The Journal Of Clinical Endocrinology And Metabolism[JOURNAL]
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200 papers
Correction to: "Magnesium sulfate may unmask subclinical excess vasopressinase-induced arginine vasopressin disorder".
J Clin Endocrinol Metab · 2026 Apr · PMID 41817669 · Publisher ↗
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Ovarian Reserve and Endothelial Health in Healthy Reproductive Age Women.
Wang A, Bleil ME, Rosen MP … +5 more , Redberg R, Lin J, Smith DL, McCulloch CE, Cedars MI
J Clin Endocrinol Metab · 2026 Mar · PMID 41817388 · Publisher ↗
CONTEXT: While literature suggests women with diminished ovarian reserve may have increased metabolic risk, implications for long-term health are unknown. OBJECTIVE: To investigate the relationship between ovarian reserv...
CONTEXT: While literature suggests women with diminished ovarian reserve may have increased metabolic risk, implications for long-term health are unknown. OBJECTIVE: To investigate the relationship between ovarian reserve markers at baseline with a subsequent measure of endothelial dysfunction, as a proxy for cardiovascular risk. DESIGN: Prospective cohort study. SETTING: Community-based setting. PATIENTS OR OTHER PARTICIPANTS: 322 subjects from the Ovarian Aging Study (OVA), an NIH-funded study of ovarian aging (average 35.4 years old at the time of baseline ovarian reserve measurements, and 45.1 years old at the time of endothelial dysfunction measurement). MAIN OUTCOMES MEASURE(S): This study investigated the association of ovarian reserve markers at baseline with a subsequent (average of 9.7 years) assessment of cardiovascular risk using the EndoPAT reactive hyperemia index (RHI) score of endothelial function. Secondary outcomes including the American Heart Association PREVENT score, metabolic syndrome, telomere length, and mitochondrial DNA were evaluated. RESULTS: RHI as a continuous outcome was significantly positively associated with both anti-Müllerian hormone (AMH) and antral follicle count (AFC) on fully adjusted models (AMH Coeff 0.052 95% CI 0.008 to 0.096, p = 0.02; AFC Coeff 0.017, 95% CI 0.001 to 0.032, p = 0.04). For secondary outcomes, the only result that was significant was the association of fully adjusted AFC with metabolic syndrome (OR 0.92, 95% CI 0.86-0.99, p = 0.02). A sensitivity analysis of the premenopausal cohort (N = 246) had similar findings. CONCLUSIONS: In this longitudinal cohort of women with normal ovarian aging, baseline ovarian reserve markers of AMH and AFC were positively associated with endothelial function as a continuous outcome. Baseline ovarian reserve markers were not related to most secondary outcomes of cellular aging and metabolic risk.
The role of high BMI from infancy forward on clinician-rated pubertal timing in a large US sample.
Sadikova E, Deardorff J, Aris IM … +4 more , Diemer E, Aghaee S, Tiemeier H, Kubo A
J Clin Endocrinol Metab · 2026 Mar · PMID 41812234 · Publisher ↗
CONTEXT: High childhood adiposity accelerates pubertal timing, particularly in females. However, it is unclear when in childhood intervention is most important. OBJECTIVE: To disentangle the associations of body mass ind...
CONTEXT: High childhood adiposity accelerates pubertal timing, particularly in females. However, it is unclear when in childhood intervention is most important. OBJECTIVE: To disentangle the associations of body mass index (BMI) during infancy, early, mid-, and late childhood with pubertal timing. METHODS: We studied 132,452 (46.6% female) full-term singletons born in Kaiser Permanente Northern California affiliated facilities between 01/01/2003 and 12/31/2011. A mediation analysis was used to disentangle how BMI during infancy (<2 years), early (2-<5 years), mid- (5-<9 years) and late (9+ years) childhood is associated with clinician-assessed Sexual Maturity Ratings (SMRs) for pubarche, thelarche, and gonadarche. Controlled direct effects isolated the impact of high BMI in earlier childhood periods only, while total effects included accumulating impact through subsequently high BMI. Risks for outcome onset (SMR≥2) were assessed for BMI 1 and 2 standard deviations above the population mean (+1SD and +2SD), respectively. RESULTS: Pubertal timing was not meaningfully associated with high BMI in infancy and early childhood (risk differences <0.001 to 0.007). High BMI in mid- and late childhood was associated with earlier pubertal onset, particularly in females. At median onset age, controlled direct effect risk differences for mid-childhood BMI +2SD ranged from 0.015, 95%CI (0.013,0.017) for male pubarche to 0.112, 95%CI (0.103,0.121) for female thelarche. Mid-childhood total effects exceeded controlled direct effects, indicating accumulation of impact due to persistence of high BMI into late childhood. CONCLUSION: Preventing high BMI in mid- and late childhood, but not in the first 4 years of life, may decelerate pubertal onset.
Circulating levels of ghrelin and hyperphagia in patients with rare genetic neurodevelopmental disorders.
Diene G, Benvegnu G, Brochado C … +14 more , Clerc A, Jouret B, Montastier E, Grunenwald S, Poitou C, Heron D, des Portes V, Cohen D, Consoli A, Demily C, Burglen L, Anfejar A, Valette M, Tauber M
J Clin Endocrinol Metab · 2026 Mar · PMID 41811759 · Publisher ↗
CONTEXT: Hyperphagia, overweight and obesity are frequent in people with rare neurodevelopmental disorders (NDDs). Prader-Willi syndrome (PWS) is a rare NDD with hyperphagia and hyperghrelinemia. OBJECTIVES: To measure g...
CONTEXT: Hyperphagia, overweight and obesity are frequent in people with rare neurodevelopmental disorders (NDDs). Prader-Willi syndrome (PWS) is a rare NDD with hyperphagia and hyperghrelinemia. OBJECTIVES: To measure ghrelin levels, hyperphagia and caregiver burden in rare NDDs patients to understand pathophysiology and improve care. DESIGN: A single-visit, non-interventional, national, multicenter, cross-sectional study. SETTING: Seven French reference centers for rare NDDs participated. PATIENTS: 130 patients (43% children) with a rare genetic NDD (27 distinct conditions) were included. Their median age was 19.8 years. Three control groups were used for comparison: "PWS" (n=153), "Obese" (n= 49), and "Lean" (n=31) groups. MAIN OUTCOME MEASURE(S): The primary endpoint was ghrelin level (total, acylated (AG), unacylated (UAG)). The first secondary endpoint was hyperphagia questionnaire (HQ) scores. RESULTS: Median total ghrelin levels were 76.7 [22.2-1110.9] pg/mL; median AG levels were 33.7 [8.0-754.3] pg/mL; and median UAG levels were 44.2 [11.5-356.6] pg/mL, which were lower than the PWS group (p<0.001) and no different from the Obese group. The mean HQ total score was 26.3 [10-46] for children and 24.0 [11-52] for adults. The HQ total score was statistically higher in children with NDDs and lower in adults compared to PWS. The mean ZBI score was 37.8 [6-74] in children and 37.6 [2-76] in adults, and was positively correlated with the HQ total score. CONCLUSIONS: Ghrelin levels were normal in our study population. Hyperghrelinemia is a biomarker of PWS. Hyperphagia is more prevalent and severe in children with NDDs compared with PWS.
Efficacy of liquid-chromatography and radioimmunoassay in false-positives' drop-off in CAH newborn screening.
Carvalho DF, Lima-Valassi HP, Hayashi GY … +9 more , Oliveira ACM, Matias GSS, Alves ANL, Miranda MC, Funari M, Madureira G, Latrônico AC, Mendonca BB, Bachega TAS
J Clin Endocrinol Metab · 2026 Mar · PMID 41811754 · Publisher ↗
CONTEXT: The main challenge in congenital adrenal hyperplasia newborn screening (CAH-NBS) is the high rate of false-positive (FP) results, emphasizing the need for specific serum confirmatory tests. Data on the effective...
CONTEXT: The main challenge in congenital adrenal hyperplasia newborn screening (CAH-NBS) is the high rate of false-positive (FP) results, emphasizing the need for specific serum confirmatory tests. Data on the effectiveness of serum 17-hydroxyprogesterone (17OHP) measurements using available methodologies remain limited. OBJECTIVES: to evaluate the efficacy of confirmatory tests using measurements of serum steroids by radioimmunoassay (RIA) and liquid chromatography tandem mass spectrometry (LC-MS/MS) methodologies. DESIGN AND SETTING: A prospective longitudinal cohort study. PATIENTS: data of 708,437 newborns (NBs) were evaluated. METHODS: neonatal-17OHP (N17OHP) results ≥ 2x 99.5th were recalled for serum dosages by RIA (17OHP), by LC-MS/MS (17OHP, 21-deoxycortisol-21DF, androstenedione-Δ4, cortisol) and positive predictive values (PPV) were determined. Altered hormonal results were submitted to CYP21A2 genotyping. Non-parametric tests and ROC-curves were used. RESULTS: Recall rate of N17OHP (first tier) was 0.03% and serum 17OHP levels remained increased in 26% (RIA) and 11% (LC-MS/MS) of NBs, yielding PPV of 30% and 49%, respectively. Fifty-eight NBs were diagnosed with classical forms, and 32 asymptomatic-NBs persisted with increased serum 17OHP levels. ROC-curves between false and true-positive tests disclosed highest diagnostic performance for 17OHP/LC-MS/MS [cutoff 48.3 ng/mL (146.3 nmol/L) = 100%-sensitivity]. The (17OHP+Δ4)/cortisol ratio presented the highest discriminative ability (cutoff 24.9 = 100%-PPV); serum 21DF presented a good performance and was comparable to 17OHP measured by LC-MS/MS (99%-specificity). CONCLUSION: Measurement of 17OHP by LC-MS/MS provides the best performance for serum confirmatory tests and may be complemented by the (17OHP+Δ4)/cortisol ratio analysis. Genotyping is useful mainly to resolve persistently indeterminate biochemical results.
Relative maternal protection against type 1 diabetes: a combined analysis of five observational studies.
Allen LA, Taylor PN, Carlsson A … +14 more , Fraser DP, Hagopian WA, Hedlund E, Hill AV, Jones AG, Ludvigsson J, Mortimer GL, Onengut-Gumuscu S, Redondo MJ, Rich SS, Williams CL, Gillespie KM, Dayan CM, Oram RA
J Clin Endocrinol Metab · 2026 Mar · PMID 41810517 · Publisher ↗
CONTEXT: Maternal (versus paternal) type 1 diabetes is associated with a relative reduction in type 1 diabetes risk in offspring during early life. OBJECTIVE: To determine whether this effect extends into later life. To...
CONTEXT: Maternal (versus paternal) type 1 diabetes is associated with a relative reduction in type 1 diabetes risk in offspring during early life. OBJECTIVE: To determine whether this effect extends into later life. To clarify the importance of intrauterine exposure to maternal type 1 diabetes, and baseline genetic susceptibility in this context. METHODS: We compared the proportion of individuals with type 1 diabetes diagnosed age 0-88 years with affected mothers and fathers across five observational studies (n=11,475), and used random-effects meta-analyses to generate overall effect estimates. We examined this by age at diagnosis, and timing of parental diagnosis relative to offspring birth. We compared the type 1 diabetes genetic risk score (T1D-GRS2) of individuals with affected mothers and fathers. RESULTS: Almost half as many individuals with type 1 diabetes had an affected mother versus father (OR 0.55 (95% CI 0.48, 0.64), p<0.0001). A lower proportion of individuals with affected mothers than fathers was apparent even amongst individuals diagnosed as adults (>18 years) (OR 0.63 (95% CI 0.43, 0.91), p=0.01). The lower proportion of individuals with maternal versus paternal type 1 diabetes was only observed if maternal diagnosis preceded offspring birth (OR 0.51 (95% CI 0.37, 0.70), p<0.001 versus OR 0.97 (95% CI 0.69, 1.38), p=0.87 after birth). T1D-GRS2 was similar between individuals with affected mothers and fathers (p=0.25). CONCLUSION: Our analyses suggest intrauterine exposure to maternal type 1 diabetes is associated with long-lasting relative protection against offspring type 1 diabetes, which is independent of genetic susceptibility as measured by T1D-GRS2.
Non-coding variants in intron 2 of HK1 associated with hyperinsulinism with variable clinical phenotype.
Boodhansingh KE, Lord K, Sigal W … +8 more , Benjet JE, Chen P, Juliana CA, Mitteer L, Bhatti T, Stanley CA, De Leon DD, Ganguly A
J Clin Endocrinol Metab · 2026 Mar · PMID 41810512 · Publisher ↗
INTRODUCTION: Non-coding variants in HK1 were first associated with congenital hyperinsulinism (HI) in a large family with diazoxide-responsive HI in 2008. Since then, additional cases have been reported in the literatur...
INTRODUCTION: Non-coding variants in HK1 were first associated with congenital hyperinsulinism (HI) in a large family with diazoxide-responsive HI in 2008. Since then, additional cases have been reported in the literature with non-coding variants in HK1 associated with variable HI phenotypes. METHODS: We sequenced a 350bp region in intron 2 of HK1 in 281 individuals with genetics negative HI to identify additional cases related to non-coding HK1 variants and to characterize the clinical features of these cases. RESULTS: We identified 16 unique non-coding variants in intron 2 of HK1 in 18 individuals with genetics negative HI (18/281, 6.4%). In seven cases (7/18, 39%), the HK1 variant was inherited from a parent (2 maternal, 5 paternal), two are known to be affected with HI. In nine cases, the HK1 variant was de novo (9/18, 50%). The age of presentation of HI ranged from day of life one to 21 months of age. Seven cases had diazoxide-responsive HI (7/18, 39%). Eleven cases were diazoxide unresponsive (11/18, 61%); five underwent pancreatectomy at ages ranging from six months to three years of age. CONCLUSIONS: Non-coding variants in intron 2 of the HK1 gene have now been associated with HI in a growing number of cases. Our findings suggest that a significant proportion of individuals with negative genetics in genes currently known to be associated with HI may harbor HK1 intron 2 variants. Identifying these cases is important for clinical care as well as for assessing recurrence risk for families.
Comparing Surrogate Indexes for Insulin Resistance as Predictors of Type 2 Diabetes (T2D).
Vazquez L, Arreola EV, Nagul M … +2 more , Krakoff J, Hanson RL
J Clin Endocrinol Metab · 2026 Mar · PMID 41805838 · Publisher ↗
CONTEXT: Decreased insulin sensitivity (insulin resistance) is associated with increased type 2 diabetes (T2D) risk. Identifying reliable surrogate indexes that use standard clinical assays might improve prevention of T2...
CONTEXT: Decreased insulin sensitivity (insulin resistance) is associated with increased type 2 diabetes (T2D) risk. Identifying reliable surrogate indexes that use standard clinical assays might improve prevention of T2D. OBJECTIVE: The objective was to compare the ability of 18 surrogate indexes of insulin resistance to predict T2D. DESIGN: Cohort study of indigenous Americans from the Southwest US. SETTING: Community-based longitudinal study. PATIENTS AND OTHER PARTICIPANTS: We studied T2D risk in 2260 people followed for up to 14.5 years (509 cases of T2D). We estimated correlation coefficients (r) of all indexes with sensitivity (M) measured by hyperinsulinemic-euglycemic clamp in 286 persons. We calculated indexes obtained from oral glucose tolerance tests (OGTTs) using fasting and 2-hr glucose and insulin measures. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Predictive performance was assessed by the hazard ratio (HR) per SD and by the area under the receiver operating curve (AUC). RESULTS: Indexes calculated from OGTTs performed best; Matsuda had the highest r with M (0.691); Gutt and Cederholm had the highest AUCs (0.728 and 0.728, P<0.05 compared with all other indexes). In indexes that only used fasting insulin levels, QUICKI and HOMA-IR had the best performance with equal r (0.644) and AUC (0.701). Among indexes that did not require insulin measurement: METS-IR and SPISE had the highest r (0.597 and 0.595) while METS-IR had the highest AUC (0.688). CONCLUSION: Surrogate measures based on OGTTs are best for predicting T2D, while measures based on fasting insulin perform better than those that do not measure insulin.
Early pregnancy biomarkers of inflammation and metabolic regulation in polycystic ovary syndrome.
Alesi S, Mason T, Ellery SJ … +10 more , Rassie K, Neven ACH, Belsti Y, Jona E, O'Reilly S, Simmons D, Teede H, Mousa A, IMPACT DIABETES B2B&ME , TOBOGM Study Groups
J Clin Endocrinol Metab · 2026 Mar · PMID 41802911 · Publisher ↗
OBJECTIVE: To profile biomarkers of inflammation and metabolic regulation in early pregnancy among women with and without polycystic ovary syndrome (PCOS), and to assess whether these biomarkers influence the relationshi...
OBJECTIVE: To profile biomarkers of inflammation and metabolic regulation in early pregnancy among women with and without polycystic ovary syndrome (PCOS), and to assess whether these biomarkers influence the relationship between PCOS and adverse maternal or neonatal outcomes. DESIGN: Cross-sectional study with interaction analyses using pooled baseline data from two international multicentre clinical trials. SUBJECTS: 151 pregnant women (at <24 weeks' gestation) at risk of gestational diabetes mellitus, including 65 with PCOS and 86 without PCOS. MAIN OUTCOME MEASURES: Early pregnancy markers of inflammation and metabolic regulation were assessed, including C-reactive protein, tumour necrosis factor-α, interleukins, monocyte chemoattractant protein-1 (MCP1), fatty acid binding protein-4 (FABP4), growth differentiation factor-15, and adipokines (total adiponectin, leptin, resistin, chemerin, vaspin and cathepsin-S. Biomarkers differing by PCOS status were further examined for interaction effects on maternal and neonatal outcomes. RESULTS: MCP1 concentrations were 15% higher in women with PCOS compared with those without (geometric mean ratio [GMR]: 1.15; 95% CI: 1.01, 1.31; p=0.04), but this association was attenuated after adjustment for maternal age and BMI. Early pregnancy FABP4 concentrations were 32% higher in women with PCOS compared to those without (GMR: 1.32; 95% CI: 1.04, 1.68; p=0.02), and this association remained significant after adjustment for maternal age (GMR: 1.34; 95% CI: 1.05-1.71; p=0.02), but was attenuated after adjustment for BMI. No other biomarkers differed by PCOS status, and MCP1 or FABP4 showed no interactions with maternal or neonatal outcomes. CONCLUSIONS: MCP1 and FABP4 concentrations were elevated in early pregnancy among women with PCOS, largely reflecting maternal adiposity. These markers did not modify associations between PCOS and pregnancy outcomes. Larger longitudinal studies are needed to clarify underlying inflammatory and metabolic pathways.
Multimodal MRI Neurodevelopmental Profiling in Type 1 Diabetes: Long-term Effects of MDI vs CSII Treatments.
Della Rosa PA, Pecco N, Calloni SF … +16 more , Canini M, Oprandi C, Pavani D, Grimaldi G, Veronese L, Favalli V, Frontino G, Gambarini A, Olivieri G, Scotti R, Pontesilli S, Ogliari A, Rigamonti A, Falini A, Baldoli C, Bonfanti R
J Clin Endocrinol Metab · 2026 Mar · PMID 41793758 · Publisher ↗
CONTEXT: The developing brain is particularly vulnerable to glycemic extremes in early-onset type 1 diabetes (T1D). However, how treatment-specific modalities may influence long-term neurodevelopmental trajectories remai...
CONTEXT: The developing brain is particularly vulnerable to glycemic extremes in early-onset type 1 diabetes (T1D). However, how treatment-specific modalities may influence long-term neurodevelopmental trajectories remains poorly understood. OBJECTIVE: To characterize multimodal MRI neurodevelopmental profiles in pediatric T1D and evaluate treatment-related effects of Multiple Daily Injections (MDI) versus Continuous Subcutaneous Insulin Infusion (CSII) on brain structure, function, and test whether HbA1c-linked imaging features relate to executive-working-memory performance. METHODS: Sixteen children with T1D (8 MDI, 8 CSII from diagnosis) and eight controls underwent structural MRI, diffusion MRI, and resting-state fMRI. Union Recursive Feature Elimination (U-RFE) selected gray-matter (GM), white-matter (WM), and functional connectivity (rs-FC) features discriminating groups; regression related selected features to long-term age-adjusted mean glycated hemoglobin (HbA1c). NEPSY-II Word List Interference (WI) was administered; control-referenced WI outcomes were examined versus HbA1c and HbA1c-associated structural features, including mediation. RESULTS: Functional features outperformed structural features (balanced accuracy 0.83 vs 0.67). MDI showed reduced GM/WM integrity and disrupted fronto-temporal and subcortical connectivity versus CSII and controls. Right inferior frontal gyrus (IFG) volume correlated with HbA1c (r=0.71, p<0.05) and predicted HbA1c (β=0.28, p=0.015). Higher HbA1c related to poorer WI repetition (r=-0.60, p=0.013), and right IFG volume related to poorer WI repetition (r=-0.70, p=0.002). Mediation supported an indirect HbA1c effect via right IFG volume (a×b=-0.676; Sobel z=-1.765, one-tailed p=0.0388), explaining ∼64% of the total association. CSII had 30% lower hyperglycemia exposure than MDI and higher WI repetition mean ranks (11.19 vs 5.81; p=0.023). CONCLUSIONS: Pediatric T1D is associated with multimodal neuroimaging alterations influenced by insulin treatment modality. CSII may confer neuroprotective benefits by improving metabolic control and preserving functional connectivity. Right IFG volume is a candidate imaging marker linking metabolic regulation to interference-sensitive executive-working-memory vulnerability.
Efficacy of 24-Weekly Versus 12-Weekly Decapeptyl SR Treatment in Central Precocious Puberty: A UK Multicentre Retrospective Cohort Study.
Varughese R, Lake L, Kothayan B … +16 more , Ahmed NS, Aitken K, Bhavsar K, Edwards J, Newsome A, P S Pinto S, Thomas D, Woodhouse A, Russell J, O'Sullivan JP, Connolly E, Sharratt I, Cheetham T, Elder CJ, Wood CL, Howard SR
J Clin Endocrinol Metab · 2026 Mar · PMID 41793064 · Publisher ↗
OBJECTIVE: To evaluate the efficacy of 24-weekly Decapeptyl SR (Triptorelin) treatment, compared with the 12-weekly regimen, in children with central precocious puberty (CPP). METHODS: A multicentre retrospective cohort...
OBJECTIVE: To evaluate the efficacy of 24-weekly Decapeptyl SR (Triptorelin) treatment, compared with the 12-weekly regimen, in children with central precocious puberty (CPP). METHODS: A multicentre retrospective cohort study was conducted on patients with CPP treated with gonadotropin-releasing hormone analogue (GnRHa) therapy between September 2008 and December 2024. Participants were recruited from three tertiary paediatric endocrinology centres in the UK: the Royal London Hospital (Barts Health NHS Trust), Sheffield Children's Hospital (Sheffield Children's NHS Foundation Trust), and the Royal Victoria Infirmary (Newcastle upon Tyne Hospitals NHS Foundation Trust). Patients received either Decapeptyl SR 11.25 mg every 12 weeks or 22.5 mg every 24 weeks. Clinical, biochemical, and radiological data were collected at baseline and follow-up to assess hypothalamic-pituitary-gonadal (HPG) axis suppression and pubertal progression. RESULTS: Of 247 patients reviewed (220 girls and 27 boys), 164 were eligible for analysis; 69 in Group 1 (12-weekly) and 95 in Group 2 (24-weekly). Both regimens achieved effective HPG axis suppression, with no significant differences in luteinising hormone, follicle-stimulating hormone or sex steroid concentrations. Clinical outcomes, including height velocity, BMI, and Tanner staging, were comparable. The 24-weekly preparation was well-tolerated and demonstrated equivalent suppression of pubertal progression. Among patients who expressed a preference, all favoured the 24-weekly schedule. CONCLUSION: This UK multicentre study provides evidence that 24-weekly Decapeptyl SR is both efficacious and well-tolerated for the management of CPP, with comparable outcomes to the standard 12-weekly regimen. This is the first comparative analysis to establish clinical equivalence between these two regimens, which is particularly important given the reduced frequency of clinical monitoring in the longer-acting preparation. Fewer injections may improve adherence and patient satisfaction, alongside potential cost savings.
Antithyroid drug treatment in pregnancy: A first report from the Danish PRETHYR multicenter study.
Uldall-Torp NM, Pedersen IB, Carlé A … +13 more , Karmisholt JS, Ebbehøj E, Grove-Laugesen D, Brix TH, Bonnema SJ, Schrijvers BF, Nygaard B, Sigurd LB, Feldt-Rasmussen U, Klose M, Rasmussen ÅK, Andersen S, Andersen SL
J Clin Endocrinol Metab · 2026 Mar · PMID 41790746 · Publisher ↗
CONTEXT: Hyperthyroidism caused by Graves' disease (GD) should be treated in pregnancy to prevent maternal and fetal complications, however, side effects observed with antithyroid drugs (ATDs) may complicate current clin...
CONTEXT: Hyperthyroidism caused by Graves' disease (GD) should be treated in pregnancy to prevent maternal and fetal complications, however, side effects observed with antithyroid drugs (ATDs) may complicate current clinical management. OBJECTIVE: To investigate current treatment practices for hyperthyroidism during pregnancy in Denmark and the characteristics of women receiving ATDs. METHODS: The Danish multicenter study PRETHYR (Pregnancy Investigations on Thyroid Disease) included women with GD and women treated with ATDs in pregnancy. Maternal characteristics, pre-conception measurements of thyroid stimulating hormone (TSH), total triiodothyronine (TT3), and TSH-receptor antibodies (TRAb), and information on the clinical management and treatment before and during pregnancy, were obtained through patient questionnaires and review of the medical record. RESULTS: Of the 121 women included, 97.5% had GD. Among the 102 women with known thyroid disease preconceptionally and no prior definitive treatment, 58.8% (n = 60) received ATDs in pregnancy. These women were more often managed by endocrinologist at conception, had lower preconception TSH and higher TT3 and TRAb compared to women not treated with ATDs. Treatment was predominantly confined to the first half of the first trimester and generally discontinued by the second or third trimester. Prior to conception, 59.1% of women treated with methimazole (MMI) were switched to propylthiouracil (PTU), and 10.7% were switched from PTU to MMI. CONCLUSIONS: This is the first report from a multicenter study on pregnant women with GD and women treated with ATDs during pregnancy. The results provide insight into the current clinical treatment practices of hyperthyroidism in Denmark.
Partial Pressure of Oxygen-Guided Adrenal Venous Sampling in Primary Aldosteronism.
Omata K, Tezuka Y, Tannai H … +13 more , Ono Y, Ishihata H, Kamada H, Oguro S, Kawasaki Y, Ito A, Yamazaki Y, Sasano H, Suzuki T, Tanaka T, Takase K, Katagiri H, Satoh F
J Clin Endocrinol Metab · 2026 Mar · PMID 41789722 · Publisher ↗
BACKGROUND: Adrenal venous sampling (AVS) plays a pivotal role in treatment optimization for primary aldosteronism (PA) to minimize the cardiovascular risks. However, technical difficulties often hinder accurate cannulat...
BACKGROUND: Adrenal venous sampling (AVS) plays a pivotal role in treatment optimization for primary aldosteronism (PA) to minimize the cardiovascular risks. However, technical difficulties often hinder accurate cannulation to the adrenal veins (AVs). This study aimed to explore the distribution of partial pressure of oxygen (pO2) in the adrenal and neighboring veins, inspired by our awareness of lighter red color of adrenal venous blood than the others. METHODS: We enrolled 179 PA patients who underwent AVS from 2021 to 2024. During AVS, we collected residual blood samples from bilateral adrenal, hepatic, inferior phrenic and external iliac veins for blood gas analysis. Statistical analysis was conducted to evaluate pO2 distributions and its associations with clinical parameters. RESULTS: Among 179 patients examined, 168 received oxygen supplementation during AVS and in those cases, the pO2 levels were significantly higher in the bilateral AVs than in the hepatic and inferior phrenic veins at baseline, whereas the levels of partial pressure of carbon dioxide were lower. Following cosyntropin stimulation, the pO2 levels in the AVs decreased but distribution patterns across the examined veins remained similar. The pO2 evaluation provided highly accurate identification of AVs both before and after cosyntropin stimulation. CONCLUSION: This is the first study to examine the pO2 dynamics in the human adrenal and non-adrenal veins, demonstrating its potential to improve AVS cannulation success rates. Our findings also presented the oxygen consumption in the adrenal glands for steroidogenesis. The pO2 measurement is a faster, easier and less-expensive tool enhancing AVS techniques.
Long-acting growth hormone for treating growth hormone deficiency in children: a meta-analysis of randomized controlled trials focusing on changes in body mass index.
Levaillant L, Bouhours-Nouet N, Emeriau F … +9 more , Donzeau A, Rouleau S, Villanueva C, Perge K, Teinturier C, Castets S, Linglart A, Reynaud R, Coutant R
J Clin Endocrinol Metab · 2026 Apr · PMID 41787735 · Full text
BACKGOUND: The purpose of this study is to compare the effect of long-acting growth hormone (LAGH) to daily GH on body mass index (BMI) in children with growth hormone deficiency (GHD). METHODS: We searched the PubMed da...
BACKGOUND: The purpose of this study is to compare the effect of long-acting growth hormone (LAGH) to daily GH on body mass index (BMI) in children with growth hormone deficiency (GHD). METHODS: We searched the PubMed database from its inception to July 2025 and identified three relevant randomized controlled trials lasting over 6 months, with extension phases providing longitudinal BMI data. Longitudinal BMI data were available for lonapegsomatropin, somatrogon, and somapacitan, but not for polyethylene glycol LAGH. RESULTS: A total of 585 patients were included in the present analysis, of which 346 were in the LAGH group, and 239 were in the daily rhGH group, derived from seven original articles and two abstracts/ePosters. At 12 months, there was a significant difference in BMI SD scores between LAGH and daily GH groups (Mean difference [MD] 0.66 SDS [95% confidence interval [CI] 0.04-1.29]). BMI SDS significantly increased in the LAGH group (MD + 0.41 SDS [95% CI 0.04-0.77] from 0 to 12 months), whereas it did not change in the daily GH group (MD -0.35 SDS [95% CI -0.76 to +0.07] from 0 to 12 months). Between 12 and 24 months, after switching from daily GH to LAGH (daily GH/LAGH), or pursuing LAGH (LAGH/LAGH) in the extension phases of the studies, BMI SDS significantly increased in the daily GH/LAGH switching group (MD + 0.75 SDS [95% CI 0.24-1.27] from 12 to 24 months), whereas it remained steady in the LAGH/LAGH group. Omitting one study at a time from the meta-analysis did not materially affect the results. CONCLUSION: An increase in body mass index SD score is associated with the first year of LAGH use.
The effects of glucose-dependent insulinotropic polypeptide on net splanchnic blood flow in lean humans.
Asmar M, Bülow J, Holst JJ … +1 more , Asmar A
J Clin Endocrinol Metab · 2026 Mar · PMID 41782271 · Publisher ↗
OBJECTIVE: The aim of this study was to examine the effects of glucose-dependent insulinotropic polypeptide (GIP) on splanchnic blood flow, both independently and in combination with hyperglycemia and hyperinsulinemia. D...
OBJECTIVE: The aim of this study was to examine the effects of glucose-dependent insulinotropic polypeptide (GIP) on splanchnic blood flow, both independently and in combination with hyperglycemia and hyperinsulinemia. DESIGN AND METHODS: In a randomized, placebo-controlled, crossover trial, eight healthy, lean male participants underwent four separate experimental conditions. Splanchnic blood flow was measured by Fick's Principle after catheterization of a hepatic vein, using indocyanine green as indicator. The interventions included intravenous infusions of either GIP at a rate of 1.5 pmol/kg/min or saline, administered alone or in combination with a hyperglycemia and hyperinsulinemia clamp, respectively. RESULTS: Splanchnic blood flow remained comparable across all experimental conditions, including GIP and saline infusions, both with and without the hyperglycemic and hyperinsulinemic clamp (P=0.42). CONCLUSION: Under the applied conditions, GIP does not appear to play a substantial role in the acute regulation of net splanchnic blood flow, either alone or in combination with induced hyperglycemia and hyperinsulinemia.
Approach to the Patient With Traumatic Brain Injury-induced Pituitary Dysfunction.
Kelestimur F, Agha A, Ioachimescu AG … +3 more , McDonald D, Karaca Z, Yuen KCJ
J Clin Endocrinol Metab · 2026 May · PMID 41782180 · Publisher ↗
Traumatic brain injury (TBI), a growing public health concern worldwide, has recently been recognized as one of the most common etiologies of hypopituitarism. Leading causes of TBI-induced pituitary dysfunction include r...
Traumatic brain injury (TBI), a growing public health concern worldwide, has recently been recognized as one of the most common etiologies of hypopituitarism. Leading causes of TBI-induced pituitary dysfunction include road traffic accidents, falls, domestic violence, sport-related injuries, and war injuries. The prevalence of hypopituitarism after TBI is about 15%, and GH is the most common pituitary hormone deficiency after TBI. Because the clinical spectrum of TBI-induced pituitary dysfunction is broad and most of the manifestations are nonspecific, the diagnosis is often delayed, and many patients remain undiagnosed and untreated. Current evidence shows that pituitary hormone deficiencies seen in patients with mild and moderate TBI may improve over time in a considerable number of patients, but some may also worsen. Since not all TBI patients develop pituitary dysfunction, testing all patients with a history of TBI is not realistic and cost-effective. Predictive factors of post-TBI hypopituitarism including number of hormone deficiencies during acute phase, radiological abnormalities, genetic polymorphism, older age, and female gender should be taken into account for the development of screening strategies. Prospective screening of pituitary functions is required in complicated mild TBI (defined as clinically mild by all severity measures but considered complicated due to a traumatic intracranial abnormality visible on neuroimaging), moderate TBI, and severe TBI patients. Increased awareness of TBI-induced hypopituitarism in the medical community may lead to earlier diagnosis and prompt treatment of hypopituitarism with appropriate replacement of deficient hormones.
Health-Related Quality of Life in Children with Multiple Endocrine Neoplasia (MEN) and their Siblings.
Zwerus D, Verrijn Stuart AA, van Santen HM … +9 more , Valk GD, de Bruin C, Sas TCJ, Bocca G, Mooij CF, Claahsen-van der Grinten HL, Straetemans S, Schepers SA, van Leeuwaarde RS
J Clin Endocrinol Metab · 2026 Mar · PMID 41779164 · Publisher ↗
CONTEXT: Multiple Endocrine Neoplasia (MEN) syndromes are rare autosomal dominant hereditary tumor predisposition syndromes affecting multiple family members. Carriers undergo health surveillance from early childhood onw...
CONTEXT: Multiple Endocrine Neoplasia (MEN) syndromes are rare autosomal dominant hereditary tumor predisposition syndromes affecting multiple family members. Carriers undergo health surveillance from early childhood onwards. Carriership or surveillance may influence Health-Related Quality of Life (HRQoL) for patients or their families. OBJECTIVE: To evaluate HRQoL in children and adolescents with genetically confirmed MEN1, MEN2A, and MEN2B, and to compare outcomes with their siblings without MEN and healthy Dutch norms. Secondary aims were to explore associations between HRQoL and clinical characteristics. METHODS: This nationwide cross-sectional study included 77 children with MEN (5-18 years) and 26 siblings (8-29 years). The Pediatric Quality of Life Inventory (PedsQL) was used to assess HRQoL, with children completing self-report questionnaires and parents providing proxy reports for their children with MEN. Sociodemographic and clinical data were obtained from medical records. RESULTS: Children with MEN1 and MEN2A reported HRQoL comparable to siblings and healthy Dutch norms. Only children with MEN2B showed significantly lower physical HRQoL. No gender or age effects were observed. Parent-proxy scores were significantly higher than child self-reports on all domains, except for emotional functioning. Children with MEN1 and MEN2B having clinical MEN-related manifestations, had significantly lower physical, social, and school functioning scores than those without clinical manifestations. CONCLUSION: Overall, children with MEN reported HRQoL comparable to siblings and age-matched Dutch norms, except for reduced physical functioning in MEN2B. Clinical manifestations negatively affected physical, social, and school functioning, suggesting that children with onset of disease may benefit from closer monitoring and targeted psychosocial support.
Timeliness of Antiresorptive Consolidation After Anabolic Therapy for Primary Fracture Prevention: A U.S. Cohort Study.
Badour S, McCoy RG, Takagi M … +7 more , Everhart AO, Parimi J, Herrin J, Karaca-Mandic P, Wermers RA, Rosen CJ, Brito JP
J Clin Endocrinol Metab · 2026 Mar · PMID 41778369 · Full text
BACKGROUND: Osteoanabolic therapy for osteoporosis should be followed by antiresorptive treatment ("consolidation") to preserve bone mass. Although osteoanabolic therapy is increasingly endorsed for primary fracture prev...
BACKGROUND: Osteoanabolic therapy for osteoporosis should be followed by antiresorptive treatment ("consolidation") to preserve bone mass. Although osteoanabolic therapy is increasingly endorsed for primary fracture prevention, real-world implementation of consolidation remains unknown. OBJECTIVE: To assess patterns and predictors of timely consolidation after osteoanabolic therapy for primary fracture prevention. DESIGN: Retrospective cohort study. SETTING: U.S. commercial, Medicare Advantage, and traditional Medicare claims. PARTICIPANTS: Adults ≥50 years initiating romosozumab, teriparatide, or abaloparatide between 2011-2022. MEASUREMENTS: The primary outcome was timely consolidation-antiresorptive initiation within 3 months of osteoanabolic completion (≥12 months of treatment with romosozumab, ≥18 months with teriparatide/abaloparatide). Secondary outcomes were delayed consolidation (>3-month gap), osteoanabolic restart after a gap, and no consolidation. Multivariable logistic regression identified predictors. RESULTS: Among 15,389 patients (mean age 70.6 years; 89% women; 85% White), 30% completed osteoanabolic therapy (median, 12.9 months for romosozumab; 23.4 months for teriparatide/abaloparatide). Overall, 25% had timely consolidation, 24% delayed consolidation, 12% restarted osteoanabolics, and 40% had no consolidation; only 12% completed therapy with timely consolidation. Timely consolidation was more likely with endocrinology (OR 1.31; 95% CI, 1.17-1.48) or rheumatology (OR 1.45; 1.30-1.62) versus primary care, and less likely among patients aged 50-64 years (OR 0.67; 0.58-0.77) versus 65-74, those enrolled in Medicare Advantage (OR,0.85; 0.74-0.98) versus traditional Medicare, or those recently hospitalized (OR 0.88; 0.80-0.97). Odds increased over time (OR 4.27; 3.63-5.05 for 2021 vs. 2011 starts). LIMITATIONS: Administrative data lack clinical context. CONCLUSION: Only 1 in 4 patients received timely consolidation therapy after osteoanabolic treatment, and 1 in 8 completed the full sequence. Strategies to improve consolidation in primary fracture prevention are needed.
Efficacy and safety of pharmacologic therapies in acromegaly: a systematic literature review and network meta-analysis.
Salvatori R, Colzani RM, Hummel N … +6 more , Kopiec A, Maliszewska Z, Wang S, Okeyo JC, Cuddihy RM, Nachtigall LB
J Clin Endocrinol Metab · 2026 May · PMID 41773305 · Full text
CONTEXT: There are limited head-to-head trials comparing pharmacological treatments for acromegaly. OBJECTIVE: Systematically review the efficacy and safety of pharmacological treatments for acromegaly and conduct a netw...
CONTEXT: There are limited head-to-head trials comparing pharmacological treatments for acromegaly. OBJECTIVE: Systematically review the efficacy and safety of pharmacological treatments for acromegaly and conduct a network meta-analysis (NMA) enabling indirect comparisons. METHODS: MEDLINE and Embase were searched to identify randomized controlled trials (RCTs) of acromegaly therapies. Screening and data extraction followed PRISMA guidelines. Feasibility assessment evaluated homogeneity and consistency assumptions required for NMA. Bayesian NMAs estimated relative treatment effects and ranking probabilities. RESULTS: Twenty-two records covering 18 RCTs were included. Biochemical control rates were comparable among long-acting injectable somatostatin receptor ligands (SRLs), including lanreotide autogel (LAN-ATG), octreotide long-acting release (OCT-LAR), pasireotide, the GH receptor antagonist pegvisomant, oral octreotide (O-OCT), octreotide subcutaneous depot (SC-OCT-D), and the once-daily oral SRL paltusotine. Paltusotine demonstrated significantly higher biochemical control vs O-OCT and SC-OCT-D (odds ratios [ORs], 95% credible intervals [CrIs]: 7.34 [1.48-36.07] and 7.85 [1.72, 36.25]). Pasireotide showed significantly higher biochemical control vs OCT-LAR (OR: 2.03 [1.29-3.23]). Paltusotine had significantly lower discontinuations due to adverse events (AEs) vs O-OCT and SC-OCT-D, (ORs: 0.022 [0.001-0.424] and 0.022 [0.001-0.343]), with similar rates to other treatments. Treatment-emergent AEs (TEAEs) and serious TEAEs were comparable across treatments. Rankings suggested paltusotine as the treatment with the highest probability of ranking as the most effective (or tolerable) treatment across all endpoints studied. CONCLUSION: This systematic review and NMA consolidate recent high-quality RCT evidence for acromegaly treatments. Paltusotine emerges as a promising alternative to injectable SRLs, with favorable efficacy, safety, and AE-related discontinuation patterns. These findings may inform clinical decision-making and guideline development, if confirmed by clinical experience.
Time trends in incidence, treatment and survival of patients with adrenocortical carcinoma, a nationwide study.
Steenaard RV, de Wit JS, Rutjens M … +5 more , van der Bruggen B, Blijdorp K, Wouters-van Poppel P, Feelders RA, Haak HR
J Clin Endocrinol Metab · 2026 Feb · PMID 41765867 · Publisher ↗
PURPOSE: We aimed to determine time trends in incidence, treatment and survival of patients with adrenocortical carcinoma in the Netherlands. METHODS: All 685 adult patients with adrenocortical carcinoma diagnosed betwee...
PURPOSE: We aimed to determine time trends in incidence, treatment and survival of patients with adrenocortical carcinoma in the Netherlands. METHODS: All 685 adult patients with adrenocortical carcinoma diagnosed between 1993 and 2020 in the Netherlands were included, using the nation-wide prospective Netherlands Cancer Registry. RESULTS: The median age-adjusted incidence rate based on the European Standard Population was 1.62 per million person-years [0.83-2.11] and was stable over time. We saw a gradual increase in stage III on diagnosis (13 to 25%) with a stable proportion of stage IV (40%). The five-year survival remained stable over time for stage I-II at 65% and stage III at 35%, while the survival for stage IV increased from 3% in 1993-1996 to 11% in 2017-2020. Since the Dutch Adrenal Network was founded in 2004, more patients were referred to an expert center (p<0.001), which was associated with increased survival (adjusted HR 0.70, 95%CI[0.57-0.85]). Multivariate cox-regression showed increased survival in all stages when treated with adrenalectomy (adjusted HR 0.53, 95%CI[0.43-0.65]) and mitotane therapy (adjusted HR 0.73, 95%CI[0.55-0.98]). In stage IV disease, adrenalectomy, surgical control of disease, chemotherapy and mitotane therapy were associated with increased survival. However, only 58% of mitotane users reached a therapeutic drug level and 59.5% discontinued treatment prematurely. CONCLUSIONS: The incidence of adrenocortical carcinoma is stable over time. The five-year survival for stage I-III remained stable, while the survival for stage IV increased. Factors associated with increased survival are centralization of care, adrenalectomy, surgical control of disease, chemotherapy and mitotane therapy.
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