Endocrine Abstracts

JOINT1921

Background: A mutation in the adrenocorticotropic hormone (ACTH) receptor gene, also known as MC2R, causes familial glucocorticoid deficiency (FGD) type 1, a rare autosomal recessive disorder. This condition is characterized by resistance to ACTH action on the adrenal cortex, leading to isolated glucocorticoid deficiency with normal mineralocorticoid activity. It typically presents in infancy or early childhood with episodes of hypoglycemia, hyperpigmentation, recurrent infections, and convulsions, which can result in coma or death if left untreated. We report the case of a 2-year-old boy with isolated hypocortisolism due to MC2R mutation.

Clinical Case: Our patient was born at 39 weeks of gestation. His growth parameters at birth were within normal limits according to INeS Charts. From first day of life he presented recurrent severe hypoglycemic episodes, so he was held in neonatal intensive care unit. Neonatal physical examination revealed areas of hyperpigmentation on the limbs, trunk, and scrotum. Diagnostic investigations, including endocrinological and metabolic blood tests, showed elevated ACTH levels (>3000 ng/l), low cortisol, and normal 17-hydroxyprogesterone, ruling out congenital adrenal hyperplasia (CAH). Given the adrenal insufficiency, continuous intravenous hydrocortisone therapy was started to prevent adrenal crisis and later switched to an oral formulation after stabilization of blood glucose levels and improvement in laboratory tests. Subsequently, an abdominal ultrasound revealed bilateral adrenal hypoplasia. To further investigate the etiology of primary adrenal insufficiency, genetic testing was performed. Whole-exome sequencing identified the c.[634delA] variant in homozygosity in the MC2R gene, which was inherited from both parents and represents a rare cause of FGD. The patient was therefore referred to our endocrinology unit. During follow-up, oral hydrocortisone therapy was maintained at a dose of 10 mg/m²/day, with regular progression in both height (-0.51 SDS) and weight (0.48 SDS), adequate height growth rate (4.41 SDS) and without any side effects.

Conclusions: Glucocorticoid deficiency is an endocrinological emergency and potentially life-threatening condition. Despite being the most common cause of primary adrenal insufficiency in pediatric patients, CAH is not the only condition that can lead to it. During the neonatal period, less common conditions should also be investigated, such as familial glucocorticoid deficiency. Beyond the correct diagnostic approach, another challenge for the pediatrician is the appropriate therapeutic management of glucocorticoid deficiency, which involves adjusting the hydrocortisone dosage over time. This aims to avoid both excess and deficiency of cortisol, while keeping the patient asymptomatic with stable biochemical parameters, ensuring regular growth and enabling normal pubertal progression.