Endocrine Abstracts

JOINT1003

Introduction: Proopiomelanocortin (POMC) deficiency is an ultra-rare monogenic form of obesity characterized by impaired synthesis of hormones derived from the hypothalamus and pituitary gland. Mutations in the POMC gene lead to distinct phenotypic features, including early-onset obesity, fair skin, and red hair. While most reported cases in the literature describe normal growth, short stature and growth hormone deficiency (GHD) have been documented in only one case. Among three POMC deficiency cases followed at our center, none demonstrated short stature, making the findings in this patient particularly noteworthy for expanding the syndrome’s clinical spectrum.

Case Presentation: A 15-year-old female was first evaluated at 3. 5 years of age with obesity, fair skin and red hair, ACTH deficiency, and recurrent episodes of severe hypoglycemia during infancy. The diagnosis of POMC deficiency was confirmed by identifying a homozygous pathogenic c. 64delA variant in the POMC gene. During follow-up, delayed puberty and hypogonadotropic hypogonadism were identified. From the age of 12 years onward, growth retardation and short stature became apparent. At age 13, the patient’s physical examination revealed a weight of 56. 7 kg (SDS: 0. 8), height of 143 cm(SDS: -2. 5), BMI of 27. 1 kg/m² (SDS: 2), and annual growth velocity of 1. 64 cm/year (SDS: -1. 61). The patient was at Tanner stage 1. Bone age, assessed at 14 years of age, corresponded to 10 years. After achieving a euthyroid state and estrogen priming, L-Dopa and clonidine stimulation tests were performed, showing peak GH levels of 0. 52 µg/l and 1. 0 µg/l, respectively. These findings confirmed a diagnosis of growth hormone deficiency(GHD). Pituitary MRI revealed normal size and morphology with no pathological findings. GH replacement therapy was initiated at 0. 035 mg/kg/day at 14 years and 3 months of age. After 8 months of therapy, the patient’s weight was 59. 8 kg(SDS: 0. 67), height was 150. 2 cm(SDS: -1. 95), BMI was 26. 51 kg/m² (SDS: 1. 79), and annual growth velocity was 11. 29 cm/year.

Discussion: Although normal stature is typically reported in POMC deficiency, the short stature and GHD observed in this case represent rare and striking finding that expand the clinical spectrum of the syndrome. The rarity of short stature in most reported cases of POMC deficiency underscores the uniqueness of our case. The etiology of GHD in POMC deficiency remains unclear. The co-occurrence of these conditions could be coincidental; however, the severe hypoglycemic episodes experienced during early infancy may have impaired hypothalamic-pituitary development and GH secretion, contributing to GHD in this patient.