BACKGROUND: Pregnancy-specific changes in thyroid physiology have prompted the use of pregnancy-specific reference intervals to diagnose thyroid disease. However, such reference intervals are not widely available, and th...BACKGROUND: Pregnancy-specific changes in thyroid physiology have prompted the use of pregnancy-specific reference intervals to diagnose thyroid disease. However, such reference intervals are not widely available, and there is no evidence of their superiority over non-pregnancy reference intervals. Preconception data are understudied benchmarks to compare pregnancy-specific and non-pregnancy-specific intervals. Moreover, the added value of FT3 measurements, for example in cases of (subclinical) hyperthyroidism, remains to be quantified. METHODS: This study was embedded within Generation R Next, a population-based prospective cohort from preconception through postpartum in Rotterdam. Prevalence of thyroid disease entities was assessed using both pregnancy-specific and non-pregnancy reference intervals during pregnancy, and using non-pregnancy reference intervals in the preconception period. FT3 concentrations of both euthyroid participants and those with thyroid disease entities were compared in the preconception period and during pregnancy. RESULTS: The study population included 1,058 women during preconception and 2,084 women during pregnancy. The prevalence of subclinical hypothyroidism during pregnancy was 1.5% with use of non-pregnancy reference intervals and 3.6% with pregnancy-specific reference intervals, versus 2.2% during preconception. The prevalence of subclinical hyperthyroidism during pregnancy was 11.1% with use of non-pregnancy reference intervals and 1.5% with pregnancy-specific reference intervals, versus 2.0% during preconception. Additional FT3 measurements would reclassify 5.6% of subclinical hyperthyroidism cases to hyperthyroidism during preconception and 14.3% during pregnancy. CONCLUSION: This is the first study to assess the prevalence of (sub)clinical thyroid disease during pregnancy comparing non-pregnancy and pregnancy-specific reference intervals, while also comparing these prevalences to preconception data from the same source population. We show that pregnancy-specific reference intervals likely result in overdiagnosis of subclinical hypothyroidism and that FT3 has limited value in diagnosing (sub)clinical thyroid disease during pregnancy.
OBJECTIVE: To assess whether daily step counts and genetic risk interact to influence the risk of developing type 2 diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from 9,501 participants in the All of Us Researc...OBJECTIVE: To assess whether daily step counts and genetic risk interact to influence the risk of developing type 2 diabetes. RESEARCH DESIGN AND METHODS: We analyzed data from 9,501 participants in the All of Us Research Program with both genetic and wearable device-derived physical activity data and without diabetes at baseline and median age of 56 years (42-66). Physical activity was quantified using daily step counts. Genetic risk was assessed using a global polygenic score. Incident type 2 diabetes was identified using electronic health record-linked diagnostic codes. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) for type 2 diabetes across genetic risk and physical activity levels. We tested for additive interaction using the relative excess risk due to interaction (RERI). In secondary analyses we used physical-activity intensity measures using wearable-derived and self-reported intensity levels. RESULTS: Type 2 diabetes incidence rates ranged from 4.1 per 1,000 person-years (95% CI, 2.5-5.7) in individuals with high physical activity and low genetic risk to 18.4 (95% CI, 15.2-21.6) in those with low physical activity and high genetic risk (HR, 6.2 (95% CI: 3.97, 9.6)). A significant additive interaction was observed (RERI, 0.20; 95% CI, 0.04-0.36; P = .007), with 15% (95% CI, 2-27) of excess risk attributed to the interaction. Similar interaction patterns were found using device-based intensity metrics and self-reported physical activity measures. CONCLUSIONS: These findings provide evidence of additive interactions between genetic risk and physical activity, underscoring the potential value of integrating genomic and device-derived data to identify individuals who would more likely benefit from increasing physical activity.
CONTEXT: The relationship between obesity, type 2 diabetes (T2D), and bone health in youth is not clear. Objective; To examine the relationship of adiposity and glucose metabolism with bone mineral content (BMC) and qual...CONTEXT: The relationship between obesity, type 2 diabetes (T2D), and bone health in youth is not clear. Objective; To examine the relationship of adiposity and glucose metabolism with bone mineral content (BMC) and quality (microarchitecture and strength) in youth across the glycemia spectrum, and evaluate sex-related differences. DESIGN: Cross-sectional study. SETTING: Research Center. PARTICIPANTS: 92 adolescents (56 females); 32% normal weight (NW), 29% overweight-normal glucose tolerance (OW-NGT), 39% OW-impaired glucose regulation (OW-IGR), including prediabetes (n=9) or T2D (n=27). MAIN OUTCOME MEASURES: Bone quality (HRpQCT), body composition and BMC (DXA), anthropometrics, OGTT with glucose and insulin indices, vitamin D and calcium metabolism. RESULTS: BMC and distal tibia bone microarchitecture and strength (modulus) measures were worse in OW-IGR and OW-NGT compared with NW in males but not in females. In multivariable models, accounting for age, Tanner stage and sex, age and lean mass (β=3.9, p<0.001) positively, while height (β=-4.5, p<0.001) and HOMA-IR (β=-4.6, p=0.005) negatively contributed to the variance in tibial volumetric BMD (vBMD) (R2=0.45, p<0.001). Similar relationships were found with radial vBMD and with whole bone modulus at the tibia and radius independent of sex. Fasting glucose was inversely related to trabecular thickness at the tibia and radius. CONCLUSIONS: There is a negative relationship between adiposity and insulin resistance with bone microarchitecture and strength in youth after accounting for age, sex, height and lean mass. There appears to be sexual dimorphism in these relationships, with more negative effect of adiposity and dysglycemia on bone quality in males.
Ohmachi Y, Nishio M, Abe I
… +38 more, Kobayashi K, Iida T, Shirakawa M, Nagata Y, Takeuchi K, Taguchi A, Kinoshita Y, Fukuhara N, Nishioka H, Tahara S, Fujio S, Ogura T, Kurosaki M, Hada Y, Susa S, Otsuka Y, Otsuka F, Ishida I, Kameda H, Oyama K, Yamada S, Kobatake M, Oi-Yo Y, Fujii G, Tomofuji S, Sasaki Y, Bando H, Yamamoto M, Iguchi G, Motomura Y, Tsujimoto Y, Yamamoto N, Suzuki M, Urai S, Takahashi M, Murakami T, Ogawa W, Fukuoka H
CONTEXT: Acromegaly poses clinical challenges in terms of early diagnosis and intervention. Therefore, the development of novel diagnostic tools is essential. Although artificial intelligence (AI) models based on externa...CONTEXT: Acromegaly poses clinical challenges in terms of early diagnosis and intervention. Therefore, the development of novel diagnostic tools is essential. Although artificial intelligence (AI) models based on external appearance have been proposed, privacy concerns have limited their use. OBJECTIVE: To develop a privacy-conscious deep learning model for detecting acromegaly using hand images. METHODS: This nationwide multicenter study enrolled 716 patients (317 with acromegaly and 399 controls) and 11 480 images from 15 Japanese pituitary centers. The inclusion criteria were age ≥18 years and care received at the participating facilities. Hand images focusing on the dorsal and fist sign, excluding the palm/fingerprint regions, were used to develop the model. The data were split into training/validation (12 centers) and test (3 centers) datasets. A ResNet-50-based model was trained using PyTorch with data augmentation and 5-fold cross-validation. For each patient, the predictions were averaged over 4 images. The performance of the model was compared with that of endocrinologists. RESULTS: The model achieved a sensitivity of 0.89, specificity of 0.91, positive predictive value of 0.88, negative predictive value of 0.93, F1-score of 0.89, and an area under the receiver operating characteristic curve of 0.96, outperforming specialists (F1-score range: 0.43-0.63). CONCLUSION: This study highlights the utility of dorsal hand and fist sign as diagnostic clues for acromegaly, which the AI model captured more accurately than endocrinologists. Using this privacy-conscious feature, this model can be deployed in public settings like health checkups. Further validation using larger datasets, including healthy individuals and diverse diseases, is necessary.
BACKGROUND: Sleep disturbances are common in women with polycystic ovary syndrome (PCOS), but no prospective studies have explored whether childhood-adolescence sleep disturbances are associated with later PCOS risk. Und...BACKGROUND: Sleep disturbances are common in women with polycystic ovary syndrome (PCOS), but no prospective studies have explored whether childhood-adolescence sleep disturbances are associated with later PCOS risk. Understanding behavioural markers may support early identification and intervention. OBJECTIVE: To examine whether poor sleep behaviours from childhood to adolescence are prospectively associated with a diagnosis of PCOS at age 14 years. MATERIALS AND METHODS: Sleep behaviour data (Child Behavior Checklist) from a longitudinal study of 226 female participants of the Raine Study cohort (37 with PCOS), assessed at ages 5, -8, -10, and -14 years, with PCOS diagnosis at age 14 years were analyzed. PCOS diagnosis was based on both hyperandrogenism and ovulatory dysfunction according to the 2023 PCOS Guideline adolescent diagnostic criteria. Generalized estimating equations examined longitudinal sleep behaviour differences by PCOS status at age 14; logistic regression explored specific sleep behaviour associations with PCOS risk at age 14. RESULTS: After adjustment for covariates, results showed higher sleep behaviour problem scores from childhood to adolescence, with differences becoming more pronounced over time among girls with PCOS at age 14 (adjusted mean difference=0.49; 95% CI=0.10-0.87; P=0.013). Analysis of individual items showed significant associations between PCOS at age 14 and 'trouble sleeping' at age 10 (OR=2.95; 95% CI=1.30-6.69) and 'sleeping less than most kids' at age 10 (OR=2.48; 95% CI=1.18 to 5.22). CONCLUSION: Sleep difficulties may serve as early, modifiable behavioural markers of PCOS risk. Poor sleep may worsen hormonal and metabolic dysfunction, promoting insulin resistance, obesity, and sleep disturbances.
CONTEXT: Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare, autosomal dominant disorder due to pathogenic heterozygous variants in POLD1. Clinical features of MDPL vary betwe...CONTEXT: Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is a rare, autosomal dominant disorder due to pathogenic heterozygous variants in POLD1. Clinical features of MDPL vary between patients, however, there is no previously reported genotype-phenotype association. OBJECTIVE: To report 14 new patients with lipodystrophy due to POLD1 variants and to compare phenotypic differences between those with p.Ser605del and missense variants. METHODS: Genetic sequencing was performed on DNA of 14 patients for POLD1 variants, including exome (n=10), genome (n=1) and candidate gene (n=3) sequencing. Comparisons of demographic, clinical features and metabolic complications between carriers of POLD1 p.Ser605del and missense variants in our cases and those reported in the literature were made using Fisher's exact test for categorical variables and Student's t-test for continuous variables. RESULTS: A total of nine different POLD1 variants were identified in our patients, including three novel variants: p.Asp25Glufs*16, p.Arg507His, and p.Trp781Cys. Compared to individuals with missense variants (n=15), those with p.Ser605del (n=26) POLD1 variant had significantly increased prevalence of mandibular hypoplasia (57% vs 100%, respectively; p=0.015), small mouth (36% vs 100%, respectively; p=0.015), crowded teeth (44% vs 91%, respectively; p=0.046), and hypogonadism in males (0% vs. 92%, respectively; p=0.046). There were no differences in the prevalence of metabolic complications, such as diabetes, hypertriglyceridemia and hepatic steatosis in the two groups. CONCLUSION: Subjects with heterozygous POLD1 p.Ser605del variant had typical MDPL with more severe phenotype compared to those with missense variants with atypical MDPL.
Canberk S, Baloch ZW, Isaza A
… +19 more, Bojarsky M, Vigliar E, Carillo AM, Dello Iacovo F, Bellevicine C, Troncone G, Simplício M, Barroca H, Akkoyunlu SZ, Günver MG, Rodrigues E, Capela J, Weiss VL, Wang H, Aydin O, Thodou E, Gücer H, Schmitt F, Bauer AJ
J Clin Endocrinol Metab
· 2026 Feb · PMID 41739856
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OBJECTIVE: Paediatric thyroid nodules are uncommon but have a higher malignancy rate than adult nodules. Existing Bethesda risk-of-malignancy (ROM) estimates are not age-stratified and are affected by verification bias....OBJECTIVE: Paediatric thyroid nodules are uncommon but have a higher malignancy rate than adult nodules. Existing Bethesda risk-of-malignancy (ROM) estimates are not age-stratified and are affected by verification bias. We aimed to generate age-specific ROM, likelihood ratios (LRs), and post-test malignancy probabilities for paediatric and young adult thyroid cytology. METHODS: We analysed 2,728 thyroid fine-needle aspirations (FNAs) from patients aged 0-25 years across multiple tertiary centres (2000-2023). All cases were classified or reclassified using the 2023 Bethesda System and grouped into four age bands (0-8, 9-14, 15-18, and 19-25 years). We calculated lower-bound ROM (ROM overall; assuming non-operated FNAs were benign) and surgery-only upper-bound ROM (ROM surgery; 991 of 2,728 cases with histology). Age-specific pretest probabilities and Bethesda-category LRs were used to compute post-test malignancy probabilities with Bayes' theorem. RESULTS: Among operated nodules, malignancy prevalence decreased with age (84.2% at 0-8 years to 64.6% at 19-25 years). Verification bias was substantial: malignancy prevalence was 24.6% (671/2,728) under the lower-bound assumption but 67.7% (671/991) among surgical cases. Upper-bound ROM values were 2-10 times higher than lower-bound values across categories. Benign cytology showed low LRs (0.07-0.15), reducing post-test malignancy probability to 0-25%. Indeterminate categories showed age-related variation; for example, a follicular neoplasm diagnosis carried a ∼71% post-test risk in a 9-year-old versus ∼49% in a 24-year-old. AUS subtyping (nuclear vs other atypia) did not consistently separate ROM. CONCLUSIONS: Age substantially modifies both pretest and post-test malignancy probabilities in paediatric thyroid cytology. An age-stratified LR framework helps quantify verification bias and provides individualized risk estimates to guide decisions about surgery, molecular testing, and follow-up.
Yoshida T, Wang F, Moon W
… +15 more, Mostoufi-Moab S, Wang H, Neupane A, Wang J, Sapkota Y, Wilson CL, Mirzaei S, Wang Z, Zhang J, Merchant TE, Armstrong GT, Ness KK, Hudson MM, Yasui Y, Delaney A
J Clin Endocrinol Metab
· 2026 Feb · PMID 41739851
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CONTEXT: Radiation to the hypothalamic-pituitary (HP) region (HP-RT) is a strong risk factor for HP deficiency among childhood cancer survivors (survivors). However, there is inter-individual variability in developing HP...CONTEXT: Radiation to the hypothalamic-pituitary (HP) region (HP-RT) is a strong risk factor for HP deficiency among childhood cancer survivors (survivors). However, there is inter-individual variability in developing HP deficiency after similar HP-RT dose exposures. OBJECTIVES: To assess the genetic contribution to developing deficiencies of GH (GHD), LH/FSH (LH/FSHD), TSH (TSHD), and ACTH (ACTHD) among survivors exposed to HP-RT. METHODS: Eligible participants included five-year survivors exposed to HP-RT (n=809; median follow-up 31.9 years) from the St. Jude Lifetime Cohort. We assessed the association between rare variants from whole-exome sequencing data [minor allele frequency (MAF)<0.01, predicted to be pathogenic by functional prediction tools] and HP deficiency rate (total counts/person-year) among 801 survivors by the exact Poisson test. Genome-wide association analysis (GWAS) was conducted among 606 survivors of European ancestry with available whole-genome sequence data, targeting variants with MAF≥0.01. The replication population was 1,328 survivors from the Childhood Cancer Survivor Study (CCSS). RESULTS: Carriers of rare variants in TNS2, a ubiquitously expressed protein-coding gene including in brain, had significantly higher rates of HP deficiencies [rate ratio 2.72 (95% confidence interval 1.81-4.09), p=1.5×10-5] compared to non-carriers, which was replicated in the CCSS. This was also observed in individual HP deficiencies: LH/FSHD [3.31 (1.28-7.99)], TSHD [5.29 (2.42-11.34)], and ACTHD [3.97 (1.05-12.31)]. There were no statistically significant variants in GWAS. CONCLUSIONS: TNS2 may contribute to radiation-induced HP deficiencies. With further validation, screening for TNS2 variants has potential to help identify individuals who would benefit from surveillance and intervention following HP-RT.
J Clin Endocrinol Metab
· 2026 Jun · PMID 41738576
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CONTEXT: Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and is associated with type 2 diabetes, which is associated with breast cancer and kidney cancer. However, little is known...CONTEXT: Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and is associated with type 2 diabetes, which is associated with breast cancer and kidney cancer. However, little is known about the risk of cancer following a GDM diagnosis. OBJECTIVE: This study aimed to test the hypothesis that a history of GDM associates with increased risk of breast, gynecological, thyroid, and kidney cancer. METHODS: National cohort study, based on Danish registry data. The study population included a group of women exposed to GDM in their pregnancy leading to delivery between 2000 and 2019 or 1978 and 1997 and a 1:10 matched nonexposed group, matched on calendar period of delivery, the woman´s age (birth year), and the woman´s registered region of residence at delivery. Poisson regression adjusting for educational level was conducted. RESULTS: Of the 314 742 deliveries included, 28 613 deliveries were in the exposed group and 286 129 in the nonexposed. The median follow-up time was 8.1 years. We found no increased risk of the selected cancers combined [adjusted incidence rate ratio (aIRR) 1.05; 95% confidence interval (CI), 0.94-1.18], breast cancer (aIRR 1.02; 95% CI, 0.89-1.17), gynecological cancer (aIRR 1.00; 95% CI, 0.79-1.26), or thyroid cancer (aIRR 1.26; 95% CI, 0.86-1.82). However, an increased risk of kidney cancer was seen in women with previous GDM compared with women without GDM (aIRR 1.92; 95% CI, 1.10-3.33), although it was a very small absolute risk. CONCLUSION: No elevated risk was found for the selected cancers combined. Women with previous GDM had an increased risk of kidney cancer, a rare cancer form.
BACKGROUND: Elevated parathyroid hormone (PTH) levels have been linked to higher cardiovascular (CV) and all-cause mortality in individuals with hyperparathyroidism or high-risk conditions (individuals with a mean age of...BACKGROUND: Elevated parathyroid hormone (PTH) levels have been linked to higher cardiovascular (CV) and all-cause mortality in individuals with hyperparathyroidism or high-risk conditions (individuals with a mean age of 75-85 years and patients undergoing coronary angiography). However, it remains uncertain whether sex- and age-related differences influence these associations among normocalcemic and middle-aged adults from the general population. METHODS: We analyzed 4736 participants from the ELSA-Brasil study (mean age, 51.7 years; 55% females), followed for a median of 11.2 years. Baseline serum PTH was measured by electrochemiluminescence immunoassay. Associations of PTH with outcomes were assessed using Cox regression for all-cause mortality, reporting hazard ratios (HRs), and Fine-Gray models for CV mortality, accounting for competing risks and reporting subdistribution hazard ratios (sHRs), adjusted for total calcium, and other relevant covariates. RESULTS: A baseline PTH concentration >56 pg/mL was independently associated with higher CV mortality (sHR 1.92; 95% CI 1.22-3.01) and all-cause mortality (HR 1.61; 95% CI 1.25-2.07). Sex- and age-stratified analyses showed that females with elevated PTH had a 179% increased CV mortality risk (sHR 2.79; 95% CI 1.37-5.70), whereas no significant association was seen in males. Elevated PTH was also associated with increased CV mortality in adults ≤64 years (sHR 1.80; 95% CI 1.05-3.09) but not in older individuals. For all-cause mortality, PTH >56 pg/mL conferred a higher risk in both females (HR 1.75; 95% CI 1.15-2.66) and males (HR 1.59; 95% CI 1.16-2.19), with consistent associations across both age groups (≤64 and >64 years). CONCLUSION: In this large, community-based cohort, PTH levels at the upper end of the reference range were associated with greater CV and all-cause mortality. The excess CV risk was restricted to females and younger adults, suggesting that PTH may serve as an early, sex-sensitive biomarker of cardiometabolic risk.
Lunati ME, Cimino V, Bernasconi D
… +17 more, Romano C, Disoteo O, Rossi A, Tinari C, Fiorina RM, Gandolfi A, Morpurgo PS, D'Addio F, Lazzaroni E, Losurdo F, Pastore I, Molteni L, Berra C, Ben Nasr M, Montefusco L, Bucciarelli L, Fiorina P
J Clin Endocrinol Metab
· 2026 Jun · PMID 41729594
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INTRODUCTION: Semaglutide, a GLP-1R agonist (GLP-1RA), has demonstrated high efficacy in the management of type 2 diabetes. Few data in literature are available regarding the use of this agent in patients affected by lat...INTRODUCTION: Semaglutide, a GLP-1R agonist (GLP-1RA), has demonstrated high efficacy in the management of type 2 diabetes. Few data in literature are available regarding the use of this agent in patients affected by latent autoimmune diabetes in adults (LADA). The purpose of this study is to analyze the efficacy of semaglutide use in patients affected by LADA. MATERIALS AND METHODS: In this retrospective study, we collected and analyzed data of 80 patients with LADA treated with semaglutide, either oral or subcutaneous, as an add-on therapy to insulin. Laboratory and clinical parameters and metrics from continuous glucose monitoring were collected where available. RESULTS: Among 80 patients, 68 continued semaglutide (57/68 oral and 11/68 subcutaneous) for at least 6 months, whereas 12/80 patients discontinued treatment. After 6 months, semaglutide users showed statistically significant reduction in glycated hemoglobin, body mass index, and insulin total daily dose. Interestingly, serum C-peptide levels and the time-in-range values increased, without changes in the time below range. Subjects with residual β-cell function showed a higher body mass index and insulin total daily dose reduction. Moreover, the subgroup of subjects with preserved β-cell mass showed a greater improvement in time in range as compared to those with poor C-peptide production. Finally, 14/68 subjects suspended insulin bolus administration after starting semaglutide. CONCLUSION: Semaglutide as an add-on treatment to insulin exerted relevant clinical beneficial effects on the glycometabolic control in patients with LADA. These effects are enhanced in those patients with preserved β-cell function.
J Clin Endocrinol Metab
· 2026 Jun · PMID 41715942
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Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-producing neuroendocrine tumors with significant systemic effects. While catecholamine-related cardiovascular manifestations are well-characterized as a...Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-producing neuroendocrine tumors with significant systemic effects. While catecholamine-related cardiovascular manifestations are well-characterized as a prominent component of the clinical presentation, other systemic effects, particularly those on bone and mineral metabolism, remain much less characterized. Bone physiology and health in patients with PPGLs can be affected through catecholamine-mediated changes, skeletal metastases, or specific skeletal abnormalities associated with syndromic PPGL forms. The catecholamine effect on bone density was first noticed in experimental murine models, where β-adrenoceptor signaling was shown to increase bone resorption. These findings were further supported by epidemiological and translational studies indicating a protective role of β-adrenoceptor blockers in maintaining bone density. Both preclinical and clinical studies draw attention to the potential alterations of bone physiology in patients with PPGLs. To date, a few retrospective studies have evaluated bone turnover markers and bone mineral density (BMD) in these patients, consistently showing lower BMD and trabecular bone score, as well as elevated serum C-terminal telopeptides levels, compared to healthy controls with partial reversibility following surgical resection of the tumor. In this review, we summarize the available mechanistic and clinical literature on bone health in PPGLs, to raise awareness among clinicians, identify opportunities for primary prevention, and ensure a better quality of life.
Li J, Isaacs SD, Pagliaro S
… +6 more, Sunusi U, Wilson JE, De Vol EB, Molinaro R, Parker N, Mechanick JI
J Clin Endocrinol Metab
· 2026 Jun · PMID 41712433
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BACKGROUND: Standardized testosterone measurement is essential for diagnosing hypogonadism, infertility, endocrine disorders, and monitoring therapy. The CDC Hormone Standardization Program for Total Testosterone (HoSt-T...BACKGROUND: Standardized testosterone measurement is essential for diagnosing hypogonadism, infertility, endocrine disorders, and monitoring therapy. The CDC Hormone Standardization Program for Total Testosterone (HoSt-TT) evaluates assay performance against ID-LC-MS/MS using clinically relevant concentrations. This study assesses the Atellica IM TSTII assay compliance to HoSt-TT criteria and its correlation with LC-MS/MS. METHODS: Analytical performance of Atellica IM TSTII and method comparison studies using HoSt-TT certification samples were analyzed, evaluated, and stratified by sex. Comparisons of TSTII TT to LC-MS/MS and calculated vs measured free testosterone (FT) were performed and analyzed using remnant patient samples, with FT calculated (Vermeulen method, ISSAM calculator). RESULTS: HoSt-TT vs Atellica IM TSTII assay results demonstrated average bias within ±6.4%, with OLS regression slopes of 1.02-1.06, r ≥ 0.98. TSTII demonstrated repeatability (2.18% CV), within-lab precision (3.46% CV), and overall total analytical error of 18.3% (IQR 11.6-31.6%). Furthermore, comparing TT on the TSTII to LC-MS/MS (LDT) using native patient samples, resulted in strong fits (slope = 0.9798, r = 0.991); and calculated FT correlated well with equilibrium dialysis/LC-MS/MS (slope = 0.9530, r = 0.965). CONCLUSION: The TSTII assay is CDC HoSt-TT certified, has strong alignment to LC-MS/MS, and shows good correlation of calculated FT with equilibrium dialysis/LC-MS/MS. Although LC-MS/MS remains the reference method for testosterone quantification, particularly at low concentrations, CDC HoSt certification of the TSTII assay supports its potential suitability for measuring testosterone concentrations in women and children within defined analytical and clinical contexts.
CONTEXT: Diabetes-associated cognitive dysfunction (DACD) is characterized by crosstalk between metabolic disturbances and neural dysfunction. Prolactin (PRL), a pituitary hormone involved in glucose regulation and neuro...CONTEXT: Diabetes-associated cognitive dysfunction (DACD) is characterized by crosstalk between metabolic disturbances and neural dysfunction. Prolactin (PRL), a pituitary hormone involved in glucose regulation and neuroinflammation, may contribute to DACD development. OBJECTIVE: This study aims to investigate the relationships and underlying mechanisms between serum PRL and DACD in patients with type 2 diabetes (T2DM) via neuroimaging. METHODS: Five hundred twenty-two with normal cognition and 418 with mild cognitive impairment (MCI) were included after age- and gender-matching among 1167 participants with T2DM. Two hundred forty-seven individuals underwent functional magnetic resonance imaging scans to assess brain structure and function. Structural equation modeling (SEM) was used to explore the mechanism linking serum PRL to cognition. RESULTS: Relative weight analysis indicated that PRL and luteinizing hormone (LH) accounted for 8.14% and 7.53% of MCI risk in T2DM across 1167 participants. However, multivariate logistic regression analysis showed that PRL, rather than LH, was an independent risk factor for MCI in T2DM (odds ratio [OR] = 0.907, 95% confidence intervals [95% CI]: 0.849-0.968, P = .003), with the lowest PRL tertile group showing significant cognitive deficits and reduced hippocampal-amygdaloid volumes. Moreover, SEM indicated that PRL positively influenced cognition and exerted an indirect effect via limbic structures, contributing 14.07% to the total effect. Additionally, the lowest PRL tertile group exhibited a significant decreased functional connectivity between the right amygdala and right frontal lobe, partially mediating the link between serum PRL and MoCA scores. CONCLUSION: Decreased serum PRL is associated with reduced hippocampal and amygdaloid volumes, impaired amygdala functional connectivity, and diminished cognitive performance in T2DM.
BACKGROUND: Radioactive iodine (RAI) has been one of the main treatments for hyperthyroidism since the 1940s, but its long-term safety, particularly regarding cancer risk, remains controversial. This study evaluated asso...BACKGROUND: Radioactive iodine (RAI) has been one of the main treatments for hyperthyroidism since the 1940s, but its long-term safety, particularly regarding cancer risk, remains controversial. This study evaluated associations between RAI treatment and cancer incidence and mortality, including overall and site-specific cancers. METHODS: We conducted a retrospective cohort study utilizing a University of Michigan de-identified electronic health record dataset. Adults (aged ≥18 years) newly diagnosed with hyperthyroidism between 2006 and 2019, without prior cancer, and treated with RAI, antithyroid medications, or thyroidectomy were included. Participants were followed until cancer diagnosis, death, or December 2022. Time-dependent Cox models estimated hazard ratios (HRs) and 95% CIs comparing RAI with other therapies using age-adjusted (age-adj) and multivariable (mv) models adjusting for demographics, lifestyle and clinical covariates. Sensitivity analysis stratified by cohort entry period, follow-up duration and restriction to ≥2 years of follow-up. RESULTS: The cohort included 6435 participants contributing 52 909 person-years (mean follow up 8.2 years; range 0.5-17 years), with 487 incident cancers and 157 cancer deaths. RAI treatment was not associated with overall cancer incidence (mv HR = 1.02 [0.76-1.47], P = .734) or cancer mortality (mv HR = 0.81 [0.45-1.44], P = .471). However, RAI was significantly associated with increased breast cancer risk among women (mv HR = 2.24 [1.21-4.17], P = .011), and among postmenopausal women (mv HR = 2.65 [1.24-5.66], P = .011). An elevated pancreatic cancer mortality was observed in those with ≥2 years of follow-up (age-adj HR = 4.05 [1.01-16.20], P = .042). CONCLUSION: RAI treatment was associated with increased breast cancer incidence but not overall cancer incidence or mortality. Findings for pancreatic cancer mortality were suggestive. These results support the importance of long-term safety monitoring among RAI-treated patients.
PURPOSE: Survivors of childhood brain tumors are at high risk of hypothalamic-pituitary dysfunction, but comparative data across cancer histotypes and treatment modalities are limited. This study evaluated the prevalence...PURPOSE: Survivors of childhood brain tumors are at high risk of hypothalamic-pituitary dysfunction, but comparative data across cancer histotypes and treatment modalities are limited. This study evaluated the prevalence, risk factors, and timing of onset of hypothalamic-pituitary disorders in a large cohort of childhood brain cancer survivors, with attention to tumor type and therapeutic exposure. METHODS: A retrospective cohort of 388 patients diagnosed with primary brain tumors before 18 years of age and followed at a tertiary center between 2000 and 2025 was analyzed. Demographic, clinical, and treatment data were extracted from medical records. Standardized endocrine assessments, including dynamic testing when indicated, were performed at diagnosis and throughout follow-up. Endocrine disorders were classified by international criteria, and onset timing was recorded. RESULTS: Glioma was the most frequent histotype (66.2%), followed by medulloblastoma (19.1%), ependymoma (6.2%), craniopharyngioma (5.2%), and germ-cell tumors (3.3%). Endocrine disorders occurred in 75.8% of patients, with the highest prevalence in craniopharyngioma and germ-cell tumors. Central hypothyroidism (27.8%) was the most common deficiency, followed by central precocious puberty (27.1%), growth hormone deficiency (25.8%), adrenocorticotropic hormone deficiency (22.7%), and central diabetes insipidus (16.8%). Early-onset deficiencies were typically related to surgical hypothalamic-pituitary injury, whereas late-onset disorders were mainly associated with radiotherapy or chemotherapy. Younger age at diagnosis and sellar/suprasellar localization independently predicted endocrine morbidity. CONCLUSION: This study provides a comprehensive analysis of endocrine outcomes by tumor histotype, treatment modality, and onset timeline, underscoring the need for individualized and lifelong endocrine surveillance in survivors of childhood brain tumors.