ESPE Abstracts

Background: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterized by specific failure of adrenocortical glucocorticoid production in response to adrenocorticotropic hormone (ACTH). Mutations of the nicotinamide nucleotide transhydrogenase (NNT) gene have recently been implicated in FGD.

Objective and hypotheses: To describe a new case of FGD with combined mineralocorticoid insufficiency and extra adrenal manifestations.

Method: Case report.

Results: Suffering from a febrile viral respiratory disease, an eight-month-old boy presented with status epilepticus caused by hypoglycemia. Multiple medical complications occurred, and invasive ventilation was required for 18 days. The results of blood tests performed during hypoglycemia revealed adrenal insufficiency (cortisol <20 nmol/l, ACTH 1382 ng/l). Renin and aldosterone levels were high but considered consistent with the mild hyponatremia (135 mmol/l) and severe hypotension. Subsequent measurements revealed persistent high renin levels (278 ng/l) with low aldosterone concentration (179 pmol/l). Hyponatremia persisted despite high-dose sodium supplementation, confirming the diagnosis of partial mineralocorticoid deficiency. The patient required hydrocortisone, fludrocortisone and sodium supplementation. ACTH levels remained high after 6 months of suitable treatment (>2000 ng/l). His parents are consanguineous and his father has a glucocorticoid deficiency since he was 18 months old, without mineralocorticoid deficiency during childhood. Genetic analysis revealed a new homozygous NNT mutation (p.Arg129*) for the child and his father. Investigations to work up any associated disorders revealed thyroid stimulating hormone deficiency, a bradycardic sinus rhythm without cardiopathy. After 6 months, he presented neurological sequelae including severe hypotonia.

Conclusion: This case illustrates combined glucocorticoid and mineralocorticoid deficiency related to a new NNT mutation and underlines intra-familial phenotype heterogeneity. NNT gene should be considered when the most common etiologies of adrenal deficiency have been eliminated even if there is mineralocorticoid deficiency, in order to limit the serious consequences by a delayed diagnosis especially in offspring and to investigate any associated disorders.