Congenital Adrenal Hyperplasia Due to a Rare Homozygous Mutation R483P in the CYP21A2 Gene and Coexisting Growth Hormone Deficiency

In CAH due to 21-OH deficiency, GH treatment combined to GC and MC replacement is still considered to be experimental. We present a patient who has benefited from such treatment. A baby girl was born in term with clitoromegaly and manifested with salt loose at neonatal period. Low serum morning cortisol and sodium with high potassium and 17-OH levels were found resulted in the clinical diagnosis of CAH. The karyotype was 46,XX. Prednisolone and DOXA, the only available hormone replacement therapy in the country, was initiated with patient condition‘s improvement. Later, the therapy was switched to hydrocortisone 12 mg/m2/day divided in 3 times, combined to small daily fludrocortisones dose, as 0,025-0,050 mg. However, the girl height was -4SDS and MPH was -1SDS. The bone age was 4 y. delayed, while the girl was euthyroid. Two GH stimulation tests performed demonstrated GH deficiency. Pituitary MRI was normal. After Institution Review Board approval, GH therapy was started at the age of 13,5 y. and completed when she was 18 y.e. after bone plate fusion. In 4,5 y. of GH treatment she has got 32 cm (3 SDS) in height. Her final adult height is 157 cm. Puberty was delayed, clitorovaginoplasty was performed at the teen age, menarche started at 18y. Due to menstrual irregularities, hydrocortisone was switched to dexamethasone 0,375mg daily, with regular cycle and no adverse metabolic effects. Finally, genetic diagnosis of CAH was done due to homozygous point mutation R483P in the CYP21A2gene. The story of our patient presents an example of the association of CAH with GH deficiency which mimics the typical clinical course of main disease. This particular case emphasizes that treatment with prednisolone at early age may worse final patient’s height; however, the patient may benefit from combined GC, mineralocorticoid and GH treatment. Finally, according to our knowledge, this is the first case of the R483P homozygous mutation in the CYP21A2gene described in patient with salt-wasting CAH.