Novel mutations of the ACTH receptor gene in a female adult patient with adrenal unresponsiveness to ACTH

We report a 30-year-old female with adrenal unresponsiveness to ACTH. Her c linical features included no adrenal crisis despite poor drug compliance, p oor pubic hair development (Tanner stage 2), well-developed breasts (Tanner stage 5), and regular menstrual cycles, Endocrinological data included blo od ACTH 1500 pmol/l, cortisol 18 nmol/l, dehydroepiandrosterone sulphate be low 0.26 mu mol/l, activated renin 0.37 pmol/l, and aldosterone 3.4 nmol/l. Direct sequencing and allele-specific amplification revealed two novel mut ations in the ACTH receptor gene. One was transition from guanine to adenin e at nucleotide position 1002, resulting in substitution of aspartate for a sparagine at codon 103, and the other was transition from cytosine to thymi ne at nucleotide 1104, leading to substitution of arginine for tryptophan a t codon 137, The present findings lend additional credence to the notions t hat adrenal androgens play an important role in female pubic hair developme nt and that ovarian development takes place independently of adrenarche.