The Journal Of Clinical Endocrinology And Metabolism[JOURNAL]
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200 papers
Harmonized Estradiol Reference Ranges: Apples to Apples At Last!
Santoro N
J Clin Endocrinol Metab · 2026 Jun · PMID 42338423 · Publisher ↗
Abstract loading — click title to view on PubMed.
Overview of Surgical Approaches and Adjuvant Therapy for Treatment of Craniopharyngiomas.
Patel NP, Lu N, Hankinson TC
J Clin Endocrinol Metab · 2026 Jun · PMID 42333799 · Publisher ↗
Craniopharyngiomas are brain tumors that occur in the sellar and suprasellar regions and are seen in both adult and pediatric patients. They are benign tumors, but their location and relation with critical neurovascular...
Craniopharyngiomas are brain tumors that occur in the sellar and suprasellar regions and are seen in both adult and pediatric patients. They are benign tumors, but their location and relation with critical neurovascular structures, including optic chiasm, hypothalamus, and pituitary gland, make their treatment challenging. Patients often present with headaches, neurologic symptoms, and pituitary dysfunction. Surgical resection is the first line of treatment. Historically, surgeries for these tumors involved open cranial approaches (OCA). However, endoscopic endonasal approaches (EEA) have become increasingly more popular in recent years. They provide similar to slightly increased rates of gross total resection and increased rates of visual preservation or improvement. Unfortunately, both options still carry significant risk of post-operative endocrinopathies for these patients. Given the involvement of these tumors with surrounding structures, especially the hypothalamus, current protocols recommend maximal safe resection followed by adjuvant therapies. Radiation therapy for tumor recurrences is often used. Intracystic therapies, including brachytherapy, bleomycin, and interferon alpha therapy, have all been tried with varying success. Lastly, advances in the understanding of molecular underpinnings of these tumors have led to promising new systemic therapies for certain subset of these tumors.
Macroprolactinemia as a diagnostic pitfall in hyperprolactinemia: a systematic review and quantitative synthesis.
Yadav P, Hamrahian AH, Salvatori R
J Clin Endocrinol Metab · 2026 Jun · PMID 42324990 · Publisher ↗
CONTEXT: Macroprolactinemia is a well-recognized cause of hyperprolactinemia and an important diagnostic pitfall in endocrine practice. However, interpretation of published quantitative prolactin data remains sparse as s...
CONTEXT: Macroprolactinemia is a well-recognized cause of hyperprolactinemia and an important diagnostic pitfall in endocrine practice. However, interpretation of published quantitative prolactin data remains sparse as studies vary in confirmation method, assay platform, polyethylene glycol (PEG) recovery cutoff, and reporting of prolactin measurement. EVIDENCE ACQUISITION: PubMed, Embase, Scopus, Web of Science, the Cochrane Library, and Google Scholar were systematically searched. Eligible studies reported macroprolactinemia-specific quantitative prolactin data in patients with confirmed macroprolactinemia defined by PEG precipitation, gel filtration chromatography (GFC), or both. Two reviewers independently performed study selection, data extraction, and quality assessment. Findings were summarized using study-level descriptive synthesis. The review was prospectively registered in PROSPERO and conducted in accordance with PRISMA 2020. EVIDENCE SYNTHESIS: Forty-five studies encompassing 2,853 macroprolactinemia cases from 21,413 screened patients with hyperprolactinemia across 22 countries were included. Among 33 studies eligible for primary quantitative analysis, the median study-level central total prolactin attributed to macroprolactinemia was 61.4 ng/mL ([IQR] 42.0-80.0; range 28.1-137.6), and the median study-level post-PEG monomeric prolactin was 11.7 ng/mL (IQR 8.3-13.2; range 4.0-38.0).). The median study-level maximum total prolactin was 264.5 ng/mL (IQR 97.0-425.5; range 81.8-663.0); extreme elevations were attributable to coexisting prolactinomas. CONCLUSIONS: In confirmed macroprolactinemia, total prolactin elevation is typically moderate, and post-PEG monomeric prolactin is usually within or near the normal range. The post-PEG monomeric prolactin value, rather than percent recovery alone, is the most informative parameter for distinguishing isolated macroprolactinemia from coexisting true hyperprolactinemia. These quantitative benchmarks may help clinicians to avoid unnecessary investigation or treatment.
Alcohol and Steatotic Liver Disease Exhibit Divergent Associations with High Plasma Small Dense LDL-C Concentration.
Matsubayashi Y, Kato K, Watanabe M … +6 more , Ito Y, Satoh N, Sato T, Kitazawa M, Yamada T, Sone H
J Clin Endocrinol Metab · 2026 Jun · PMID 42319754 · Publisher ↗
BACKGROUND: Within the metabolic dysfunction-associated steatotic liver disease (MASLD)/MASLD with increased alcohol intake (MetALD)/alcohol-associated liver disease (ALD) framework, cardiovascular risk varies by alcohol...
BACKGROUND: Within the metabolic dysfunction-associated steatotic liver disease (MASLD)/MASLD with increased alcohol intake (MetALD)/alcohol-associated liver disease (ALD) framework, cardiovascular risk varies by alcohol exposure. As small dense low-density lipoprotein cholesterol (sdLDL-C) is highly atherogenic, this study assessed the relative effects of steatotic liver disease (SLD) and alcohol consumption on sdLDL-C elevation and the effects of conventional fasting lipids [low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C)/triglycerides (TGs)] on these associations. METHODS: This cross-sectional study enrolled 55,745 participants who underwent health screenings in Niigata, Japan between April 2024 and March 2025. Alcohol consumption was self-reported as low, moderate, or excessive. Participants were grouped by SLD status and alcohol consumption. sdLDL-C was directly measured, with high sdLDL-C defined as ≥35 mg/dL. Multivariable linear regression (sdLDL-C) and logistic regression (high sdLDL-C) analyses used two models: model 1 was adjusted for age, sex, body mass index, smoking, lipid-lowering medication, antihypertensive medication, and diabetes, and model 2 was further adjusted for LDL-C, HDL-C, and TGs. Marginal standardized prevalence and standardized prevalence differences (PDs) were estimated using g-computation with 2000 bootstrap iterations. RESULTS: The crude prevalence of high sdLDL-C was influenced by SLD and alcohol consumption, being highest in the SLD(+)/excessive alcohol consumption group (76.4%). In model 2, SLD-related associations were attenuated, whereas alcohol-related associations remained robust, as the PD was lower for SLD(+) than for SLD(-) within each alcohol category. CONCLUSION: Alcohol exposure contributes to an atherogenic sdLDL-C phenotype beyond conventional fasting lipids within contemporary SLD categories, indicating potential relevance for risk profiling in MetALD/ALD.
Approach to the patient: Precision Medicine-Guided Evaluation and Treatment of Acromegaly.
Puig-Domingo M, Marques-Pamies M, Sampedro M … +7 more , Gil J, Araujo-Castro M, Martínez-Hernández R, Biagetti B, Jordà M, Valassi E, Marazuela M
J Clin Endocrinol Metab · 2026 Jun · PMID 42314069 · Publisher ↗
ABSTRACT: Acromegaly is a heterogeneous disease in which delayed biochemical control remains common despite the availability of multiple therapeutic options. Traditional stepwise medical treatment algorithms often rely o...
ABSTRACT: Acromegaly is a heterogeneous disease in which delayed biochemical control remains common despite the availability of multiple therapeutic options. Traditional stepwise medical treatment algorithms often rely on the use of first-generation somatostatin ligands (fgSRLs) as the first line drugs with the empirical escalation and trial-and-error approaches, prolonging patients' exposure hormonal excess.Cluster analyses indicate that overall, three main classes of patients with acromegaly representing distinct biological phenotypes can be recognized: (1) young patients with invasive macroadenomas and frequent resistance fgSRLs; (2) older patients with noninvasive tumors and SRL responsiveness in the majority of them; and (3) patients with intermediate features often requiring combination medical therapy in whom prediction of response is more challenging.From a practical perspective, biomarker-guided treatment selection based on T2-weighted MRI signal intensity, the short acute octreotide test, and tumor immunohistochemistry, following the strategy validated in the ACROFAST study, is applicable in clinical practice. It allows a prompt biochemical control and tumor volume reduction, a rationale leading to superior effectiveness performance than the classic sequencing therapy involving the universal utilization of fgSRLs as first option.In the era of integrative and participative medicine, such a protocol enables the early identification of most patients unlikely to respond to fgSRLs, thus supporting timely initiation of pegvisomant, pasireotide or combination therapy, and to achieve hormonal control in nearly 80% of patients. CONCLUSIONS: Precision medicine has become a practical reality in acromegaly. A biomarker-guided strategy improves therapeutic efficiency and should be incorporated into contemporary clinical practice.
Thyroid-Joint Crosstalk: A Systematic Review and Meta-Analysis of Thyroid Autoimmunity and Dysfunction in Juvenile Idiopathic Arthritis.
Liguoro I, D'Agostini M, Franco F … +1 more , Martini G
J Clin Endocrinol Metab · 2026 Jun · PMID 42306887 · Publisher ↗
BACKGROUND: Recent observational studies outlined the concomitant presence of autoimmune diseases in children with juvenile idiopathic arthritis (JIA), including endocrine autoimmunity. Despite the growing evidence of th...
BACKGROUND: Recent observational studies outlined the concomitant presence of autoimmune diseases in children with juvenile idiopathic arthritis (JIA), including endocrine autoimmunity. Despite the growing evidence of thyroid involvement in JIA, available data are heterogeneous and fragmented. We aimed to systematically review the available evidence on the prevalence of thyroid autoantibody positivity and thyroid dysfunction in patients with JIA. METHODS: PubMed/Medline, Cochrane, and Scopus databases were approached to identify studies reporting data on thyroid autoantibody positivity and dysfunction in children with JIA. RESULTS: A total of 15 studies were included in the final analysis, encompassing 19,015 children with JIA (13,225 females, 69.6%) with a weighted mean age of 8.0 years (range 1.8-21 years). The pooled prevalence estimates of anti-thyroid antibody positivity and thyroid dysfunction were 0.04 (95% CI: 0.03-0.05) and 0.04 (95% CI: 0.03 - 0.08), respectively. The risk difference for thyroid autoantibody positivity between children with JIA and controls was 0.08 (95% CI: 0.02-0.14). Possible risk factors were analyzed: the presence of family history for thyroid autoimmune disease (OR 3.91, 95%CI 1.86-8.25), concurrent ANA positivity (OR 1.62, 95%CI 1.13-2.31) and older age (MD 2.10 years, 95% CI 1.32-2.89) were associated with thyroid autoantibody positivity and/or thyroid dysfunction in children with JIA. No significant difference emerged for the specific JIA form. CONCLUSION: Thyroid dysfunction may be detected in children with JIA, with a significant risk difference in comparison to healthy controls. Specific clinical characteristics, such as family history, ANA positivity, and older age at JIA onset, may suggest which patients should benefit from thyroid autoantibody screening.
Serum free triiodothyronine as an adjunctive marker for thyroid hormone status in athyreotic patients on levothyroxine.
Nagayama Y, Tachibana S, Fukuda T … +7 more , Tatsushima D, Mori Y, Shindo H, Takahashi H, Sato S, Nakashima M, Yamashita H
J Clin Endocrinol Metab · 2026 Jun · PMID 42306861 · Publisher ↗
CONTEXT: Athyreotic patients receiving levothyroxine (LT4) for hypothyroidism sometimes exhibit low serum free triiodothyronine (FT3) levels despite normal TSH, and experience hypothyroid-like symptoms and signs, suggest...
CONTEXT: Athyreotic patients receiving levothyroxine (LT4) for hypothyroidism sometimes exhibit low serum free triiodothyronine (FT3) levels despite normal TSH, and experience hypothyroid-like symptoms and signs, suggesting reduced peripheral thyroid hormone action. OBJECTIVE: The present study aimed to identify the most reliable biochemical marker for assessing peripheral thyroid hormone status in such patients. METHODS: This was a single-center retrospective, cross-sectional study of athyreotic patients on LT4. Patients were classified according to TSH, FT3 and FT4, and selected metabolic markers potentially influenced by peripheral thyroid hormone status were compared across groups. RESULTS: In 426 athyreotic patients taking ≥1.2 μg/kg of LT4, the majority (58%) of patients exhibited normal serum FT3 and FT4, followed by 21% with normal FT3 and elevated FT4, 18% with low FT3 and normal FT4, and 2% with low FT3 and elevated FT4. This classification corresponded well with the differences in FT3/FT4 ratios that reflect the efficiency of T4 to T3 conversion. Among 156 patients not taking anti-hyperlipidemic drugs and selected with the propensity score matching using gender as a covariate, the metabolic markers of alanine transaminase, and body mass index were significantly elevated in those with low FT3 than in those with normal FT3. CONCLUSION: In our cohort, lower FT3 was associated with selected metabolic markers in LT4-treated athyreotic patients, suggesting that FT3 may provide additional information on peripheral thyroid hormone status in selected patients. Prospective studies with standardized sampling and adjustment for confounding are warranted to establish FT3 as a validated marker or support FT3-guided dosing.
Single nucleus RNA sequencing reveals testosterone replacement therapy-associated multicellular remodelling of skeletal muscle in hypogonadal men with Klinefelter Syndrome.
Hasselholm EB, Ridder LO, Schou AN … +5 more , Wang J, Farup J, Lin L, Just J, Gravholt CH
J Clin Endocrinol Metab · 2026 Jun · PMID 42306858 · Publisher ↗
BACKGROUND: Klinefelter syndrome (KS) is characterized by hypogonadism, resulting in metabolic disturbances and altered body composition, including reduced muscle mass. Although testosterone replacement therapy (TRT) is...
BACKGROUND: Klinefelter syndrome (KS) is characterized by hypogonadism, resulting in metabolic disturbances and altered body composition, including reduced muscle mass. Although testosterone replacement therapy (TRT) is a standard treatment, its effects on skeletal muscle remain incompletely understood. METHODS: Single-nucleus RNA-sequencing was applied to vastus lateralis biopsies from patients with KS (n = 4), collected at the time of diagnosis and again after one year of TRT. Reference material was retrieved from age-matched male controls (n = 4). We profiled nuclear transcriptomes across ten cell types residing within the skeletal muscle. RESULTS: At diagnosis, sex hormone measurements confirmed hypogonadism in the untreated KS group. One year of TRT effectively normalized serum testosterone and reduced LH and FSH levels. Furthermore, three in four KS patients gained muscle mass.We obtained transcriptomic data from 81,786 individual nuclei. At baseline, untreated KS muscle exhibited pervasive transcriptional reprogramming with indications of changes to myogenic differentiation and heightened fibrotic, adipogenic, and inflammatory transcriptomic profiles. Pseudotime trajectory analysis indicated altered progression from muscle stem to progenitor states. After TRT, gene expression shifted toward gene-patterns linked to improved structural integrity, regeneration, and vascular remodelling. Nevertheless, a substantial KS-specific signature persisted including increased inflammatory signalling. CONCLUSION: In this exploratory pilot study, TRT was associated with a shift toward a more pro-regenerative skeletal muscle transcriptional environment in patients with KS, though only partially mitigating some of the adverse effects of long-standing hypogonadism and KS.
Impact of Cortisol Circadian Rhythm on Psychological Well-Being in Treated Cushing Syndrome: A Cross-Sectional Study.
Theodorou A, Tan EC, Reiner AS … +5 more , Sazo M, Cohen MA, Lin AL, Tabar V, Geer EB
J Clin Endocrinol Metab · 2026 Jun · PMID 42290613 · Publisher ↗
CONTEXT: Patients with Cushing syndrome (CS) often experience impaired quality of life (QoL) and mood despite biochemical control. The relationship between late-night salivary cortisol (LNSC) and psychological outcomes r...
CONTEXT: Patients with Cushing syndrome (CS) often experience impaired quality of life (QoL) and mood despite biochemical control. The relationship between late-night salivary cortisol (LNSC) and psychological outcomes remains poorly characterized. OBJECTIVE: Assess QoL and mood outcomes in biochemically controlled CS patients based on circadian rhythm restoration. DESIGN: Cross-sectional. SETTING: Tertiary-care center. PARTICIPANTS: Ninety treated, biochemically controlled patients with CS (84 Cushing disease (CD); 6 adrenal CS), stratified into three groups: normal LNSC (Group A), abnormal LNSC (Group B), on long-term GC replacement (Group C). MAIN OUTCOME MEASURES: Hospital Anxiety and Depression Scale (HADS), CushingQoL questionnaire, Nottingham Health Profile (NHP). RESULTS: Group A had lower HADS-Anxiety (4 vs 7, A vs B; p=0.006) and (HADS-Depression 2.5 vs 6 vs 9, A vs B; p=0.006, A vs C; p<0.001). QoL was better in group A vs C in psychosocial (67.5 vs 39.5; p<0.001) and physical (63.9 vs 44.3; p=0.005) domains. Group A had better Emotional Reaction (0 vs 24; p=0.002), A vs B; Energy Level (0 vs 63; p=0.001) and Sleep (13 vs 56; p<0.001), A vs C. In multivariable analyses excluding group C, LNSC normalization was consistently associated with better outcomes in all HADS domains, CushingQoL psychosocial, NHP Emotional Reaction, Social Isolation, Physical Abilities and Home Relationships. Group B had the highest diabetes rate. Among patients with surgically remitted CD, 18.6% had abnormal LNSC, characterizing a previously unrecognized clinical phenotype. CONCLUSIONS: In biochemically controlled CS, LNSC normalization correlates with QoL, mood, and metabolic outcomes, and could represent a therapeutic target.
A systematic review supporting the Endocrine Society clinical practice guidelines on central precocious puberty.
Firwana M, Ramachandran N, Allababidi AK … +11 more , Billstein LE, Shah VP, Bandi SSS, Bagewadi S, Aldin ST, Basha AS, Al Nofal A, Prokop LJ, Latronico AC, Roberts SA, Murad MH
J Clin Endocrinol Metab · 2026 Jun · PMID 42287191 · Publisher ↗
CONTEXT: Central precocious puberty (CPP). OBJECTIVE: To summarize the available supporting evidence for the Endocrine Society guidelines about the management of CPP. METHODS: Multiple databases (MEDLINE, EMBASE, Scopus)...
CONTEXT: Central precocious puberty (CPP). OBJECTIVE: To summarize the available supporting evidence for the Endocrine Society guidelines about the management of CPP. METHODS: Multiple databases (MEDLINE, EMBASE, Scopus) were searched to identify studies that addressed the Endocrine Society Guideline Development Panel's 10 clinical questions. Identified studies were selected and appraised, and data were extracted by pairs of independent trained reviewers. RESULTS: The systematic review yielded 3796 citations, of which 32 citations were included. The systematic review and meta-analysis demonstrate that in children with CPP, with no central nervous system symptoms, the rate of magnetic resonance imaging identification of pathogenic lesions (ie, hamartomas and brain tumors) was 6% (35 noncomparative studies with 5541 children with CPP). For girls with idiopathic CPP, gonadotropin-releasing hormone agonist (GnRHa) treatment was associated with +2.7 cm adult height gain compared to those who did not receive treatment (21 comparative observational studies with 1835 girls [mean age 8.20 ± 1.08 years]). The review did not identify any studies that assessed the clinical questions on: benefits of additional evaluation in cases of early thelarche, differentiation of slowly vs rapidly progressing CPP, order of biochemical testing to establish and monitor the diagnosis of CPP, genetic testing for individuals diagnosed with CPP, and chronological age and/or bone age for discontinuation of GnRHa treatment. CONCLUSION: This systematic review addresses various aspects of CPP evaluation and treatment of CPP and will support the development of the Endocrine Society guidelines.
Central precocious puberty: an Endocrine Society clinical practice guideline.
Latronico AC, Roberts SA, Alonzo M … +15 more , Argente J, Canton APM, Carel JC, Cassorla F, Charmandari E, Eugster EA, Grandone A, Greenspan LC, Hawse EC, Juul A, Kaplowitz PB, Murad MH, Street ME, Walker V, McCartney CR
J Clin Endocrinol Metab · 2026 Jun · PMID 42287186 · Publisher ↗
BACKGROUND: Central precocious puberty (CPP), which is traditionally defined as the development of secondary sexual characteristics before age 8 years in girls and age 9 years in boys, results from the premature activati...
BACKGROUND: Central precocious puberty (CPP), which is traditionally defined as the development of secondary sexual characteristics before age 8 years in girls and age 9 years in boys, results from the premature activation of the hypothalamic-pituitary-gonadal (HPG) axis. CPP can be associated with short adult stature, adverse psychosocial outcomes, and increased cardiometabolic and cancer risks in adulthood. Gonadotropin-releasing hormone (GnRH) agonists can effectively suppress premature activation of the HPG axis and have the potential to increase adult height as well as improve psychosocial and long-term health outcomes among patients with CPP. However, as secular trends have continued to shift toward earlier age of pubertal onset, some subpopulations of children with CPP, as it is currently defined, may not require the same extent of diagnostic evaluation and treatment. OBJECTIVE: Develop evidence-based recommendations related to the diagnosis and treatment of CPP. METHODS: A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to address 10 clinical questions related to the diagnosis and treatment of CPP. Systematic reviews of health-related benefits and harms were conducted for each clinical question. The guideline development panel (GDP) also used the GRADE evidence-to-decision (EtD) framework to address stakeholder values and preferences, costs and required resources, cost-effectiveness, acceptability, feasibility, and potential impacts on health equity. RESULTS: In girls with thelarche (Tanner stage B2) between ages 7.0 and 8.0 years, the GDP suggests watchful waiting via periodic physical examinations (every 4-6 months) rather than immediately performing evaluation with laboratory testing or radiologic imaging. In addition, the GDP suggests that all girls with breast development (ie, Tanner stage B2) before age 7 years should first be observed for 4 to 6 months to differentiate unsustained or slowly progressive puberty vs rapidly progressive puberty. These recommendations are largely based on evidence that girls with slowly progressive puberty attain a normal adult height without treatment. When hormonal evaluation is performed to confirm central (GnRH-dependent) activation as the cause of precocious puberty, the GDP suggests starting the evaluation with ultrasensitive basal luteinizing hormone (LH) concentration rather than routine GnRH/GnRH agonist (GnRHa) stimulation testing for all patients. While brain magnetic resonance imaging has been a traditional part of CPP evaluation, the GDP suggests that it should not be routinely performed in girls ages 6.0 to 8.0 years and boys ages 8.0 to 9.0 years without central nervous system (eg, neuro-ophthalmologic) symptoms, largely based on a low prevalence of pathologic intracranial findings in these age groups. The GDP suggests against routine genetic testing for patients with CPP, although they judged that genetic testing (eg, MKRN3 sequencing) should be considered for patients with familial CPP through a shared decision-making process. The GDP suggests GnRHa treatment for many children with CPP, although available evidence suggests that some patient subgroups (eg, older girls with slowly progressive CPP) may be less likely to receive a net benefit with this treatment. Rather than always starting GnRHa treatment with a monthly injectable formulation, the GDP suggests that treatment should be initiated with the formulation (such as a longer-acting formulation) that is anticipated to be used long-term. The GDP suggests against routine addition of growth hormone therapy to increase adult height. They also suggest against the routine biochemical testing (eg, LH, sex steroids) to monitor pubertal suppression while receiving GnRHa, instead reserving biochemical testing to confirm clinically suspected treatment failure. Finally, the GDP suggests against routinely continuing GnRHa treatment beyond chronologic age 10.0 to 11.0 years (girls) or 11.0 to 12.0 years (boys) and/or bone age 11.0 to 12.0 years (girls) or 12.0 to 13.0 years (boys). CONCLUSION: These clinical recommendations were developed to address important uncertainties in the diagnosis and treatment of children with CPP. They are based on the best available scientific evidence regarding clinical outcomes judged to be most important to patients and families. The GDP's overarching goal was to suggest diagnostic and therapeutic strategies that will most likely provide net clinical benefits while simultaneously considering important contextual factors such as cost and feasibility. The guideline-development process highlighted important knowledge gaps and the substantial need for additional research.
The Utility of Salivary 11-Dehydrodexamethasone as a Marker of Dexamethasone Absorption.
Marshall DJ, Issa BG, Keevil BG
J Clin Endocrinol Metab · 2026 Jun · PMID 42275605 · Publisher ↗
BACKGROUND: The 1 mg overnight dexamethasone suppression test (ONDST) is recommended for the investigation of hypercortisolism and adrenal incidentalomas. Measurement of cortisol and dexamethasone (DXM) has been shown to...
BACKGROUND: The 1 mg overnight dexamethasone suppression test (ONDST) is recommended for the investigation of hypercortisolism and adrenal incidentalomas. Measurement of cortisol and dexamethasone (DXM) has been shown to improve diagnostic sensitivity of the ONDST. Recent work has shown that salivary cortisone collection can be undertaken at home replacing serum sampling, but previous studies have found poor performance of salivary DXM after the ONSDT. Herein we introduce the concept of measuring 11-dehydrodexamethasone (11-DHD): a DXM metabolite produced in the salivary duct by metabolism of 11β-hydroxysteroid dehydrogenase type 2, as a surrogate marker for DXM absorption. METHODS: Paired 0900h serum and saliva samples (n=90) were collected post-ONDST. Independent liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays were used to measure serum cortisol and DXM. A novel LC-MS/MS assay was developed to measure salivary cortisol, cortisone, DXM and 11-DHD. Results were compared and correlations were assessed using Pearson's correlation coefficient. RESULTS: Serum and salivary DXM results exhibited a poor correlation (R-squared = 0.135). Salivary DXM and 11-DHD also correlated poorly (R-squared = 0.163). Serum DXM and salivary 11-DHD yielded a positive correlation with an R-squared of 0.75. CONCLUSION: The positive relationship between serum DXM and salivary 11-DHD is novel. At higher concentrations of DXM, the correlation becomes somewhat curvilinear and more variable. A similar relationship is seen between salivary cortisol and cortisone. The development of a salivary 11-DHD LC-MS/MS assay has the potential to improve the current patient pathway. Patients could administer the drug and collect a 0900h-saliva sample at their convenience, prior to posting for analysis.
Focal congenital hyperinsulinism: spontaneous glycemic improvement before surgery.
Arnoux JB, Mayer C, Jhaouat I … +13 more , Saint-Martin C, Bérat CM, Altenburger L, Brassier A, Bouchereau J, Querciagrossa S, Bustarret O, Jugie M, Barbet P, Aveline C, Montravers F, Capito C, de Lonlay P
J Clin Endocrinol Metab · 2026 Jun · PMID 42274546 · Publisher ↗
CONTEXT: Congenital hyperinsulinism (CHI) is the most common genetic cause of hypoglycaemia in infants. Severe CHI may result from a focal pancreatic lesion (FoCHI), which can be surgically removed, although postoperativ...
CONTEXT: Congenital hyperinsulinism (CHI) is the most common genetic cause of hypoglycaemia in infants. Severe CHI may result from a focal pancreatic lesion (FoCHI), which can be surgically removed, although postoperative complications may occur, particularly after pancreatic head resections. OBJECTIVE: To describe the spontaneous glycaemic evolution of FoCHI before surgery and to assess the potential role of conservative management. DESIGN & SETTING: We retrospectively reviewed medical records of patients with FoCHI managed at a single referral centre. CHI severity was classified according to the need for continuous gastric tube feeding (TF) to maintain glycaemic control prior to surgery, defining a TF group and a no-tube feeding (NTF) group. RESULTS: Thirty-nine patients were included: 12 (30.8%) in the NTF group and 27 (69.2%) in the TF group. Patients in the NTF group were diagnosed later (p = 0.022), had less severe initial hypoglycaemia (p = 0.003), and 4/12 did not undergo surgery and were cured of hypoglycaemia before 6 years of age. We developed an exploratory predictive score for early disease evolution, showing a specificity of 97%. Surgery was curative in most patients (96.3% in the TF group, 100% in the NTF group). Long-term complications were uncommon (8.6% vs. 0%) and consisted exclusively of exocrine pancreatic insufficiency, occurring only after pancreatic head surgery (15.8%). CONCLUSION: Approximately 30% of infants with FoCHI demonstrated rapid early improvement. While surgery remains the standard curative treatment, a conservative approach may be considered in selected infants with pancreatic head lesions who show early favourable glycaemic evolution, potentially after surgical exploration to assess postoperative risk.
Approach to the Patient: Cases of Hormonal Management in Older Transgender and Gender Diverse Adults.
Rothman MS, van Heesewijk JO, Ariel D … +1 more , Iwamoto SJ
J Clin Endocrinol Metab · 2026 Jun · PMID 42274359 · Publisher ↗
As the general population continues to shift to an older demographic, more transgender and gender diverse (TGD) adults will seek out endocrinologists and other healthcare providers to help them navigate both initiation a...
As the general population continues to shift to an older demographic, more transgender and gender diverse (TGD) adults will seek out endocrinologists and other healthcare providers to help them navigate both initiation and continuation of gender-affirming hormone therapy (GAHT) concurrent with the potential development of age-associated diseases. The purpose of this Approach to the Patient article is a case-based approach to management considerations in older TGD adults in the settings of neurocognitive disorder, increased cardiovascular disease risk, prostate cancer, bone health and menopause. While evidence-based guidelines for these aging-related conditions do not exist specifically for TGD adults, clinical practice and data from studies in TGD and cisgender adults are discussed to support the approaches to these patient cases. Future research in these areas can inform best practices and clinical guidelines for care of older TGD adults.
Cancer Risk in Acromegaly: Reassessing the Evidence and Impact of Biochemical Control.
Fleseriu M, Melmed S
J Clin Endocrinol Metab · 2026 Jun · PMID 42274358 · Publisher ↗
Abstract loading — click title to view on PubMed.
Gestational Hypothyroidism and Pregnancy Outcomes Following Hemithyroidectomy: A Nationwide Matched Cohort Study.
Atias D, Allon R, Ben-Basat N … +4 more , Kovo M, Melamed G, Saciuk Y, Patalon T
J Clin Endocrinol Metab · 2026 Jun · PMID 42274355 · Publisher ↗
BACKGROUND: Hemithyroidectomy is increasingly performed in women of reproductive age, but its implications for thyroid function during pregnancy and obstetric outcomes remain unclear. OBJECTIVE: To assess gestational hyp...
BACKGROUND: Hemithyroidectomy is increasingly performed in women of reproductive age, but its implications for thyroid function during pregnancy and obstetric outcomes remain unclear. OBJECTIVE: To assess gestational hypothyroidism and the risks of preterm birth and pregnancy loss among pregnancies in women with prior hemithyroidectomy versus matched pregnancies in women without thyroid surgery. METHODS: We conducted a retrospective matched cohort study using anonymized electronic medical records from Maccabi Healthcare Services, Israel, from 2002 to 2023. Pregnancies with at least one TSH measurement were included. Pregnancies after hemithyroidectomy were matched to pregnancies without thyroid surgery using exact matching on maternal age, gravidity, and pregnancy year, followed by propensity-score matching on sociodemographic and clinical covariates. Gestational hypothyroidism was defined as TSH >4.0 mIU/L or levothyroxine initiation during pregnancy and analyzed using generalized estimating equations. Pregnancy loss and preterm birth were analyzed using a weighted time-varying Cox model with gestational age as the time scale, incorporating thyroid status and levothyroxine treatment as time-varying covariates and a hemithyroidectomy-by-trimester interaction. RESULTS: The matched cohort included 463 pregnancies after hemithyroidectomy and 2,293 matched controls. Prior hemithyroidectomy was associated with higher odds of gestational hypothyroidism (adjusted odds ratio, 4.2; 95% CI, 2.9-6.3; p<0.01). In the time-varying outcome analysis, hemithyroidectomy was not associated with increased first-trimester pregnancy loss (hazard ratio [HR], 0.9; 95% CI, 0.7-1.1; p=0.29), but was associated with higher hazard of preterm birth or pregnancy loss during the second and third trimesters (HR, 1.6; 95% CI, 1.3-2.0; p<0.01). CONCLUSIONS: Prior hemithyroidectomy was associated with gestational hypothyroidism and modestly higher later-gestation hazard of preterm birth or pregnancy loss, supporting enhanced thyroid surveillance during pregnancy.
Distinct Genetic Alterations Drive Cushing Disease Versus Silent Corticotroph Adenomas.
Paes T, Zhang Q, Borges CO … +10 more , Mohan DR, Vaz V, Soares BS, Carroll RS, Kaiser UB, Smith TR, Bi WL, Meredith D, Lerario AM, Abreu AP
J Clin Endocrinol Metab · 2026 Jun · PMID 42273717 · Publisher ↗
BACKGROUND: Corticotroph adenomas include functioning tumors causing Cushing disease (CD) and silent corticotroph adenomas (SCA), which differ markedly in size, clinical presentation, and aggressiveness. The molecular ba...
BACKGROUND: Corticotroph adenomas include functioning tumors causing Cushing disease (CD) and silent corticotroph adenomas (SCA), which differ markedly in size, clinical presentation, and aggressiveness. The molecular basis for these differences remains incompletely understood. OBJECTIVE: To characterize genomic and transcriptomic alterations underlying the divergent clinical behavior of CD and SCA. METHODS: Thirty-eight tumors from 34 patients underwent whole-exome sequencing, copy-number variation (CNV) analysis, and mRNA sequencing. Molecular findings were integrated with clinical, radiological, and pathological data. RESULTS: USP8/USP48 mutations were present in 10 of 21 CD tumors (48%) and were associated with low CNV levels, minimal invasion, and favorable post-operative remission. In contrast, five of 13 SCAs harbored TP53/ATRX/DAXX mutations, all had markedly elevated CNV, and aggressive clinical features. Transcriptomic analysis identified an ATRX-FAM138A mRNA fusion, resulting in loss of ATRX expression in an aggressive tumor. Unsupervised transcriptome analyses defined four clusters. All USP8/USP48-mutant CD clustered together had low CNV and low recurrence rates. Cluster 2 consisted of a mixture of CD and SCA, with intermediate CNV and non-aggressive behavior. Cluster 3 included USP8-wildtype CD with heterogeneous yet generally non-aggressive courses. Cluster 4 represented high-CNV tumors enriched for TP53/ATRX/DAXX alterations, with the highest rates of radiological invasion, persistent disease, and recurrence or progression. Across the cohort, higher CNV was significantly associated with parameters of aggressiveness. CONCLUSION: Corticotroph adenomas comprise distinct molecular subtypes. USP8/USP48-mutant CD represents a low-CNV, low-risk group, whereas tumors harboring TP53/ATRX/DAXX mutations exhibit high CNV and aggressive clinical behavior. CNV and mutation profiling may assist in postoperative risk stratification.
Cardiovascular effects of metyrapone treatment in patients with mild autonomous cortisol secretion: a secondary analysis.
Niziolek H, Just I, Baumgartner C … +20 more , Tosin A, Habisch H, Fellinger P, Beiglböck H, Poledniczek M, Bellach L, Luger A, Kautzky-Willer A, Trattnig S, Zeyda M, Scherer T, Schernthaner-Reiter MH, Kiefer FW, Vila G, Kammerlander A, Madl T, Leutner M, Krssak M, Krebs M, Wolf P
J Clin Endocrinol Metab · 2026 Jun · PMID 42272038 · Publisher ↗
CONTEXT AND OBJECTIVE: Mild autonomous cortisol secretion (MACS) is associated with increased mortality, mainly because of cardiovascular disease. Here we investigated the effects of cortisol-lowering medical treatment o...
CONTEXT AND OBJECTIVE: Mild autonomous cortisol secretion (MACS) is associated with increased mortality, mainly because of cardiovascular disease. Here we investigated the effects of cortisol-lowering medical treatment on blood pressure regulation, cardiac fat depots, heart function and morphology, and other cardiovascular risk factors. DESIGN, SETTING AND INTERVENTION: In this secondary analysis of our prospective, open-label, single-center study at the Medical University of Vienna, we investigated 15 patients with MACS (12 females; age 59 [53-64] years) before and after 12 weeks of treatment with evening doses of metyrapone (500 mg at 6 p.m. and 250 mg at 10 p.m.). OUTCOME MEASURES AND METHODS: Cardiac fat stores, morphology and myocardial function were evaluated using cardiac magnetic resonance imaging and spectroscopy. Orthostatic blood pressure regulation was measured by standardized protocols. Lipidomics, renin-angiotensin-aldosterone-system activity and branched-chain amino acid (BCAA) concentrations were assessed. RESULTS: Mean supine systolic (137[121-139] vs 122[115-129] mmHg; p=0.041) and diastolic (89[80-93] vs 75[71-86] mmHg; p=0.045) blood pressure decreased after treatment in patients without changes in concomitant antihypertensive medication. Epicardial fat was lower at follow up compared to baseline (1032.70[894.23-1482.90] vs 929.37[736.12-1317.15]mm2; p=0.022). No changes in paracardial- and intramyocardial fat, as well as in cardiac function and morphology were observed. The aldosterone-to-angiotensin II ratio was lower at follow up (1.56[0.87-2.82] vs 1.21[0.98-1.92]; p=0.042) and alterations in lipid profiles, but not in BCAA levels were identified. CONCLUSIONS: Treatment with evening doses of metyrapone improved blood pressure and reduced epicardial adipose tissue.
Comprehensive Analysis of Disease Spectrum and Mortality in Sanjad-Sakati Syndrome: An International Rare Disease Registry Study.
Almutair A, Karas K, Al Subaihin A … +17 more , Al Dibasi O, Melha M, Al-Ghamdi H, Yadav B, Alghnam S, Alanazi A, AlSaedi A, Althobaiti E, Al Senani A, Al Azkawi H, Al Enezi A, Bakkar A, Ali A, Al Juraibah F, Alyaarubi S, Al Sagheir A, Högler W
J Clin Endocrinol Metab · 2026 Jun · PMID 42267904 · Publisher ↗
BACKGROUND: Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism-intellectual disability-dysmorphism syndrome, is a rare autosomal recessive disorder caused by a TBCE founder mutation. The full disease spectrum...
BACKGROUND: Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism-intellectual disability-dysmorphism syndrome, is a rare autosomal recessive disorder caused by a TBCE founder mutation. The full disease spectrum remains poorly understood. AIM: To comprehensively analyze growth, phenotype, endocrine manifestations, and mortality in a large multicenter SSS cohort. METHODS: Clinical and genetic data were collected from 135 individuals across centers in the Gulf region using a REDCap survey. RESULTS: The median age at inclusion was 9.1 years (range: birth-30 years; 50.3% female). The homozygous TBCE founder mutation (c.155_166del; p.Ser52_Gly55del) was detected in all genetically tested individuals (n = 68). Intrauterine growth restriction (mean birth weight -3.0 SD, length -3.3 SD) and dysmorphic features were universal. Postnatal growth showed severe failure to thrive during infancy, followed by persistently low height z-scores (-7 to -8). Endocrine features included hypoparathyroidism in all patients, primary hypothyroidism (16.5%), hypoglycemia (27.8%), non-autoimmune insulin-dependent diabetes (1.6%) and pituitary hormone deficiencies. Other findings included developmental delay (100%), hypocalcemic seizures (64.2%), tetany (53.3%), nephrocalcinosis (62.1%), gastroesophageal reflux (29.1%), and recurrent respiratory (63.7%) and bacterial infections (53.8%). Antibiotic prophylaxis was used in 35% of patients. Kaplan-Meier analysis estimated a median survival of 27.2 years, with respiratory failure causing 84% of deaths (21/25). The estimated overall survival at an age of 18 years was 62.4%. CONCLUSION: This largest reported SSS cohort highlights the high prevalence of associated endocrine, respiratory, and gastrointestinal manifestations, with respiratory failure as the leading cause of death. These data support the need for multidisciplinary care guidelines.
Classification of glucose profile in Japanese patients with type 1 diabetes and its association with complications.
Masuda T, Katakami N, Taya N … +4 more , Miyashita K, Takahara M, Kato K, Shimomura I
J Clin Endocrinol Metab · 2026 Jun · PMID 42258635 · Publisher ↗
CONTEXT: The importance of utilizing continuous glucose monitoring (CGM) to optimize glycemic profiles and thereby prevent the onset of diabetic complications in patients with type 1 diabetes has been increasingly recogn...
CONTEXT: The importance of utilizing continuous glucose monitoring (CGM) to optimize glycemic profiles and thereby prevent the onset of diabetic complications in patients with type 1 diabetes has been increasingly recognized. Nevertheless, studies evaluating the risk of diabetic complications in patients with type 1 diabetes through machine learning approaches based on CGM data remain limited. OBJECTIVE: To classify the glycemic profiles of Japanese patients with type 1 diabetes using a data-driven cluster analysis based on CGM and clarify the association between these clusters and diabetic complications. METHODS: In this cross-sectional study, a cluster analysis using glycemic metrics from CGM of 153 Japanese patients with type 1 diabetes was performed. Logistic regression analysis adjusted for age, sex, and duration of diabetes was performed to compare the risk of diabetic complications by cluster. RESULTS: The cluster analysis identified four clusters. Cluster 1 (n = 53) exhibited an optimal glycemic profile. Cluster 2 (n = 46) demonstrated an extended duration of hyperglycemia and a higher risk of elevated brachial-ankle pulse wave velocity than Cluster 1. Cluster 3 (n = 39) demonstrated an extended duration of hypoglycemia and a higher risk of severe hypoglycemia than Cluster 1. Cluster 4 (n = 15) demonstrated large glycemic variability associated with hyperglycemia and hypoglycemia. Cluster 4 had higher risks of polyneuropathy, elevated brachial-ankle pulse wave velocity, and higher cardiovascular disease risk scores than Cluster 1. CONCLUSION: High-risk diabetic complications were identified for each cluster classified by glycemic profile.
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