ESPE Abstracts

A 12-month-old boy was admitted to the emergency department in Spain for a tonic-clonic seizure. The initial evaluation revealed metabolic acidosis (pH 7,33, bicarbonate 18,5 mEq/L), glycemia 50 mg/dL, sodium 135 mEq/L and potassium 7,3 mEq/L. After treatment for hypoglycemia, he was admitted for investigation. Physical examination was unremarkable. There was no family history of hereditary disorders nor consanguinity. Pregnancy was uneventful and the Portuguese neonatal screening was normal. He had a normal development. The etiological study showed: 17-hydroxyprogesterone 0 ng/mL [reference value (RV) 0.16-0.74 ng/mL], cortisol <0,2 ug/dL (RV 1.73-10.76 ug/dL), dehydroepiandrosterone <0,1 ug/dL (RV 32.7-276.0); ACTH >1250 pg/mL (RV 0-46 pg/mL); active renin 57,1 uUI/ml (RV 21.1-93.1 ng/dL) and aldosterone 29,5 ng/dL (RV 7-93 ng/dL). Metabolic screening was normal. Thus, a diagnosis of primary adrenal insufficiency (PAI) was established. The child was started on hydrocortisone 10 mg/m²/day and fludrocortisone 0,1 mg/day and was referred to our centre in Lisbon. He was seen in the Paediatric Endocrinology outpatient clinic at 14 months; he weighed 14,8 kg (+3,55 SDs), for 80 cm (+0,77 SDs) [BMI 23,1 kg/m² (+4,01 SDs)] and did not have skin hyperpigmentation. Subsequent investigation of PAI aetiology were negative for congenital adrenal hyperplasia, autoimmune adrenal insufficiency and X-linked adrenoleukodystrophy. Adrenal glands showed normal morphology on magnetic resonance imaging. Next generation sequencing revealed a homozygous mutation in the MRAP (melanocortin 2 receptor accessory protein) gene, responsible for type 2 familial glucocorticoid deficiency. Segregation studies were performed and both parents were asymptomatic carriers, consistent with autosomal recessive inheritance. During follow-up his weight always remained on >2 SDs, with substantial hyperphagia, despite dietary measures. Fludrocortisone withdrawal was attempted, leading to a rise of active renin, without ionic imbalance, prompting fludrocortisone re-introduction. Familial Glucocorticoid Deficiency (FGD) encompasses a broad spectrum of monogenic recessive disorders that abrogate cortisol biosynthesis and is a rare cause of PAI. MRAP is a transmembrane protein, which promotes the activity of melanocortin receptor 2, resulting in ineffective ACTH signaling. MRAP mutations are responsible for 20% of FGD cases. The present case demonstrates a rare cause of PAI and an atypical phenotype of type 2 FGD with mineralocorticoid deficiency, obesity instead of failure to thrive, and no skin hyperpigmentation. To date, it is not known whether MRAP is associated with obesity, as there is only a single case report showing this association.