Endocrine Abstracts

Introduction: The term congenital adrenal hyperplasia (CAH) encompasses a group of autosomal recessive disorders, each of which involves a deficiency of an enzyme involved in the synthesis of cortisol, aldosterone, or both. Deficiency of 21-hydroxylase, resulting from mutations or deletions of CYP21A, is the most common form of CAH, accounting for more than 90% of cases.

Case report: Two female siblings were referred to endocrine clinic with the complain of amenorrhea and hirsutism. İn their medical history; The elder sister presented to the paediatrics team at 4 years old with progressive enlargement of the clitoris, acne, muscular built and labioscrotal hyperpigmentation. There was no history of salt-losing crisis or hypoglycaemia. A diagnosis of CAH was made. The younger sister at 2 years old, presented with clitoral enlargement and acne. Similar investigations were performed and the diagnosis of CAH was confirmed. Both sisters were started on hydrocortisone upon diagnosis. Clitoral reduction and vaginal reconstruction surgery was performed for both sisters soon after the diagnosis. Although the seriousness of the illness was explained to their parents, replacement therapy were interrupted by them due to difficult social and economic status of the family, who lived for many years without basic medical care. 15 years later, at the age of 19 and 17; they were seen at the endocrine clinic. On physical examination, they were noted to have a short stature with body height of 1.48 and 1.52 cm. Physical examination revealed extreme virilisation. They were observed marked hirsutism, male type pubic hair, deepening of the voice, cliteromegaly, without breast development and primary amenorrhea. Hormonal analysis showed significantly elevated serum levels of 17-OHP (416, 513 nmol/l) and serum testosterone (30, 49 nmol/l). Mutational analysis of the CYP21A2 gene by multiplex ligation-dependent probe amplification and by polymerase chain reaction (PCR) followed by direct DNA sequencing showed homozygotes I172N mutation.

Discussion: Here we present two sisters with classic simple virilising form of 21-OHD with homozygotes I172N mutation diagnosed infancy who virilised after interruption of the glucocorticoid replacement therapy. If replacement therapy was discontinued, like our cases, there were serious consequences; risk of life, virilisation, change in psycho-social orientation.