

Patients: One hundred eighty men with type 2 diabetes and 92 healthy men in the reference cohort.

Measurements: Sex steroid hormones were measured alongside body composition, metabolic biomarkers, adipose tissue aromatase gene expression, and genetic variants of aromatase. T-scores for testosterone and estradiol were calculated using a healthy reference cohort.

Results: HbA1c (p < 0.001), BMI (p = 0.007), leptin (p = 0.009) and insulin resistance (p = 0.026) were associated with lower total testosterone (<10 nM). Lower CFT (<220pM) was associated with age (p = 0.049), BMI (p < 0.001), interleukin-6 (p < 0.001), leptin (p = 0.003) and insulin (p = 0.020). Men with type 2 diabetes and low testosterone had relative estrogen excess (Estradiol T score-Testosterone T score 1.63 [0.94, 2.76]) compared to healthy controls (0.06 [-0.74, 0.51], p < 0.001). A common CYP19A1 variant was associated with increased adipose CYP19A1 expression (p = 0.044) and low CFT (p = 0.042). Multivariable analysis identified BMI (p < 0.001), CYP19A1 expression (p = 0.020) and HbA1c (p = 0.006) as independently associated with CFT.

Conclusion: In men with type 2 diabetes, low testosterone is associated with adiposity, glycaemic control, and increased adipose aromatase expression. Relative estrogen excess may contribute to hypothalamic-pituitary-testicular axis suppression and represents a novel target for diagnostic and therapeutic strategies.

Objective: Patients living with pituitary neuroendocrine tumours (PitNETs) present with a spectrum of clinical manifestations and often follow a circuitous route to diagnosis, resulting in diagnostic delays. The objective of this study is to identify and report the various sources of referrals for patients who underwent pituitary resection for PitNETs in a tertiary referral centre for pituitary disease.

Design: Retrospective population-based cohort study.

Patients: Patients undergoing a first surgery for management of PitNET in Northern Ireland between 01/01/2000-19/07/2019.

Measurements: Demographics, referral sources, incidentaloma rates, apoplexy rates, symptoms, age at diagnosis and diagnostic delay according to referral source.

Results: Data were retrospectively analysed for 520 patients in whom the referral source leading to diagnosis was known. Fifty-seven percent of patients were male. Median age at diagnosis was 54 years (range 18-85). Patients were referred from 29 different sources. The majority of referrals came from general practice (23%), ophthalmology (14%), emergency medicine (9%), optician/optometry (9%) and internists (8%). Twenty-nine patients were referred following radiological discovery of an incidentaloma. Twenty-seven patients were referred with an initial presentation of pituitary apoplexy, with emergency medicine accounting for 70% of these referrals. Visual disturbance and headache were the most frequently documented symptoms. Median diagnostic delay was 2 years (range 0-25 years).

Conclusions: Patients with PitNETs encounter a range of clinical services in their journey to pituitary surgery. Raising awareness of these tumours and educating healthcare professionals across all disciplines could reduce diagnostic delays, thereby minimising the adverse sequelae of delayed diagnosis.

Background: Hyperprolactinaemia has been linked to adverse metabolic profiles, but the metabolic consequences of prolactin (PRL) normalisation remain insufficiently characterised.

Objective: To evaluate changes in anthropometric, blood pressure, and metabolic parameters following PRL normalisation, with analyses stratified by sex and age.

Methods: We retrospectively analysed 445 patients (286 women, 159 men) treated with cabergoline who had paired clinical and biochemical measurements before and after PRL normalisation. Pre-post differences were assessed overall and stratified by sex and age (< 50 vs. ≥ 50 years). Additional multivariable models examined independent predictors of metabolic changes.

Results: Men exhibited more severe baseline disease, including higher PRL levels, greater prevalence of macroadenomas, hypopituitarism, and cardiometabolic comorbidities. After PRL normalisation, body weight, BMI, and blood pressure showed no clinically relevant changes. Small but statistically significant reductions were observed in total cholesterol (185 → 181 mg/dL; p < 0.001), LDL-C (110 → 106 mg/dL; p = 0.038), and triglycerides (91 → 82 mg/dL; p < 0.001). These lipid changes, however, were not independently explained by sex, age, PRL dynamics, cabergoline exposure, or gonadal status in multivariable analyses. Fasting glucose and HDL-C remained largely unchanged. By contrast, the TyG index decreased significantly across sexes and age groups, and multivariable modelling identified higher initial cabergoline dose and baseline hypogonadism as independent determinants of greater TyG reduction.

Conclusions: PRL normalisation with cabergoline was associated with modest improvements in conventional lipid fractions and a more consistent reduction in the TyG index, suggesting a preferential impact on insulin-resistance-related pathways. The absence of independent effects of sex, age, PRL dynamics, or cabergoline exposure on lipid changes underscores the need for cautious interpretation of statistically significant but small absolute shifts.

Objective: Advances in oncological and haematological treatments have markedly improved childhood survival, yet gonadotoxic therapies often compromise testicular function. Testicular tissue extraction (TTE) with cryopreservation is increasingly offered to prepubertal boys at high risk of infertility; however, data on long-term endocrine and fertility outcomes remain limited. This study evaluated the long-term endocrine and exocrine testicular function of males who underwent TTE prior to gonadotoxic therapy.

Design and patients: This was a retrospective, observational, single-centre study including 50 males treated between 2009 and 2022 at Lille University Hospital (median age at TTE: 5.6 years; median age at last follow-up: 14.6 years). Underlying conditions comprised malignant haematological disorders (52%), non-malignant diseases (34%), and solid tumours (14%); 80% underwent allogeneic haematopoietic stem cell transplantation.

Measurements: Serial clinical assessments and biochemical markers of Leydig and Sertoli cell function (LH, FSH, testosterone, inhibin B, AMH) were recorded from puberty onset to young adulthood. Data were stratified by treatment intensity, pubertal timing, and disease type. Post-pubertal semen analysis was performed in consenting individuals.

Results: All participants experienced spontaneous pubertal onset. Sertoli cell dysfunction, evidenced by elevated FSH and persistently low inhibin B, was detectable early in puberty and persisted into adulthood. At Tanner stage 5, 18% had elevated LH, 75% elevated FSH, and 89% low inhibin B; comparable rates were observed in adulthood. Radiotherapy was associated with higher gonadotropin levels at equivalent chemotherapy doses, and Sertoli cell impairment was more pronounced in malignant disease and peri-pubertal treatment. Among 12 semen analyses, spermatozoa were detected in 42%, all in non-malignant cases without radiotherapy.

Conclusions: Males undergoing TTE prior to gonadotoxic therapy frequently develop persistent Sertoli cell dysfunction, with limited fertility potential in many cases. These findings underscore the importance of systematic, long-term andrological surveillance and personalised fertility counselling in this high-risk population.

Objective: Time-restricted eating (TRE) represents a novel intervention that may improve hyperinsulinaemia and reduce weight, but has not been studied in polycystic ovarian syndrome (PCOS). In a randomised interventional study (NCT05126199 [1]), we investigated the feasibility of TRE in PCOS including recruitment, compliance, safety, drop-out rate, and effect on insulin-related parameters, anthropometrics, nutritional intake and metabolic indices.

Methods: Participants were randomised to a 12-week TRE regimen (18 h fast/6 h eating window) or 'ad libitum' regimen (no time-restriction), and then crossed over to the alternative regimen for a further 12 weeks.

Results: TRE was a feasible intervention with near-total compliance in those completing the intervention; however, there were considerable difficulties with recruitment. A total of 70 were eligible to participate, of which ultimately 15 were recruited, and 11 completed the study (4 [27%] drop-outs due to commitment/study duration). There were no serious adverse events in the TRE group. Compliance [%(SD)] with TRE was 94.7(4.5)%, and 10 participants were keen to continue the intervention post-study. Whilst the study was not powered to detect changes in metabolic or anthropometric indices, exploratory analysis showed a decrease in HbA1c (p = 0.04), weight (p = 0.001), BMI (p = 0.001), hip circumference (p = 0.05) and waist circumference (p = 0.001) in the TRE group compared to the ad libitum eating group.

Conclusion: In a 12-week cross-over feasibility study, TRE was a safe and feasible intervention. Recruitment was challenging and with limited numbers, the TRE group showed a decrease in HbA1c and anthropometric indices compared to the 'ad libitum' group.

Trial registration: NCT05126199.

Objective: To identify pre-treatment determinants of hypothyroidism and decision regret (DR) following radioiodine (RAI) therapy in Graves' disease (GD), and to assess their longitudinal impact on health-related quality of life (QoL).

Methods: Prospective cohort of 500 GD patients receiving RAI. Machine learning models predicted hypothyroidism (3/6 months) and high DR using clinical indices, socio-economic factors, and ThyPRO-39 QoL scores. Longitudinal QoL was assessed at baseline, 3 and 6 months.

Results: Unmarried (p < 0.001), unemployed (35.50 ± 23.15 vs. 27.01 ± 6.95; p = 0.032), and higher income patients (> 5000 CNY/month: 29.67 ± 6.94 vs. 26.10 ± 7.95; p = 0.018) had significantly higher DR. Longer pre-RAI medication (> 12 months: 30.31 ± 15.96 vs. 27.48 ± 10.42; p = 0.015) increased regret. Hypothyroidism models showed poor discrimination (AUC ≤ 0.59). DR prediction was robust (LR AUC = 0.81), driven by pre-treatment stress (β = 1.32, p < 0.001) and anxiety (β = 0.98, p = 0.003). QoL improved in goitre (p < 0.001) and hypermetabolic symptoms (p < 0.001) at 3 months, while overall QoL (p < 0.001) and depression (p = 0.006) improved by 6 months. Cognitive deficits persisted beyond 3 months (p > 0.05).

Conclusion: Non-clinical factors (marital/employment/income status) and psychological states strongly predict post-RAI regret. Hypothyroidism remains unpredictable, but high DR risk can be accurately identified (AUC = 0.81) for targeted intervention. Persistent cognitive impairment requires clinical attention despite biochemical normalisation.

Background: Radioiodine therapy (RIT) is an effective treatment for Graves' disease (GD). However, some patients experience transient exacerbation of thyrotoxicosis in the mid-to-late-phase period (2 weeks to several months post-RIT), and its risk factors are poorly understood. This study aimed to investigate the clinical predictors of mid-to-late-phase transient exacerbation of thyrotoxicosis following RIT.

Methods: We conducted a retrospective cohort study involving 200 Japanese patients with GD who received RIT at a single university hospital. Patients were categorized according to the clinical course as follows: no exacerbation, transient exacerbation or persistent exacerbation, likely due to residual or worsening GD. An exacerbation was defined as an increase of ≥ 1.0 pg/mL in free triiodothyronine (FT3) or ≥ 1.0 ng/dL in free thyroxine. Multivariable logistic regression, guided by the Akaike Information Criterion, was used to identify risk factors.

Results: Transient thyrotoxicosis was observed in 62 patients (31.0%). Multivariate logistic regression identified a higher ¹³¹I dose as a significant independent risk factor (odds ratio [OR] = 1.338, 95% confidence interval [CI] = 1.048-1.710, p = 0.020). Although not statistically significant, high pre-RIT FT3 levels and potassium iodide (KI) administration were identified as relevant predictors in the model.

Conclusions: A higher ¹³¹I dose was an independent risk factor for mid-to-late-phase transient thyrotoxicosis after RIT. Higher pre-RIT FT3 levels and KI use may contribute to this risk. Identifying patients with these factors may be helpful for closer post-RIT monitoring to prevent complications and avoid misdiagnosing this transient event as a treatment failure.

We report additional evidence supporting growth hormone (GH) therapy in 5q35 duplication syndrome based on a patient case. A recent publication described a positive GH response in patients with NSD1-containing 5q35 duplications. Our case shows a similar favorable outcome, reinforcing previous findings in this ultra-rare disorder, for which clinical trials are not feasible due to low patient numbers. Well-documented individual cases remain valuable for guiding families, clinicians, and healthcare providers in treatment decisions.

Introduction: Whereas hypergonadotropic hypogonadism is incriminated for poor bone mass in adults with Turner syndrome (TS), studies are limited on bone mass acquisition in pubertal girls with this condition. In previous studies reporting low bone mass in pubertal girls with TS, the bone-mineral-density (BMD) was not adjusted for height, a major determinant of BMD in this group. The present study was designed to address this knowledge gap by looking at the effect of height-adjustment on BMD in pre-pubertal girls with TS.

Materials and methods: Eighty pre-pubertal girls with TS aged 12-18 years who did not receive GH or pubertal induction before the study, and 85 age-matched controls underwent BMD assessment by dual-energy X-ray absorptiometry (DXA) followed by stature corrections as per ISCD official positions. Bone turnover markers, P1NP (formation) and beta-CTX (resorption) were also assessed.

Results: TS patients had lower BMD both at lumbar spine (0.763 ± 0.116 gm/cm² vs. 0.938 ± 0.153 gm/cm², p < 0.001), total-body-less-head (0.696 ± 0.087 gm/cm2 vs. 0.761 ± 0.187 gm/cm2, p = 0.002) and non-dominant distal radius (0.592 ± 0.063 gm/cm² vs. 0.690 ± 0.081 gm/cm², = 0.006) compared to healthy controls. However, the differences disappeared at all sites following adjustment of the BMD values for stature using the bone mineral apparent density (BMAD) (0.275 ± 0.032 gm/cm³ vs. 0.286 ± 0.047 gm/cm³, p = 0.357) and height adjusted Z scores (-0.9 ± 1.3 vs. -1.5 ± 3.9, p = 0.496). The lower beta-CTX values in TS indicated reduced bone resorption. (0.81 ± 0.37 ng/mL vs. 1.05 ± 0.59 ng/mL, p = 0.036).

Conclusion: When adjusted for stature, bone mineral density in Turner Syndrome is not different from that of healthy girls of the same age.