Background and Objectives: The transition from pediatric to adult endocrine care represents a vulnerable period for patients with congenital adrenal hyperplasia (CAH), given the risk of loss to follow-up and the evolving physiological and healthcare requirements associated with the transition to adulthood. This study aimed to compare structured and non-structured transition pathways in patients with CAH, focusing on the continuity of adult endocrine care and disease-specific hormonal, clinical, and treatment-related outcomes. Materials and Methods: This single-center, retrospective, observational study included patients with CAH who transitioned from pediatric to adult endocrine care and met predefined pediatric and adult follow-up eligibility criteria. Patients were classified according to whether the transition occurred through a structured multidisciplinary transition program or without participation in the structured program. Outcomes were evaluated during predefined observation periods before and after transfer and included continuity-of-care measures, 17-hydroxyprogesterone (17-OHP) and androstenedione concentrations, achievement of predefined hormonal targets, body mass index (BMI), glucocorticoid and mineralocorticoid treatment, and CAH-related clinical outcomes. Results: Among 67 patients assessed for eligibility, 29 were included: 20 in the structured transition group and 9 in the non-structured transition group. Overall, 62.1% of the study population was female. No significant between-group differences were observed in continuity-of-care measures, including the pediatric-to-adult care gap, first-year adult visit frequency, maximum visit-free interval, first-year loss to follow-up, or active adult endocrine follow-up at the study cutoff. Pre-transition and post-transfer 17-OHP and androstenedione concentrations and achievement of predefined hormonal targets did not differ significantly between groups. No significant longitudinal changes in hormonal outcomes, BMI, or body-surface-area-adjusted hydrocortisone-equivalent glucocorticoid doses were observed within either group. At the study cutoff, 85.0% of patients in the structured group and 77.8% in the non-structured group remained under active adult endocrine follow-up. Conclusions: In this small single-center cohort, no significant differences in the continuity of adult endocrine follow-up or disease-specific outcomes were observed between structured and non-structured transition pathways. Most patients remained engaged with adult endocrine care, and hormonal control showed no evident deterioration following transfer in either group. Given the small sample size and high overall retention, these findings should not be interpreted as evidence of equivalence between the two transition approaches.

This case report describes a newborn diagnosed with very-early-onset autosomal dominant polycystic kidney disease (VEO-ADPKD) and congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The patient presented with prenatally detected kidney cysts and exhibited clinical and laboratory features consistent with salt-wasting, including markedly elevated 17-hydroxyprogesterone levels, requiring treatment with hydrocortisone, fludrocortisone, and sodium chloride. Genetic analysis revealed a de novo truncating variant in PKD1 and two variants in CYP21A2. Hypertension developed at 3 years and 7 months despite unchanged steroid replacement doses, requiring antihypertensive treatment, and resolved after mineralocorticoid dose reduction. This case highlights the competing therapeutic demands of concurrent salt-wasting CAH and VEO-ADPKD, underscoring the importance of early genetic evaluation and integrated multidisciplinary surveillance.

Objective: Polycystic ovary syndrome (PCOS) and nonclassic congenital adrenal hyperplasia (NCAH) overlap clinically, but direct comparative data specifically addressing non-National Institutes of Health (non-NIH) Rotterdam phenotypes of polycystic ovary syndrome are limited. We compared women with polycystic ovary syndrome, of whom 66.7% were classified as having non-NIH Rotterdam phenotypes, with women with nonclassic congenital adrenal hyperplasia and healthy controls to characterize the extent of phenotypic overlap and evaluate the discriminatory performance of individual androgen measures. Methods: This single-center, prospective, exploratory cross-sectional study evaluated 58 women divided into three groups: PCOS (n = 24, Rotterdam criteria), NCAH due to 21-hydroxylase deficiency (n = 16, previously confirmed by adrenocorticotropic hormone (ACTH)-stimulated 17-hydroxyprogesterone (17-OHP)), and healthy controls (n = 18). Demographic, clinical, metabolic, and hormonal parameters were compared using analysis of variance (ANOVA), Kruskal-Wallis with Dunn's post hoc test (Bonferroni-adjusted), and chi-square or Fisher's exact tests. A sensitivity analysis was performed after excluding 12 participants receiving oral contraceptives (n = 8) or glucocorticoids (n = 4). Results: Within the PCOS group, 66.7% had non-NIH Rotterdam phenotypes. Hirsutism, defined as a modified Ferriman-Gallwey (mFG) score ≥ 8, was more frequent in both patient groups than in controls (p = 0.003) but did not differ between PCOS and NCAH. Total testosterone levels were 0.40 [0.20-0.60], 0.59 [0.45-0.94], and 0.20 [0.15-0.20] ng/mL in the PCOS, NCAH, and control groups, respectively, and androstenedione levels were 1.40 [1.20-2.20], 2.55 [1.64-4.07], and 0.87 [0.56-1.00] ng/mL, respectively; both were higher in the patient groups than in controls (both p < 0.001), without differing between PCOS and NCAH. Basal 17-OHP was the only parameter distinguishing NCAH from both PCOS and controls (p < 0.001). Dehydroepiandrosterone sulfate (DHEAS) levels were 356.5 [217-422], 292 [156-448], and 219 [146-240] µg/dL, respectively (p = 0.020), with a significant difference only between PCOS and controls. Anti-Müllerian hormone (AMH) levels were 3.27 [3.02-4.13], 3.13 [2.87-3.54], and 3.34 [2.93-5.37] ng/mL, respectively, with no between-group difference (p = 0.600). Other metabolic parameters, gonadotropins, estradiol, and prolactin showed no between-group differences. The principal hormonal findings remained unchanged after excluding women receiving oral contraceptives or glucocorticoids. Conclusions: In this PCOS cohort, in which 66.7% of women were classified as having non-NIH Rotterdam phenotypes, PCOS and NCAH showed substantial clinical, metabolic, and hormonal overlap, whereas basal early-follicular 17-OHP was the only parameter that consistently distinguished NCAH from both PCOS and healthy controls. These findings support the inclusion of basal 17-OHP in the evaluation of women presenting with hyperandrogenism.

Nonclassic P450 oxidoreductase (POR) deficiency (PORD) may remain suspected but unconfirmed in adult women with long-standing menstrual irregularity and infertility when skeletal anomalies, virilization, and overt adrenal insufficiency are absent. We report a 45-year-old Japanese woman in whom PORD had been suspected during infertility care at age 34 because of an inappropriately elevated, nonluteal progesterone value with no marked 17-hydroxyprogesterone elevation, but genetic testing was not pursued. Reevaluation for recurrent abnormal uterine bleeding and a large ovarian cyst prompted 3-point liquid chromatography-tandem mass spectrometry (LC-MS/MS) steroid profiling at baseline, after cosyntropin 250 µg, and during combined dexamethasone-hydrocortisone treatment. Adrenocorticotropic hormone (ACTH) stimulation produced disproportionate accumulation of adrenal steroid intermediates, which decreased markedly during combined glucocorticoid treatment, supporting ACTH-dependent adrenal steroid accumulation. Targeted POR sequencing and family segregation analysis supported compound heterozygosity for a maternally inherited p.Arg457His allele and an inferred paternal allele carrying p.Arg550Trp and p.Gly413Ser in cis. This case illustrates the value of resolving a long-standing diagnostic suspicion through dynamic steroid profiling, targeted POR sequencing, and segregation analysis; the combined glucocorticoid time point was supportive but not a stand-alone diagnostic test.

Sex differences in the humoral immune responses to the seasonal quadrivalent influenza vaccine (QIV) in young adults (YA; 18-49 years old) or high-dose QIV in old adults (OA; 75+ years old) were analyzed to determine how age-related changes, including in steroids, impact sex differences in B cells. Among YAs, females had greater H3N2, but not H1N1, neutralizing antibody titers, and greater proportions of hemagglutinin (HA)+ CD19+ B cells and HA+ memory B cells than males through 28 days post-vaccination (DPV), that was not observed among OAs. Machine learning algorithms illustrated that baseline (0 DPV) steroids, including 17-hydroxyprogesterone, estrogens, and testosterone, as well as HA+ CD19+ B cells and HA+ antibody-secreting B cells (ASCs), were major predictors of seroconversion at 28 DPV, particularly in YA. Single-cell RNA sequencing demonstrated that CD19+ B cells from YA females had greater transcriptional activity at 7 DPV than YA males, with upregulation of genes with estrogen-response elements (EREs) along NF-κB-mediated TNF signaling pathways in B-cell subsets, which was mitigated in OA. Estradiol treatment of ASCs from YA females, but not males, increased the number and size of HA+ IgG+ cells and expression of ERE genes along the NF-κB-mediated TNF signaling pathway,that was inhibited by an estrogen receptor antagonist. Pharmacological inhibition of either NF-κB or TNF signaling blocked the ability of E2 to upregulate antibody secretion in cells from YA females. This study provides mechanistic insights into estrogen-mediated increases in influenza vaccine-induced antibody responses among reproductive-aged females and suggests a role for estrogen signaling in the reduction of sex differences in vaccine-induced immunity with old age.

Congenital Adrenal Hyperplasia (CAH) is primarily caused by 21-hydroxylase deficiency, leading to abnormal adrenal hormone production. Accurate measurement of 17-hydroxyprogesterone (17-OHP) is critical for diagnosing and managing CAH. Traditionally, 17-OHP levels are assessed using ELISA, but methods like chemiluminescent immunoassays (CLIA) offer potential improvements in accuracy and efficiency. We evaluated the Maglumi[®] X-8 CLIA system for measuring 17-OHP levels and compared its performance with the established ELISA method. The study included serum samples from 39 patients, analyzed for accuracy, precision, linearity, and reportable range. The correlation between CLIA and ELISA results was assessed using regression analysis and Bland-Altman plots. The Maglumi[®] X-8 CLIA demonstrated acceptable precision, with low coefficients of variation (CVs) at both low and high 17-OHP concentrations. The assay showed strong correlation with the ELISA method (slope: 0.961, intercept: 1.712) and consistent accuracy across a broad reportable range (0.10 to 320 ng/mL). The CLIA system also proved to be faster and more automated, reducing the potential for human error and facilitates faster results for clinical decision making. The Maglumi[®] X-8 CLIA is a highly precise, accurate, and efficient method for measuring 17-OHP levels, making it a suitable alternative to ELISA in clinical laboratories. Its integration into routine workflows offers faster results and improved reliability.

The aim of this study was to develop and psychometrically assess a client-experience-of-care metric tailored for women in Lilongwe, Malawi, using self-administered or provider-administered depot medroxyprogesterone acetate subcutaneous (DMPA-SC) and to assess differences in experiences of care between the two groups. A client exit interview was administered to 400 Malawian women who had self-injected (n = 198) or received provider-administered (n = 202) DMPA-SC within the three months preceding the study. Iterative exploratory factor analysis with a polychoric matrix was performed. Cronbach's alpha was used to assess scale reliability. Bivariate and multivariate generalized linear regression models with robust standard errors were used to test for differences in client experience between self-administered and provider-administered clients. Exploratory factor analysis yielded a two-factor solution, identifying a unifying scale for client experience of care (eight items) and a subscale for empowerment (ten items). The client experience of care scale had moderate construct validity, explaining 40 percent of the variance, high criterion validity with a positive and statistically significant (p < 0.05) correlation coefficient, and low-to-moderate reliability (alpha = 0.68). In adjusted models, statistically significant differences in client experience of care were detected by injection method, with self-injecting clients reporting better experiences of care compared to provider-administered clients.