SAT-434 Case Report - MC2R Heterozygous Mutation ( FDG 1) Who Becoming Obese After Glucocorticoid Replacement

Abstract Disclosure: H.N. Phatale: None. S. Phatale: None. P. Phatale: None. N. Arora: None. Background: Melanocortin-2 receptor (MC2R), a member of the G protein coupled receptor family, is selectively activated by adrenocorticotropic hormone (ACTH). variants in MC2R are associated with family glucocorticoid deficiency 1 (FGD1). The 15-year-old boy was referred to our hospital for early morning hypoglycaemia. He was born after 38 weeks of gestation via normal delivery to non-consanguineous parents. His birth weight and height were normal, with no history of asphyxia or birth trauma. The patient had documented early morning hypoglycemia with altered sensorium and Whipple's triad. Laboratory findings revealed low plasma cortisol, elevated TSH with low free T4, and documented convulsions. MRI revealed a 4.3 × 4.1 mm lesion in the right sella, likely an incidentaloma. The patient was on levetiracetam (500 mg daily), levothyroxine (75 mcg daily), and oral hydrocortisone (10 mg at 8 AM and 4 PM). Patient was referred to Samrat Endocrine Institute. Medical Examination : He exhibited a tall stature 176 cm (attained MPH), weighing 50 kg, with significant skin pigmentation typical of Addisonian pigmentation. Sexual maturation was complete (adult stage). Following the withdrawal of hydrocortisone for 48 hours, laboratory tests revealed undetectable plasma cortisol and plasma ACTH > 1250 pg/mL at 8 AM. Despite the severe hormonal imbalance, glucose, electrolytes, and renin levels remained normal. Gonadotropin and testosterone levels were in the pubertal range. Computed tomography of the adrenal glands showed bilateral adrenal hypoplasia. Whole genome sequencing identified a mutation in the MC2R gene on chromosome 18, confirming the diagnosis of FGD1. The heterozygous missense variant c.424G>T; p.(Val142Leu), has been detected in the MC2R gene on chromosomal position chr18:13885095:C>A. It is located in exon 2 of the transcript NM_000529 and it leads to change in amino acid from Valine to Leucine at codon 142. This variant has been reported in ClinVar as pathogenic (VCV000444066.2). Patient has responded to oral hydrocortisone, levothyroxine. We have continued levetiracitam 500 mg daily. In one year he has put on 22 kg weight. He became hyperphagic within 3 months of glucocorticoid replacement. Levetiracitam is not kown to cause weight gain nor physiological replacement of steroid doses. His hyperphagia has responded to metformin and has lost 4 kg. His lost weight is maintained with life style modification and metformin. None of previous case report of FDG 1 has mentioned hyperphagia and massive weight gain after glucocorticoid replacement. So also pituitary incidentiloma was not reported in all previous case reports. Hyperphagia and Obesity is feature of FDG 2 and MC4R mutations. But in this patient of MC2R mutation ( FDG 1 ) we noticed hyperphagia and weight gain causing obesity. Presentation: Saturday, July 12, 2025