Clinical Endocrinology最新文献

Objective: Transgender and gender-diverse individuals undergoing estradiol therapy for gender affirmation are typically treated with oral or transdermal estradiol, with transdermal estradiol recommended for those aged > 45 years. There are limited data evaluating estradiol gel in gender-affirming hormone therapy regimens. We aimed to assess the serum estradiol concentrations achieved with estradiol 0.06% gel in transgender and gender-diverse adults.

Design: Retrospective cross-sectional audit of transgender and gender-diverse adults at endocrine clinics in Melbourne, Australia.

Patients: Eighty-one adults treated with estradiol 0.06% gel.

Measurements: Outcomes were estradiol 0.06% gel dose, serum estradiol concentration and proportion of individuals achieving target serum estradiol concentrations in consensus guidelines.

Results: Median serum estradiol concentration was 396 pmol/L (233-681) on 1.5 mg (1.5-2.25) estradiol 0.06% gel daily. Forty-six percent of individuals achieved serum estradiol concentrations within target range (250-600 pmol/L) of Australian consensus guidelines; 27% were below range and 27% were above range. There was a weak positive correlation between estradiol gel dose and serum estradiol concentration (r = 0.23, p = 0.04).

Conclusion: Estradiol 0.06% gel achieves target serum estradiol concentrations in a significant proportion of transgender and gender-diverse adults. This represents an alternative estradiol formulation for individuals desiring estradiol therapy for gender affirmation.

Objectives: We aimed to study the daily variation in first-morning urinary total luteinizing hormone (U-LH) determination and validate it as a noninvasive method for analyzing age- and pubertal stage-related changes in LH immunoreactivity (LH-ir) levels to predict imminent onset of central puberty.

Methods: We determined three consecutive first-morning total U-LH along with spot serum LH and follicle-stimulating hormone concentrations in 354 children (160 boys aged 2.8-17.8 yr and 194 girls aged 2.6-18.0 yr) with known pubertal stages. The samples were analyzed using an immunofluorometric assay (Delfia, PerkinElmer, Finland). The net day-to-day variation (net CV%) in U-LH-ir levels was calculated by subtracting the inter-assay CV% of the assay reported by the manufacturer from the gross inter-assay CV% calculated from three consecutive samples. U-LH-ir levels were classified as prepubertal (< 0.60 IU/L), highly likely pubertal (0.60-0.99 IU/L), and pubertal (≥ 1.00 IU/L).

Results: On average, the gross and net inter-assay CV% values for different U-LH concentrations measured on three consecutive mornings were 37.6% and 32.7%, respectively. Despite this level of day-to-day variation, only 3.6% of the test results for boys and 4.9% for girls were inconsistent in classifying total U-LH-ir levels as prepubertal, peripubertal, or pubertal. Our results showed that the activation of the hypothalamo-pituitary-gonadal hormone axis, which signals the onset of puberty, occurs at a similar age in both boys and girls, confirming our earlier findings that the timing of this process is independent of sex. Further, our findings confirmed that the onset of pubertal gonadotropin secretion in boys occurs already at a testicular volume of 1 to 2 mL, well before clear clinical signs of puberty.

Conclusions: A single first-morning total U-LH measurement appears to be a valid clinical test for classifying children or adolescents into prepubertal, peripubertal, and pubertal groups. This study validates the recently reported finding that the timing of central puberty onset is sex-independent. The duration between the initial activation of gonadotropin secretion and the first clinical signs of puberty was longer in boys than in girls.

Objective: The relationship between biochemical premature adrenarche (PA) in girls and metabolic alterations during puberty it is well described. A part of these circulating androgens undergoes aromatization in peripheral tissues to estrogens. This raises the question whether the metabolic effects are due to the action of androgens or estrogens. Our aim was to assess whether levels of urinary estrogens are associated with metabolic risk at late stages of puberty in girls with and without PA.

Methods: This prospective observational study included 321 girls from the Growth and Obesity Chilean Cohort Study (GOCS). Anthropometric and biochemical variables included in metabolic syndrome score (MetS) were measured along with urinary estrogens at Tanner stage B4, 1-year (M1) and 4-years after menarche (M4). Relationships between urinary estrogens and metabolic syndrome were analyzed during these periods. Furthermore, we analyzed whether metabolic disturbances in patients with biochemical PA (based on DHEA-S levels at age ~7) were mediated by androgens or estrogens.

Results: In multilevel analysis urinary estrone correlated positively with anthropometric variables (BMI, WC and fat percentage) and MetS score in adolescent girls. In contrast, urinary estradiol was not associated with metabolic risk. Interestingly, urinary estrogens were not associated with metabolic score in patients with biochemical PA.

Discussion: Our investigation suggests that metabolic risk in patients without biochemical PA are mostly associated with estrone levels. In contrast, in patients with biochemical PA, androgens are associated with MetS. Therefore, metabolic disturbances throughout puberty might be generated by different pathways in girls with and without biochemical PA.

Objective: Lenvatinib, a tyrosine kinase inhibitor, is approved for the treatment of radioiodine refractory differentiated thyroid cancer (RR-DTC) at a dose of 24 mg/day. Given its significant toxicity profile, the present study aimed to compare the safety and efficacy of initial low-dose lenvatinib to that of higher starting doses in patients with RR-DTC.

Methods: This retrospective study included patients with RR-DTC who were classified as: Group-A: patients receiving 10mg/day, and Group-B: patients receiving ≥ 14mg/day of lenvatinib as starting dose. Safety, radiological response (as per RECIST 1.1) and progression-free survival (PFS) outcomes were analysed and compared.

Results: A total of 105 patients with RR-DTC were included in this study (Group-A: 60, Group-B: 45). The study found that Group-B experienced significantly higher rates of drug interruptions (68.9% vs 48.3%, p = 0.035) and dose reductions (60% vs 11.7%; p < 0.001) compared to Group-A. Adverse events such as hand-foot skin reaction (77.8% vs 58.3%), diarrhea (28.9% vs 11.7%), hepatotoxicity (33.3-40% vs 11.7-18.3%), and electrolyte imbalance (15.6% vs 3.3%) were also more frequent in Group-B (p-values < 0.05). However, both groups showed similar objective response rates (47.1% vs 46.3%; p = 0.936) and comparable PFS outcomes (restricted mean survival time at 24 months: 22.8 vs 21.4 months, p = 0.128).

Conclusions: The study suggests that starting with lower doses of lenvatinib, followed by dose escalation if tolerated, may offer a safer approach with significantly lower rates of drug interruptions and dose reductions, with comparable efficacy in RR-DTC patients. Further validation by larger prospective trials is warranted.

Objective: Pituitary hormone deficiencies are associated with considerable morbidity, yet the variability of presentation and evolution of congenital hypopituitarism remains unexplored. This study investigated differences in presentation of congenital isolated pituitary hormone deficiency (cIPHD) versus congenital multiple pituitary hormone deficiency (cMPHD) and the progression of cIPHD to multiple deficiencies.

Design/patients/measurements: We conducted a single centre retrospective chart review of children ≤ 3 years old with abnormal brain/pituitary imaging and ≥ 1 pituitary hormone deficiency. cIPHD was defined as 1 hormone deficiency diagnosed within 1 month of endocrine consultation; cMPHD was ≥ 2 deficiencies. Data were summarised by descriptive statistics; Wilcoxon tests (continuous variables) and chi-square or Fisher's exact tests (categorical variables) were used for comparisons with significance at p < 0.05.

Results: Fifty-six individuals were identified; 46.4% presented with cIPHD and 53.6% with cMPHD. Those with cIPHD were older at initial endocrine consultation (median 62.5 days [IQR 7.3-240.8]) vs. those with cMPHD (10.0 days [6.3-26.5], p = 0.02). Reason for consultation (e.g., abnormal imaging or hypoglycemia) was associated with presentation as cIPHD or cMPHD (p = 0.01). The most common cIPHD at presentation was AVP deficiency (34.6%); the most common cMPHD at presentation was combined ACTH and TSH deficiencies (43.3%). Most individuals with cIPHD (65.4%) progressed to multiple hormone deficiencies by 3 years of age.

Conclusions: Individuals with cMPHD were more likely to be identified earlier and present with hypoglycemia than those with cIPHD. As the majority with cIPHD evolved to cMPHD, close monitoring is necessary to facilitate timely detection and treatment of evolving hormone deficiencies.

Background: Despite steroid replacement therapy, patients with adrenal insufficiency (AI) experience excessive infections and related hospital admissions. However, data examining the evolution of admissions, healthcare resources utilisation and cost burden is sparce.

Design: Analysis of National Hospital Episode Statistics (HES) data set which contains details of all admissions and outpatient appointments at NHS hospitals in England.

Methods and measurements: Spells spanning financial years 2018/19 to 2022/23, focusing on HES codes E27.1 (Primary Adrenocortical Insufficiency; PAI) [n = 57,125], E27.2 (Addisonian Crisis; AC) [n = 12,640] and E27.4 (Other and Unspecified AI; UAI) [n = 79,965] were analysed for admissions, main diagnosis, bed-days, costs, follow-up, and readmissions.

Results: Over the study period, admissions for AC remained stable; admissions involving UAI increased, whereas PAI admissions reduced transiently during COVID-19. Mean length of stay for AC increased from 5.1 to 6.8 days (34%). Patients with primary pneumonia and AI had longer hospital stays than those without AI and were more likely to require critical care. Mean cost per hospital stay increased, rising 25% for AC since 2019/20, reaching £2959 per stay. 10% of patients had >1 non-elective readmission within 12 months. Endocrinologist follow-up was lower than expected. Centres treating > 225 spells/year reviewed 20-46% of AI patients within 26 weeks of admission, and only 46% with a main diagnosis of AC in 2022/23.

Conclusions: AI admissions have increased since 2018/19. Bed-days and cost for AC episodes have also risen. Patients with concomitant AI were more likely to have longer stays and be re-admitted. Endocrinology follow-up appears surprisingly low despite published guidelines.

Objective: To provide clinicians involved in managing menopause with a summary of current evidence surrounding menopause hormone therapy (MHT).

Design: The authors evaluate and synthesize existing pooled evidence relating to MHT's clinical indications, efficacy, and safety and explore the limitations of existing data.

Patients: The review focuses on MHT-related outcomes in women with natural-timed menopause captured within observational studies, RCTs, and pooled data from pivotal meta-analyses and reviews.

Measurements: Available published data are scrutinized. Available evidence and notably lacking data from women not adequately represented in published MHT trials, such as those with socioeconomic adversity, significant comorbidities, and minority ethnic backgrounds, are highlighted and deliberated.

Results: The impact of MHT differs significantly between demographics. Current consensus recommendations for MHT emphasize the importance of tailoring type, route, dose, and duration of therapy to individual needs and risk/benefit ratio through shared decision-making. MHT impact can change over time. Current MHT data support its benefits for treating menopause symptoms and a potential window of opportunity in midlife to benefit skeletal health. Limitations of current evidence highlight menopause health inequalities and underscores the need for further research.

Conclusions: This review recommends tailored use of MHT for well-defined indications, recognizing its value for menopause symptom relief and skeletal benefits for many midlife women. MHT may be used as long as benefits outweigh risks, through shared decision-making. There is insufficient clinical evidence to support the long-term use of MHT in some contemporary cohorts of women accessing MHT in clinical practice.

Background: Primary hyperparathyroidism (PHPT) is associated with hypertension, left ventricular hypertrophy, and myocardial and valvular calcifications, leading to increased mortality rates. While the association between PHPT and diastolic dysfunction has been well-documented, data on systolic dysfunction and its reversal after curative parathyroidectomy (PTX) remains limited.

Purpose: To evaluate the effect of PTX on cardiovascular parameters, especially systolic dysfunction, in PHPT patients using conventional and speckle-tracking echocardiography (STE).

Methods: This prospective study was conducted at a tertiary care hospital from August 2016 to September 2019; 59 patients underwent successful PTX based on standard criteria, with 58 completing the study. Preoperative and 6-month postoperative biochemical and cardiovascular evaluations, including echocardiography, were performed. Global longitudinal strain (GLS) was assessed using speckle-tracking echocardiography (STE).

Results: The mean age of subjects was 45.2 ± 10.4 years with a male-to-female ratio of 1.5:1. Normalization of serum calcium and phosphorus with significant reductions in serum intact PTH, alkaline phosphate, total cholesterol, HDL, and uric acid levels (p ≤ 0.0001) were seen after curative PTX. Echocardiographic evaluations significantly improved diastolic parameters, including E velocity (cm/s) and E/A(atrial) ratio. Systolic dysfunction also showed significant improvement on conventional echocardiography and STE, as evidenced by reduced left ventricular (LV) mass, ejection fraction (EF), and postoperative GLS. Although a relative drop in EF was noted postprocedure, STE findings suggested a significant improvement in systolic dysfunction, signifying GLS as a more appropriate means of assessing systolic dysfunction. Serum PTH demonstrated a strong positive correlation (r = 0.638, p < 0.001) with changes in GLS, while serum calcium showed a weak correlation (r = 0.291, p = 0.027) with changes in GLS following surgery.

Conclusion: This study demonstrates significant improvements in diastolic and systolic functions, as evidenced by conventional echocardiography and STE, and suggests that PTX benefits cardiovascular health in PHPT patients.