The Journal Of Clinical Endocrinology And Metabolism[JOURNAL]
Sun
200 papers
Metabolic and muscular effects of switching from somatropin to somapacitan in adults with growth hormone deficiency.
Oi-Yo Y, Urai S, Yamamoto M … +9 more , Tomofuji S, Ohmachi Y, Sasaki Y, Bando H, Takahashi M, Iguchi G, Harada R, Sakai Y, Fukuoka H
J Clin Endocrinol Metab · 2026 Apr · PMID 41955533 · Publisher ↗
CONTEXT: Once-weekly somapacitan is approved for treating adults with growth hormone deficiency. Phase 3 trials support its non-inferiority to daily growth hormone (GH); however, its effect on comprehensive metabolic out...
CONTEXT: Once-weekly somapacitan is approved for treating adults with growth hormone deficiency. Phase 3 trials support its non-inferiority to daily growth hormone (GH); however, its effect on comprehensive metabolic outcome, including muscle strength, during routine care, remains unclear. OBJECTIVE: To compare the metabolic and functional outcomes in patients who switched from daily GH to somapacitan with those who continued daily GH. DESIGN: Prospective, observational, non-randomized comparative study conducted from baseline to 52 weeks. SETTING: A single-center providing routine endocrine management. PATIENTS: Fifty-seven adults on growth hormone replacement therapy were self-selected to receive either once-weekly or continued daily GH. INTERVENTION: Switching from daily GH to once-weekly somapacitan, or continuing daily treatment based on patient preference. MAIN OUTCOME MEASURES: The prespecified primary endpoint was the dual-energy x-ray absorptiometry-derived change in total lean mass from baseline to week 52. Exploratory endpoints included body composition, lipid profile, and physical performance. RESULTS: Baseline and week 52 insulin-like growth factor 1 standard deviation scores distributions were similar between the groups; yet the increase was greater with daily GH than with somapacitan. The primary endpoint showed no between-group difference (mean difference -0.2 kg; 95% CI -1.5 to 1.1). Somapacitan was associated with increased adiposity indices, yet it improved high-density lipoprotein-cholesterol. Exploratory analyses revealed improvements in handgrip strength and Timed Up and Go Test. No new safety concerns were observed. CONCLUSIONS: In routine practice, switching to once-weekly somapacitan was associated with improved functional outcomes, despite less favorable adiposity trajectories, compared with daily therapy. Further studies are required to clarify long-term effects.
Steroids, stress, and body mass index interact to accelerate female pubertal development.
Houghton LC, Siegel E, Wei Y … +14 more , Wudy SA, Hartmann MF, Stanczyk F, Knight JA, Andrulis IL, Bradbury AR, Schwartz L, Buys SS, Daly MB, John EM, Chung WK, Santella RM, Romeo RD, Terry MB
J Clin Endocrinol Metab · 2026 Apr · PMID 41955216 · Publisher ↗
CONTEXT: Estrogens underlie puberty in girls, but the steroid metabolome may also regulate pubertal timing in response to elevated stress and increasing body mass index (BMI). OBJECTIVE: Our objective was to identify ste...
CONTEXT: Estrogens underlie puberty in girls, but the steroid metabolome may also regulate pubertal timing in response to elevated stress and increasing body mass index (BMI). OBJECTIVE: Our objective was to identify steroid metabolome patterns linked to accelerated puberty and test whether BMI and stress markers modify this relationship. METHODS: From the LEGACY Girls Study, a longitudinal cohort followed for 6 years, we selected 327 girls aged 5 to 13 years at baseline to measure 36 steroid metabolites of glucocorticoids, androgens, progesterone, and estrogens in 2 urine samples collected before and during puberty. Parents reported the age at onset of breast development (thelarche), which had a high correlation in the subset with clinically assessed Tanner. Study staff measured height and weight and administered questionnaires, including the Internalizing Composite Scale, a parental proxy of child stress. We estimated hazard ratios (HRs) for the association between doubled steroid metabolites and ages at thelarche, pubarche, and menarche using Weibull survival models, testing interactions with stress and BMI z-scores. RESULTS: Accelerated thelarche was associated with higher prepubertal urinary metabolites of glucocorticoids (HR = 1.9, 95% CI: 1.5-2.5), androgens (HR = 3.9, 95% CI: 2.7-5.6), and progesterone (HR = 6.7, 95% CI: 4.1-10.9). Girls with high glucocorticoid metabolites combined with high BMI and stress reached thelarche 7 months earlier than their counterparts with low measures in these parameters. CONCLUSION: Elevated metabolites of glucocorticoids, androgens, and progesterone are associated with accelerated pubertal onset, and BMI and stress modify this association. Previous studies have focused on estrogens, menarche, and BMI; our results suggest that androgens and stress impact the timing of thelarche as well, explaining secular declines in pubertal timing.
Correction to: "Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement".
J Clin Endocrinol Metab · 2026 May · PMID 41947386 · Full text
Abstract loading — click title to view on PubMed.
Real-world Effectiveness of Burosumab Across Age Groups: X-linked Hypophosphatemia (XLH) Disease Monitoring Program.
Ward LM, Carpenter TO, Cassinelli H … +10 more , Florenzano P, Imel EA, Khan AA, Johnson B, Yang E, Vincent M, Heerssen HM, Li Z, Simmons JH, XLH Disease Monitoring Program Investigators
J Clin Endocrinol Metab · 2026 Apr · PMID 41934635 · Publisher ↗
CONTEXT: X-linked hypophosphatemia (XLH) is a rare disorder characterized by excess fibroblast growth factor 23 (FGF23), leading to chronic hypophosphatemia, osteomalacia, and rickets. OBJECTIVE: To evaluate outcomes up...
CONTEXT: X-linked hypophosphatemia (XLH) is a rare disorder characterized by excess fibroblast growth factor 23 (FGF23), leading to chronic hypophosphatemia, osteomalacia, and rickets. OBJECTIVE: To evaluate outcomes up to 3 years following initiation of treatment with anti-FGF23 antibody (burosumab) in a real-world setting among individuals with XLH, stratified by age group, including those excluded from clinical trials (< 1, 13-17, and ≥ 65 years). METHODS: The XLH Disease Monitoring Program is a prospective, longitudinal, long-term-outcomes program for individuals with XLH. This analysis included participants who were burosumab-naive at baseline and who had initiated burosumab between baseline and the Year 1 visit. Changes from baseline in biochemistry, clinical outcomes, and patient-reported outcomes (PROs) were assessed at Year 1 (Y1) and Year 3 (Y3) visits. RESULTS: Among participants (n = 139), burosumab led to significant and sustained improvements in mean (SD) serum phosphate z-scores at Y1 and Y3 (change from baseline: 1.4 [1.1]; P < .0001 for each timepoint). Among pediatric participants, serum alkaline phosphatase z-scores, Rickets Severity Scores, and patient-reported pain interference declined significantly at Y1 and Y3; non-significant changes were observed in fatigue and physical function mobility. Adults showed significant improvements in PRO measures of pain, stiffness, and physical function, with higher proportions of participants achieving minimal clinically important differences at Y3 vs Y1. Trends observed in overall cohorts were generally consistent across age sub-groups, with statistical significance reached for many endpoints. CONCLUSION: This analysis demonstrated the real-world effectiveness of burosumab for XLH, which appears evident across age groups.
Defining disease or delaying care? A conceptual and clinical appraisal of the Lancet obesity framework.
Muniyappa R, Chukir T, Desai D … +4 more , Weintraub MA, Corrigan MD, Gianchandani R, Rothberg AE
J Clin Endocrinol Metab · 2026 May · PMID 41925581 · Publisher ↗
The Lancet Diabetes & Endocrinology Commission undertook the complex task of addressing limitations in existing definitions and classification of obesity. Its consensus framework moves beyond body mass index (BMI) toward...
The Lancet Diabetes & Endocrinology Commission undertook the complex task of addressing limitations in existing definitions and classification of obesity. Its consensus framework moves beyond body mass index (BMI) toward direct or surrogate measures of excess adiposity and distinguishes "clinical obesity" (excess adiposity plus objective organ/system dysfunction or functional limitation attributable to adiposity) from "preclinical obesity" (excess adiposity without such evidence). The Endocrine Society (ES) recognizes the substantial effort and expertise underlying this work and its intent to improve diagnostic precision and therefore provides an independent appraisal of the framework's conceptual coherence, empirical support, operational feasibility, and implications for coverage, equity, and clinical implementation. The shift away from BMI-only screening is supported by evidence that central adiposity and fat distribution better predict cardiometabolic risk than BMI alone. Validation studies (All of Us; UK Biobank) demonstrate elevated risk among individuals classified with "preclinical" obesity and even higher risk among those with "clinical" obesity, underscoring the importance of safeguards against undertreatment in the preclinical state. At the same time, lack of standardized anthropometric measurement protocols, increased resource utilization, limited distinction between subcutaneous and visceral fat depots, and insufficient data regarding the long-term implications of obesity-related disease absence prompted the ES to pause before fully endorsing the Commission's consensus. Accordingly, we outline an evaluation framework addressing available evidence, feasibility, coverage and equity considerations, and clinical impact. We advocate harmonization with established staging systems (EOSS, EASO), explicit measurement protocols, age-, sex-, and ancestry-specific thresholds, integration of mental health and patient-reported outcomes, and policies that prevent unintended care restrictions. The Commission's reframing represents a meaningful conceptual advance; broader adoption will require practical and equitable implementation.
The association between PFAS exposure, menstrual cycle parameters, and reproductive hormones in adolescent girls.
Malave-Ortiz S, McNeley SAM, Denslow S … +4 more , Bangma J, Ferguson KK, Fenton SE, Shaw ND
J Clin Endocrinol Metab · 2026 Apr · PMID 41921573 · Publisher ↗
CONTEXT: Perfluoroalkyl and polyfluoroalkyl substances (PFAS), sometimes referred to as "forever chemicals", are widespread. Certain PFAS exposures have been associated with reproductive abnormalities in women but limite...
CONTEXT: Perfluoroalkyl and polyfluoroalkyl substances (PFAS), sometimes referred to as "forever chemicals", are widespread. Certain PFAS exposures have been associated with reproductive abnormalities in women but limited data exist in adolescents. OBJECTIVE: To investigate the relationship between PFAS, menstrual cycle length/variability, and reproductive hormones in adolescents. METHODS: Thirty-eight girls completed menstrual diaries and contributed daily urine samples to measure creatinine (Cr)-corrected luteinizing hormone (LH), estrone-3-glucuronide (E1G), and pregnanediol-3-glucuronide (PdG). Twenty-four PFAS were measured (n=88 serum samples, average 2.32 samples/participant over the course of 1.20 ± 1.34 years) using mass spectrometry. Linear mixed effects models were used to assess associations between PFAS and total cycle, follicular phase, and luteal phase lengths and hormone levels. Models were performed unadjusted and adjusted for gynecologic age, body fat percent, and race/ethnicity. RESULTS: Participants were 12.8 ± 1.0 years old (mean ± SD) with a gynecologic age of 0.3 ± 0.2 years. Most were non-Hispanic White and of normal weight. Four PFAS were consistently detected: perfluorobutanesulfonic acid (PFBS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), and perfluorooctanesulfonic acid (PFOS). There were no associations between PFAS and cycle length or variability. PFBS was positively associated with peak E1G levels (β = 0.15, 95% CI [0.00, 0.29], p=0.049), but no species was associated with peak LH or PdG levels. CONCLUSION: PFAS were widely detected in healthy girls. PFBS was positively associated with E1G levels, suggesting potential ovarian effects. Analyses are ongoing to understand PFAS exposure sources and to determine if ongoing exposure may impact reproductive health.
Glucocorticoid reduction after starting crinecerfont in adult patients with classic CAH: practical perspectives.
Hamidi O, Auchus RJ, Correa R … +5 more , Levine AC, Wierman ME, Hartzell AL, Lin VH, Bancos I
J Clin Endocrinol Metab · 2026 Jun · PMID 41921547 · Full text
CONTEXT: Crinecerfont, a first-in-class corticotropin-releasing factor type 1 receptor antagonist, is FDA-approved as an adjunct to the physiologic glucocorticoid (GC) required to treat the underlying adrenal insufficien...
CONTEXT: Crinecerfont, a first-in-class corticotropin-releasing factor type 1 receptor antagonist, is FDA-approved as an adjunct to the physiologic glucocorticoid (GC) required to treat the underlying adrenal insufficiency in patients (≥4 years old) with classic congenital adrenal hyperplasia (CAH). By reducing elevated adrenocorticotropic hormone, crinecerfont controls excess adrenal androgens, thereby enabling lower GC doses. However, there are no published recommendations for how to reduce supraphysiologic GC doses after initiating crinecerfont. This manuscript aims to provide a framework developed by experienced endocrinologists for reducing supraphysiologic GC doses in patients taking crinecerfont. EVIDENCE ACQUISITION: An experienced panel of 11 endocrinologists discussed strategies and considerations when reducing GC doses and developed an algorithm to guide GC dose reductions after introducing crinecerfont in adults with CAH. EVIDENCE SYNTHESIS: Approaches to GC reduction should be individualized based on the patient's therapeutic goals, cortisol needs, lifestyle preferences, and the clinician's experience to set appropriate targets for clinical parameters, androgens, and GC dose regimen. In general, GC doses should be reduced gradually to minimize the risks of developing symptoms of GC withdrawal or adrenal insufficiency. GC doses should be adjusted to the lowest level needed to maintain androgens at goal, without reducing below what is needed for cortisol replacement. Practical considerations during GC dose reduction include switching from longer- to shorter-acting GCs (eg, from dexamethasone to hydrocortisone), optimizing dose distribution to mimic normal circadian cortisol exposure, and consolidating or eliminating doses to improve adherence. CONCLUSION: This framework for reducing supraphysiologic GC doses in adult patients taking crinecerfont may become increasingly relevant as treatment of CAH shifts toward physiologic GC replacement with adjunctive control of adrenal androgens.
Association between puberty timing and metabolic health at Young adulthood.
Pereira A, Corvalán C, Mericq V
J Clin Endocrinol Metab · 2026 Apr · PMID 41921546 · Publisher ↗
INTRODUCTION: Metabolic syndrome (MetS) is a cluster of abnormalities that increase the risk of type 2 diabetes and cardiovascular disease. Cross-sectional studies in adults suggest that early pubertal timing is associat...
INTRODUCTION: Metabolic syndrome (MetS) is a cluster of abnormalities that increase the risk of type 2 diabetes and cardiovascular disease. Cross-sectional studies in adults suggest that early pubertal timing is associated with a higher risk of MetS. We aimed to determine whether early puberty onset in boys and girls increases the risk of developing MetS at 18 years. METHODS: We conducted a longitudinal study within the Growth and Obesity Chilean Cohort Study. Pubertal timing was assessed by Tanner stage (breast stage 2 [B2] in girls; gonadarche stage 2 [G2; testicular volume >3 cc] in boys) and age at menarche (AAM). MetS and insulin-resistance markers were evaluated at age 18 (n=729). Logistic regression models were used to examine associations between early pubertal markers and MetS and related metabolic parameters, adjusting by body mass index at puberty and maternal education. RESULTS: At age 18, boys had higher prevalence of MetS (9.8% vs. 4.1%), elevated blood pressure (9.8% vs. 0.3%), and elevated triglycerides (18.1% vs. 8.5%). In boys, only crude models showed inverse associations between age at G2 and MetS, waist circumference, and waist-to-height ratio. In girls, fully adjusted models confirmed and inverse association of AAM and the risk of MetS (OR: 0.54, 95%CI 0.33-0.90), high triglycerides (OR: 0.57, 95%CI:0.39-0.83) and high triglycerides/glycemia ratio (OR: 0.63, 95%CI 0.43-0.92). No associations were observed for B2. CONCLUSION: Earlier puberty is associated with adverse metabolic outcomes, but this persists after adjustment only in girls. Secular trends toward earlier pubertal timing may therefore have significant public health implications.
Mapping of sex hormones in the testicular vein of healthy men.
Hufnagel A, Frederiksen H, Albrethsen J … +5 more , Johannsen TH, Juul A, Jensen RJ, Rehfeld A, Barrès R
J Clin Endocrinol Metab · 2026 Apr · PMID 41921126 · Publisher ↗
CONTEXT: The testis produces hormones controlling sex differentiation, development, and reproduction. Their quantification in physiological conditions can aid our understanding of the endocrine function of the testis. OB...
CONTEXT: The testis produces hormones controlling sex differentiation, development, and reproduction. Their quantification in physiological conditions can aid our understanding of the endocrine function of the testis. OBJECTIVE: To measure the concentrations of steroid hormones and FSH, LH, inhibin B, anti-Müllerian hormone (AMH), and insulin-like factor 3 (INSL3) in the testicular and femoral veins, femoral artery, and seminal fluid in healthy men. DESIGN: Sample collection was made by angiographic catheterization under fluoroscopy from the testicular and femoral veins. Femoral artery samples were collected via needle puncture and seminal fluid was isolated from semen samples. Hormones were measured via liquid chromatography mass spectrometry and immunoassays. PARTICIPANTS: Seven volunteers (aged 22-49 years) without self-reported diseases and normal semen quality were included. MAIN OUTCOMES: Concentrations of steroid hormones, FSH, LH, inhibin B, AMH, and INSL3 in the testicular vein, femoral artery, femoral vein, and seminal fluid. RESULTS: Expectedly, testosterone was 66-fold higher in the testicular vein compared to the femoral artery, but surprisingly, levels of 11-deoxycortisol and 11-deoxycorticosterone were 4- and 20-fold higher in the testicular vein compared to the femoral artery. In line with their production site in the testis, INSL3 and inhibin B were 200- and 2-fold higher in the testicular vein compared to the femoral artery. Unexpectedly, concentration of AMH was not different between the testicular vein and femoral artery despite its documented production in the testis. CONCLUSION AND RELEVANCE: Our results provide insight into the endocrine function of the testis under physiological conditions and constitute a reference for further research in male reproductive function.
Cytokine Dynamics Following Initiation of Gender-Affirming Hormone Therapy in Transgender Subjects.
Sertons Y, Collet S, Vervalcke J … +8 more , Defreyne J, Mueller SC, Hofmans M, Bonroy C, D'Onofrio V, Snaterse G, T'Sjoen G, Lapauw B
J Clin Endocrinol Metab · 2026 Apr · PMID 41920908 · Publisher ↗
BACKGROUND: Sex is an important determinant for various immune system-related pathologies and sex steroids might possess immunomodulatory properties. OBJECTIVE: To study the effects of sex steroid exposure on the serum l...
BACKGROUND: Sex is an important determinant for various immune system-related pathologies and sex steroids might possess immunomodulatory properties. OBJECTIVE: To study the effects of sex steroid exposure on the serum levels of immune-related biomarkers (irBMS), using a model of transgender individuals receiving gender-affirming hormone therapy (GAHT). MATERIAL AND METHODS: Serum samples were collected from hormone-naïve trans women (TW) (n=30) and trans men (TM) (n=30) who initiated GAHT at baseline and after ±6 months of treatment. Cisgender men (n=10) and cisgender women (n=10) were included as controls. High-sensitivity C-reactive protein (hs-CRP) was measured using immunoassay. Serum levels of several irBMs, including cytokines and chemokines were determined using a commercial multiplex assay (Olink®). Serum estradiol and testosterone were determined using liquid-chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: After ±6 months of GAHT in TW, serum levels of ten cytokines (CCL2, CCL7, CCL11, CCL13, CCL19, CXCL9, CXCL10, CXCL11, IL15 and TNFSF10) significantly decreased, whereas IL7 increased. In TM, eight factors significantly increased (CCL2, CCL7, CCL11, CCL13, CCL19, IL17C, MMP1 and TNFSF10). Other immune-related biomarkers were not significantly affected, and levels of hs-CRP did not show a clinically relevant change over time. CONCLUSION: Six months of estrogen with antiandrogen treatment resulted in decreased serum levels of several cytokines and chemokines in TW, whereas cytokine and chemokine levels often increased in TM upon treatment with testosterone. These distinct and generally opposite changes suggest a sex steroid-dependent impact, which could contribute to sex-related disparities in (auto)inflammatory diseases. However, additional research should explore potential clinical consequences, as well as the mechanisms involved.
Effect of Real-World Androgen Abuse on Body Composition: A Prospective Cohort Study.
Verdegaal TJ, Bond P, de Ronde W … +1 more , Smit DL
J Clin Endocrinol Metab · 2026 Mar · PMID 41915785 · Publisher ↗
CONTEXT: Androgens are widely abused by recreational athletes to improve physique, yet the durability of body composition changes after cycle cessation is poorly characterized in prospective studies. OBJECTIVE: To assess...
CONTEXT: Androgens are widely abused by recreational athletes to improve physique, yet the durability of body composition changes after cycle cessation is poorly characterized in prospective studies. OBJECTIVE: To assess changes in body composition during and after self-initiated androgen cycles. DESIGN: Prospective cohort study conducted between 2022 and 2024 with follow-up from baseline through three months after androgen cycle cessation. SETTING: General community. PARTICIPANTS: Seventy-nine adult men (median age 30 years) planning a self-initiated androgen cycle. INTERVENTION(S): No study-assigned intervention. Self-initiated androgen abuse cycle with a median duration of 10 weeks and median weekly dose of 600 mg. MAIN OUTCOME MEASURE: Changes in total body weight, fat-free mass, and fat mass measured by dual-frequency bioelectrical impedance analysis at baseline (T0), during the cycle (T1), and three months after cessation (T2). RESULTS: From T0 to T1, body weight increased by 4.9 kg (95% CI, 3.9-5.9) and fat-free mass by 4.4 kg (95% CI, 3.7-5.1; both p<.001). At T2, gains were markedly attenuated, with mean retention of 1.6 kg body weight (95% CI, 0.5-2.6) and 1.2 kg fat-free mass (95% CI, 0.4-2.0; both p<.001). Similar patterns were observed in intermittent and continuous androgen abusers. Fat mass remained unchanged at all time points. CONCLUSION: Real-world androgen cycles produce marked short-term increases in fat-free mass, but most gains are lost within months after cessation. These findings challenge the assumption that androgen abuse results in substantial durable improvements in body composition and contextualize the magnitude of the desired effects of androgen abuse relative to its well-documented health risks.
The FT3/FT4 Ratio Predicts Relapse After Antithyroid Drug Withdrawal in Pediatric Autoimmune Hyperthyroidism.
Abbate M, Vincenzi G, Mora S … +6 more , Tarantola G, Petralia IT, Santagiuliana C, Del Giacco L, Zanelli S, Vigone MC
J Clin Endocrinol Metab · 2026 Mar · PMID 41913979 · Publisher ↗
CONTEXT: The likelihood of remission in patients with autoimmune hyperthyroidism (AH) depends on several prognostic factors. The FT3/FT4 ratio has been suggested as a potential marker of disease severity and prognosis. O...
CONTEXT: The likelihood of remission in patients with autoimmune hyperthyroidism (AH) depends on several prognostic factors. The FT3/FT4 ratio has been suggested as a potential marker of disease severity and prognosis. OBJECTIVE: To evaluate the prognostic value of FT3/FT4 ratio in predicting the likelihood of relapse in patients with AH. METHODS: This retrospective cohort study included 80 patients with AH diagnosed between 2000 and 2021. Clinical and biochemical data were collected at diagnosis and during follow-up to assess the likelihood of remission in patients attempting to discontinue ATD therapy. ROC analysis and logistic regression were used to identify predictors of relapse. RESULTS: Of the 48 patients who discontinued antithyroid therapy, 24 (50%) relapsed, predominantly within 12 months. The FT3/FT4 ratio was significantly higher in patients who relapsed both at diagnosis (median 0.46 vs 0.36; p 0.001) and at ATD withdrawal (median 0.43 vs 0.33; p < 0.001). An FT3/FT4 ratio ≥0.42 at diagnosis predicted relapse with 83% sensitivity and 66% specificity. In a multivariate analysis, FT3/FT4 ratio ≥0.42 at diagnosis (OR 7.18; p 0.012) and the presence of orbitopathy were identified as independent predictors of relapse. Longer time to FT3 normalization (p 0.02) and orbitopathy were associated with relapse in univariate analyses (p 0.039). CONCLUSION: The FT3/FT4 ratio, measured both at diagnosis and before antithyroid drug withdrawal, is a significant predictor of relapse in autoimmune hyperthyroidism. This parameter may represent a useful tool for guiding decisions about treatment duration and withdrawal.
Acromegaly is Associated with an Increased Incidence of Primary Malignant Tumors: Data from a National Study in Sweden.
Tsatsaris E, Robèrt J, Burman P … +9 more , Berinder K, Bonelli L, Dahlqvist P, Höybye C, Ragnarsson O, Vouzouneraki K, Åkerman AK, Ekman B, Engström BE
J Clin Endocrinol Metab · 2026 Mar · PMID 41913644 · Publisher ↗
CONTEXT: Growth hormone (GH) excess and elevated insulin-like growth factor-1 (IGF-1) in acromegaly are considered to promote cancer development. OBJECTIVE: To investigate cancer incidence and outcome in patients with ac...
CONTEXT: Growth hormone (GH) excess and elevated insulin-like growth factor-1 (IGF-1) in acromegaly are considered to promote cancer development. OBJECTIVE: To investigate cancer incidence and outcome in patients with acromegaly in relation to biochemical control. METHODS: Matched cohort study in patients with acromegaly diagnosed from 1991 to 2018 and ten controls per case from the Swedish population. Cancer diagnoses and fatalities were obtained from the Swedish Pituitary and National Patient Registers. Adjusted hazard ratio (HR) and 95% confidence intervals (CIs) for cancer incidence and death were estimated using a Cox proportional hazard regression model adjusted for age, sex, and comorbidity. RESULTS: We included 1035 patients with acromegaly (49.5% female; median age 52.0 years) and 10,261 matched controls. Patients had higher adjusted HR (95% CI) for all cancer (1.28, 1.11-1.49), colorectal cancer (1.84, 1.28-2.64), lung cancer (1.95, 1.22-3.11), hematologic cancer (1.68, 1.03-2.73), and breast cancer in women (1.46, 1.02-2.11) from 5 years before acromegaly diagnosis. Second cancers after diagnosis tended to be increased (1.54, 0.98-2.44). Death from cancer was only significantly elevated in patients 40-60 years of age (1.48, 1.19-1.85). Patients with persistently elevated IGF-1 had a higher overall mortality rate (1.50, 1.10-2.01) but no increase in cancer incidence nor cancer-related mortality compared to biochemically controlled patients. CONCLUSIONS: This nationwide, matched cohort study showed an increased risk of cancer in patients with acromegaly, underscoring the importance of vigilance for early signs of cancer after acromegaly diagnosis. Biochemical control had minor effects on increased cancer development, indicating an effect beyond GH hypersecretion.
Real-world Impact of Treatment on Growth in Children With X-Linked Hypophosphatemia.
Fukumoto S, Haffner D, Imel EA … +10 more , Ozono K, Brandi ML, Ishii H, Li Z, Sandilands K, Joos-Vandewalle P, Lee C, Kanematsu M, McCullough KP, Carpenter TO
J Clin Endocrinol Metab · 2026 Mar · PMID 41911946 · Publisher ↗
CONTEXT: X-linked hypophosphatemia (XLH) is a rare, genetic, progressive, lifelong disorder manifest by impaired growth and disproportionate short stature. Burosumab, a monoclonal antibody against fibroblast growth facto...
CONTEXT: X-linked hypophosphatemia (XLH) is a rare, genetic, progressive, lifelong disorder manifest by impaired growth and disproportionate short stature. Burosumab, a monoclonal antibody against fibroblast growth factor 23, is approved for treating patients with XLH. OBJECTIVE: To understand the impact of burosumab treatment on growth in a real-world setting. DESIGN: Interim data from three ongoing, real-world observational studies (NCT03651505, NCT03193476, NCT03745521), were unified into a single study (APEX). SETTING: Outpatient clinics. PATIENTS: Children aged 2-17 years with XLH. INTERVENTION(S): Subcutaneous burosumab versus oral phosphate salts and active vitamin D or no treatment. MAIN OUTCOME MEASURE(S): Retrospective and prospective height data from children enrolled in APEX were analyzed to provide long-term estimation of the impact of treatment on growth. Growth and height were estimated by a mixed regression model with separate models for children and adolescents. RESULTS: In total, 641 participants were analyzed (402 female) with 498 burosumab-treated and 143 burosumab-naïve. Median (interquartile range [IQR]) enrollment ages were 8 (5-12) years for burosumab-treated and 10 (4-14) years for burosumab-naïve participants. Burosumab-treated participants experienced improved growth over burosumab-naïve participants (additional growth velocity: 0.085 Z-score/year for children [P < 0.0001]; 0.121 Z-score/year for adolescents [P < 0.0001]). Modeling predicted greater adult height among burosumab-treated participants. CONCLUSION: Burosumab had a robust, positive association with improved growth outcomes in male and female children and adolescents with XLH. Modeling based on a median of 3.3 years of follow-up predicted burosumab can support improvement of growth that will likely result in greater adult height.
Patterns of Thyroid-Stimulating Hormone Test After GLP-1 RAs Initiation in Patients on Levothyroxine: A Trial Emulation Study.
Chen Y, Du F, Singh Ospina NM … +5 more , Brito JP, Shao H, Liu Q, McCoy RG, Jiao T
J Clin Endocrinol Metab · 2026 Mar · PMID 41902399 · Publisher ↗
CONTEXT: GLP-1 RAs are widely prescribed for type 2 diabetes and obesity and can lead to substantial weight loss. In patients taking levothyroxine, weight loss can reduce thyroid hormone requirements, potentially associa...
CONTEXT: GLP-1 RAs are widely prescribed for type 2 diabetes and obesity and can lead to substantial weight loss. In patients taking levothyroxine, weight loss can reduce thyroid hormone requirements, potentially associated adverse effects. TSH monitoring is essential but unclear whether thyroid function is routinely reassessed after GLP-1 RAs initiation. OBJECTIVE: Examine the changes in the timing of TSH testing after GLP-1 RAs. DESIGN: Retrospective cohort study emulating a target trial using Medicare from January 1, 2011, to December 31, 2020. The primary analysis followed an intention-to-treat approach. Patients were matched 1:1 using propensity scores. Logistic regression models and informed by LASSO variable selection were used. SETTING: The 15% sample of U.S. Medicare fee-for-service claims data. PATIENTS OR OTHER PARTICIPANTS: Adults aged ≥65 years with type 2 diabetes on a stable levothyroxine dose at baseline. INTERVENTION(S): Initiation of GLP-1 RAs versus initiation/ongoing use of SGLT-2is. MAIN OUTCOME MEASURE(S): TSH testing during follow-up. RESULTS: Among 5,370 matched patients, the mean age was 73.2 years. 71.6% were women, and 87.1% were White. Approximately 83.0% of patients in both treatment groups receive a TSH testing within a 1-year follow-up. The mean time to TSH testing was approximately 130.5 days for both groups. CONCLUSIONS: TSH testing patterns did not differ between GLP-1 RAs and SGLT-2is, despite the greater likelihood of requiring levothyroxine dose adjustment associated with weight loss seen with GLP-1 RAs therapy. Given levothyroxine's widespread use, this gap suggests missed opportunities for timely and weight-responsive thyroid monitoring.
Molecular Profile of Advanced Radioiodine-refractory Thyroid Cancer and Response to Lenvatinib Treatment.
Minaldi E, Ramone T, Ciampi R … +10 more , Romei C, Casalini R, Gambale C, Prete A, Lorusso L, Agate L, Torregrossa L, Piaggi P, Matrone A, Elisei R
J Clin Endocrinol Metab · 2026 Mar · PMID 41891781 · Publisher ↗
CONTEXT: The predictive role of mutational status in the response to lenvatinib in advanced radioiodine-refractory thyroid cancer (RAIR-TC) is not yet defined. OBJECTIVE: To identify a molecular signature of RAIR-TC trea...
CONTEXT: The predictive role of mutational status in the response to lenvatinib in advanced radioiodine-refractory thyroid cancer (RAIR-TC) is not yet defined. OBJECTIVE: To identify a molecular signature of RAIR-TC treated with lenvatinib and its impact on clinical response to lenvatinib. DESIGN: This is a retrospective study including 49 RAIR-TC patients treated with first-line lenvatinib and followed at least 1 year [median follow-up 9.2 years (interquartile range 6-14.1)]. Next-generation sequencing on tissues was used to detect genetic alterations. SETTING: The study was performed in a referral center for the treatment of thyroid cancer. RESULTS: Among 49 cases, BRAF (38.7%) and RAS (22.4%) were the most frequent driver mutations, while TERT and TP53 were mutated in 57.1% and 6.1%. No driver mutations were found in 34.6%. Driver mutations co-occurred with TERT or TP53 in 44.9%. In 10/49 (20.4%), no mutations were found. Cases with ≥1 mutation had longer progression-free survival (PFS) than cases negative for any mutation (P = .004). Both BRAF-mutated and RAS-mutated cases showed better PFS and overall survival (OS), although this was not statistically significant with respect to wild-type cases. Cases with a single driver mutation (group 1) showed longer PFS than cases without driver mutations (group 3) (P = .04) but no difference with cases with driver + TERT or TP53 (group 2) (P = .13). Group 1 showed longer OS than group 2 (P = .026) and group 3 (P = .034). CONCLUSIONS: The RAIR-TC molecular profile is heterogeneous with TERT being the most frequent mutation. Cases negative for all mutations and cases presenting the coexistence of TERT + driver mutation had a worse response to lenvatinib. Conversely, the presence of 1 driver mutation correlated with a better response to lenvatinib.
Initial Disease Severity and Methimazole Titration for Graves' Disease: A Retrospective Longitudinal Cohort Study.
Smith AH, Priscu A, Morkos M
J Clin Endocrinol Metab · 2026 Mar · PMID 41886602 · Publisher ↗
CONTEXT: Graves' Disease (GD) is the most common cause of thyrotoxicosis. Medical therapy with methimazole is the most common way to treat GD, but it has a narrow and dynamic therapeutic index, requiring frequent monitor...
CONTEXT: Graves' Disease (GD) is the most common cause of thyrotoxicosis. Medical therapy with methimazole is the most common way to treat GD, but it has a narrow and dynamic therapeutic index, requiring frequent monitoring for titration. It is unclear how much initial disease severity (IDS) affects titration patterns. OBJECTIVE: Identify associations between IDS with methimazole dose and thyrotoxicosis control after initiation of therapy. DESIGN: Retrospective longitudinal cohort study (2018-2024). SETTING: A single tertiary medical center. PATIENTS OR OTHER PARTICIPANTS: The study included 152 patients, aged 18 and older, diagnosed with GD. It encompassed 1432 encounters. MAIN OUTCOME MEASURE(S): The analysis focused on the association of IDS, age, and sex with average decrease in methimazole dose per encounter, biochemical thyroid status per encounter, time until first euthyroid encounter, and dose of methimazole after 180 days of treatment. RESULTS: IDS was positively associated with percentage dose reduction of methimazole per encounter (P = 0.012) and proportion of hypothyroid encounters (P = 0.0101). There was no association of IDS with the proportion of hyperthyroid encounters (P = 0.088), methimazole dose after 180 days (P = 0.222), nor time to first encounter with euthyroid status. Age and sex were not associated with changes in dose or biochemical thyroid status. CONCLUSIONS: When given a larger dose of methimazole, patients with severe thyrotoxicosis from GD reach euthyroid status as quickly as other patients with GD. However, these patients have more lability in thyroid control and may benefit from more frequent monitoring. After 6 months, severity of initial thyrotoxicosis was not associated with methimazole dose.
Associations of endocrine disrupting chemicals with anogenital distance across infancy.
Cinzori ME, Ryva BA, Murphy A … +3 more , Gardiner JC, Schantz SL, Strakovsky RS
J Clin Endocrinol Metab · 2026 Mar · PMID 41885617 · Publisher ↗
CONTEXT: Pregnant women are ubiquitously exposed to endocrine disrupting chemicals (EDCs). Anogenital distance (AGD) is a hormone-dependent marker of reproductive system development. OBJECTIVE: We evaluated associations...
CONTEXT: Pregnant women are ubiquitously exposed to endocrine disrupting chemicals (EDCs). Anogenital distance (AGD) is a hormone-dependent marker of reproductive system development. OBJECTIVE: We evaluated associations of maternal EDCs with infant AGD at birth and mini-puberty (5-months), and AGD growth across infancy. DESIGN: Pregnant women enrolled in I-KIDS (Illinois Kids Development Study) - an observational longitudinal study (2013-2019). SETTING: Participants were recruited from two OBGyn clinics in Champaign-Urbana, IL. PATIENTS OR OTHER PARTICIPANTS: This study includes 563 mother/infant pairs at birth and 5-months of age. INTERVENTION(S)/EXPOSURE: We measured ten phthalates/replacements and nine phenols in five pooled first-morning urine samples collected across pregnancy. MAIN OUTCOME MEASURES: In newborns and 5-month-olds, we divided short and long AGD measures by body length (termed anogenital index, AGI) and calculated %AGI growth across infancy. We evaluated covariate-adjusted associations of phthalates/replacements or phenols separately (quantile g-computation) or combined (hierarchical Bayesian kernel machine regression), with AGI measures. RESULTS: Associations of phthalates/replacements with newborn AGI in females and phenols in males were inconsistent. However, in 5-month-old females, each quartile increase in the phthalate/replacement mixture was associated with -4.13mm/m shorter AGIShort (95% confidence interval (CI): -7.22, -1.05), -3.89mm/m shorter AGILong (95%CI: -7.55, -0.23), -39.49% less AGIShort growth (95%CI: -62.44, -16.54), and -8.78% less AGILong growth (95%CI: -16.06, -1.51); associations with AGILong growth were strongest at lower mixture quantiles. CONCLUSIONS: AGD in mini-puberty and growth across infancy may reflect EDC-mediated hormonal disruption in utero, particularly in females, supporting the need to investigate these markers as predictors of long-term reproductive health.
Automated Insulin Delivery in Young Children with Type 1 Diabetes: A Systematic Review and Meta-Analysis.
Oktavian P, Kencono Wungu CD, Amin IM … +1 more , Mudjanarko SW
J Clin Endocrinol Metab · 2026 Mar · PMID 41877382 · Publisher ↗
BACKGROUND: Automated insulin delivery (AID) in young children (<7 years) with type 1 diabetes has not yet been systematically evaluated. MATERIALS AND METHODS: Web of Science, PubMed, Scopus, CENTRAL, and ClinicalTrials...
BACKGROUND: Automated insulin delivery (AID) in young children (<7 years) with type 1 diabetes has not yet been systematically evaluated. MATERIALS AND METHODS: Web of Science, PubMed, Scopus, CENTRAL, and ClinicalTrials.gov were searched from inception to December 9, 2025. Studies reporting glycemic outcomes in children younger than 7 years were included in this meta-analysis. Studies not published in English were excluded. The primary outcome was the change in time-in-range (TIR; 70-180 mg/dL). Pooled estimates were calculated using random-effects models and expressed as mean changes (MCs) with 95% confidence intervals (CIs). RESULTS: This study included 30 studies (9 randomized controlled trials, 7 single-arm studies, and 14 cohort studies) involving 1,155 young children. AID systems were associated with a significant increase in TIR (MC, 9.88% [95% CI 9.14 to 10.62], I2 = 8%, p < 0.0001, moderate certainty), equivalent to 2.37 h/day. Favorable improvement was also observed during the daytime (MC, 6.88% [95% CI 5.70 to 8.07]) and overnight (MC, 16.85% [95% CI 13.48 to 20.22]). TIR improvements were comparable across devices: MiniMed 670G (9.65%), MiniMed 780G (10.04%), CamAPS FX (10.58%), Control-IQ (9.51%), Omnipod 5 (10.25%), and Open Source (6.77%). AID use was also associated with reduced hyperglycemia exposure and modest reductions in glycated hemoglobin, without significant changes in hypoglycemia exposure. Episodes of severe hypoglycemia and diabetic ketoacidosis were infrequent. CONCLUSION: This systematic review with meta-analysis revealed that AID systems have greater benefits for improving glycemic outcomes and have good safety profiles in young children with type 1 diabetes.
Increased MAP-1 and lectin complement activation capacity in Klinefelter syndrome.
Chang S, Just J, Skakkebæk A … +6 more , Hasselholm EB, Nielsen C, Garred P, Gravholt CH, Münster AB, Palarasah Y
J Clin Endocrinol Metab · 2026 Mar · PMID 41873701 · Publisher ↗
CONTEXT: Klinefelter syndrome (KS) is a congenital condition linked to immune dysregulation and metabolic dysfunction with increased risk of autoimmune, metabolic, and cardiovascular diseases. OBJECTIVE: We examined comp...
CONTEXT: Klinefelter syndrome (KS) is a congenital condition linked to immune dysregulation and metabolic dysfunction with increased risk of autoimmune, metabolic, and cardiovascular diseases. OBJECTIVE: We examined complement activation through the lectin pathway in men with KS and its relationships with hypogonadism, body composition, and fibrinolytic function. METHODS: We conducted a cross-sectional study comparing men with KS with age-matched controls. We measured lectin pathway complement activation capacity, individual lectin complement factors including the lectin pathway regulator MAP-1, and the main complement split product, C3dg, using ELISAs. Body composition was assessed by dual-energy X-ray absorptiometry, and fibrin clot lysis was analyzed via turbidometry. Additionally, we analyzed skeletal muscle mRNA expression of the MASP1 gene splice variant MASP1-201, which encodes MAP-1. RESULTS: Lectin pathway activation capacity was higher in 45 men with KS compared to 45 male controls (mean ± SD, 106.2 ± 51.6% versus 64.0 ± 30.1%, p<0.0001). Serum MAP-1 levels were also elevated in KS patients. MASP1-201 expression was increased in KS. Serum C3dg levels were not different between KS and controls. The lectin pathway activation capacity was not strongly linked to sex hormone levels and only had a weak association with body fat. The lectin pathway contributed to fibrin clot lysis variability in KS, and levels of the fibrinogen-C3dg complex were similar in both KS and controls. CONCLUSIONS: Men with KS demonstrate increased lectin complement pathway activation capacity, increased MAP-1 and MASP1-201 expression. Altered immune function could be a specific characteristic of KS contributing to the comorbidity burden.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe