Are Current Normal Values of 11DOC Useful for Diagnosis of Non Classical Congenital Adrenal Hyperplasia Due to 11β- Hydroxylase Deficiency?

Abstract

Background: A non-classic form of 11β-hydroxylase deficiency (NC 11β-OHD) has been reported to cause mild androgen excess, with a clinical presentation of precocious puberty, menstrual cycle abnormalities, or hirsutism during adolescence. Since genetic diagnosis of NC 11βOHD is yet not routinely available, the current gold standard for biochemical diagnosis is elevated 11 DOC levels after corticotropin stimulation test (ACTHstimT). However, there are no clear hormone level cutoffs. One of the accepted references for basal and stimulated levels for the pediatric population was published in 1991 by Lashansky et al1. Aim: To determine the correlation between 11DOC levels measured during ACTHstimT, clinical symptoms attributed to NC11βOHD and androgen levels at presentation, and long-term follow-up among children and adolescents with hyperandrogenism. Methods: a retrospective study including all patients who underwent ACTHstimT between 20072015, in one center, during which 11 DOC levels were routinely measured as part of the test. Clinical data was collected from the patients’ medical files and, by telephone calls for complete long-term follow-up. 11DOC levels before and after ACTHstimT were categorized as elevated according to both pre-defined cut-offs; greater than 1.5 times the 95th percentile according to Lashansky1 normal level for sex and age, and greater than 1.5 times the upper limit of the normal level of the commercial kit. Results: Data were complete at presentation for 136 patients, 92 females, and for long for 98 patients, 68 females, mean follow up duration of 3.1 years (1.37,5.09). There was no statistically significant difference in the number of cases with elevated 11DOC according to both cut-offs, among patients with precocious and early puberty, premature adrenarche nor acne. Higher baseline and stimulated 11 DOC levels were demonstrated in females who presented with mild hirsutism and regular menses. Long term data demonstrated no statistically significant difference in the number of cases with elevated 11DOC levels among patients with compromised final adult height, PCOS or hyperandrogenism. There was negative correlation between stimulated 11 DOC levels and basal levels of testosterone, androstenedione and DHEAS levels. Conclusions: This report demonstrates that the current interpretation of 11DOC levels, basal and ACTHstimulated in children, according to 1.5 times the highest range, of both, the Lashansky1 acceptable norms for children, and some of the laboratory’s kit, are not clinically applicable.1Lashansky G, Saenger P, Fishman K, Gautier T, Mayes D, Berg G and Reiter E. Normative data for adrenal steroidogenesis in a healthy pediatric population: Age- and sex-related changes after adrenocorticotropin stimulation. J. Clin. Endocrinol. Metab. 1991; 73(3): 674-686.