ABSTRACTObjectiveTransgender 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.DesignRetrospective cross‐sectional audit of transgender and gender‐diverse adults at endocrine clinics in Melbourne, Australia.PatientsEighty‐one adults treated with estradiol 0.06% gel.MeasurementsOutcomes were estradiol 0.06% gel dose, serum estradiol concentration and proportion of individuals achieving target serum estradiol concentrations in consensus guidelines.ResultsMedian 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).ConclusionEstradiol 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.

ABSTRACTObjectivesWe 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.MethodsWe 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).ResultsOn 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.ConclusionsA 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.

ABSTRACTObjectiveThe 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.MethodsThis 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.ResultsIn 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.DiscussionOur 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.

ABSTRACTBackgroundDespite 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.DesignAnalysis of National Hospital Episode Statistics (HES) data set which contains details of all admissions and outpatient appointments at NHS hospitals in England.Methods and MeasurementsSpells 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.ResultsOver 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.ConclusionsAI 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.

ABSTRACTObjectiveLenvatinib, 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.MethodsThis 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.ResultsA 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).ConclusionsThe 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.

ABSTRACTObjectivePituitary 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/MeasurementsWe 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.ResultsFifty‐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.ConclusionsIndividuals 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.

ABSTRACTObjectiveThis review seeks to provide endocrine clinicians with a comprehensive analysis of breast cancer risk, diagnostic modalities and management strategies in women with endocrine disorders, with particular emphasis on the influence of metabolic factors such as diabetes and obesity, and the role of Menopausal Hormone Therapy (MHT).DesignThe review examines a spectrum of endocrine disorders commonly encountered in clinical practice, including Multiple Endocrine Neoplasia Types 1 (MEN1), 2 (MEN2) and 4 (MEN4), Von Hippel‐Lindau syndrome (VHL), Pheochromocytoma and Paraganglioma (PPGL), Acromegaly, Hyperprolactinaemia, Polycystic Ovary Syndrome (PCOS), Congenital Adrenal Hyperplasia (CAH), Turner Syndrome, alongside metabolic conditions such as diabetes and obesity and the effects of MHT. The review critically appraises each disorder's association with breast cancer risk, screening implications and therapeutic management.PatientsThis analysis focuses on women with the aforementioned endocrine and metabolic disorders, assessing their specific breast cancer risk profiles, informed by the latest clinical evidence and molecular insights.MeasurementsThe review comprehensively evaluates current evidence‐based approaches to screening, diagnostic accuracy and treatment in this patient cohort. Emphasis is placed on the metabolic derangements, hormonal influences and genetic predispositions that modulate breast cancer risk, providing disorder‐specific recommendations for individualised care.ResultsThe findings indicate a significantly elevated breast cancer risk in patients with MEN1, necessitating early initiation of MRI screening by age 40. In MEN2, emerging evidence suggests that combining RET inhibitors with endocrine therapy may yield clinical benefits, although further research is needed to validate this approach. The breast cancer risk associated with MEN4 and VHL syndromes, while documented, remains less well‐characterised, requiring further investigation. Diabetes and obesity are confirmed as major modifiable risk factors, particularly in postmenopausal women, where hyperinsulinemia and metabolic dysfunction contribute to increased incidence and poorer outcomes, notably in triple‐negative breast cancer (TNBC). The role of MHT, particularly combined oestrogen‐progestogen therapy, is strongly associated with increased breast cancer risk, particularly for hormone receptor‐positive malignancies, necessitating cautious use and personalised treatment planning. In contrast, oestrogen‐only MHT appears to confer a reduced risk in women post‐hysterectomy. For patients with PCOS, CAH and Turner Syndrome, while definitive evidence of elevated breast cancer risk is lacking, individualised screening strategies and careful hormone therapy management remain essential due to the complex interplay of hormonal and metabolic factors.ConclusionsThe review highlights the need for personalised breast cancer screening and management protocols in women with endocrine and metabolic disorders. For high‐risk groups such as MEN1 patients, early initiation of MRI screening is warranted. In women with diabetes and obesity, targeted interventions addressing hyperinsulinemia and metabolic dysfunction are critical to mitigating their increased cancer risk. The association between MHT and breast cancer underscores the importance of individualised risk stratification in hormone therapy administration, particularly in women with predisposing genetic or endocrine conditions. Enhanced surveillance tailored to the unique risk profiles of endocrine disorder patients will facilitate early detection and improve clinical outcomes. However, further large‐scale studies are necessary to refine these associations and develop robust, evidence‐based guidelines.

ABSTRACTObjectiveTo provide clinicians involved in managing menopause with a summary of current evidence surrounding menopause hormone therapy (MHT).DesignThe authors evaluate and synthesize existing pooled evidence relating to MHT's clinical indications, efficacy, and safety and explore the limitations of existing data.PatientsThe 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.MeasurementsAvailable 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.ResultsThe 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.ConclusionsThis 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.

ABSTRACTBackgroundPrimary 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.PurposeTo evaluate the effect of PTX on cardiovascular parameters, especially systolic dysfunction, in PHPT patients using conventional and speckle‐tracking echocardiography (STE).MethodsThis 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).ResultsThe 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.ConclusionThis 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.

ABSTRACTDespite a high burden of osteoporosis and minimal trauma fractures worldwide, there is still a treatment gap in timely diagnosis and optimal treatment. There is also a lack of international consensus and guidelines on the management of bone fragility in premenopausal women. This review article provides an overview of the current understanding of factors impacting women's bone health across the adult lifespan, as well as dilemmas in the diagnosis, assessment and management of osteoporosis in premenopausal and postmenopausal women, premature ovarian insufficiency and bone health following breast cancer.

ABSTRACTObjectivesThis study aimed to compare the clinical efficacy of dual‐time 68Ga‐pentixafor PET/CT with adrenal vein sampling (AVS) in PA lateralization.Methods and MethodsWe retrospectively analysed 161 patients with PA. We assessed the diagnostic performance of dual‐time 68Ga‐pentixafor PET/CT in diagnosing unilateral primary aldosteronism (UPA) and aldosterone‐producing adenoma (APA). We also explored the relationship between 68Ga‐pentixafor PET/CT findings, postoperative outcomes, and the presence of the KCNJ5 gene mutation.ResultsThe diagnostic accuracy of 68Ga‐pentixafor PET at 10 and 40 min for UPA (75.2% and 76.4%, respectively) surpassed that of CT (55.3%, p < 0.01). The optimal cutoff for diagnosing APA was 10 min lesion‐to‐normal adrenal ratio = 1.95, yielding an AUC of 91.9%, with sensitivity, specificity, and accuracy of 76.0%, 91.3%, and 83.3%, respectively. This high diagnostic efficacy extended to subgroups with nodules ≥ 1 or < 1 cm, and the largest AUC of 68Ga‐pentixafor PET/CT for diagnosis APA with lesions ≥ 1 and < 1 cm is 88.2% and 97.0%, respectively. The lateralization results provided by 68Ga‐pentixafor PET/CT corroborated the surgical treatment decision in 92.0% of PA patients, and more than 95% achieved clinical and/or biochemical cure or improvement. The PET positive rate of KCNJ5 mutation was higher than that of KCNJ5 wild‐type, with optimal diagnostic efficacy at 40 min lesion‐to‐liver ratio = 4.79 (AUC 81.3%, sensitivity 90.0%, specificity 66.7%).ConclusionDual‐time 68Ga‐pentixafor PET/CT exhibits robust diagnostic efficacy in PA lateralization. Furthermore, 68Ga‐pentixafor PET/CT holds promise as an imaging marker for predicting the presence of the KCNJ5 mutation in PA patients.

ABSTRACTBackgroundNeck ultrasound (US) and serum thyroglobulin (Tg) measurements are mainstays of long‐term differentiated thyroid cancer (DTC) surveillance. Given the high sensitivity of serum Tg, we aimed to assess the utility of neck US in DTC patients who underwent total thyroidectomy and have undetectable serum Tg.MethodsWe performed a retrospective cohort analysis of DTC patients who underwent a total thyroidectomy at our institution (2010–2023) and received US‐guided fine needle aspiration (FNA) during their surveillance. Patients were categorised into three lab categories based on serum Tg and Tg antibody (Tg Ab) status before the biopsy: (1) ‘Negative Tg' if undetectable Tg ( < 0.2 ng/dL) and Tg Ab, (2) 'Positive Tg' if detectable Tg and undetectable Tg Ab, and (3) 'Positive Tg Ab' if detectable Tg Ab. To calculate the positive predictive value (PPV) of neck US, we defined the 'true positive' of US as findings that prompted an FNA biopsy resulting with DTC, and 'false positive' findings prompting an FNA biopsy that did not result as DTC.ResultsA total of 118 patients were included, encompassing 146 FNA biopsies: 33 (23%) had Negative Tg, 84 (57%) had Positive Tg, and 29 (20%) had Positive Tg Ab lab results before their biopsies. The PPV of neck US in the setting of Negative Tg was 3% (one true positive, 32 false positives), while the PPV was 50% (42 true positives, 42 false positives) for Positive Tg, and 52% (15 true positives, 14 false positives) for Positive Tg Ab cohorts. Sub‐analysis of the Positive Tg cohort using different serum Tg level cutoffs revealed a PPV of 29% at just detectable serum Tg of 0.2 ng/dL, and PPV of 38% for Tg < 1.0 ng/dL. The PPV stabilised at 58% for Tg levels ≥ 1 ng/dL.ConclusionWith the low PPV of neck US, high cost of surveillance, and the advent of ultra‐sensitive serum Tg measurements, future guidelines should consider reducing routine neck US surveillance in patients with undetectable serum Tg and only performing it when there is a rise in serum Tg levels.

ABSTRACTObjectivesThe relationship between iodine status and gestational diabetes mellitus (GDM) is inconclusive. This study aimed to explore the trajectories of urinary iodine concentrations (UIC) in pregnant women before GDM diagnosis and to assess the associations between maternal UIC trajectories and the risk of developing GDM.MethodsA prospective cohort study was conducted in China. Data from 1076 pregnant women who were recruited between August 2019 and December 2021 were analyzed. GDM screening was performed at the 28th week of pregnancy. Arsenic and cerium catalysis spectrophotometry was used to measure UIC. The latent class model was used to identify distinct UIC trajectories in pregnant women, using multiple urine specimens. We evaluated the association of UIC trajectories with the risk of GDM by logistic regression analysis.ResultsThree maternal UIC trajectories were identified: (1) high‐stable trajectory (72.12%), (2) high‐decreasing trajectory (3.07%), and (3) low‐stable trajectory (24.81%). Compared with the pregnant women in high‐stable trajectory group, women in the low‐stable UIC trajectory group showed an increased risk of GDM before adjustment of covariates (OR: 1.58, 95% CI: 1.08–2.27). After adjusting for different covariates, a statistically significant association was observed only between low‐stable trajectory trajectories and GDM.ConclusionsThis study highlights a relationship between UIC and the risk of GDM. To better prevent iodine deficiency and GDM, persistent sufficient iodine status from pregnancy to delivery, should be emphasized.

ABSTRACTObjectiveTransition is important for continuity of care for patients with chronic health conditions. The aim of this service evaluation was to determine the effectiveness of a transition clinic at a tertiary hospital with long‐term attendance in the adult endocrine service.DesignRetrospective case notes review of patients seen by paediatric endocrinology at the Royal Hospital for Children, Glasgow, at the time of transition to adult services, between 2012 and 2022. Patients with type 1 diabetes were excluded.MeasurementsEngagement was measured through clinic attendance and dropout rate. The ‘dropped out patients’ were those who were seen in the transition clinic with a transition plan but did not attend appointments in the adult service.ResultsOf the 267 individuals offered a transition clinic, data on discharge status were available for 248 (94%). Of these, 52% (n = 129) remained in the same tertiary centre, 29% (n = 61) were transferred to other endocrine centres in the West of Scotland; 17% (n = 42) were discharged to primary care. Overall, 91% (172/190) of young patients remained engaged with the adult service. Male patients had a higher drop out rate compared to females (14% vs. 4%, p < 0.05). Those from more deprived areas also had higher drop out rates compared to those from more affluent areas (17% vs. 3%, p < 0.05).ConclusionOur clinic model for transitioning from paediatric to adult endocrine care is effective in introducing and retaining patients to the adult service with only a 9% drop out rate. Factors associated with poor attendance in adult services include deprivation and being male. Additional support may be required for these individuals to improve engagement in adult services.

ABSTRACTObjectivesThe ideal model of care for individuals with Differences of Sex Development (DSD) continues to evolve, with multiple models proposed. This study aimed to explore current care models for individuals with DSD in Australia and New Zealand (NZ) and to identify clinician perceptions of gaps and barriers in current practice.MethodsCross‐sectional anonymous online questionnaire, conducted via Research Electronic Data Capture (REDCap) software. Clinicians involved in the diagnosis and management of individuals with DSD in Australia and NZ were contacted through multimodal recruitment approaches. Themes included demographics of respondents, preferred terminology, composition of the DSD multidisciplinary team (MDT) and availability of a database.ResultsSeventy‐nine eligible participants from centers in all states and territories of Australia and NZ commenced the survey with 63 complete responses. Almost One‐third (31%) of participants are not currently part of a DSD MDT meeting at their center. While three quarters (76%) of respondents identified changes to DSD care over the past 5 years, three quarters (75%) also identified barriers to current care provision. Only 20% of respondents reported psychology being a current part of their MDT and 70% identified psychology as a desired but missing part of their team.ConclusionsResponses to the survey identify gaps and barriers to DSD care across Australia and NZ, particularly a lack of psychosocial supports. Current models fall short of international recommendations and services need to explore the reasons for these gaps further.

ABSTRACTObjectiveThe risk of aortic dissection is increased in Turner Syndrome (TS). Aortic dilation is thought to contribute to this risk and may be managed with elective aortic surgery. New TS guidance has lowered the aortic size thresholds for consideration of aortic surgery. We investigated the impact of new guidance on potential heart team referrals in a UK cohort of TS individuals.MethodsA cross‐sectional study of 156 individuals with TS was performed. Up to date transthoracic echocardiography or cardiac MRI derived aortic dimensions, anthropometric data and the presence of aortic dissection risk factors were analysed.ResultsTwenty‐one individuals (13%) met updated guideline criteria for consideration of aortic surgery, 15 more than met 2016 TS guideline criteria. Use of aortic size index (ASI) and aortic height index (AHI) together identified additional individuals meeting criteria for surgical consideration compared with the use of ASI or AHI alone. Z‐score identified no additional individuals for surgical consideration, nor did it reclassify any individuals into moderate or severe aortic dilation groups. Twelve of 13 individuals with moderate aortic dilation met criteria for surgical consideration due to the presence of additional risk factors for aortic dissection. There was no positive correlation between height or body surface area and ascending aorta diameter in this cohort.ConclusionsNew TS guidelines are likely to significantly increase the number of individuals with TS who might be considered for elective aortic surgery. Centres caring for individuals with TS should re‐evaluate their TS cohorts for aortic dissection risk considering these new guidelines.

ABSTRACTBackgroundKlinefelter syndrome (KS) is an uncommonly recognised condition typified by gynaecomastia, small testes and aspermatogenesis. It is caused by a supernumerary X chromosome, resulting in a 47 XXY karyotype. Since its first description, the phenotype of KS has evolved and there is a much greater appreciation of the subtle features of the condition.MethodIn this review, we explore the phenotype of the KS with particular consideration to patients with pre‐natal and early infancy diagnosis, given that this is becoming increasingly common. The current understanding of the genetic mechanisms of KS, caused by supernumerary X chromosome are explored and the genotype‐phenotype correlation are discussed.ResultsThe implications of the condition both in childhood and later development are explored in detail, with particular focus on social and educational implications. Potential treatments, with emphasis on preservation of fertility are discussed. We highlight the optimal therapeutic conditions in which fertility preservation is most likely to be achieved, compared to those which can be more challenging. Finally, we discuss the other health challenges which can be associated with KS. These include poor bone health, diabetes, cardiovascular complications, and malignancy. The challenges in managing these co‐morbid conditions and most up‐to‐date management recommendations are also explored.

ABSTRACTObjectiveThis study aimed to evaluate the long‐term effects of hormone therapies on the body composition, adipokines and metabolic parameters of adult men with congenital hypogonadotropic hypogonadism (CHH).MethodsSixty‐six patients with CHH and 21 healthy controls were recruited. Patients were divided into untreated (n = 33) and treated (n = 33) groups based on hormone therapy history. Body composition was assessed using dual‐energy X‐ray absorptiometry (DXA), and adipokines and metabolic parameters were measured in all participants.ResultsCompared to the healthy control group, patients in the treated group had lower serum testosterone levels (p < 0.001), increased body fat percentage (BFP) and visceral adipose tissue (VAT) volume, decreased lean soft tissue (LST) and bone mineral content (BMC) (p < 0.05), increased serum leptin levels accompanied by decreased adiponectin (ADP) (p < 0.05), higher HOMA‐IR with lower QUICKI (p < 0.05). Compared to the untreated group, patients in the treated group (therapy duration 4.8 ± 2.3 years) had higher serum testosterone levels (p < 0.001), decreased BFP and VAT volume, increased LST and BMC (p < 0.05), decreased serum leptin levels (p < 0.001), and decreased HOMA‐IR accompanied by increased QUICKI (p < 0.05). Among them, VAT volume, LST, BMC, HOMA‐IR and QUICKI reached healthy control levels (p > 0.05). Multiple stepwise linear regression analysis showed serum testosterone levels were negatively correlated with BFP (β = −0.564, p < 0.001) and VAT volume (β = −0.260, p = 0.045), positively correlated with LST (β = 0.305, p = 0.018) and BMC (β = 0.423, p = 0.001). Serum testosterone levels were independently negatively correlated with leptin levels (β = −0.277, p = 0.004).ConclusionsPatients with untreated CHH had impaired body composition, adipokines and metabolic parameters. While hormone therapies can improve body composition and glucolipid metabolism in patients with CHH, this imperfect treatment does not fully rescue body composition abnormalities when compared to healthy individuals. Abnormal metabolic parameters in patients with CHH are associated with increased fat mass and abnormal serum leptin level. Serum testosterone levels were independently negatively correlated with leptin levels.

ABSTRACTObjectiveGhrelin is emerging as a promising therapeutic option for heart failure (HF) due to its potent inotropic, anabolic, and cardioprotective properties. This review aims to critically examine the available clinical evidence on ghrelin therapy in HF, while also incorporating key findings from preclinical studies that support its therapeutic potential.MethodsA comprehensive search was conducted in PubMed and the Cochrane Library up to September 15, 2024, using the keywords “heart failure” and “ghrelin.” From 247 identified records, four randomized controlled trials, one open‐label trial, one observational study, and key preclinical studies were included. Two independent authors performed the screening and quality assessment, with any discrepancies resolved through consensus.ResultsClinical trials investigating ghrelin's acute effects in HF patients have demonstrated significant improvements in cardiac output, ranging from 15% to 30%. Moreover, one study showed that a 3‐week course of ghrelin therapy significantly increased maximal oxygen consumption, lean body mass, and grip strength in HF patients. Preclinical studies further support these clinical findings, highlighting additional benefits of ghrelin, including modulation of the autonomic nervous system, promotion of vasodilation, enhancement of endothelial function, prevention of myocardial remodeling, reduction of arrhythmogenic risk, and increased muscle mass in HF models.ConclusionsGhrelin is a promising therapeutic option for HF, particularly as an inotropic agent with multifaceted benefits, including autonomic nervous system modulation, anabolic effects, and metabolic regulation. However, further trials are required to confirm its long‐term efficacy and safety and assess whether its benefits can translate into reductions in hard clinical endpoints.

ABSTRACTBackgroundThe International Medullary Thyroid Carcinoma Grading System (IMTCGS) was recently introduced in medullary thyroid carcinoma (MTC). This study aimed to assess the predictive value of the IMTCGS for disease response and survival, and compare its predictive ability with that of other traditional risk factors in a Chinese MTC cohort.MethodsThe data of 137 MTC patients undergoing initial surgery between January 2004 and June 2023 were included for analysis. Histologic features were reviewed by two pathologists. Kaplan‐Meier survival analysis and Cox proportional hazard model were performed to analyse the association between risk factors (including IMTCGS high vs low grade) and progression‐free survival (PFS) and disease‐specific survival (DSS). ROC analysis and Delong's test were used to compare the predictive ability of IMTCGS with that of other risk factors.ResultsLocal recurrence, distant metastasis, and disease‐specific death were observed in 14/134 (10.45%), 3/134 (2.24%), and 6/137 (4.38%) MTC patients, respectively. IMTCGS, TNM stage, postoperative calcitonin, postoperative CEA, and vascular invasion were associated with PFS in Kaplan‐Meier survival analysis (all p < 0.05). Postoperative calcitonin was the only independent predictor for PFS in multivariate analysis (HR = 1.002, p = 0.002). ROC analysis and Delong's test showed that postoperative calcitonin had superior predictive value for structural recurrence than IMTCGS (AUC 0.90 vs. 0.64, p = 0.002). IMTCGS, TNM stage, and vascular invasion were associated with DSS in Kaplan−Meier survival analysis (both p < 0.05). In multivariate analysis, IMTCGS was the only independent predictor for DSS (HR = 11.23, p = 0.05). The AUC of IMTCGS was 0.81 (p = 0.01) for disease‐specific death.ConclusionIn this Chinese MTC cohort, IMTCGS was a powerful predictor of disease‐specific death, while postoperative calcitonin was a powerful predictor of structural recurrence.