Endocrine Abstracts

Introduction: 11-beta-dehydroxysteroid dehydrogenase-1 (11BHSD1) is a bidirectional enzyme which converts inactive cortisone and 11-dehydrocorticosterone to active cortisol and corticosterone and vice-versa. The direction is dependent on NADPH availability and the action of the cofactor enzyme hexose-6-phosphate dehydrogenase (H6PDH). Cortisone reductase deficiency is a rare disorder caused by defects in 11BHSD1 or H6PDH, leading to inability to regenerate active glucocorticoid. This condition is characterised by increased cortisol metabolic clearance, stimulating ACTH mediated adrenal hyperandrogenism. Here, we present the case of an 8 year old boy with 11BHSD1 deficiency who presented with premature adrenarche.

Case: An 8.1 year old boy presented with a 6-12 month history of increasing body odour, axillary and pubic hair. Auxology showed height was 134.9 cm (SDS: +1.19), weight 31.6 kg and BMI 17.98 kg/m2. Tanner staging P2A2G1 and testicular volume 3ml were consistent with premature adrenarche.

Results: Investigations showed elevated adrenal androgens: DHEAS 5.1umol/l (0-0.4 umol/L), androstenedione 0.8 nmol/L (0—0.4 nmol/L). Synacthen test showed adequate response with peak cortisol 667 nmol/L and normal 17-OHP. Gonadotropins were in the prepubertal range (FSH- 1.5 U/L, LH <1.0 U/L) with testosterone <1.0 nmol/L. Growth hormone, IGF-1 and thyroid function were normal. Bone age was significantly advanced. At chronological age 8.1 years, Greulich and Pyle bone age was 11.6 years and Tanner-Whitehouse 10.8 years (+3.85 SD). Urine steroid profiles showed a very low ratio (0.07) of cortisol (11-hydroxy) to cortisone (11-oxo) metabolites (NR age 6-8 years; mean ratio 0.7 with SD 0.2) confirming 11BHSD1 deficiency. Genetic testing for mutations in HSD11B1 and H6PD genes is pending.

Conclusions: Urine steroid profiling (USP) has identified 11BHSD1 deficiency as a rare cause of premature adrenarche in this child. This defect is causing ACTH mediated excess adrenal androgens as illustrated by high DHEAS resulting in premature adrenarche with significantly advanced bone age. There are very few other cases reported in the literature and minimal experience regarding potential treatment options to alleviate the hyperandrogenaemia. Currently we have not initiated treatment but are closely monitoring his progress. This case illustrates the benefit of USP in cases of premature adrenarche.