Endocrine Abstracts

Background: Congenital adrenal hyperplasia, (CAH) is a common autosomal recessive condition, 95% of which is attributable to mutations in the 21-hydroxylase (CYP21) gene. There is a wide range of clinical features and genotype phenotype correlations for common mutations are well described.

Case: EG presented to the endocrine clinic at the age of 3.5 years with pubarche of 6 months duration and Tanner staging of PH3, B1and clitoromegaly (Prader stage 1) Urinary steroid profile, high 17OHP (undiluted>500 nmol/l) and testosterone (8.4 nmol/l) levels were all consistent with classical 21 hydroxylase deficiency. Blood pressure was 75 to 90th centile for height on several occasions and her plasma renin activity (elevated at 9.5 pmol/ml per h) normalised almost immediately on hydrocortisone treatment. There was no evidence of salt losing even during documented past admissions with gastroenteritis and urinary tract infections. TW3 bone age was advanced by 3.5 years.

Genetics: Compound heterozygote for two missense mutations (c.515T>A;p.lle172Asn-associated with simple virilising forms and the rarer c.1277G>A;p.Arg426His associated with salt wasting/simple virilising CAH).

Discussion: Unusually late presentation of a classical CAH with the genotype suggestive of more severe disease. Few previously described patients with this genetic combination had a varied clinical presentation ranging from virilisation requiring surgery to precocious puberty and advanced bone age. EG has also been difficult to manage requiring a higher glucocorticoid (17 mg/m²) dose to suppress her ACTH drive and her accelerated bone age has persisted despite treatment. Should fludrocortisone be used in the setting of a normal renin and no salt wasting as mentioned in the literature?

Conclusion: This case highlights the fact that though genotype is useful, therapeutic decisions need to be made in conjunction with the clinical picture and the role of the clinician in performing appropriate hormonal studies at diagnosis as well as on treatment is essential to optimize therapy for each individual patient.