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      Steroid 17-Hydroxyprogesterone in Hair Is a Potential Long-Term Biomarker of Androgen Control in Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

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          Introduction: To evaluate scalp hair steroid concentrations as a monitoring tool for androgen control and metabolic outcomes in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Methods: 17-hydroxyprogesterone (17-OHP), androstenedione, testosterone, cortisol, cortisone, progesterone, prednisolone, and prednisone concentrations were measured in scalp hair by means of LC-MS/MS in 27 women and 15 men with CAH and controls (37 women, 42 men). Results: In CAH men and women, 17-OHP levels in hair showed a significant positive correlation with corresponding levels in serum (ρ = 0.654; p = 0.01; ρ = 0.553, p = 0.003 respectively), while total testosterone levels were only significantly correlated in CAH men (ρ = 0.543; p = 0.036). Androstenedione levels did not show a significant correlation. Receiver-operating characteristic (ROC) curve analysis indicated that a cutoff value of 21.7 pg/mg for 17-OHP in hair provided a sensitivity of 100% and a specificity of 88.9% for identifying men with elevated serum androstenedione. Hair 17-OHP in women showed a poorer performance in terms of identifying those with elevated androstenedione serum levels. However, when applying a cutoff value of 5.5 for the free androgen index as a marker of significant hyperandrogenism in CAH women, 17-OHP >27.6 pg/mg in hair provided a sensitivity of 100% and a specificity of 95.8% (AUC 0.986, 95% CI 0.945–1.000; p < 0.001). Neither hair cortisol nor markers of adrenal androgen control in hair showed significant associations with cardiometabolic outcome or bone health. Conclusion: This study shows that scalp hair 17-OHP concentrations may be a promising noninvasive long-term parameter for treatment monitoring in adult patients with CAH.

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          Most cited references 27

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          Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

           P C White (2000)
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            Measurement of cortisol in human Hair as a biomarker of systemic exposure

            Purpose: Current methods for measuring long-term endogenous production of cortisol can be challenging due to the need to take multiple urine, saliva or serum samples. Hair grows approximately 1 centimeter per month, and hair analysis accurately reflects exposure to drug abuse and environmental toxins. Here we describe a new assay for measurement of cortisol in hair, and determined a reference range for non-obese subjects. Methods: For measurement of cortisol in hair we modified an immunoassay originally developed for measuring cortisol in saliva. We compared hair samples obtained from various parts of the head, and assessed the effect of hair dying. We analyzed hair samples from non-obese subjects, in whom we also obtained urine, saliva and blood samples for cortisol measurements. Results: The mean extraction recovery for hair cortisol standards of 100 ng/ml, 50 ng/ml and 2 ng/ml (n=6) was 87.9%, 88.9% and 87.4%, respectively. Hair cortisol levels were not affected by hair color or by dying hair samples after they were obtained. Cortisol levels were decreased in hair that was artificially colored before taking the sample. The coefficient of variation was high for cortisol levels in hair from different sections of the head (30.5 %), but was smaller when comparing between hair samples obtained from the vertex posterior (15.6%). The reference range for cortisol in hair was 17.7-153.2 pg/mg of hair (median 46.1 pg/mg). Hair cortisol levels correlated significantly with cortisol in 24-hour urine (r=0.33; P=0.041). Conclusion: The correlation of hair cortisol with 24-hour urine cortisol supports its relevance as biomarker for long-term exposure.
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              Splitting hair for cortisol? Associations of socio-economic status, ethnicity, hair color, gender and other child characteristics with hair cortisol and cortisone.

              The aim of this study was to examine associations of SES and ethnicity with hair cortisol and cortisone and to identify potential child and family characteristics that can assist in choosing covariates and potential confounders for analyses involving hair cortisol and cortisone concentrations. Hair samples were collected in 2484 6-year-old children from the Generation R Study, a prospective cohort in Rotterdam, the Netherlands. Measurements for cortisol and cortisone were used as the outcome in regression analyses. Predictors were SES, ethnicity, hair color and child characteristics such as birthweight, gestational age at birth, BMI, disease, allergy, and medication use. Lower family income, more children to be supported by this income, higher BMI and darker hair color were associated with higher hair cortisol and cortisone levels. Boys also showed higher levels. Ethnicity (Dutch and North European descent) was related to lower levels. High amounts of sun in the month of hair collection was related to higher levels of cortisone only. More recent hair washing was related to lower levels of cortisol and cortisone. Gestational age at birth, birth weight, age, medication use, hair washing frequency, educational level of the mother, marital status of the mother, disease and allergy were not associated with cortisol or cortisone levels. Our results serve as a starting point for choosing covariates and confounders in studies of substantive predictors or outcomes. Gender, BMI, income, the number of persons in a household, ethnicity, hair color and recency of hair washing are strongly suggested to take into account.

                Author and article information

                S. Karger AG
                October 2020
                12 November 2019
                : 110
                : 11-12
                : 938-949
                aMedizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
                bInstitute of Doping Analysis and Sports Biochemistry, Kreischa, Germany
                Author notes
                *Prof. Nicole Reisch, Medizinische Klinik and Poliklinik IV, Klinikum der Universität München, Ziemssenstrasse 1, DE–80336 München (Germany), E-Mail Nicole.reisch@med.uni-muenchen.de
                504672 Neuroendocrinology 2020;110:938–949
                © 2019 S. Karger AG, Basel

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                Page count
                Figures: 4, Tables: 2, Pages: 12
                Research Article


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