Clemens Kamrath1, Lisa Wettstaedt1, Michaela F Hartmann1, Stefan A Wudy1. 1. Division of Pediatric Endocrinology and Diabetology, Laboratory for Translational Hormone Analysis in Pediatric Endocrinology, Steroid Research & Mass Spectrometry Unit, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany.
Abstract
BACKGROUND: Treatment of children with classic congenital adrenal hyperplasia (CAH) with glucocorticoids is a difficult balance between hypercortisolism and hyperandrogenism. Biochemical monitoring of treatment is not well defined. Achievement of a normal growth rate is the most important therapeutic goal. METHODS: We retrospectively evaluated 123 24-h GC-MS urinary steroid metabolome analyses together with their corresponding one-year height velocity (HV) z-scores in 63 prepubertal children aged 7.2 ± 1.6 years with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone. RESULTS: Multivariate linear mixed effects model analysis revealed a positive influence of CAH-specific z-scores of summed urinary androgen metabolites (B= 0.97 ± 0.20, t-value = 4.97, P < 0.0001) and a negative influence of the cortisol metabolite tetrahydrocortisol (B= -1.75 ± 0.79, t-value = -2.20, P = 0.03) on HV z-scores. ROC analysis demonstrated that adrenal androgen excess, defined as HV > 1.5 z, was best determined by a z-score of all urinary androgen metabolites of > 0.512 (accuracy 66.2%, sensitivity 57.1 %, specificity 74.4%, positive prediction values (PPV) 66.7%, negative prediction values (NPV) 65.9%). Tetrahydrocortisol excretion > 1480 µg/ m2 BSA/ d in conjunction with suppressed urinary androgen metabolites < 0.163 z indicated overtreatment, defined as HV < -1.5 z (accuracy 79.6 %, sensitivity 40.0 %, specificity 94.9%, PPV 75.0%, NPV 80.4%). CONCLUSION: We could establish target values for urinary steroid metabolite excretions in children with CAH based on their growth rate. Urinary steroid metabolome analysis represents a highly suitable method for monitoring metabolic control in CAH children.
BACKGROUND: Treatment of children with classic congenital adrenal hyperplasia (CAH) with glucocorticoids is a difficult balance between hypercortisolism and hyperandrogenism. Biochemical monitoring of treatment is not well defined. Achievement of a normal growth rate is the most important therapeutic goal. METHODS: We retrospectively evaluated 123 24-h GC-MS urinary steroid metabolome analyses together with their corresponding one-year height velocity (HV) z-scores in 63 prepubertal children aged 7.2 ± 1.6 years with classic CAH due to 21-hydroxylase deficiency treated with hydrocortisone and fludrocortisone. RESULTS: Multivariate linear mixed effects model analysis revealed a positive influence of CAH-specific z-scores of summed urinary androgen metabolites (B= 0.97 ± 0.20, t-value = 4.97, P < 0.0001) and a negative influence of the cortisol metabolite tetrahydrocortisol (B= -1.75 ± 0.79, t-value = -2.20, P = 0.03) on HV z-scores. ROC analysis demonstrated that adrenal androgen excess, defined as HV > 1.5 z, was best determined by a z-score of all urinary androgen metabolites of > 0.512 (accuracy 66.2%, sensitivity 57.1 %, specificity 74.4%, positive prediction values (PPV) 66.7%, negative prediction values (NPV) 65.9%). Tetrahydrocortisol excretion > 1480 µg/ m2 BSA/ d in conjunction with suppressed urinary androgen metabolites < 0.163 z indicated overtreatment, defined as HV < -1.5 z (accuracy 79.6 %, sensitivity 40.0 %, specificity 94.9%, PPV 75.0%, NPV 80.4%). CONCLUSION: We could establish target values for urinary steroid metabolite excretions in children with CAH based on their growth rate. Urinary steroid metabolome analysis represents a highly suitable method for monitoring metabolic control in CAH children.
Authors: Hedi L Claahsen-van der Grinten; Phyllis W Speiser; S Faisal Ahmed; Wiebke Arlt; Richard J Auchus; Henrik Falhammar; Christa E Flück; Leonardo Guasti; Angela Huebner; Barbara B M Kortmann; Nils Krone; Deborah P Merke; Walter L Miller; Anna Nordenström; Nicole Reisch; David E Sandberg; Nike M M L Stikkelbroeck; Philippe Touraine; Agustini Utari; Stefan A Wudy; Perrin C White Journal: Endocr Rev Date: 2022-01-12 Impact factor: 19.871
Authors: Brittany K Wise-Oringer; Anne Claire Burghard; Patrick O'Day; Abeer Hassoun; Aviva B Sopher; Ilene Fennoy; Kristen M Williams; Patricia M Vuguin; Renu Nandakumar; Donald J McMahon; Richard J Auchus; Sharon E Oberfield Journal: Horm Res Paediatr Date: 2021-02-02 Impact factor: 2.852