Search

Oxcarbazepine (OXC) induces cytochrome CYP3A4 activity, lowering female sex steroid concentrations. To date, similar effects on corticosteroid concentrations have not been reported. The observation of an adolescent boy with Addison's disease requiring high hydrocortisone replacement doses while on OXC for epilepsy led us to investigate effects of OXC on CYP3A4 induction and steroid metabolism. Six young epileptic men on OXC monotherapy and six controls collected 24-h urines and had blood taken for steroid analysis. Accelerated cortisol elimination was confirmed by greater relative 24-h urinary 6-hydroxycortisol/cortisol excretion (4.67 (1.25) ug/day vs controls 2.32 (0.5) ug/day, p=0.001). Patients on OXC had lower serum oestradiol and dehydroepiandrosterone sulphate levels, but only tendencies remained after age adjustment. This study shows that OXC-induced CYP3A4 activity increases cortisol elimination. The effect is small in subjects with healthy adrenals. However, caution is warranted for patients with adrenal failure on high doses of OXC where choosing an alternative anticonvulsant may be advisable. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In children with idiopathic short stature (ISS), studies investigating body mass index (BMI) or parameters of satiety regulation are scarce, and studies analyzing eating behavior are lacking. METHODS: We recruited 214 children (123 index cases and 91 siblings) with ISS from 123 families. Affected children had to have a body height <5th percentile, or, in the case of siblings, the body height of 1 child had to be <5th percentile and the other <15th percentile. Medical histories were recorded by using structured and standardized interviews. Eating behavior was assessed by using the Child Eating Behavior Questionnaire. Percent energy intake as fat was assessed by using the Leeds Food Frequency Questionnaire. Endocrine markers of body weight regulation (leptin, ghrelin) were determined in serum. RESULTS: Compared with population norms, BMI was significantly lower (mean: -0.33 standard deviation score). Furthermore, there was decreased food responsiveness (mean Child Eating Behavior Questionnaire score: 1.9; population mean: 2.4), reduced enjoyment of food (3.2 vs 3.9), emotional undereating (2.6 vs 3.0), lower desire to drink (2.0 vs 2.8), and increased fussiness over food (3.2 vs 2.9). When the sample was subdivided into the 2 groups of 'good' and 'poor' eaters according to the mothers' assessment of the current eating behavior, reduction in BMI as well as the behavioral characteristics already delineated in the total sample were found to be even more consistent in the subgroup of poor eaters. In the total sample of our children, as well as in both subgroups, serum leptin (adjusted for gender, BMI, and Tanner stage) was found to be moderately raised but did not differ between poor and good eaters. Total serum ghrelin was not different between poor and good eaters. CONCLUSIONS: Our clinical, behavioral, and endocrinologic findings in patients with ISS point to an altered eating behavior that possibly contributes to their short stature. [ABSTRACT FROM AUTHOR]

Background: Increases in phosphorus intake have been observed over the past years in adult populations. However, biomarker-based data are lacking on whether or not phosphorus intake also increased in children., Objective: The aim of this study was to examine 24-hour urinary phosphate excretion (PO4-Ex) and diet-related biomarkers potentially influencing phosphorus status in German children and adolescents from 1985 to 2015., Design: This longitudinal noninvasive biomarker-based cohort study examined 24-hour urine samples from children and adolescents of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study, collected over 3 decades., Participants/setting: Examined individuals (n = 1,057) were healthy participants of the Dortmund Nutritional and Anthropometric Longitudinally Designed Study, situated in Dortmund, Germany, who had been asked to collect one yearly 24-hour urine sample. Six thousand seven hundred thirty-seven samples collected from participants aged 3 to 17 years between 1985 (baseline) and 2015, were included., Main Outcome Measures: phosphorus intake was examined biomarker-based by analyzed PO4-Ex in 24-hour urine samples. Whether acid-base status and intakes of protein, salt, and fruits and vegetables, may have relevantly contributed to PO4-Ex levels was assessed by determining 24-hour excretions of net acid, urea-nitrogen, and sodium as well as specific standardized excretions of potassium plus oxalate., Statistical Analyses Performed: Trend analysis over 30 years and potentially influencing diet factors were examined using linear mixed-effect regression models (PROC-MIXED). Adjustments for sex, age, and body surface area were performed., Results: No change was identifiable for PO4-Ex over the 3 decades; neither in 3 to 8, 9 to 13, nor in 14 to 17 year olds. However, sodium excretion increased (P = .001). PROC-MIXED analysis on intraindividual changes in PO4-Ex revealed direct relationships with net acid excretion, urea-nitrogen, and sodium excretion and an inverse relationship with a biomarker of fruit and vegetable intake., Conclusions: Despite a direct relationship between PO4-Ex and a biomarker of industrially processed food consumption; that is, sodium excretion, which showed an increasing time trend, phosphorus intake was found to remain stable over decades in children and adolescents., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In adults, cortisol levels show a pronounced 24-hour rhythm with a peak in the early morning. It is unknown at what age this early-morning peak in cortisol emerges during infancy, hampering the establishment of optimal dosing regimens for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency. Therefore, we aimed to characterize daily variation in salivary cortisol concentration across the first year of life., Methods: We conducted a systematic review followed by an individual participant data meta-analysis of studies reporting on spontaneous (i.e., not stress induced) salivary cortisol concentrations in healthy infants aged 0-1 year. A one-stage approach using linear mixed-effects modelling was used to determine the interaction between age and time of day on cortisol concentrations., Findings: Through the systematic review, 54 eligible publications were identified, reporting on 29,177 cortisol observations. Individual participant data were obtained from 15 study cohorts, combining 17,079 cortisol measurements from 1,904 infants. The morning/evening cortisol ratio increased significantly from 1.7 (95% CI: 1.3-2.1) at birth to 3.7 (95% CI: 3.0-4.5) at 6-9 months (p < 0.0001). Cosinor analysis using all available data revealed the gradual emergence of a 24-hour rhythm during infancy., Interpretation: The early-morning peak in cortisol secretion gradually emerges from birth onwards to form a stable morning/evening ratio from age 6-9 months. This might have implications for hydrocortisone replacement therapy in infants with an inborn form of adrenal insufficiency., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Adrenocortical carcinomas are very rare malignancies in childhood associated with poor outcome in advanced disease. Most adrenocortical tumors (ACT) are functional, causing signs and symptoms of adrenal hormone excess. In most studies, endocrine manifestations were reported 4 to 6 months prior to diagnosis., Objective: We sought to extend knowledge on endocrine manifestations with regard to age and sex to facilitate early diagnosis., Methods: We retrospectively analyzed features of adrenal hormone excess in children and adolescents with ACT registered with the GPOH-MET studies between 1997 and 2022. Stage of puberty was defined as prepubertal in females < 8 years of age and males < 9 years., Results: By December 2022, 155 patients (110 female, 45 male) with data on endocrine manifestations had been reported. Median age at ACT diagnosis was 4.2 years [0.1-17.8], median interval from first symptoms was 4.2 months [0-90.7]. In 63 girls of prepubertal age, the most frequently reported manifestations were pubarche (68.3%), clitoral hypertrophy (49.2%), and weight gain (31.7%); in 47 pubertal female patients, the most frequent manifestations were excessive pubic hair (46.8%), acne (36.2%), and hypertension (36.2%). Leading symptoms in 34 boys of prepubertal age were pubarche (55.9%), penile growth (47.1%), and acne (32.4%), while in 11 pubertal male patients, leading symptoms were weight gain (45.5%), hypertension (36.4%), excessive pubic hair (27.3%), and cushingoid appearance (27.3%). In pubertal patients, symptoms of androgen excess were mainly unrecognized as part of pubertal development, while symptoms of Cushing syndrome were more frequently apparent., Conclusion: The endocrine phenotype induced by pediatric ACT is age- and sex-dependent., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Adverse environments during pregnancy impact neurodevelopment including cognitive abilities of the developing children. The mediating biological alterations are not fully understood. Maternal stress may impact the neurotrophic regulation of the offspring as early as in utero and at birth. Brain-derived neurotrophic factor (BDNF) is essential for neurodevelopment. Short-term higher levels of BDNF in mice upon stressors associate with lower BDNF later in life, which itself associates with depression in animals and humans. Stress including glucocorticoids may impact BDNF, but there is a lack of data at birth. This study investigated if stress near term associates with fetal BDNF at birth in humans., Methods: Pregnant women near term who underwent primary cesarean sections (at 38.80±0.64 weeks), were included in this study (n=41). Stress at the end of pregnancy was assessed before the cesarean section by determining maternal depressive symptoms (EDPS), maternal state and trait anxiety (STAI-S and STAI-T), maternal prenatal distress (PDQ), stress over the past month (PSS), prenatal attachment to the offspring (PAI), maternal social support (F-Sozu), maternal early life stress (CTQ), socioeconomic status, and the glucocorticoids cortisol and cortisone (n=40) in amniotic fluid at birth. The association with fetal BDNF was analyzed. Cord blood serum of n=34 newborns at birth was analyzed for BDNF and newborn anthropometrics (weight, length and head circumference per gestational age at birth) were assessed. The association of fetal BDNF with anthropometrics at birth was analyzed., Results: After a BDNF-outlier (>3 SD) was removed, higher fetal BDNF associated significantly with maternal depressive symptoms (r=0.398, p=0.022), with lower socioeconomic status as assessed by the average number of people per room in the household (r=0.526, p=0.002) and with borderline significance with net income per person in the household (r=-0.313, p=0.087) in the bivariate analyses. In multivariable analysis, BDNF stayed positively associated with maternal depressive symptoms (β=0.404, 95% CI [7.057, 306.041], p=0.041) and lower net income per person in the household (β=-0.562, 95% CI [-914.511, -60.523], p=0.027) when controlling for maternal age, maternal pre-pregnancy BMI, fetal sex and gestational age. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed in bivariate analyses or in multivariable analyses when controlling for maternal BMI and fetal sex., Conclusion: Maternal depressive symptoms and lower socioeconomic status associated with higher fetal BDNF when controlling for confounders. Fetal BDNF did not associate with newborn anthropometrics with the outlier removed. Further studies should investigate how early altered BDNF associate with the development and possibly psychopathology of the offspring., Competing Interests: Declaration of Competing Interest Eva Kathrin Lamadé received the Seed Money for Research grant from the Central Institute of Mental Health., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: TBX19 mutations cause isolated ACTH-deficiency. While this classically results in severe hypocortisolism, potential consequences for mineralocorticoid biosynthesis have not been described to date. Liquid chromatography mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) allow novel insights into the steroid metabolism of pediatric endocrine diseases., Case Presentation: Patient 1 (female) presented right after birth with hypoglycemia and hyponatremia (minimum sodium 126 mmol/L). She recovered under therapy with hydrocortisone, fludrocortisone and initial NaCl. Patient 2 (male) presented after birth with prolonged cholestatic jaundice. Only at the age of 3.5 months, repeated episodes of hypoglycemia occurred. Both patients showed severely reduced ACTH. LC-MS/MS analyses on plasma samples demonstrated combined reduced glucocorticoid- and mineralocorticoid biosynthesis confirmed by GC-MS analyses on spot urine. In contrast to patient 1, patient 2 (currently 8 years old) never suffered from hyponatremia. Both patients carry the same homozygous c.172A&gt;G, p.(Thr58Ala) mutation in the TBX19 gene proving isolated ACTH-deficiency., Conclusion: Isolated ACTH-deficiency can be associated with reduced mineralocorticoids and hyponatremia. We hypothesize that sufficient pituitary ACTH secretion is an important predisposition for regular adrenal mineralocorticoid biosynthesis., (© 2024 S. Karger AG, Basel.)

Introduction: At the maternal-fetal interface in pregnancy, stress during pregnancy can lead to an increased vulnerability to later psychopathology of the fetus. Potential mediators of this association have scarcely been studied and may include early alterations of fetal brain-derived neurotrophic factor (BDNF). Amniotic fluid is of particular interest for effects on fetal endocrine alterations, as the assessment in amniotic fluid allows for measurements over a time integral. This study hypothesized that maternal psychometrics, socioeconomic status and glucocorticoids are related to BDNF levels in amniotic fluid at birth. The association of fetal BDNF with newborn anthropometrics was tested., Methods: Women near term who underwent elective cesarean section and their newborns were investigated (n = 37). Maternal psychometrics, socioeconomic status and glucocorticoids (the sum of cortisol and cortisone) in amniotic fluid at birth were analyzed for an association with fetal BDNF in amniotic fluid at birth. Newborn anthropometrics were assessed by length, weight, head circumference and gestational age at birth., Results: In bivariate analysis, maternal psychometrics and socioeconomic status were not related to fetal BDNF in amniotic fluid at birth. The sum of cortisol and cortisone related to increased fetal BDNF in amniotic fluid at birth (r = 0.745, p < 0.001). BDNF in amniotic fluid was associated negatively with fetal birth weight per gestational age (r = -0.519, p < 0.001), length per gestational age (r = -0.374, p = 0.023), head circumference per gestational age (r = -0.508, p = 0.001), but not with gestational age at birth. In multiple regression analysis, the sum of cortisol and cortisone (p < 0.001) and birth weight per gestational age (p = 0.012) related to higher fetal BDNF levels in amniotic fluid at birth (R 2  = 0.740, p < 0.001) when controlling for fetal sex and maternal age. Head circumference per gestational age predicted fetal BDNF with borderline significance (p = 0.058) when controlling for confounders., Conclusion: Glucocorticoids in amniotic fluid were positively associated with high fetal BDNF at birth, which may be an adaptive fetal response. Maternal psychological variables and socioeconomic status did not link to fetal BDNF. Birth weight and head circumference per gestational age were inversely associated with fetal BDNF at birth, which may represent a compensatory upregulation of BDNF in fetuses with low anthropometrics. Longitudinal studies are needed to assess the role of stress during pregnancy on later offspring development. The analysis of additional fetal growth factors and inflammation upon maternal stress in further biomaterials such as the placenta is warranted, to understand mechanistic alterations of how maternal stress links to fetal development and an increased vulnerability for psychopathology., Competing Interests: Eva Kathrin Lamadé acknowledges a Seed Money for Research grant from the Central Institute of Mental Health., (© 2024 The Authors.)

Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder impairing cortisol synthesis due to reduced enzymatic activity. This leads to persistent adrenocortical overstimulation and the accumulation of precursors before the blocked enzymatic step. The predominant form of CAH arises from mutations in CYP21A2 , causing 21-hydroxylase deficiency (21-OHD). Despite emerging treatment options for CAH, it is not always possible to physiologically replace cortisol levels and counteract hyperandrogenism. Moreover, there is a notable absence of an effective in vivo model for pre-clinical testing. In this work, we developed an animal model for CAH with the clinically relevant point mutation p.R484Q in the previously humanized CYP21A2 mouse strain. Mutant mice showed hyperplastic adrenals and exhibited reduced levels of corticosterone and 11-deoxycorticosterone and an increase in progesterone. Female mutants presented with higher aldosterone concentrations, but blood pressure remained similar between wildtype and mutant mice in both sexes. Male mutant mice have normal fertility with a typical testicular appearance, whereas female mutants are infertile, exhibit an abnormal ovarian structure, and remain in a consistent diestrus phase. Conclusively, we show that the animal model has the potential to contribute to testing new treatment options and to prevent comorbidities that result from hormone-related derangements and treatment-related side effects in CAH patients.

Adrenal function is essential for survival and well-being of preterm babies. In addition to glucocorticoids, it has been hypothesized that C 19 -steroids (DHEA-metabolites) from the fetal zone of the adrenal gland may play a role as endogenous neuroprotective steroids. In 39 term-born (≥37 weeks gestational age), 42 preterm (30-36 weeks) and 51 early preterm (<30 weeks) infants 38 steroid metabolites were quantified by GC-MS in 24-h urinary samples. In each gestational age group, three distinctive cluster were identified by pattern analysis ( k -means clustering). Individual steroidal fingerprints and clinical phenotype were analyzed at the 3rd day of life. Overall, the excretion rates of C 21 -steroids (glucocorticoid precursors, cortisol, and cortisone metabolites) were low (<99 μg/kg body weight/d) whereas the excretion rates of C 19 -steroids were up to 10 times higher. There was a shift to higher excretion rates of C 19 -steroids in both preterm groups compared to term infants but only minor differences in the distribution of C 21 -steroids. Comparable metabolic patterns were found between gestational age groups: Cluster 1 showed mild elevation of C 21 - and C 19 -steroids with the highest incidence of neonatal morbidities in term and severe intraventricular hemorrhage in early preterm infants. In cluster 2 lowest excretion in general was noted but no clinically unique phenotype. Cluster 3 showed highest elevation of C 21 -steroids and C 19 -steroids but no clinically unique phenotype. Significant differences in steroid metabolism between clusters are only partly reflected by gestational age and disease severity. In early preterm infants, higher excretion rates of glucocorticoids and their precursors were associated with severe cerebral hemorrhage. High excretion rates of C 19 -steroids in preterm infants may indicate a biological significance.

Mitochondrial dysfunction is a hallmark of cellular senescence and many age-related neurodegenerative diseases. We therefore investigated the relationship between mitochondrial function in peripheral blood cells and cerebral energy metabolites in young and older sex-matched, physically and mentally healthy volunteers. Cross-sectional observational study involving 65 young (26.0 ± 0.49 years) and 65 older (71.7 ± 0.71 years) women and men recruited. Cognitive health was evaluated using established psychometric methods (MMSE, CERAD). Blood samples were collected and analyzed, and fresh peripheral blood mononuclear cells (PBMCs) were isolated. Mitochondrial respiratory complex activity was measured using a Clarke electrode. Adenosine triphosphate (ATP) and citrate synthase activity (CS) were determined by bioluminescence and photometrically. N-aspartyl-aspartate (tNAA), ATP, creatine (Cr), and phosphocreatine (PCr) were quantified in brains using 1 H- and 31 P-magnetic resonance spectroscopic imaging (MRSI). Levels of insulin-like growth factor 1 (IGF-1) were determined using a radio-immune assay (RIA). Complex IV activity (CIV) (- 15%) and ATP levels (- 11%) were reduced in PBMCs isolated from older participants. Serum levels of IGF-1 were significantly reduced (- 34%) in older participants. Genes involved in mitochondrial activity, antioxidant mechanisms, and autophagy were unaffected by age. tNAA levels were reduced (- 5%), Cr (+ 11%), and PCr (+ 14%) levels were increased, and ATP levels were unchanged in the brains of older participants. Markers of energy metabolism in blood cells did not significantly correlate with energy metabolites in the brain. Age-related bioenergetic changes were detected in peripheral blood cells and the brains of healthy older people. However, mitochondrial function in peripheral blood cells does not reflect energy related metabolites in the brain. While ATP levels in PBMCs may be be a valid marker for age-related mitochondrial dysfunction in humans, cerebral ATP remained constant., (© 2023. The Author(s).)

High dietary phosphorus intake (P-In) and high acid loads may adversely affect kidney function. In animal models, excessive phosphorus intake causes renal injury, which, in humans, is also inducible by chronic metabolic acidosis. We thus examined whether habitually high P-In and endogenous acid production during childhood and adolescence may be early indicators of incipient renal inflammatory processes later in adulthood. P-In and acid-base status were longitudinally and exclusively determined by biomarker-based assessment in 277 healthy children, utilizing phosphate and net acid excretion (NAE) measurements in 24 h urine samples repeatedly collected between the ages of 3 and 17 years. Standard deviation scores (by sex and age) were calculated for anthropometric data and for the urinary biomarkers available within age range 3-17 years. Multivariable linear regression was used to analyze the relations of phosphate excretion and NAE with the adulthood outcome circulating interleukin-18 (IL-18), a marker of inflammation and kidney dysfunction. After adjusting for growth- and adulthood-related covariates and pro-inflammatory biomarkers to rule out confounding by non-renal inflammatory processes, regression models revealed a significant positive relationship of long-term NAE ( p = 0.01), but not of long-term phosphate excretion with adult serum IL-18. Similar significant positive regression results were obtained after replacing NAE with 24 h urinary ammonium excretion as the exposition variable. Our results suggest that even moderate elevations in renal ammonia production, as caused by habitually higher acid loading during growth, may affect the intrarenal pro-inflammatory system in the long-term, known to be boosted by acidosis-induced raised ammoniagenesis.

Context: Androgen levels are generally measured in serum samples, but urine may be a more feasible option, especially in children, as it is a noninvasive alternative., Objective: To assess the correlations of 10 urinary androgen metabolites with 4 serum androgens [dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, and total and free testosterone] and assess if their correlations differ by participant characteristics., Methods: Our study consisted of 44 girls, ages 6-13, who participated in the New York site of the LEGACY Girls Study and had both serum and urine samples collected at the same visit. We performed Pearson's correlation coefficient tests between 4 serum and 10 individual urinary metabolite measures and their sum. We examined the influence of participant characteristics on the magnitude and direction of the correlations., Results: The summed urinary metabolite measures had the highest correlation with free testosterone in serum (global sum, r = 0.83) and correlated least with DHEA-S in serum (global sum, r = 0.64). The correlation between individual urinary metabolites and serum androgens ranged from 0.08 to 0.84.Two 11-oxygenated urinary metabolites (5α-androstane-3α-ol-11,17-dione5β-androstane-3α,11β-diol-17-one) were weakly correlated with all serum androgens. Participant age, weight, height, waist:hip ratio, and pubic hair growth stage changed the correlations between urinary and serum androgens measures between 10% and 213%., Conclusion: The sum of urinary androgen metabolites was a good marker of circulating androstenedione, testosterone, and free testosterone. Individual urinary metabolites provide additional information about the metabolic processes of disease development compared to the antecedent serum androgens., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Diagnosing Cushing's syndrome (CS) is highly complex. As the diagnostic potential of urinary steroid metabolome analysis by gas chromatography-mass spectrometry (GC-MS) in combination with systems biology has not yet been fully exploited, we studied a large cohort of patients with CS., Methods: We quantified daily urinary excretion rates of 36 steroid hormone metabolites. Applying cluster analysis, we investigated a control group and 168 patients: 44 with Cushing's disease (CD) (70% female), 18 with unilateral cortisol-producing adrenal adenoma (83% female), 13 with primary bilateral macronodular adrenal hyperplasia (PBMAH) (77% female), and 93 ruled-out CS (73% female)., Findings: Cluster-Analysis delineated five urinary steroid metabotypes in CS. Metabotypes 1, 2 and 3 revealing average levels of cortisol and adrenal androgen metabolites included patients with exclusion of CS or and healthy controls. Metabotype 4 reflecting moderately elevated cortisol metabolites but decreased DHEA metabolites characterized the patients with unilateral adrenal CS and PBMAH. Metabotype 5 showing strong increases both in cortisol and DHEA metabolites, as well as overloaded enzymes of cortisol inactivation, was characteristic of CD patients. 11-oxygenated androgens were elevated in all patients with CS. The biomarkers THS, F, THF/THE, and (An + Et)/(11β-OH-An + 11β-OH-Et) correctly classified 97% of patients with CS and 95% of those without CS. An inverse relationship between 11-deoxygenated and 11-oxygenated androgens was typical for the ACTH independent (adrenal) forms of CS with an accuracy of 95%., Interpretation: GC-MS based urinary steroid metabotyping allows excellent identification of patients with endogenous CS and differentiation of its subtypes., Funding: The study was funded by the Else Kröner-Fresenius-Stiftung and the Eva-Luise-und-Horst-Köhler-Stiftung., Competing Interests: Declaration of interests Several authors received funding as mentioned below. FB has received travel support by Novo Nordisk. Furthermore, he has a patent (PCT/EP2022/053142) for biomarkers for the diagnosis and treatment of endocrine hypertension, and methods of identification thereof. He also participated on an advisory board for Bayer (indication outside of the topic of the manuscript). All the other authors have no conflict of interest to report., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: Interference from isomeric steroids is a potential cause of disparity between mass spectrometry-based 17-hydroxyprogesterone (17OHP) results. We aimed to assess the proficiency of mass spectrometry laboratories to report 17OHP in the presence of known isomeric steroids., Methods: A series of five samples were prepared using a previously demonstrated commutable approach. These samples included a control (spiked to 15.0 nmol/L 17OHP) and four challenge samples further enriched with equimolar concentrations of 17OHP isomers (11α-hydroxyprogesterone, 11β-hydroxyprogesterone, 16α-hydroxyprogesterone or 21-hydroxyprogesterone). These samples were distributed to 38 participating laboratories that reported serum 17OHP results using mass spectrometry in two external quality assurance programs. The result for each challenge sample was compared to the control sample submitted by each participant., Results: Twenty-six laboratories (68 % of distribution) across three continents returned results. Twenty-five laboratories used liquid chromatography-tandem mass spectrometry (LC-MS/MS), and one used gas chromatography-tandem mass spectrometry to measure 17OHP. The all-method median of the control sample was 14.3 nmol/L, ranging from 12.4 to 17.6 nmol/L. One laboratory had results that approached the lower limit of tolerance (minus 17.7 % of the control sample), suggesting the isomeric steroid caused an irregular result., Conclusions: Most participating laboratories demonstrated their ability to reliably measure 17OHP in the presence of the four clinically relevant isomeric steroids. The performance of the 12 (32 %) laboratories that did not engage in this activity remains unclear. We recommend that all laboratories offering LC-MS/MS analysis of 17OHP in serum, plasma, or dried bloodspots determine that the isomeric steroids are appropriately separated., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)