Endocrine Abstracts

Congenital lipoid adrenal hyperplasia (CLAH) is a severe disorder characterized by early impairment of both adrenal and gonadal steroidogenesis, leading to early adrenal failure and male sex reversal. The most common aetiology of CLAH is mutation of Steroidogenic acute regulatory protein (StAR) gene.

Objective: We report evolution over 20 years of a 46XX patient harbouring a novel StAR gene mutation.

Methods: Clinical, hormonal and imaging data were retrospectively collected; molecular analysis was performed by direct sequencing of the StAR gene.

Results: This 46XX patient had a younger 46XY phenotypically female sibling who died of acute adrenal failure at 4 months of age. A novel homozygous 719delC StAR gene frame shift mutation was found, leading to large modifications of the C-terminal end. The child presented at 10 days of life with salt-wasting and recovered on adrenal replacement therapy. She had normal psychomotor development. Early overweight was observed despite elevated ACTH and plasmatic renin activity on high doses of hydrocortisone. Gonadal replacement therapy was initiated at age 13 year, while spontaneous onset of puberty was observed at age 12. After 2 months discontinuation of the oestroprogestative therapy, no ovulation occurred, but development of large ovarian cysts was noticed. Imaging did not show any lipid deposit in adrenals or gonads during follow-up, but right adrenal hypoplasia. Cerebral MRI showed white matter abnormalities.

Conclusion: This long-term follow-up report illustrates spontaneous evolution of 46XX patients presenting CLAH due to a StAR gene mutation. In such patients, adrenal replacement therapy should be adapted on the basis of clinical rather than biological data and gonadal substitution should not be interrupted because of risks of life-threatening ovarian cyst.