ESPE Abstracts (2016) 86 P-P2-90

A Genetic Diagnosis of Familial Glucocorticoid Deficiency Resulting in Cessation of Long-term Mineralocorticoid Treatment in Three Siblings

Emily Cottrell & Talat Mushtaq

Leeds Teaching Hospitals NHS Trust, Leeds, UK

Background: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by ACTH resistance and leads to isolated glucocorticoid deficiency. Mutations in the gene encoding the ACTH receptor (MC2R) are responsible for around 25% of cases.

Case report: The female index case was hyperpigmented at birth. At one week of age her ACTH level was >1200 ng/ml, plasma renin activity (PRA) 11.4 pmol/ml/h with an aldosterone of 520 pmol/l. Adrenal ultrasound scan did not identify the left adrenal but the right adrenal appeared to be of a normal size. She was diagnosed with adrenal hypoplasia congenita (AHC) and commenced on hydrocortisone and fludrocortisone supplements. Investigations revealed persistently elevated ACTH levels often >1250 ng/l/h yet persistently low PRA below 2 nmol/l/h. Subsequently a male and female sibling were also diagnosed with AHC and received hydrocortisone and fludrocortisone supplementation. They similarly had persistently low plasma renin levels. Genetic testing revealed a homozygous mutation of the MC2R gene in all 3 siblings resulting in a diagnosis of FGD. Therefore fludrocortisone supplementation was gradually weaned then stopped. Subsequent blood pressure readings and sodium levels remained within normal limits. The index case, who had been taking fludrocortisone for 14 years, had ambulatory blood pressure monitoring pre and post withdrawal of mineralocorticoid. This was normal. Extended testing showed that both parents and a number of other family members to be heterozygous for the MC2R gene mutation.

Conclusion: In our family, despite many years of treatment it was possible to withdraw the fludrocortisone and thus potentially prevent unnecessary iatrogenic effects such as hypertension. A genetic cause should be pursued in all individuals with AHC. In the presence of persistently low or normal PRA levels a diagnosis of FGD should be considered.

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