Hormone Replacement Research Articles

Integrated immune, hormonal, and transcriptomic profiling reveals sex-specific dysregulation in long COVID patients with ME/CFS.

The brain is among the most critical target organs for thyroid hormones. Therefore, both congenital and acquired hypothyroidism can have significant neuropsychiatric consequences. Learning and memory problems, concentration disorders, and some psychiatric disorders such as depression can be observed in diseases causing acquired hypothyroidism. Although thyroid hormone therapy is the standard treatment, it does not always fully reverse these neuropsychiatric complications. Several studies have demonstrated the positive effects of magnesium L-threonate (MgT) supplementation on cognitive functions. Research suggests that MgT may help alleviate cognitive deficits, particularly in neurodegenerative conditions like Alzheimer's disease, where it has been associated with improvements in memory and reductions in hippocampal amyloid-β accumulation. However, there is limited data on the effect of MgT supplementation on hypothyroid conditions in the brain. The purpose of this study was to evaluate the effects of MgT supplementation on cognitive functions in hypothyroid rats. We report that while MgT supplementation did not significantly improve cognitive performance in behavioral tasks or inflammatory markers in hypothyroid rats, it did increase hippocampal BDNF levels in euthyroid animals and reduced hippocampal amyloid-β load under both euthyroid and hypothyroid conditions. The reduction in amyloid beta load under hypothyroid conditions suggests that MgT may exert partial therapeutic effects even in the absence of thyroid hormone replacement. These findings highlight the need for further studies to evaluate the therapeutic potential of MgT, particularly in combination with thyroid hormone replacement.

Additional progesterone administration during the luteal phase enhances reproductive outcomes in Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) cycles in patients with low serum progesterone (P4). In this study we wanted to explore the use of urine P4 as a diagnostic tool during the luteal phase. This prospective observational cohort included a total of 464 HRT-FET cycles. The protocol entailed oral oestradiol (6 mg/24 h), followed by vaginal micronised progesterone (400 mg/12 h). On the day of blastocyst transfer, urine and serum samples were collected. Urine samples were analysed using an ARCHITECT automated immunoassay. A significant difference was found in median urine P4 between patients with serum P4 higher or lower than 11 ng/mL: 6400 ng/mL IQR [2528; 11,930] vs. 3408 ng/mL IQR [592; 6688], p < 0.001. The optimal cut-off to achieve live birth was a urine P4 ≥ 4000 ng/mL. The live birth rate was significantly higher in patients with urine P4 ≥ 4000 ng/mL, 48% (107/222) vs. 35% (45/130), respectively (p = 0.013). The odds ratio for live birth was 1.8 in patients with urine P4 ≥ 4000 ng/mL, 95% CI [1.067; 3.018], p = 0.028. The findings of the present study suggest that urine progesterone could be a valuable diagnostic tool to evaluate the need for additional progesterone in HRT-FET cycles.

Menopause often triggers a variety of physiological and psychological discomforts such as hot flashes, anxiety, insomnia, and mood swings, significantly impacting women's quality of life. Many women seek natural alternatives to hormone replacement therapy, leading to increased interest in aromatherapy and essential oils as complementary treatments. This study aimed to analyze and synthesize scientific evidence regarding the effectiveness of aromatherapy and essential oils in alleviating menopausal symptoms. Using a literature review method, this study systematically reviewed studies published between 2000 and 2025 through databases including PubMed, ScienceDirect, Scopus, and Google Scholar. The results revealed that essential oils, particularly lavender, clary sage, peppermint, and geranium, show significant potential in improving emotional stability, sleep quality, and vasomotor regulation. Thematic content analysis demonstrated that aromatherapy influences mood and hormonal balance through neurochemical and physiological mechanisms related to the limbic system and endocrine function. Despite variations in methodology, the findings consistently support aromatherapy as a safe, non-invasive, and effective complementary therapy for menopausal women. This study contributes to holistic healthcare by strengthening the integration of evidence-based aromatherapy into women's health strategies while emphasizing the need for further standardized, long-term clinical trials.

Introduction: Immune checkpoint inhibitor (ICI) induced hypothyroidism is a common immune related adverse event during cancer immunotherapy, but the association with cardiovascular (CV) risk is unknown. Methods: All patients receiving ICI therapy for solid organ malignancy from 2015-2023 at a single academic center were identified (n~6000), and an algorithm designed to detect ICI-associated thyroid dysfunction (ICI-TD) was developed using thyroid stimulating hormone labs and thyroid hormone replacement medications. Sensitivity and specificity were assessed using clinician diagnosis as the gold standard. Cancer types and CV events were identified using ICD codes. Chi-Squared was used where appropriate, and univariate logistic regression was used to assess the likelihood of each CV outcome, with results visualized on a forest plot. Kaplan-Meier curves were generated to illustrate the time to onset of cardiac events in ICI-TD and Non-ICI-TD populations. Results: The algorithm (Figure 1A) was found to have a sensitivity of 92% and a specificity of 93% to detection of ICI-TD. Among patients receiving ICI therapy with normal thyroid function prior to their first dose of ICI therapy (Baseline Population; n=4720), ICI-TD was observed in 795 (16.8%) patients with significant variation across cancer types (p<0.001). Compared against those without ICI-TD (n=3925), coronary artery disease (CAD) (9.75% vs 5.36%, p<0.001) and arrhythmias (8.78% vs 6.51%, p=0.03) were associated with ICI-TD (Figure 1B). Heart failure, acute coronary syndrome, myocarditis, and pericarditis were not associated with ICI-TD. There were no significant differences in the time to onset of arrhythmias (p=0.22) or CAD (p=0.21) between patients with ICI-TD and those without (Figures 1C and 1D). Conclusion(s): An algorithm can detect ICI-TD with high sensitivity and specificity. ICI-TD is associated with long term risk of CAD and arrhythmia, highlighting a high-risk group that may benefit from increased CV monitoring and risk modification.

Introduction: Artificial intelligence–enhanced electrocardiography (AI-ECG) models can accurately predict sex, and sex misclassification is associated with adverse cardiovascular (CV) outcomes and more male-like cardiac (e.g. greater left ventricular mass and chamber volumes) and non-cardiac phenotypes (e.g. higher muscle mass, lower body fat) in women. However, the underlying factors contributing to sex discordance besides traditional CV risk factors—such as sex-specific CV risk factors—remain unexplored. Objective: To evaluate whether elevated AI-ECG sex-discordance scores are associated with sex-specific risk factors in women, while accounting for social determinants of health (SDoH). Methods: In the community-based ELSA-Brasil cohort baseline (2008-2010), we evaluated whether sex-discordance scores in women—measured by an AI-ECG model—were associated with female-specific CV risk factors: early menarche (≤11 years), menopause status, non-spontaneous menopause, multiparity, infertility, polycystic ovary syndrome, hormone replacement therapy >60 years or >10 years post-menopause, menstrual cycle length, history of abortion, hormonal contraceptives, history of eclampsia, and pregnancy weight gain >30 kg. The sex-discordant score (absolute difference between AI-predicted and self-reported sex, with 0=men, 1=women) was treated as a continuous variable. Associations were tested using multivariable robust linear regression with an M-estimator at 95% efficiency, adjusted for age, race, education, and per capita income. Results: Among 13,730 participants (mean age=52 years,SD:9.1; 54% women; 45% Black), higher sex-discordance scores were significantly associated with menopause (β = 0.092; 95%CI: 0.025–0.159), hormone and chemotherapy induced menopause (β = 0.215; 95%CI: 0.007–0.423), and multiparity (≥4 live births) (β = 0.169; 95%CI: 0.086–0.252), history of eclampsia (β = 0.157; 95%CI: 0.052–0.260), pregnancy-related weight gain >30 kg (β = 0.234; 95% CI: 0.117–0.352), early menarche (β = 0.154; 95% CI: 0.073–0.235), and use of hormonal contraceptives (β = 0.104; 95%CI: 0.002–0.207). All associations remained significant after adjustment for SDoH (Table 1). Conclusions: Higher AI-ECG sex-discordance scores are associated with multiple female-specific CV risk factors. These findings suggest that the score may serve as a novel biomarker for identifying women at increased CV risk.

Background: Hormone replacement therapy (HRT) is commonly prescribed to alleviate menopausal symptoms, but its cardiovascular safety—especially its impact on arrhythmias and acute heart failure hospitalizations—remains debated. This study primarily evaluated the association of HRT use with arrhythmia risk, and secondarily with acute heart failure hospitalizations, in menopausal women. Methods: This retrospective study utilized TriNetX, a federated health research network including data from 91 healthcare organizations across the U.S. Two cohorts were defined: menopausal women with HRT use and those without HRT. Propensity score matching (1:1) was performed on age and sex to balance baseline characteristics. Outcomes assessed included atrial fibrillation (AF), atrial flutter, ventricular tachycardia (VTach), supraventricular tachycardia (SVT), and acute heart failure hospitalizations, evaluated up to 3 years after cohort entry. Statistical analyses included risk differences, odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs). A p-value <0.05 was considered significant. Results: After matching, 172,086 patients (86,043 per group) were analyzed. HRT use was associated with significantly higher risks of AF (risk difference 0.018, 95% CI [0.016, 0.019], HR 2.74, 95% CI [2.55, 2.95]), atrial flutter (risk difference 0.002, 95% CI [0.001, 0.002], HR 2.79, 95% CI [2.16, 3.60]), VTach (risk difference 0.004, 95% CI [0.003, 0.004], HR 2.04, 95% CI [1.79, 2.32]), and SVT (risk difference 0.014, 95% CI [0.013, 0.016], HR 2.33, 95% CI [2.17, 2.51]), all p<0.001. Additionally, HRT use was associated with a higher risk of acute heart failure hospitalization (risk difference 0.003, 95% CI [0.003, 0.004], HR 2.19, 95% CI [1.90, 2.54], p<0.001). Survival probabilities at the end of follow-up were consistently lower in the HRT group across all outcomes. Conclusions: In this large, propensity-matched cohort study, HRT use in menopausal women was associated with a significantly increased risk of arrhythmias and acute heart failure hospitalizations. The elevated HRs highlight the potential impact of HRT on cardiac electrophysiology and heart failure risk. These findings underscore the need for careful risk-benefit discussions when considering HRT, particularly in women with underlying cardiovascular risk factors. Further research should focus on understanding the mechanisms driving these and identifying subgroups at highrisk for personalized decision-making.

Health Implications of Inadequate Follow-Up for Women on Hormone Replacement Therapy in Primary Care: A Questionnaire-Based Cross-Sectional Study

Background Adrenal crisis, characterized by acute cortisol deficiency, is a rare, life-threatening condition that can precipitate cardiovascular collapse and heart failure (HF). Its role in HF with preserved ejection fraction (HFpEF) is underrecognized, particularly in cancer patients receiving therapies that impair adrenal function. This case series examines the clinical features, management, and outcomes of HFpEF induced by adrenal crisis, emphasizing early diagnosis and treatment. Methods We retrospectively analyzed four patients diagnosed with HFpEF secondary to adrenal crisis between January 2022 and January 2025 at Qingdao Central Hospital and Qingdao Municipal Hospital. Inclusion criteria included clinical evidence of adrenal crisis (low cortisol, hypotension, steroid responsiveness) and echocardiographic confirmation of HFpEF (EF ≥50%). Data on demographics, clinical presentation, laboratory findings, echocardiography, and outcomes were analyzed descriptively. Results The cohort comprised three males and one female (aged 41–77 years), all with HFpEF (EF 50%–60%). Two presented with myocardial infarction (one NSTEMI, one STEMI), and two had malignancy with adrenal metastasis (renal, lung). Three exhibited hypotension. Initial BNP levels ranged from 518.93–619.13 pg/mL, decreasing to 108.06–287.63 pg/mL pre-discharge after hormone replacement therapy and HF management. Mean EF improved by 1.75% (range: 0%–3%) at one-month follow-up, with BNP further declining to 20.36–177.24 pg/mL. All patients achieved symptom resolution with no recurrence reported. Conclusion Adrenal crisis is a rare, reversible etiology of HFpEF in patients with diverse underlying conditions, potentially including those with cancer-related adrenal dysfunction or prior therapies. Prompt steroid therapy appears to improve cardiac function and outcomes, suggesting a need for heightened awareness and consideration of adrenal screening in at-risk populations, such as those with malignancy, tuberculosis, or other causes of adrenal insufficiency. Larger studies are needed to confirm these preliminary findings and establish the prevalence of this etiology across different subpopulations.

Background: Heart failure with mildly reduced ejection fraction (HFmrEF), defined by a left ventricular ejection fraction (LVEF) of 41–49%, is a transitional state between preserved (HFpEF) and reduced (HFrEF) ejection fractions. Postmenopausal women are disproportionately affected, likely due to reduced cardioprotective estrogen. The impact of hormone replacement therapy (HRT) on HFmrEF remains ambiguous. Objective: To assess the effects of HRT on clinical outcomes, cardiac remodeling, and use of guideline-directed medical therapy (GDMT) in postmenopausal women with HFmrEF. Methods: A PRISMA-guided literature review was conducted across PubMed, Embase, Cochrane, Scopus, and SciSpace. Twenty studies—including systematic reviews, meta-analyses, and observational cohorts—met inclusion criteria, focusing on postmenopausal women aged 45–65 with heart failure. Due to limited HFmrEF-specific data, findings from HFrEF populations were included due to historical classification overlap. Primary outcomes included echocardiographic parameters, natriuretic peptides, hospitalizations, and GDMT use. Due to heterogeneity across studies, a narrative synthesis approach was used. Results: A meta-analysis of 25,047 women found no significant association between HRT and incident heart failure. However, in women with existing HF, HRT was linked to a 35% reduction in all-cause mortality (RR 0.65; 95% CI, 0.49–0.87; p = 0.003). Transdermal estradiol improved diastolic function, reducing E/e′ ratios and left atrial volume index. Conversely, a systematic review reported no significant effect on first HF hospitalization (RR 1.02; 95% CI, 0.94–1.10), suggesting limited preventative value. A meta-analysis of 33 trials (n = 44,639) found no mortality reduction overall, although early HRT use improved endothelial function. Women with HFmrEF or HFrEF were 23% less likely than men to receive GDMT (HR 0.77; 95% CI, 0.71–0.83), especially RAS inhibitors and β-blockers. Estrogen may enhance RAS inhibitor efficacy via nitric oxide and aldosterone modulation, though caution is advised due to potential hypotension and hyperkalemia. Conclusion: Transdermal HRT, particularly estradiol, may provide structural and clinical benefits for postmenopausal women with HFmrEF. Underuse of GDMT in this group highlights a persistent care gap. Further sex-specific research is needed to clarify HRT's role and optimize outcomes in women with HFmrEF.

Description of Case: A 53 year old female with past medical history of autoimmune thyroid disease post-thyroidectomy (not on levothyroxine for over one year), chronic lower extremity edema, generalized anxiety disorder, hysterectomy, and cholecystectomy, presented with 2 day history of progressive bilateral leg swelling and right lower extremity erythema. She reported worsening exertional dyspnea and orthopnea over several months. She denied chest pain, syncope, fever, chills, nausea, or diaphoresis. Initial labs were notable for anemia with a hemoglobin of 8.3, potassium 3.3, elevated TSH 38.21, with a low free T3 1.8 and low free T4 0.25, normal BNP 36 and elevated D-dimer 1.32. Chest X-ray showed cardiomegaly with mild perihilar pulmonary congestion. EKG showed normal sinus rhythm and nonspecific findings of an old anterior myocardial infarction. Transthoracic echocardiogram (TTE) revealed a large pericardial effusion with right atrial and right ventricular collapse, consistent with cardiac tamponade. Urgent pericardiocentesis was performed under echocardiographic and fluoroscopic guidance, and 500 mL of straw-colored pericardial fluid was aspirated. Post-procedural TTE confirmed complete resolution of the effusion and normalization of cardiac chamber function without evidence of residual tamponade physiology. The pericardial fluid was sent for diagnostic analysis which was exudate. A pericardial drain was left in place and removed after 24 hours. Plan is for repeat TTE in 2 weeks. Discussion: Hypothyroidism is a known but rare cause of large pericardial effusions and tamponade. This case underscores that while pericardial effusion is a relatively common finding in hypothyroidism, progression to tamponade is rare due to the typically slow accumulation of fluid. However, delayed recognition or additional stressors can tip a patient into hemodynamic compromise. Clinicians should maintain a high index of suspicion for pericardial effusion in patients with long-standing or untreated hypothyroidism presenting with dyspnea or hemodynamic instability. Prompt echocardiographic evaluation and thyroid hormone replacement are essential for optimal outcomes.

Traumatic brain injury (TBI) in childhood is a major global health concern and a leading cause of morbidity and mortality in the pediatric population. Its incidence is rising worldwide, with early childhood and adolescence representing the most vulnerable age groups. Beyond acute neurological injury, post-traumatic endocrine dysfunction has emerged as an underrecognized but clinically significant sequela, with potential long-term consequences for growth, puberty, metabolism, and overall quality of life. The hypothalamic–pituitary axis (HPA) is uniquely vulnerable due to its anatomical and vascular characteristics, making pituitary cells—particularly somatotrophs and gonadotrophs—susceptible to ischemic, traumatic, and inflammatory damage. Reported prevalence of post-TBI pituitary dysfunction in children ranges from 5 to 57%, reflecting a deep heterogeneity in injury severity, diagnostic methods, and timing of evaluations. Growth hormone deficiency (GHD) is the most frequently reported abnormality, with presentations varying from transient to persistent forms. Gonadal axis disturbances, including hypogonadotropic hypogonadism and, less commonly, central precocious puberty, highlight the impact of TBI on pubertal development. Adrenal dysfunctions, though less frequent, may be life-threatening if unrecognized, while posterior pituitary disorders, such as diabetes insipidus, usually revealed acutely, are often transient. Importantly, many endocrine sequelae manifest months to years after the initial trauma, complicating a timely diagnosis. Current evidence underscores the need for structured, longitudinal endocrine surveillance after pediatric TBI, with baseline and follow-up assessments at defined intervals. Early recognition and intervention, including hormone replacement when appropriate, may improve neurocognitive recovery and overall rehabilitation outcomes. Future multicenter studies and standardized screening protocols should be considered essential to clarify incidence, natural history, and optimal management strategies for post-traumatic endocrine dysfunction in children.

Chronic pelvic pain syndrome (CPPS) in women is a debilitating condition with a high prevalence (5-25%), yet its etiology remains unclear. This prospective observational study aimed to identify clinical and medical history covariates associated with CPPS to elucidate potential pathophysiological mechanisms. A total of 225 women were evaluated in a gynecological pain clinic in Germany, including 41 patients with CPPS (≥ 6months of lower abdominal pain) and 184 control patients undergoing routine gynecological screening. Exclusion criteria included pregnancy, pelvic malignancy, acute pelvic inflammation, and abnormal uterine bleeding. Covariates were assessed through structured clinical history and physical examination. Significant associations with CPPS were observed for prior pelvic surgery (72% vs. 45%, p = 0.003), bowel constipation (37% vs. 11%, p = 0.002), history of endometriosis (33% vs. 10%, p = 0.043), and prior trauma (27% vs. 11%, p = 0.013). In contrast, there were no significant differences in rates of depression (p = 0.376), use of psychopharmaceuticals (p = 0.757), pelvic floor abnormalities (p = 0.503), uterine retroversion (p = 0.330), or pelvic congestion (p = 0.455). Dysmenorrhea (59% vs. 42%) and vulvar pain (31% vs. 8%) were more frequent in the CPPS group, though not statistically significant. No differences were found in delivery mode, use of intrauterine devices, analgesics, hormonal replacement therapy, and other medications, or comorbidities such as diabetes, thyroid disease, hypertension, other pain diseases, or musculoskeletal disorders. CPPS was not associated with several commonly suspected cofactors, including psychosomatic factors, pelvic congestion, or pelvic floor dysfunction. The findings suggest the existence of two subgroups of CPPS, the endometriosis-associated type and the neurovegetative type, associated with prior pelvic surgery, constipation, and trauma. This concept allows for the development of new targeted therapeutic strategies to successfully treat CPPS.

Serum levels of leucine-rich α-2 glycoprotein 1 (LRG1), pro-neurotensin (PNT), fatty acid-binding protein 4 (FABP4) and furin in pediatric growth hormone deficiency before and after 1-year growth hormone replacement therapy.

Characterization of Crinone®: progesterone vaginal gel.

Complete Androgen Insensitivity Syndrome (CAIS) is caused by mutations in the androgen receptor gene (AR), leading to androgen resistance. Early recognition is crucial for management. To evaluate clinical presentations, hormonal profiles, genetic characteristics, and decisions regarding gonadectomy in pediatric CAIS. Factors influencing gonadectomy, including malignancy risk, gonadal function, and psychological well-being were assesed. Medical records of 16 children genetically confirmed CAIS patients, aged 3 days-18 years, diagnosed between 2004 and 2024 at a tertiary referral center were retrospectively reviewed. Clinical, hormonal, genetic, and histological data were analyzed. Twelve patients (75%) were diagnosed prepubertally, most commonly due to inguinal hernia. Familial recurrence occurred in 4 cases (25%). Novel pathogenic AR variants not previously reported in public databases were identified in three patients. Prepubertal patients with hormone data (n=5) demonstrated AMH >150 pM. Pubertal patients (n=9) had markedly elevated testosterone levels [median at 1361.3 ng/dl, range 367-3460 ng/dl]. Gonadal biopsy was performed in 3 cases (19%). Gonadal preservation was recommended in 11 children (69%), while 5 (31%) underwent gonadectomy followed by estrogen replacement therapy. Most CAIS cases in this pediatric cohort were detected early through inguinal hernia or family screening. Delayed gonadectomy allowed spontaneous pubertal development and feminization. While gonadectomy results in lifelong hormone dependence and may raise identity-related concerns, surveillance-based gonadal preservation appears safe during childhood. The identification of novel AR variants expands the mutational spectrum of CAIS and highlights the need for multicenter registries and improved biomarkers to optimize individualized care.

Hormone Replacement Therapy (HRT) remains underutilised and under-researched in low- and middle-income countries (LMICs), despite its potential to alleviate menopausal symptoms. This study explored pharmacists’ perspectives on the use, cost, and availability of HRT across six LMICs. A cross-sectional survey was conducted from January 1 to March 31, 2025, as part of the Global Menopause Project. Pharmacists working in community, hospital, and private sector settings in Malaysia, Sri Lanka, Nepal, Nigeria, Ghana, and Tanzania were recruited. Participants completed an anonymous online questionnaire. The questionnaire was piloted prior to dissemination, assessed HRT availability, pricing, and perceived barriers to use. A total of 331 pharmacists responded: Ghana (18·4%), Sri Lanka (17·5%), Tanzania (16·9%), Nepal (16·6%), Malaysia (15·4%), and Nigeria (15·1%). The respondents were almost equally distributed between sexes (50·8% were female), and most were aged 26–35 years (49·0%). The majority worked in private community pharmacies (41·7%) or government hospitals (32·6%), and 57·4% were based in urban areas. From the sample, 68·9% of pharmacists reported that HRTs were available for dispensing in their respective countries (highest proportion was reported in Nepal, 92·7% and lowest in Nigeria, 42%). HRT costs varied widely, with Sri Lanka reporting the highest prices and Malaysia the lowest. Key barriers identified included low health literacy, economic constraints, and limited healthcare access. Significant disparities exist in HRT access, availability and affordability across LMICs, with urban-rural gaps further compounding inequities. Pharmacists’ insights underscore the urgent need for inclusive, equitable strategies in menopausal care and women’s health policy in resource-limited settings.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-18083-x.

Multiple endocrine neoplasia type 2A (MEN 2A) is a rare autosomal dominant disorder characterized by the co-existence of medullary thyroid carcinoma (MTC), pheochromocytoma, and, less commonly, primary hyperparathyroidism. Here we present a case of a 43-year-old female who presented with recurrent hyperadrenergic spells along with sustained hypertension, bilateral loin pain, and unintentional weight loss for 1 year. Physical examination revealed thyromegaly and hyperpigmented patches in the interscapular region. Laboratory investigations showed elevated 24-hour urinary fractionated metanephrine, raised serum calcitonin and carcinoembryonic antigen, along with a normal serum calcium profile. A CT scan of the adrenal gland was suggestive of bilateral adrenal pheochromocytoma. Ultrasound of the thyroid gland demonstrated bilateral neoplastic nodules in both lobes of the thyroid gland. A provisional diagnosis of MEN 2A was made. Bilateral adrenalectomy was done, followed by total thyroidectomy with prophylactic central lymph node dissection. Her postoperative evolution was favourable. She is currently maintained on appropriate hormone replacement therapy. Genetic counseling was done, and family screening was advised. This case highlights the importance of early detection and timely surgical intervention in MEN 2A, which are pivotal for improving outcomes and enabling preventive family screening. [J Assoc Clin Endocrinol Diabetol Bangladesh, 2025;4(Suppl 1): S55]

The aims of this review are to describe the rates of diagnosis of true thyroid disease (and subsequent treatment) in children with an elevated TSH referred to pediatric endocrinology, risk factors associated with elevated TSH secondary to thyroid disease, and TSH threshold level associated with thyroid disease. To accomplish these aims, our team searched through four databases to curate 211 articles regarding TSH values in healthy children ages 1-18years without an underlying risk for hypothyroidism. Five studies met our criteria and were analyzed to create the conclusions about rates of hypothyroidism requiring treatment (6.3-59 %), risk factors to developing hypothyroidism (TSH>10 mIU/L, goiter, and anti-thyroid antibodies), and high-risk TSH value (9.6 mIU/L when averaged among four studies). The results are helpful in guiding practitioners about when to repeat TSH value before considering referral to endocrinology, when to refer, and when to anticipate the need of thyroid hormone replacement.

Tetrasomy X (48, XXXX) is an exceptionally rare sex chromosome aneuploidy, with fewer than a few hundred cases documented worldwide. Clinical features vary widely, from mild developmental delay to pronounced dysmorphism, gonadal dysfunction, and tall stature. We report a young female who presented with menstrual irregularities and delayed pubertal development. On physical examination, she was unusually tall (height 182 cm, arm span 194 cm) with a low upper-to-lower segment ratio (0.91), consistent with eunuchoid body proportions. Tanner staging revealed discordant pubertal progression, with breast development at stage B4 but pubic hair at stage P1. Laboratory evaluation demonstrated hypergonadotropic hypogonadism, evidenced by elevated follicle-stimulating hormone (37.93 mIU/ml), elevated luteinizing hormone (16.61 mIU/ml), and low estradiol (17.21 pg/ml). Other biochemical and systemic evaluations, including thyroid, renal, hepatic, and cardiac assessments, were within normal limits. Karyotyping confirmed 48, XXXX, establishing the diagnosis of tetrasomy X. This case emphasizes the diagnostic challenge posed by such rare aneuploidies, particularly in individuals presenting with tall stature and reproductive dysfunction but without overt dysmorphic features. Early recognition is crucial for initiating hormonal replacement, addressing fertility concerns, and ensuring multidisciplinary long-term care. [J Assoc Clin Endocrinol Diabetol Bangladesh, 2025;4(Suppl 1): S60]