Late Diagnosis of Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Introduction

21-hydroxylase deficiency, causing more than ninety percent of cases of congenital adrenal hyperplasia (CAH), results from mutations in the cytochrome CYP21A2 gene leading to the failure to synthesize cortisol due to the impaired conversion of 17α-hydroxyprogesterone to 11-deoxycortisol. The loss of negative feedback due to the decreased cortisol levels causes increased ACTH secretion resulting in hypertrophy of the adrenal glands and excessive synthesis of androgens. In seventy-five percent of cases aldosterone production is impaired because of failure to convert progesterone to 11-deoxycorticosterone (DOC). Several distinct clinical forms of classical 21-hydroxylase deficiency are distinguished, including the salt wasting form due to a concomitant failure in aldosterone synthesis presenting with salt-wasting crisis and hypotension within the first weeks of life, or the simple virilizing form with apparently normal aldosterone secretion leading to sexual ambiguity in females. Furthermore two non-classical forms are discerned that may be asymptomatic (cryptic) or may present with signs of hyperandrogenism in adolescence (late onset form) ([White and Speiser, 2000]). Cases of 21-hydroxylase deficiency diagnosed in late adulthood are rare; however, they require clinical attention. Therefore, we contribute a further case reporting on the clinical, biochemical, and genetic characterization of a patient with a 21-hydroxylase deficiency diagnosed at the age of 39 years.

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