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Jan Idkowiak, Stephen O'Riordan, Nicole Reisch, Ewa M. Malunowicz, Felicity Collins, Michiel N. Kerstens, Birgit Köhler, Luitgard Margarete Graul-Neumann, Maria Szarras-Czapnik, Mehul Dattani, Martin Silink, Cedric H. L. Shackleton, Dominique Maiter, Nils Krone, Wiebke Arlt, Pubertal Presentation in Seven Patients with Congenital Adrenal Hyperplasia due to P450 Oxidoreductase Deficiency, Endocrinology, Volume 152, Issue 2, 1 February 2011, Pages 741–742, https://doi.org/10.1210/endo.152.2.zee741b
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Abstract
Context: P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17α-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents neonatally, with disordered sex development in both sexes, skeletal malformations, and glucocorticoid deficiency.
Objective: The aim of the study was to describe the clinical and biochemical characteristics of ORD during puberty.
Design: Clinical, biochemical, and genetic assessment of seven ORD patients (five females, two males) presenting during puberty was conducted.
Results: Predominant findings in females were incomplete pubertal development (four of five) and large ovarian cysts (five of five) prone to spontaneous rupture, in some only resolving after combined treatment with estrogen/progestin, GnRH superagonists, and glucocorticoids. Pubertal development in the two boys was more mildly affected, with some spontaneous progression. Urinary steroid profiling revealed combined CYP17A1 and CYP21A2 deficiencies indicative of ORD in all patients; all but one failed to mount an appropriate cortisol response to ACTH stimulation indicative of adrenal insufficiency. Diagnosis of ORD was confirmed by direct sequencing, demonstrating disease-causing POR mutations.