Journal of the Endocrine Society最新文献

Context: Lifestyle habits, such as exercise, alcohol consumption, and smoking, are known to be closely associated with the risk of osteoporotic fracture. However, little is known regarding the association between osteoporotic fracture and dietary habits such as skipping breakfast and having a late dinner.

Objective: This study aimed to examine the association between lifestyle habits, including diet, and the risk of osteoporotic fracture.

Methods: Individuals aged 20 years or older were enrolled using the results of lifestyle questionnaires in health checkup data and the DeSC database, a Japanese claims database. Outcome was defined as the diagnosis of osteoporotic fracture (hip, distal forearm, vertebral, and humeral fractures). A Cox proportional-hazards model was used to calculate the association between osteoporotic fracture risk and lifestyle, adjusting for conventional risk factors. In the lifestyle questionnaires, those who answered "yes" to each question were compared to those who answered "no."

Results: Altogether, 927 130 participants were included, with a median follow-up duration of 2.6 years. The adjusted hazard ratios (95% CI) for lifestyle factors of smoking, daily alcohol consumption, exercise habits, fast gait speed, enough sleep, skipping breakfast, and late dinner were 1.11 (1.06-1.17), 0.91 (0.88-0.95), 0.99 (0.97-1.02), 0.84 (0.82-0.86), 0.95 (0.93-0.98), 1.18 (1.12-1.23), and 1.08 (1.04-1.12), respectively.

Conclusion: Our study is the first to demonstrate that skipping breakfast and having a late dinner are independently associated with a higher risk of osteoporotic fracture, using a large health checkup cohort.

Context: Data on diagnostic accuracy of dehydroepiandrosterone sulfate (DHEA-S) for mild autonomous cortisol secretion (MACS) and adrenal insufficiency (AI) are discrepant.

Objective: We conducted a systematic review and meta-analysis of published studies assessing the accuracy of DHEA-S in diagnosing MACS or AI.

Methods: From inception to January 8, 2024, we searched databases for original studies of at least 20 participants with MACS or AI. MACS was defined as postdexamethasone cortisol greater than 1.8 mcg/dL or postsurgical hypocortisolism. AI was defined by abnormal dynamic testing. QUADAS-2 was used to assess the risk of bias. Bivariate random effects meta-analysis was used to generate pooled diagnostic accuracy estimates.

Results: Seven studies on DHEA-S accuracy in diagnosing MACS (574 patients with MACS, 830 referent individuals), and 2 studies on DHEA-S accuracy in diagnosing AI (52 patients with AI, 59 referent individuals) were included. A meta-analysis of studies using DHEA-S cutoff between 60 and 70 mcg/dL to diagnose MACS demonstrated a sensitivity of 82% (95% CI, 64%-93%) and a specificity of 82% (95% CI, 74%-88%). In the 2 studies evaluating DHEA-S in diagnosing AI, the reference standard was a 1-mcg cosyntropin stimulation test. The sensitivity of DHEA-S for diagnosing AI ranged from 70.3% to 86.7%, and the specificity was 87.1%. Most studies were at a moderate risk of bias.

Conclusion: Based on limited heterogeneous evidence, measurement of DHEA-S provides additional value in diagnosing MACS, as well as AI.

Introduction: Prediabetes is increasing in India and progresses rapidly to type 2 diabetes. The impact of vitamin D3 supplementation on telomerase activity and leukocyte telomere length (LTL) among people with prediabetes has been poorly researched.

Research design and methods: In this 18-month prospective trial, we enrolled 121 women with prediabetes and randomized them into intervention (vitamin D3 supplementation, n = 61) and placebo (n = 60) groups. LTL and telomerase activity were measured.

Results: In the current study, LTL and telomerase activity were assessed at visit 1 (week 0), visit 2 (week 52), and visit 3 (week 78). LTL increased significantly in the intervention group by week 52 (P = .004) and became more pronounced at week 78 (P = .001), representing a 14.5% increase from baseline. Similarly, telomerase activity showed progressive enhancement with vitamin D treatment, achieving significance by week 52 (P = .001) and continuing through week 78 (P < .0001), reflecting a 16.2% increase from baseline. Within-group analysis confirmed significant improvements over time in the vitamin D group (P = .002) but not in placebo (P = .18) group. After adjusting for potential confounders including body mass index, subscapular skinfold thickness, fasting blood glucose, and PTH, serum 25-hydroxyvitamin D levels maintained a significant independent association with both LTL (OR = 2.053; 95% CI, 1.410-2.243; P = .001) and telomerase activity (OR = 2.032; 95% CI, 1.410-2.254; P = .001) in the intervention group.

Conclusion: Vitamin D supplementation, over 78 weeks, is independently associated with increased LTL and telomerase activity in Asian Indian women with prediabetes.

Obesity arises from a complex interaction of genetic, hormonal, dietary, and behavioral factors that drive chronic energy imbalance, excessive fat accumulation, systemic inflammation, and insulin resistance, thus increasing the risk of metabolic diseases. Recent evidence suggests a significant role for epigenetic mechanisms, such as changes in patterns of DNA methylation, histone modifications, and chromatin accessibility, in the aetiology, progression, and intergenerational transmission of obesity risk. In this review, we first explore the link between cellular metabolism and epigenetics in the context of an obesogenic environment and highlight the mechanisms leading to cell-type and sex-specific epigenetic changes. We then highlight recent human studies that uncovered epigenetic alterations in key metabolic organs that distinguish metabolically healthy obesity from obesity complicated with insulin resistance, metabolic syndrome, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease. Mechanistic studies performed in the mouse support an important role for epigenetic mechanisms in driving the metabolic comorbidities of obesity. Given the difficulty of accessing tissues directly implicated in metabolic homeostasis, peripheral blood epigenetic biomarkers offer insights into the pathogenesis of these metabolic comorbidities of obesity and may predict their future development. The dynamic and reversible nature of obesity-associated epigenetic changes underscores their therapeutic potential. Future research should address challenges such as tissue specificity, interactions with genetic variants, and the functional impact of epigenetic alterations. Expanding studies on intergenerational inheritance, RNA modifications, and the development of epigenetic therapies hold promise for mitigating the impact of obesity-related metabolic comorbidities and informing precision interventions in clinical practice.

Context: There is an evolving role for radioactive iodine (RAI) in thyroid cancer treatment. Radioactive iodine treatment usually involves a pre-RAI whole-body iodine scan and a posttherapy scan. The clinical utility of pre-RAI therapy scans has been increasingly questioned.

Aim: To evaluate the clinical utility of pre-RAI whole-body iodine scans.

Methods: We retrospectively reviewed the medical records of differentiated thyroid cancer patients treated with RAI. Using records blinded for pre-RAI scans, 3 endocrinologists developed empiric RAI treatment plans for each patient based on surgical pathology. This was repeated using the unblinded records, and the treatment plans made with and without pre-RAI scan results were compared.

Results: A total of 164 patients met the inclusion criteria: 89 patients (54.3%) were low risk, 61 (37.2%) intermediate risk, and 14 (8.5%) high risk for thyroid cancer recurrence. After blinded review, RAI treatment was recommended for 122 patients (74.3%); 46 were determined to be appropriate for a low-dose RAI, 75 a medium dose, and 1 a high dose. When unblinded, different recommendations were made for only 7 patients (5.7%), with 6 being recommended for a higher RAI dose. In addition, the prescan RAI results prompted recommendations for additional testing, such as neck ultrasounds or computed tomography or postoperative thyroglobulin levels. Pre-RAI scans affected patient care plans in only 7 (5.7%) of the 164 patients in the study.

Conclusion: In most patients with thyroid cancer who may need RAI, pre-RAI scans may not affect management, and empiric RAI doses may be a more cost-effective and convenient option.

Context: Polycystic ovary syndrome (PCOS) is a common yet underdiagnosed endocrine disorder with substantial reproductive and metabolic consequences. Although disparities in PCOS care have been documented, few studies have employed spatial methods to identify areas of potential underdiagnosis.

Objective: This study uses geospatial analysis to detect cold spots of PCOS clinical encounters across Texas and investigates neighborhood characteristics associated with these areas.

Methods: We analyzed inpatient and outpatient encounter data from the Texas Public Use Data File (PUDF) between 2018 and 2024 to identify PCOS-related visits (International Classification of Diseases, revision 10: E28.2). ZIP code tabulation area (ZCTA)-level PCOS encounter prevalence was calculated per 1000 females and stabilized using empirical Bayes smoothing to account for rate instability. The Anselin local Moran's I statistic was used to detect spatial clusters. ZCTAs with statistically significant low-prevalence clusters (cold spots) were identified. Logistic regression assessed associations between cold spot status and neighborhood-level variables, including rural-urban commuting area codes, socioeconomic indicators, and health-related factors.

Results: Cold spots were concentrated in rural and periurban areas, suggesting potential underdiagnosis in communities with limited health-care access. This highlights the need for targeted public health interventions, including expanded provider training and diagnostic outreach in rural settings.

Conclusion: Significant spatial disparities in PCOS diagnosis suggest differential health-care access, diagnostic practices, or population health behaviors across the state. Targeted health interventions in rural communities may improve PCOS recognition and care. Further research is needed to explore the role of infrastructure and provider practices in causing these geographic disparities.

The skeleton is a storehouse of mineral that can be borrowed from in times of need, such as for reproduction. Skeletal resorption is normally modest during pregnancy but can be excessive when dietary calcium intake or absorption are insufficient for maternal and fetal needs. In contrast, substantial skeletal resorption is hormonally programmed to occur during lactation, with a loss of 5% to 10% of bone density from the spine over the first 6 months, independent of dietary calcium intake. The maternal skeleton is the main source of calcium in milk. Normally bone resorption during reproduction is without clinical consequences because the skeleton is restored to its prior mineral content and strength after weaning, such that parity and lactation are not risk factors for osteoporosis. However, bone strength is transiently reduced particularly during lactation, and can rarely lead to fragility fractures, especially if the skeleton was not normal before pregnancy. Women can present with fragility fractures during pregnancy but more often during lactation, sometimes with a frightening cascade of 5 to 10 vertebral compression fractures. This mini-review covers the epidemiology, pathophysiology, diagnostic approaches, and treatment considerations for this condition. Pharmacotherapy is often given in a desperate effort to do something, using agents that are not indicated in premenopausal women. The skeleton appears to recover, even in women who have fractured, such that it remains uncertain as to whether pharmacotherapy is necessary. Randomized trials are needed to determine when and in whom pharmacotherapy is needed, and which agent(s) might be preferable.

Context: Bone age (BA) evaluation in children presenting growth problems is time-consuming. Artificial intelligence (AI) BA assessment programs are increasingly used. However, agreement between different commercially available methods in the same population, or possible age-, puberty- or sex-related differences have not been sufficiently evaluated.

Methods: BA assessment of 521 left hand radiographs of patients aged 2-19 years with IB-lab-PANDA® and BoneXpert® were compared. Of the 521 radiographs, 213 were compared to the Greulich-Pyle (GP) reference. We analyzed gender, age, diagnosis, body mass index (BMI) and puberty categories. Accuracy was calculated as mean-absolute-deviation (MAD) and root-mean-square-error (RMSE).

Results: MAD was 0.61 years and the RMSE 0.83 years between BoneXpert and IB-lab-PANDA, with poor agreement in girls over 14 years (MAD 1.18 years).Compared to the manual rating, both methods showed a positive bias in boys (0.28 years BoneXpert vs 0.51 years IB-lab-PANDA) and in children with pathologies associated with BA delay (BoneXpert 0.18 years vs IB-lab-PANDA 0.35 years). IB-lab-PANDA underestimated BA in girls after 14 years (-0.67 years). IB-lab-PANDA had a MAD of 0.64 years and RMSE of 0.85 years compared to manual assessment, whereas BoneXpert had a MAD of 0.63 years and RMSE of 0.82 years.BoneXpert was significantly more accurate than IB-lab-PANDA in prepubertal children (MAD 0.7 vs 0.83 years; P = .027).

Conclusion: The direct agreement between IB-lab-PANDA® and BoneXpert® falls within human inter-rater variability. Their agreement on manual BA determination is equivalent except in prepubertal children, where BoneXpert seems more accurate. Both are fast, valuable tools for determining BA accurately and efficiently.

Context: Ketoconazole (KTZ) and metyrapone (MET) are used to normalize cortisol in Cushing syndrome (CS). Available recommendations can delay time to control.

Objective: This work aimed to identify predictors of treatment success and hepatotoxicity during rapid titration of KTZ and MET and to assess differences in blood pressure or potassium.

Methods: A retrospective evaluation was conducted at a tertiary referral center. Participants included 52 patients receiving treatment for adrenocorticotropin (ACTH)-dependent CS from 2004 to 2023. Interventions included KTZ or MET. The main outcome measures included the number of patients achieving target morning serum cortisol (AM F), defined as 12 mcg/dL or less (≤331 nmol/L), or increased liver function tests (LFTs) suggesting drug-induced liver injury (alanine/aspartate transaminase and alkaline phosphatase ≥3-fold upper limit of normal [≥3ULN], total bilirubin [Bili] ≥2ULN).

Results: KTZ achieved target AM F in 39% (95% CI 24%-56%) of patients, compared to 74% (95% CI 49%-90%) on MET. Lower baseline AM F predicted success only with MET. Among KTZ responders, maximal effect occurred by 2 days after a dose increase. LFTs worsened with KTZ and improved with MET. A similar proportion of patients had an LFT reach or exceed 3ULN with KTZ (22%; 95% CI 10%-39%) and MET (25%; 95% CI 4%-64%). Higher doses of KTZ, but not MET, predicted this. Bili reached or exceeded 2ULN in 3% (95% CI 0%-15%) of patients receiving KTZ and none receiving MET. Blood pressure and hypokalemia improved with KTZ but did not change with MET.

Conclusion: Hypercortisolism can likely be controlled faster with rapid titration of KTZ or MET. LFT abnormalities increased with KTZ but were common with MET treatment, likely reflecting underlying liver pathology in CS.

Context: Delayed gastric emptying caused by glucagon-like peptide-1 receptor agonists (GLP-1RAs) has raised concerns about increased aspiration risk during surgical and endoscopic procedures. In June 2023, the American Society of Anesthesiologists (ASA) recommended discontinuing GLP-1RAs one day (daily users) or one week (weekly users) before elective surgery or endoscopic esophagogastroduodenoscopy (EGD). In October 2024, the ASA reversed the initial recommendation and advised most patients to continue taking GLP-1RAs before elective surgery.

Objective: We conducted a systematic review of the evidence for or against the original recommendation.

Methods: We searched PubMed for retrospective cohort studies published between June 2023 and March 2025 investigating the association between GLP-1RA use and the risk of aspiration/pneumonia in patients undergoing elective surgery or endoscopic procedures. We calculated a summary risk ratio for studies that could be combined.

Results: We identified 3 studies of elective surgery and 4 of EGD using large databases to identify an increased risk of aspiration/pneumonia associated with GLP-1RA use. The 3 elective surgery studies had a combined risk ratio of 1.00 [0.76, 1.30]. The 4 EGD studies had a combined risk ratio of 1.10 [0.95, 1.27]. In one study, a parallel analysis of the aspiration/pneumonia risk associated with opioid medications found a risk ratio of 2.68 [1.89, 3.81], indicating that the methodology could detect an increased risk of aspiration/pneumonia from a motility inhibitor.

Conclusion: Although GLP-1RAs cause delayed gastric emptying, retrospective cohort studies using large real-world evidence databases have not consistently identified a GLP-1RA-associated risk of aspiration/pneumonia for elective surgical and endoscopic procedures.