The Journal Of Clinical Endocrinology And Metabolism[JOURNAL]
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200 papers
Impact of Mild Autonomous Cortisol Secretion on Bone Density, Metabolism, and Microstructure: A Cross-sectional Study.
Zhang CD, Saini J, Singh S … +9 more , Suresh M, Thangamuthu K, Nathani R, Ebbehoj A, Fell V, Achenbach SJ, Atkinson EJ, Khosla S, Bancos I
J Clin Endocrinol Metab · 2026 Apr · PMID 41988710 · Publisher ↗
CONTEXT: Patients with mild autonomous cortisol secretion (MACS) have higher rates of vertebral fractures compared to patients with non-functioning adrenal nodules, yet bone density is not always reduced. OBJECTIVE: To c...
CONTEXT: Patients with mild autonomous cortisol secretion (MACS) have higher rates of vertebral fractures compared to patients with non-functioning adrenal nodules, yet bone density is not always reduced. OBJECTIVE: To characterize the effect of MACS on bone density, metabolism, and microstructure as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). DESIGN: Cross-sectional study, 2019-2022. SETTING: Tertiary referral center. PARTICIPANTS: 75 patients with MACS and 75 age-, sex-, and gonadal status matched referent subjects. MEASUREMENTS: Bone turnover markers, dual-energy x-ray absorptiometry (DXA) scan, and HR-pQCT. OUTCOMES: Areal and volumetric bone mineral density (aBMD, vBMD), trabecular bone score (TBS), microstructural parameters including trabecular bone volume to total volume (BV/TV) ratio. RESULTS: While no differences in aBMD were observed at any skeletal site, patients with MACS had decreased TBS (1.389 vs 1.475, P < 0.001) and lower osteocalcin concentration (17.1 vs 19.5 ng/mL, P = 0.030) than referent subjects. On HR-pQCT at the tibia, patients with MACS had reduced trabecular BV/TV (0.220 vs 0.233, P = 0.015) compared to referent subjects. On multivariable analysis, MACS was associated with lower TBS (OR per SD decrease 2.87 [1.65-5.00]), lower trabecular BV/TV at the radius (OR per SD decrease 2.58 [1.33-5.00]), and lower trabecular BV/TV at the tibia (OR per SD decrease 4.06 [2.10-7.86]). CONCLUSION: Patients with MACS have microstructural deterioration that may not be evident on routine DXA aBMD testing.
Current controversies in acromegaly care.
Spencer-Segal JL, Nachtigall LB
J Clin Endocrinol Metab · 2026 Jun · PMID 41981973 · Full text
Persistent disease after surgery for acromegaly is common. Expanding medical management options improves long-term biochemical and clinical outcomes, but controversies in acromegaly care remain. We review literature and...
Persistent disease after surgery for acromegaly is common. Expanding medical management options improves long-term biochemical and clinical outcomes, but controversies in acromegaly care remain. We review literature and provide recommendations regarding accelerating diagnosis, biochemical monitoring, symptom variability, preconception/pregnancy management, predictors of treatment response, and alternative dosing regimens. Delayed diagnosis of acromegaly persists, associated with increased morbidity. Advances in artificial intelligence may reduce diagnostic delay; but ethics, privacy issues, and application in diverse populations present challenges. Symptom variability is observed in patients receiving long-acting somatostatin receptor ligands (SRLs) and with other regimens, even when biochemical control is achieved. Dose titration intervals vary across therapies; discordance between biochemical and clinical response requires consideration of signs and symptoms in addition to insulin-like growth factor 1 levels. Premenopausal women with uncontrolled acromegaly are at risk of increased complications during pregnancy. Data on fertility, pregnancy, and fetal effects of acromegaly drugs are limited to case reports and series. Pregnancies and spontaneous conceptions occur in patients with acromegaly, typically with good maternal and fetal outcomes. Predictive algorithms identifying for whom first-line SRLs will be effective have been validated in investigational contexts, but implementation strategy, accuracy, and standardization in clinic practice are yet undetermined. Finally, alternative dosing regimens show promise for decreasing medication burden, cost, and/or improving control. We conclude that while there has been progress in emerging medical treatment options, controversies in acromegaly care persist, particularly with regard to patient-centered outcomes and utility of personalized approaches in real-life, large-scale clinical practice.
3D volume growth rate may open new perspectives for the classification of aggressive pituitary adenomas.
Graillon T, Tabouret E, Appay R … +11 more , Albarel F, Morange I, Sahakian N, Romanet P, Barlier A, Brue T, Mansourt A, Figarella-Branger D, Castinetti F, Cuny T, Dufour H
J Clin Endocrinol Metab · 2026 Apr · PMID 41973981 · Publisher ↗
PURPOSE: The 2022 WHO classification states no histological grading exists to assess pituitary adenoma (PA) aggressiveness. The European Society of Endocrinology refers to the term "unusually rapid growth rate" when defi...
PURPOSE: The 2022 WHO classification states no histological grading exists to assess pituitary adenoma (PA) aggressiveness. The European Society of Endocrinology refers to the term "unusually rapid growth rate" when defining an aggressive PA. This study aimed to evaluate three-dimensional volume growth rate (3DVGR) in multiple PAs and correlate it with tumor progression and histopathology. METHODS: Patients with growing or proliferative PAs who underwent surgery were retrospectively selected. Gadolinium-enhanced 3D T1-weighted MRI was required. RESULTS: A total of 76 3DVGR measurements were performed on 50 nonproliferative and 25 proliferative PAs, with median 3DVGRs of 21.2%/year and 60.2%/year, respectively (P < .0001). ROC analysis (AUC 0.992, P < .001) defined three 3DVGR groups: <50%/year, ≥50%, and <80%/year, ≥80%/year with a median PFS of 99.0, 39.0, and 7.0 months, respectively. In tumors with 3DVGR <50%/year, proliferative status had no significant progression-free survival impact (P = .381). In contrast, proliferative tumors with 3DVGR ≥50%/year had worse outcomes than those with 3DVGR <50%/year (P < .001). In multivariate analysis, only 3DVGR ≥50%/year predicted early progression (P < .001), unlike proliferative status. Combining 3DVGR ≥80%/year or 50% ≤3DVGR < 80%/year with Ki67 ≥ 8% identified 12 PAs with a median PFS of 8.5 months vs 64 months in others. CONCLUSION: PA proliferation may be categorized as: <10%/year: non and/or slowly progressive, 10-49%/year: slowly progressive, 50-79%/year: progressive, ≥80%/year: highly progressive. 3DVGR appears to be a valuable tool to evaluate PA proliferation alongside histology.
Diabetes technology: an update.
Prahalad P, Zaharieva D, Maahs DM
J Clin Endocrinol Metab · 2026 Jun · PMID 41973910 · Publisher ↗
Diabetes is one of the most prevalent chronic diseases worldwide, with rates that continue to increase. More than 30 years ago, the Diabetes Control and Complications Trial demonstrated that intensive glucose management...
Diabetes is one of the most prevalent chronic diseases worldwide, with rates that continue to increase. More than 30 years ago, the Diabetes Control and Complications Trial demonstrated that intensive glucose management decreased long-term vascular complications. Unfortunately, many people with diabetes still struggle to meet glycemic goals. In this mini-review, we highlight advances in diabetes technology that are associated with improvements in glycemic management. Continuous glucose monitoring (CGM) and automated insulin delivery systems are associated with significant improvements in glycated hemoglobin (HbA1c), time in range (70-180 mg/dL), and decreases in severe hypoglycemia and diabetic ketoacidosis in people with both type 1 and type 2 diabetes. Recent data show that these technologies improve outcomes early in the course of type 1 diabetes. CGM is also being explored as a tool to monitor progression through early-stage type 1 diabetes (2 antibodies positive) to identify individuals who may benefit from disease-modifying therapies as well as to prevent the onset of diabetic ketoacidosis at onset of stage 3 (insulin-requiring) type 1 diabetes. Adjunctive pharmacologic therapies and artificial intelligence may further expand and improve therapies, offering potential synergistic benefits. However, there continue to be significant disparities in access to diabetes technologies and access to insulin worldwide. This mini-review summarizes recently published data, highlights emerging applications, and underscores the need to pair technological innovation with strategies that promote equitable access and support for diabetes care to improve outcomes for all people with diabetes.
Combination treatment for the management of chronic kidney disease and type 2 diabetes: a review and practical guidance.
Mohsen M, Yi TW, Faruque L … +13 more , Ke C, Cafazzo JA, Pham Q, Sridhar VS, Levin A, Abdel-Qadir H, Persson F, Wanner C, Jüni P, Butler J, Marx N, Cherney DZI, Odutayo A
J Clin Endocrinol Metab · 2026 Jun · PMID 41973867 · Full text
CONTEXT: Renin-angiotensin system inhibitors (RASi), sodium glucose cotransporter-2 inhibitors (SGLT2i), non-steroidal mineralocorticoid receptor antagonists (nsMRA), and glucagon-like peptide-1 receptor agonists (GLP-1R...
CONTEXT: Renin-angiotensin system inhibitors (RASi), sodium glucose cotransporter-2 inhibitors (SGLT2i), non-steroidal mineralocorticoid receptor antagonists (nsMRA), and glucagon-like peptide-1 receptor agonists (GLP-1RA) are key components of guideline-directed medical treatments (GDMT) for chronic kidney disease (CKD) with type 2 diabetes (T2D). However, the combined use of these medications remains uncommon in clinical practice, in part, due to the absence of specific guidance on implementing combination treatment. Herein, we aim to (1) summarize the evidence supporting combination GDMT in CKD with T2D, (2) propose a practical algorithm to guide the accelerated implementation of quadruple treatment, and (3) discuss strategies to improve the uptake of combination treatment. EVIDENCE ACQUISITION: We searched PubMed from inception to present for English-speaking studies using the search terms: "renin-angiotensin system inhibitor," "sodium glucose cotransporter-2 inhibitor," "nonsteroidal mineralocorticoid receptor antagonist," "glucagon-like peptide-1 receptor agonist," and "diabetes." We focused on clinical guidelines, randomized controlled trials (RCTs), and, if necessary, large observational studies. EVIDENCE SYNTHESIS: SGLT2i, nsMRA, and GLP-1RA confer early cardiovascular and kidney protection through independent mechanisms, allowing them to be combined. RCTs support the use of each agent on top of "standard care," and multiple clinical guidelines endorse combination treatment. However, the optimal order and timing for medication initiation and the approach to managing treatment-related side effects remain uncertain, thereby limiting the uptake of combination treatment. CONCLUSION: Current evidence supports the use of combination GDMT in CKD with T2D. We propose a combination treatment algorithm that may combat clinical inertia and achieve greater cardiorenal risk reduction in high-risk patients with CKD and T2D.
Increasing incidence and prevalence of biochemically confirmed primary hyperparathyroidism in Stockholm, 2006-2020.
Thorsteinsson D, Granath F, Bränström R … +3 more , Zedenius J, Carrero JJ, Nilsson IL
J Clin Endocrinol Metab · 2026 Apr · PMID 41972345 · Publisher ↗
CONTEXT: Primary hyperparathyroidism (PHPT) prevalence appears to be rising, but substantial underdiagnosis persist. Accurate epidemiological data are needed, requiring population-based studies using strict biochemical c...
CONTEXT: Primary hyperparathyroidism (PHPT) prevalence appears to be rising, but substantial underdiagnosis persist. Accurate epidemiological data are needed, requiring population-based studies using strict biochemical criteria. OBJECTIVE: To determine incidence and prevalence of biochemically confirmed PHPT in Stockholm and characterize clinical recognition and surgical management. DESIGN: Population-based healthcare cohort study using prespecified biochemical diagnostic algorithms. SETTING: Stockholm Region, Sweden, 2006-2020, using the Stockholm CREAtinine Measurements database covering two-thirds of the adult population, including ≥90% of individuals ≥65 years. PATIENTS: Adults aged ≥20 years with paired calcium and parathyroid hormone (PTH) measurements meeting biochemical criteria for PHPT. Individuals with eGFR ≤30 mL/min/1.73 m2, secondary hyperparathyroidism, or prior parathyroid surgery were excluded. MAIN OUTCOME MEASURE: Annual incidence rate and point prevalence of biochemically confirmed PHPT. RESULTS: Among 176,780 individuals contributing 578,227 PTH measurements, 10,190 patients fulfilling biochemical PHPT criteria were identified. Age- and sex-adjusted incidence rate increased from 2.81 (95% CI, 2.55-3.09) to 4.28 (95% CI, 3.98-4.59) per 10,000 person-years between 2009 and 2020, with the steepest increase among women aged ≥70 years. Prevalence increased from 0.35 to 4.76 per 1,000 individuals. Median ionized calcium was 1.39 mmol/L. Clinical diagnosis of PHPT was documented in 5,346 (52%) patients of which, 2,800 (52%) underwent parathyroidectomy, with surgery-rates stabilizing after 2013 at 4-5% annually. CONCLUSIONS: Using a large healthcare database, we observed substantially increasing PHPT incidence and prevalence, predominantly in older individuals. Only 52% received clinical diagnosis, underscoring the need for studies evaluating the long-term clinical burden of undiagnosed PHPT.
Sex- and Pubertal Stage-Specific Bone Microarchitecture and Strength in Adolescents With Type 1 Diabetes.
Brossfield AV, Williams KM, Kim TJ … +10 more , Gjeci J, Ali A, Mathur DV, Mehta A, Texeira NG, McMahon DJ, Agarwal S, Guo XE, Sopher AB, Rubin MR
J Clin Endocrinol Metab · 2026 Apr · PMID 41968580 · Publisher ↗
CONTEXT: Adults with type 1 diabetes (T1D) have elevated fracture risk, but the effects of T1D on bone accrual during adolescence remain unclear. OBJECTIVE: To assess group differences in bone microarchitecture and stren...
CONTEXT: Adults with type 1 diabetes (T1D) have elevated fracture risk, but the effects of T1D on bone accrual during adolescence remain unclear. OBJECTIVE: To assess group differences in bone microarchitecture and strength between adolescents with type 1 diabetes and controls during sex-specific stages of pubertal bone accrual. DESIGN: Cross-sectional. SETTING: Tertiary medical center. PARTICIPANTS: Forty youth with T1D and 40 matched controls; early pubertal girls (Tanner 2-3) and mid-pubertal boys (Tanner 3-4). MAIN OUTCOME MEASURES: Assessments included dual-energy X-ray absorptiometry, high-resolution peripheral quantitative computed tomography (HR-pQCT) with individual trabecula segmentation, and micro-finite element analysis, as well as HbA1c, continuous glucose monitoring (CGM), advanced glycation end-products (AGEs: skin autofluorescence [SAF], pentosidine), IGF-1, and bone turnover markers. RESULTS: Compared with control boys, boys with T1D had lower trabecular bone volume fraction (-14%; p=0.033), plate-like trabeculae (-23%; p=0.007), and failure load (-12%; p=0.008) at the distal tibia, and lower cortical area (-8%; p=0.026) at the proximal tibia, with similar deficits at the radius. In contrast, compared with control girls, girls with T1D in early puberty showed no deficits. In boys, higher HbA1c was linked to fewer plate-like trabeculae (β = -0.31, p=0.038) and reduced strength, while lower IGF-1 predicted decreased trabecular volume and strength. Across the T1D cohort, CGM hyperglycemia and higher SAF correlated with suppressed bone turnover. CONCLUSIONS: T1D exerts sex- and pubertal stage-specific skeletal effects. Mid-pubertal boys show trabecular and cortical deficits with reduced strength, whereas early-pubertal girls show no deficits. Mid-puberty in boys represents a critical window for skeletal vulnerability and potential intervention.
Approach to the Patient: Management of bone fragility in patients with chronic hypoparathyroidism.
Tournis S, Kassi E, Palermo A … +5 more , Yavropoulou MP, Adamidou F, Anagnostis P, Makras P, Anastasilakis AD
J Clin Endocrinol Metab · 2026 Apr · PMID 41968412 · Publisher ↗
Parathyroid hormone (PTH) is the main hormonal regulator of bone remodeling; thus, chronic hypoparathyroidism (HypoPT) leads to low bone turnover that might compromise bone strength, despite the normal or even high bone...
Parathyroid hormone (PTH) is the main hormonal regulator of bone remodeling; thus, chronic hypoparathyroidism (HypoPT) leads to low bone turnover that might compromise bone strength, despite the normal or even high bone mineral density. Recent studies suggest that fracture risk might be increased in patients with HypoPT. Given that all available treatments for osteoporosis affect bone remodeling, management of bone fragility of any etiology in patients with HypoPT is challenging and lacks clinical evidence in terms of fracture risk reduction. In the present article we describe the changes in bone remodeling and bone strength in patients with chronic HypoPT managed by conventional therapy and under PTH-replacement. In addition, based on pathophysiology and the limited existing evidence, we discuss which osteoporosis medication could be used in patients with HypoPT and concurrent increased bone fragility. In HypoPT patients under conventional treatment with calcium and active vitamin D, administration of potent antiresorptives (bisphosphonates, denosumab) should be done under close monitoring, given their antiremodeling action that might result in hypocalcemia, while the effect on bone material properties is not known. Teriparatide is probably the best available option, at least in the short-term. In contrast, patients with HypoPT on long-term PTH replacement therapy who experience fragility fractures, should probably be treated with antiresorptives, although the optimal therapeutic regimen, in terms of safety and efficacy, is yet unknown.
Letter to the editor from Miller et al: "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".
Miller BS, Sävendahl L, Højby M … +1 more , Polak M
J Clin Endocrinol Metab · 2026 Jun · PMID 41968405 · Full text
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A Phase II Basket Trial of Vosoritide in Children with RASopathies, ACAN and NPR2 Deficiency.
Dauber A, Zhang A, Shafaei N … +5 more , Seaforth R, Pitner K, Dham N, Kanakatti Shankar R, Merchant N
J Clin Endocrinol Metab · 2026 Apr · PMID 41967490 · Publisher ↗
CONTEXT: Genetic defects in many biological pathways, including activation of the Ras-MAPK pathway, cause short stature. Vosoritide, a C-type natriuretic peptide analog that inhibits this pathway, has been approved for u...
CONTEXT: Genetic defects in many biological pathways, including activation of the Ras-MAPK pathway, cause short stature. Vosoritide, a C-type natriuretic peptide analog that inhibits this pathway, has been approved for use in achondroplasia. OBJECTIVE: To determine whether vosoritide improves growth in children with disorders of the Ras-MAPK pathway including RASopathies, ACAN and NPR2 deficiency. DESIGN: Prospective phase 2 basket trial. SETTING: Academic medical center. PARTICIPANTS: Thirty pre-pubertal children aged 3 to 11 years with a RASopathy, ACAN or NPR2 deficiency and height <-2.25 SD. INTERVENTION: 6-month observation period followed by 12-month treatment with vosoritide subcutaneously 15 micrograms/kg/day. MAIN OUTCOME MEASURES: Co-primary outcomes included incidence of adverse events, change in annualized growth velocity (AGV) and height standard deviation scores. RESULTS: The AGV increased from 4.53+1.61 cm/yr to 8.09+1.58 cm/yr with treatment (p<0.0001). This corresponded to a 4.0 SD (95%CI 3.08-4.91) increase in age and sex-adjusted AGV Z-score (p<0.0001). The increase in AGV was seen in all genetic subgroups. There was a height increase of 0.65 SD (95%CI 0.53-0.77) in the treatment versus observation period (p<0.0001).Short-term safety was reassuring with mild injection site reactions being the most common adverse events. However, with longer use, five subjects discontinued medication due to adverse events including three slipped capital femoral epiphyses and four cases of genu valgum. CONCLUSIONS: Vosoritide led to marked increases in growth velocity in children with RASopathies, ACAN and NPR2 deficiency, raising the possibility that vosoritide could be an effective precision medicine for all growth disorders affecting the MAPK pathway.
Genetics of familial acromegaly and pituitary gigantism.
De Sousa SMC, Daly AF
J Clin Endocrinol Metab · 2026 Jun · PMID 41965096 · Full text
The subset of pituitary adenomas with a heritable genetic basis is small but clinically striking. Somatotropinomas are amongst the most frequent pituitary adenoma subtypes encountered in this setting, with germline varia...
The subset of pituitary adenomas with a heritable genetic basis is small but clinically striking. Somatotropinomas are amongst the most frequent pituitary adenoma subtypes encountered in this setting, with germline variants being enriched in familial acromegaly kindreds and people with a childhood or adolescent history of GH hypersecretion manifesting as pituitary gigantism. The genetic causes of familial acromegaly and pituitary gigantism include variants in established pituitary adenoma predisposition genes (AIP, especially, but also MEN1, CDKN1B, MAX, and PRKAR1A), X-linked acrogigantism due to Xq26.3 microduplications, and McCune-Albright syndrome due to postzygotic gain-of-function GNAS variants. Potential associations include variants in emerging pituitary adenoma predisposition genes, including NF1, PRKACB, PAM, and CHEK2. Given the potential for gene-specific therapeutic implications in these diseases, multimodal genetic testing arranged by experienced pituitary subspecialists and conducted in expert, clinically accredited laboratories is needed to fully evaluate the genetic basis of disease. Key investigations include next-generation sequencing, chromosome microarray, and droplet digital polymerase chain reaction. Exploratory research-based genetic testing may help uncover new genetic causes of familial acromegaly kindreds and pituitary gigantism in people with negative results on standard testing, benefiting those being tested as well as advancing our understanding of the heritable basis of somatotropinomas.
Current treatment landscape of acromegaly.
Castinetti F, Ioachimescu AG
J Clin Endocrinol Metab · 2026 Jun · PMID 41965092 · Full text
Treatment of acromegaly includes surgery followed by chronic medical therapy for persistent growth hormone (GH) excess, and, in some patients, radiation. Treatment is aimed at biochemical normalization, which improves su...
Treatment of acromegaly includes surgery followed by chronic medical therapy for persistent growth hormone (GH) excess, and, in some patients, radiation. Treatment is aimed at biochemical normalization, which improves survival and comorbidities. However, many patients experience lifelong burden related to persistent acromegaly manifestations and adverse treatment effects. Long-acting somatostatin receptor ligand (SRL) therapy with octreotide or lanreotide has been the cornerstone of management. Pasireotide long-acting release, a somatostatin receptor multiligand, achieves more favorable biochemical control rates but is associated with an increased risk of hyperglycemia. Pegvisomant, a GH receptor antagonist, can be used as monotherapy or in combination with SRLs. The spectrum of medical therapy has expanded with the advent of oral octreotide capsules; the oral selective somatostatin receptor subtype 2 agonist, paltusotine; and monthly self-administered subcutaneous octreotide. This review outlines the updates to current acromegaly treatment options and their impact on patient outcomes.
Levothyroxine treatment response of cardiometabolic biomarkers in older adults with subclinical hypothyroidism.
Ao L, Noordam R, Trompet S … +13 more , van Vliet NA, Sattar N, Rodondi N, Moutzouri E, Atighetchi S, Kearney PM, Quinn T, Jukema JW, Gussekloo J, Mooijaart SP, Willems van Dijk K, Poortvliet RKE, van Heemst D
J Clin Endocrinol Metab · 2026 Apr · PMID 41965091 · Publisher ↗
CONTEXT: Randomized controlled trials (RCTs) found no cardioprotective effects of levothyroxine therapy in older adults with subclinical hypothyroidism. OBJECTIVE: To assess levothyroxine effects on cardiometabolic bioma...
CONTEXT: Randomized controlled trials (RCTs) found no cardioprotective effects of levothyroxine therapy in older adults with subclinical hypothyroidism. OBJECTIVE: To assess levothyroxine effects on cardiometabolic biomarkers, which may serve as more sensitive treatment indicators. DESIGN: Post hoc analysis using (baseline and 12-month) data from two double-blind randomised controlled trials in older adults (≥ 65 years) with subclinical hypothyroidism. MAIN OUTCOME MEASURE(S): Cardiometabolic biomarkers included seven clinically relevant lipid measures (apolipoprotein B (ApoB), total cholesterol (Total-C), non-high-density lipoprotein cholesterol (non-HDL-C), remnant cholesterol (RC), low-density lipoprotein cholesterol (LDL-C), HDL-C, and triglycerides (TG)) and 167 standardised metabolomic measures from nuclear magnetic resonance. Analyses were additionally stratified by baseline TSH levels. RESULTS: Among 286 included participants (48% women; median age 75 [70, 82] years; median baseline TSH 6.44 [5.36, 7.81] mIU/L), 142 were randomized to levothyroxine. Overall, levothyroxine showed no effects on ApoB (-0.03 [95% CI: -0.07, 0.00] g/L), Total-C (-0.17 [-0.34, 0.00] mmol/L), non-HDL-C (-0.15 [-0.31, 0.00] mmol/L), RC (-0.09 [-0.16, -0.01] mmol/L), LDL-C (-0.07 [-0.15, 0.02] mmol/L), and TG (-0.07 [-0.15, 0.01] mmol/L). In participants with baseline TSH ≥10 mIU/L (n=27), potentially beneficial changes (P-values < 0.05, but not significant after multiple-testing correction) were observed for all clinically relevant lipids except HDL-C, as well as for ApoB-containing lipoproteins, VLDL size and fatty acids. CONCLUSION: In older adults with subclinical hypothyroidism, levothyroxine treatment showed no effects on cardiometabolic biomarkers, although potentially favourable changes in lipids and lipoproteins were observed for individuals with baseline TSH ≥ 10 mIU/L.
Quantitative Effects of Sex Hormones on Hair Growth and Patient Satisfaction.
de Kroon RWPM, Strating J, Heijboer AC … +1 more , den Heijer M
J Clin Endocrinol Metab · 2026 Apr · PMID 41964649 · Publisher ↗
BACKGROUND: Gender-affirming hormone therapy (GAHT) alters hair distribution, a key aspect of gender transition. Transgender women often seek hair reduction, while transgender men typically desire increased hair growth....
BACKGROUND: Gender-affirming hormone therapy (GAHT) alters hair distribution, a key aspect of gender transition. Transgender women often seek hair reduction, while transgender men typically desire increased hair growth. Previous studies relied on subjective hair assessments, with limited understanding of psychosocial effects. OBJECTIVES: To investigate changes in terminal hair growth in transgender men and women (both lasered and non-lasered) using digital microscopy, and their relation to body image during the first 12 months of GAHT. METHODS: In this longitudinal study, 36 participants (20 transgender men, 16 transgender women) initiating GAHT were assessed at baseline, and after 3 and 12 months of GAHT. Hair densities were measured using digital microscopy. Psychosocial outcomes were evaluated using the Body Appreciation Scale-2 and satisfaction questionnaires. RESULTS: After 12 months, transgender women showed significant reductions in hair density on the upper lip (-17 hairs/cm2, CI -32, -2), chin (-28 hairs/cm2, CI -47, -8), and upper abdomen (-6 hairs/cm2, CI -12,0), with no significant differences between lasered and non-lasered women. Transgender men exhibited significant increases on the upper lip (+21 hairs/cm2, CI 11-30), chin (+13 hairs/cm2, CI 3-24), upper (+17 hairs/cm2, CI 8-23) and lower abdomen (+20 hairs/cm2, CI 11-28), and thighs (+14 hairs/cm2, CI 7-21). Both groups reported improved body appreciation, satisfaction with hair growth, and gender congruence. CONCLUSIONS: GAHT induces measurable, location-specific changes in terminal hair growth in transgender women and men, accompanied by improvements in body image and satisfaction. Digital microscopy provides a valuable tool for future studies comparing GAHT regimens.
Clinical picture of early infancy PTH resistance syndromes: is it time to improve diagnostic criteria?
Del Sindaco G, Berkenou J, Pagnano A … +5 more , Audrain C, Ferrante E, Rothenbuhler A, Linglart A, Mantovani G
J Clin Endocrinol Metab · 2026 Apr · PMID 41964640 · Publisher ↗
BACKGROUND: Clinical presentation of inactivating PTH/PTHrP signaling disorders (iPPSDs, historically pseudohypoparathyroidism (PHP)) exhibits pronounced age-dependence. Indeed, main features, including PTH resistance an...
BACKGROUND: Clinical presentation of inactivating PTH/PTHrP signaling disorders (iPPSDs, historically pseudohypoparathyroidism (PHP)) exhibits pronounced age-dependence. Indeed, main features, including PTH resistance and brachydactyly, develop during late childhood, whilst other features (ectopic ossifications, obesity and hypothyroidism) are the most prevalent in toddlers. The latter are included among minor diagnostic criteria; therefore, a significant diagnostic delay has been reported. Aim of this work is to describe the early natural history of a large cohort of iPPSD/PHP patients, in order to improve the diagnosis, with the final goal of proposing new diagnostic criteria for early infancy and reducing the diagnostic delay. METHODS: We included 117 patients regularly followed up in two European Endocrinology tertiary centres and we retrospectively collected data on the age of onset of main clinical and hormonal features. RESULTS: In our cohort the median age at diagnosis was 5.9 years. Age of onset of PTH resistance and brachydactyly, major criteria for diagnosis, was significantly different from that of both TSH resistance and obesity (median age 6.1, 5.8, 1.85 and 2 years, respectively). Minor diagnostic criteria were more represented than major criteria in children before 2 years (p=0.002). Indeed, in 64% of patients before 2 years none of the major criteria were observed, conversely 71% had already developed at least one minor criterion; in particular, 20% had developed TSH resistance and obesity. CONCLUSION: Clinical picture of iPPSD/PHP in early infancy differs from that of mid-late infancy and adults, thus current diagnostic criteria may not be appropriate for children. We suggest that the combination of early onset obesity and elevated TSH should raise the suspicion and trigger genetic screening before 2 years of age.
Copeptin kinetics in healthy aging.
Lustenberger S, Riehle F, Blattmann L … +4 more , Vogt DR, Schärer N, Refardt J, Christ-Crain M
J Clin Endocrinol Metab · 2026 Apr · PMID 41964423 · Publisher ↗
CONTEXT: The risk for disturbances in water homeostasis-resulting in hypo- or hypernatremia-increases with age. Age-related changes in arginine vasopressin (AVP) kinetics have been suggested, but findings are inconclusiv...
CONTEXT: The risk for disturbances in water homeostasis-resulting in hypo- or hypernatremia-increases with age. Age-related changes in arginine vasopressin (AVP) kinetics have been suggested, but findings are inconclusive due to challenges in quantifying AVP. Copeptin is a stable surrogate marker for AVP secretion, yet no data on age-related changes of copeptin kinetics are available. OBJECTIVE: We investigated copeptin kinetics in healthy ageing, hypothesizing a reduced within-subject range of copeptin in older individuals. METHODS: For this randomized controlled cross-over trial, 16 healthy older adults aged ≥60 years and 16 healthy younger adults aged 18-30 years were recruited. Participants underwent 1 copeptin stimulation test (infusion of 10 mL/kg of 3% saline in 60 minutes) and 1 copeptin suppression test (ingestion of 20 mL/kg tap water in 60 minutes) in randomized order. During both tests, copeptin was measured at baseline and at 15, 30, 45, 60, and 120 minutes. The primary outcome was the within-subject copeptin range in older adults compared with younger controls. RESULTS: Median (interquartile range) age of older adults was 67 (64, 72) years and 26 (23, 28) years in younger controls. In both groups, 50% were female. The within-subject copeptin range in older adults was 12.6 (8.5, 18.7) pmol/L and comparable with that of younger controls with 14.2 (8.5, 16.6) pmol/L (P = .867). While the copeptin response to stimulation was comparable between groups (β = +3.9 [95% CI: -2.9, +10.7; P = .020] pmol·h/L for older adults), older adults exhibited a smaller decrease than younger controls during suppression (β = + .8 [95% CI: +0.3, +1.3; P = .005] pmol·h/L). CONCLUSION: Copeptin kinetics are mostly preserved in healthy older adults, yet the ability to suppress copeptin after hydration is diminished. This may contribute to the higher prevalence of hyponatremia in older individuals and should be considered in future fluid intake guidelines.
What is the future of acromegaly therapy?
Schilbach K, Strasburger CJ
J Clin Endocrinol Metab · 2026 Jun · PMID 41964414 · Full text
Acromegaly is a chronic multisystem disorder in which biochemical control remains suboptimal for many patients. Even when control is achieved, treatment burden is often high despite surgery and a spectrum of established...
Acromegaly is a chronic multisystem disorder in which biochemical control remains suboptimal for many patients. Even when control is achieved, treatment burden is often high despite surgery and a spectrum of established safe and effective therapies. In this narrative review of multinational late-stage clinical trials through October 2025, we summarize drug developments that may broaden individualized medical strategies. Oral somatostatin receptor ligands are now available in the United States, underscoring a shift toward more convenient long-term management. In parallel, non-oral innovations continue to advance. Octreotide subcutaneous depot (CAM2029) maintains biochemical control with acceptable safety and may reduce treatment burden. Emerging pituitary-directed therapy with longer application intervals (Debio 4126) also shows pharmacologic activity consistent with effective disease control. Growth hormone (GH) receptor-directed agents (ALXN2420, MAR002) likewise demonstrate activity aligned with considerable biochemical and clinical benefit. Collectively, these agents may address unmet needs by broadening the scope of options to control production of hepatic insulin-like growth factor I (IGF-I) and to attenuate additional extrahepatic GH signaling. They may also help ease the practical burden of chronic therapy.
Studying endocrine disrupting chemicals from molecular targets to mixture model approach: lessons from the thyroid model.
Coperchini F, Greco A, Franchi E … +2 more , Denegri M, Rotondi M
J Clin Endocrinol Metab · 2026 Jun · PMID 41961635 · Full text
Endocrine-disrupting chemicals (EDCs) pose a significant global health risk by interfering with hormonal balance. The thyroid is particularly suitable for studying endocrine disruption due to its crucial role in developm...
Endocrine-disrupting chemicals (EDCs) pose a significant global health risk by interfering with hormonal balance. The thyroid is particularly suitable for studying endocrine disruption due to its crucial role in development, metabolism, and cognitive function, alongside established molecular targets and regulatory frameworks. This review summarizes current knowledge on thyroid-disrupting chemicals (TDs), focusing on mechanistic pathways acting at both intrathyroidal and extrathyroidal levels. Particular attention is given to molecular initiating events, such as interference with iodide uptake, thyroperoxidase activity, thyroglobulin processing, and thyroid hormone signaling, and to their integration within the adverse outcome pathway (AOP) framework. In addition, the review discusses methodological strategies for assessing thyroid disruption, spanning in silico, in vitro, in vivo, and human epidemiological approaches. Finally, emerging challenges related to real-world exposure to chemical mixtures are addressed, highlighting the need for AOP-informed, mixture-based strategies to improve risk assessment and regulatory decision-making.
Changing understanding of acromegaly epidemiology and early mortality risk.
Esposito D, Johannsson G
J Clin Endocrinol Metab · 2026 Jun · PMID 41961594 · Full text
Epidemiologic research for rare diseases such as acromegaly is challenging due to low prevalence, heterogeneous data sources, and regional variability. Here, we review recent epidemiologic studies and provide a synthesis...
Epidemiologic research for rare diseases such as acromegaly is challenging due to low prevalence, heterogeneous data sources, and regional variability. Here, we review recent epidemiologic studies and provide a synthesis of the changing landscape of acromegaly and an overview of mortality rates and their determinants. Over the past few decades, the reported incidence and prevalence of acromegaly have increased, likely due to improved diagnostic tools, earlier diagnosis, and more efficient management of the disease, leading to increased life expectancy. Available data suggest that the delay in diagnosis of acromegaly has progressively declined, and there is now a considerable increase in the rate of biochemical control-achieved in up to 90% of patients in some centers. This progress reflects improvements in disease management with the expanding use of multimodal and personalized treatment strategies. Consequently, mortality rates have substantially declined, approaching those of the general population. Despite these advances, most patients continue to be diagnosed only after acromegaly complications have developed. Comorbidities still have an independent and adverse effect on mortality and morbidity. Therefore, improved management of comorbidities is the optimal goal in the overall treatment of patients with acromegaly.
The use of denosumab in rare bone diseases in adults: a systematic review from the ECTS Rare Bone Disease Action Group.
Bulaicon OO, van Haalen FM, Clunie GPR … +11 more , Grasemann C, Lems WF, Makras P, Mortier G, Oheim R, Raimann A, Siggelkow H, Tabacco G, van der Wal RJP, de Witte PB, Appelman-Dijkstra NM
J Clin Endocrinol Metab · 2026 Jun · PMID 41955566 · Full text
CONTEXT: Rare bone diseases (RBDs) may display a disrupted RANKL-RANK-osteoprotegerin pathway causing increased osteoclastogenesis and enhanced bone resorption. Although bisphosphonates are commonly used, they often fall...
CONTEXT: Rare bone diseases (RBDs) may display a disrupted RANKL-RANK-osteoprotegerin pathway causing increased osteoclastogenesis and enhanced bone resorption. Although bisphosphonates are commonly used, they often fall short of desired outcomes. Denosumab, an anti-RANKL antibody, provides a promising alternative by swiftly and strongly suppressing bone turnover (faster and more potent suppression of bone resorption than bisphosphonates), though its effects are reversible on discontinuation. The use of denosumab has been highlighted, especially in pediatric cases, but not substantially in adults. EVIDENCE ACQUISITION: A targeted evidence search was conducted to retrieve studies reporting denosumab use in RBDs in adults. EVIDENCE SYNTHESIS: Denosumab administration may lead to pain reduction, lesion reduction, or bone formation. Treatment dosage, schedules, and duration varied, however, a dose of 120 mg dosed monthly or every 3 months for almost 1 year reached the desired treatment effect in most patients. Denosumab is generally well tolerated in adults, with mild common side effects such as (asymptomatic) hypocalcemia and hypophosphatemia. Serious adverse effects such as osteonecrosis of the jaw or atypical femoral fractures are rarely reported. Main concerns regard rebound effect after denosumab discontinuation, with disease recurrence in some cases. Zoledronic acid after discontinuation of denosumab might be advisable, but is seldom reported. CONCLUSION: Denosumab is a feasible treatment in adults with RBDs when managed by multidisciplinary teams with knowledge of both the underlying disease and potential surgeries as well as the medical site of treatment. Denosumab discontinuation management is paramount to prevent recurrence and severe complications. The paucity of data supports the need for data collection through rare disease registries for future pertinent evidence-based recommendations.
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