Journal of the Endocrine Society最新文献

Context: It is unclear if nonfunctional adrenal tumors (NFAT) are associated with higher cancer incidence.

Objective: To analyze the cancer incidence in patients with NFAT.

Methods: In this national register-based retrospective cohort study, consecutive patients with NFAT identified in Sweden 2005-2019 and matched control individuals without adrenal tumors were followed up to 15 years. Outcome data were collected from national registers and adjusted for confounders. Both cases and controls were followed until newly diagnosed malignancy, death, or until 2019. Individuals with adrenal hormonal excess or prior malignancy were excluded.

Results: Among 17 726 cases, 10 777 (60.8%) were women, and the median age was 65 (IQR, 57-73) years. Among 124 366 controls, 69 514 (55.9%) were women, and the median age was 66 (IQR, 58-73) years. The incidence of any cancer was higher in patients with NFAT compared to controls (hazard ratio [HR] 1.35 95% CI 1.29-1.40; adjusted HR 1.31, 95% CI 1.26-1.37). NFAT was associated with a higher incidence of adrenal, thyroid, lung, stomach and small intestine, kidney, pancreatic, breast, and colorectal cancer. Sensitivity analyses did not change the overall results, but associations were not significantly increased after adjustment in patients with NFAT and appendicitis or gallbladder/biliary tract/pancreas disorders. Cancer incidence may have been underestimated by adjusting for unclear and benign tumors.

Conclusion: The incidence of cancer was increased in patients with NFAT. Long-term follow-up may be indicated.

Context: Metabolomics is becoming increasingly popular for detecting markers that indicate the presence of a specific disease. However, it is usually applied to studying individual ailments, yielding results that may not be directly relevant to people with multiple health conditions.

Objective: Our study proposes a different approach to explore metabolic crosstalk between various disease states.

Design setting and patients: We conducted a study on subjects at medium to high risk of developing coronary artery disease. We measured the plasma levels of 83 metabolites using nuclear magnetic resonance and analyzed the connections between these metabolites and various risk factors such as diabetes, hypertension, and dyslipidemia. Linear regression and multivariate analysis were combined for this purpose.

Results: Inspection of the metabolic maps created by our analysis helped us efficiently compare profiles. In this way, it was possible to discover opposing metabolic features among single conditions and their combination. Furthermore, we found compensating metabolic effects between diabetes, hypertension, and dyslipidemia involving mainly ketone body metabolism and fatty acid β-oxidation.

Conclusion: Our study introduces a novel approach to investigating how metabolism reacts to the simultaneous presence of multiple health conditions. This has allowed the detection of potential compensatory effects between diabetes, hypertension, and dyslipidemia, highlighting the complexity of metabolic crosstalk in patients with comorbidities. A better understanding of metabolic crosstalk like this could aid in developing focused treatments, resulting in improved therapeutic results.

Objective: This study examined the influence of a pregnancy and postnatal multicomponent lifestyle intervention for women with gestational diabetes mellitus (GDM) and overweight/obesity from 6 weeks to 12 months postnatal. The primary outcome was weight at 12 months. Secondary outcomes included change in body mass index (BMI), waist circumference (WC) and fasting plasma glucose (FPG).

Methods: The study involved 235 pregnant women with GDM and BMI ≥ 25 kg/m² during pregnancy. Intervention components included an educational session, activity tracker (Fitbit), monthly phone calls, weekly motivational text messages, 12-week voucher for a commercial weight management organization and anthropometric, biochemical, and clinical measurements taken at 6 weeks, 6 months, and 12 months postnatal. The control group received routine local maternity care.

Results: A mean weight change of -2.0 (SD 7.1) kg was observed in the intervention group compared with -0.6 (SD 8.0) kg in the control group, difference -1.4 (95% CI -4.4, 1.5) kg from 6 weeks to 12 months postnatal, but this was not statistically significant (P = .34). Neither were significant differences obtained for any secondary outcomes: BMI -0.6 (-1.6, 0.5) kg/m², WC -1.0 (-5.1, 3.2) cm and FPG 0.07 (-0.15, 0.29) mmol/L.

Conclusion: This lifestyle intervention among women with overweight/obesity and GDM resulted in a statistically nonsignificant 1.4 kg greater weight loss compared with routine care at 12 months postnatal. Further research is needed to understand how the different components of this lifestyle intervention might be better applied to elicit more successful results.

Context: The real world efficacy and tolerabiltiy of NTRK inhibitor larotrectinib has not yet been reported in the literature although trial data has shown promising results.

Objective: We report a retrospective analysis of patients with thyroid cancer harboring NTRK fusions who underwent treatment with larotrectinib.

Methods: A single-institution, retrospective case series of patients with NTRK fusion-positive thyroid cancers treated with neurotrophic tyrosine receptor kinase (NTRK) inhibitors from January 1, 2007, to January 1, 2023, was performed. This study was conducted at a single academic tertiary referral center. Patients with confirmed NTRK-fusion thyroid cancer who received larotrectinib were included. Larotrectinib was administered in accordance with clinical judgment from oncology providers. The primary end point was progression-free survival (PFS).

Results: Eight patients with NTRK fusion-positive thyroid cancer treated with larotrectinib were identified: 4 with papillary thyroid cancer (PTC) (50%), 3 with poorly differentiated thyroid cancer (PDTC) (38%), and 1 with anaplastic thyroid cancer (ATC) (12%). The median PFS (mPFS) for all patients was 24.7 months (95% CI, 11.3-38.1). mPFS in PTC was higher than PDTC (34.6 months [24.7-48.7 months] vs 17.5 [7.1-21.1 months]; P = .017). The median overall survival (OS) was 43.8 months (29.8-56.8 months) overall. The single patient with ATC had a PFS and OS of 23 months. Two patients remained on treatment/alive at data cutoff, with a duration of response of 33.5 months and a median follow-up of 52 months. Patients achieved 1 complete response (12%), 6 partial responses (75%), and 1 stable disease (12%).

Conclusion: In this single-institution cohort of patients with NTRK fusion-positive thyroid cancer, NTRK inhibition led to an mPFS of 25 months, with survival surpassing historic benchmarks for ATC and PDTC.

Context: Although biological findings show that estrogens are beneficial for muscular mass maintenance and bone resorption inhibition, the association of hormonal exposure with physical performance are controversial.

Objective: We investigated the association of reproductive history and exogenous hormone use with hand-grip strength (GS) in women.

Methods: Using the data from the CONSTANCES French prospective population-based cohort study, we ran linear mixed models to investigate the association of reproductive history and exogenous hormones use with maximal GS in 37 976 women aged 45 to 69 years recruited between 2012 and 2020. We used multiple imputation by chained equations to control missing values and corrections for multiple testing.

Results: The mean age of women was 57.2 years. Mean GS was 26.6 kg. After adjustment for age and confounders, GS increased with age at menarche (β_{+1 year} = 0.14; 95% CI, 0.10-0.17) and duration of breastfeeding (β _{for ≥10 months vs <5 months} = 0.39; 95% CI, 0.20-0.59; P for linear trend <.01). Compared to nonmenopausal women, postmenopausal women had significantly lower GS (β = -0.78; 95% CI, -0.98 to -0.58). GS was negatively associated with hormone therapy (HT) past use (β = -0.25; 95% CI, -0.42 to -0.07).

Conclusion: Our results suggested that menopausal transition was strongly associated with lower GS. However, despite our hypothesis, increased age at menarche and duration of breastfeeding were associated with higher GS and HT past users presented lower GS than HT never users. These findings could help identify women at high risk of poor physical performance.

Introduction: Prediabetes (PD) is becoming more common, and management is complicated by high rates of loss to follow-up. We evaluated variables associated with lost to follow-up status for pediatric patients with PD referred to endocrinology for evaluation and management.

Methods: We evaluated new patients referred to Children's of Alabama Endocrinology for PD from March 2017 through March 2021. Variables included patient medical and demographics as well as county-level metrics. Comparisons of patients who returned to clinic and those who were lost to follow-up were assessed by chi-square for categorical variables and Student's t-test/Wilcoxon rank sum test for continuous normal/skewed variables, respectively. Univariate logistic regression modeling identified risk factors for coming lost to follow-up and odds ratios with 95% confidence intervals were reported with a 2-sided P-value for significance of <.05.

Results: A total of 524 patients were included in the analysis. Almost one-fourth of patients were lost to follow-up (24.6%). The odds of returning to clinic were higher in patients with the Children's Health Insurance Plan, who were prescribed endocrine medications, who had a concurrent diagnosis of cholesterol disorder, who had referral to the endocrine clinic before COVID-19, and who were offered a telehealth visit. No other assessed variable was significantly associated with the likelihood of returning to clinic.

Conclusion: Independent of obesity severity, age, sex, race, county-level health, and economic variables, the factor most strongly associated with returning to clinic was having a telemedicine visit scheduled. Our data suggest that offering telemedicine visits may reduce lost to follow-up rates in this patient population.

Context: Body composition and glucose metabolism change with aging. Whether different levels of body-mass-index (BMI) are needed to define diabetes risk across the adult lifespan is unknown.

Objective: This work aimed to investigate whether BMI similarly reflects relative fat mass (FM) and diabetes risk across age groups.

Methods: Participants without diabetes from the Baltimore Longitudinal Study of Aging (973 men, 1073 women), stratified by age (<50, 50-59, 60-69, ≥70 years) and categorized by either World Health Organization (WHO)-defined BMI categories (for normal weight, overweight or obesity) or BMI quartiles. The primary exposure was BMI. The primary outcome was diabetes incidence. The relationship of BMI to dual-energy x-ray absorptiometry-derived FM was also investigated in older vs younger participants.

Results: The median (range) follow-up time was 7.1 years (range, 0-29.0 years). Within WHO-defined BMI categories, different age groups demonstrated significantly different FM percentage, FM/lean mass, and waist circumference (P < .05). WHO-defined BMI categories for overweight and obesity were generally related to higher diabetes risk compared to normal weight in all ages except 50 to 59 years. When BMI was categorized by quartiles, diabetes incidence increased dramatically beginning in quartile 2 (23-25 kg/m²) in older groups. BMI cutoffs with equivalent diabetes incidence rate as BMI 25 kg/m² and 30.0 kg/m² in individuals younger than 50 years were 22.7 kg/m² and 25.2 kg/m² for ages 50 to 59 years; 22.8 kg/m² and 25.0 kg/m² for ages 60 to 69 years; and 23.2 kg/m² and 25.8 kg/m² for ages 70 years and older, respectively.

Conclusion: WHO-defined BMI categories do not reflect similar diabetes risk across the lifespan. Diabetes incidence is greater at lower levels of BMI in older adults and may lead to underestimation of diabetes risk with aging, particularly among those traditionally classified as normal-weight individuals.

Objective: To assess the usefulness of the upright posture stimulation test (UPT) in the confirmation of primary aldosteronism (PA) in patients in whom saline tests (ST) were inconclusive.

Methods: One hundred eighty-seven adult patients with possible PA were retrospectively included and compared to 25 control subjects. Blood samples were obtained after a 1-hour supine posture and during 2 hours of ambulation. An increase in plasma aldosterone concentration (PAC) ≥ 50% with a suppressed renin (≤10.1 ng/L; ≤1 ng/mL/hour) and a cortisol increase ≤50% were considered abnormal.

Results: PA patients had higher basal PAC and lower basal direct renin concentration (DRC) (P < .0001) and a higher maximal PAC (P = .0025) and lower maximal DRC (DRC_max) (P < .0001) during UPT compared to controls. PA was confirmed in 145 patients (77.5%), based on either oral/IV ST or UPT. DRC_max ≤12 ng/L during UPT was a predictor of PA (receiver operating characteristic curve sensitivity 93.8%, specificity 88%), and 95.6% of PA patients increased PAC ≥50% on UPT (median 222.2%), while renin remained suppressed. All 41 PA patients with false-negative IV ST (PAC < 162 pmol/L) and 88.9% with borderline response (162-240 pmol/L) had a DRC_max ≤12, while, respectively, 97.6% and 100% increased aldosterone by ≥50%. Similar responses to UPT were found in lateralized (28/63) and bilateral PA source (35/63). PA diagnosis increased from 23.6% to 88.8% using UPT results instead of IV ST and were confirmed at pathology and clinical outcome after adrenalectomy (n = 22).

Conclusion: UPT can be useful to confirm PA, particularly in patients with suspected false-negative ST.

Mounting evidence indicates that whereas some fundamental aspects of bone cell differentiation and function are similar in females and males, there is a clear contribution of sex/gender on the effects of signaling molecules on bone mass and strength and, consequently, on the effects of pharmacologic approaches to treat skeletal disorders. However, until recently, most studies were designed and performed using only 1 sex, resulting in a scarcity of published information on sexual dimorphism of the musculoskeletal system, including the mandible/masticatory muscles and the axial and appendicular bones and skeletal muscles. Further, it is now recognized that scientific rigor requires the study of both males and females. Therefore, there is an increasing need to understand the molecular and cellular basis for the differential outcomes of genetic manipulations and therapeutic agent administration depending on the sex of the experimental animals. Studies have shown higher muscle mass, cancellous bone mass, and long bone width in males compared with females as well as different traits in the pelvis and the skull, which are usually used for gender identification in forensic anthropology. Yet, most reports focus on the role of sex hormones, in particular, the consequences of estrogen deficiency with menopause in humans and in ovariectomized animal models. In addition, emerging data is starting to unveil the effects of gender-affirming hormonal therapy on the musculoskeletal system. We summarize here the current knowledge on the sex/gender-dependent phenotypic characteristics of the bone and skeletal muscles in humans and rodents, highlighting studies in which side by side comparisons were made.

Recent studies have highlighted leptin, a key hormone that regulates energy intake and induces satiety, due to the worldwide prevalence of obesity. In this study, we analyzed plasma leptin measurements from 18 women with premenopausal obesity before and after bromocriptine treatment. By using underlying pulses recovered through deconvolution, we modeled the leptin secretory pulses as marked point processes and applied statistical distributions to evaluate the dynamics of leptin, including the interpulse intervals and amplitudes of the secretion. We fit the generalized inverse Gaussian and lognormal distributions to the intervals and the Gaussian, lognormal, and gamma distributions to the amplitudes of pulses. We evaluated the models' goodness of fit using statistical metrics including Akaike's information criterion, Kolmogorov-Smirnov plots, and quantile-quantile plots. Our evaluation results revealed the effectiveness of these statistical distributions in modeling leptin secretion. Although the lognormal and gamma distributions performed the best based on the metrics, we found all distributions capable of accurately modeling the timing of secretory events, leading us to a better understanding of the physiology of leptin secretion and providing a basis for leptin monitoring. In terms of pulse amplitude, the evaluation metrics indicated the gamma distribution as the most accurate statistical representation. We found no statistically significant effect of bromocriptine intake on the model parameters except for one distribution model.