Endocrine Abstracts

Case history: Two Syrian refugee siblings aged 21 and 20 years, were referred. Ambiguous genitalia had been identified at birth and had been raised as males. They wished a more masculine habitus and had concerns regarding their fertility. The elder sibling had ambiguous genitalia at birth and a 46,XX karyotype. Long-term steroid treatment had been initiated and corrective genital surgery performed at 9 months of age. For unknown reasons, steroids were stopped after 9 years. He identified himself as male and underwent puberty with development of male secondary sex characteristics. There were no adrenal crises. Height was only 130 cm with male pattern pubic hair, cliteromegaly, labia majora and a vaginal opening. The younger sibling had an almost identical presentation. He was 139 cm in height, and had a micropenis of 1.5 cm and fused labia majora without a vaginal introitus.

Investigations: A diagnosis of congenital adrenal hyperplasia (CAH) was considered. In the older sibling basal and tetracosactide-stimulated cortisol levels were 109 nmol/L and 108 nmol/L, respectively. Basal 17-hydroxyprogesterone was 52 nmol/L and rose further to 456 nmol/L following stimulation, thereby confirming CAH. Baseline testosterone was 17.8 nmol/L. In the younger sibling basal and stimulated cortisol levels were 50 nmol/L and 55 nmol/L, respectively, with basal 17-hydroxyprogesterone 670 nmol/L rising to 735 nmol/L, and baseline testosterone 15.5 nmol/L. Their karyotype was 46,XX.

Results and treatment: Following the diagnosis of classic CAH, both siblings were initiated on hydrocortisone and fludrocortisone with subsequent reduction of 17-hydroxyprogesterone levels. Their testosterone levels, however, dropped below the male reference range. Due to their wish for a more masculine body habitus, testosterone replacement was initiated.

Conclusion and points for discussion: CAH is the commonest cause of sexual ambiguity in genetic females. Early diagnosis and treatment is of vital importance in order to achieve timely discussion regarding gender assignment and to institute treatments to normalize growth and pubertal development, and to prevention long-term complications. It is remarkable that these siblings survived into adulthood without suffering adrenal crises but the final heights they achieved were poor and their desire for fertility raises significant challenges. In this country we take for granted the early and appropriate management for classic CAH by a dedicated paediatric endocrinologist and multidisciplinary team. The clinical scenarios we present highlight that patients in other parts of the World with CAH may be denied essential investigation and treatment.