Endocrine Abstracts

JOINT2192

Introduction: Growth hormonal (GH) deficiency (GHD) is typically associated with impaired growth and short stature. Nevertheless, instances of normal growth have been reported in some pathological conditions, such as combined pituitary hormone deficiency following the resection of craniopharyngioma, septo-optic dysplasia and overgrowth syndromes despite GHD. We report two patients with obesity and multiple pituitary deficiencies exhibiting normal growth.

Patient 1: A 11-year-old female was evaluated for obesity. Height was 145.6 cm (-0.17SDS) within the mid-parental target, BMI 25.9 (+2.37SDS). Pubertal evaluation was B1 PH1 AH1. Homa index 3.2. History was positive for transient hypoglycemia at birth, normal postnatal growth and minor language delay. Endocrine assessment disclosed low FT₄ with inappropriately normal TSH consistent with central hypothyroidism; patient revealed significantly low IGF-1 (39 ng/ml), IGFBP-3 (2.04 mg/dL), and central ACTH deficiency. GH stimulation tests showed absent GH response. Magnetic resonance imaging (MRI) revealed a small adenohypophysis, absent pituitary stalk, and ectopic neurohypophysis. So, diagnosis was congenital panhypopituitarism was made and the patient began treatment with hydrocortisone, L-thyroxine, and GH. Genetic investigations are ongoing.

Patient 2: A 11-year-old male was evaluated for severe obesity. Height was 158.65 cm (+1.44SDS) above his mid-parental target, BMI 33.5 (+2.59SDS). Tanner stage was T 10 ml PH3 AH2. Abdominal ultrasonography indicated severe steatosis with metabolic syndrome and very high leptin level. Oral glucose tolerance test disclosed severe insulin resistance. Thyroid evaluation revealed secondary hypothyroidism, low IGF-1 levels (39 ng/ml) that persisted after L-thyroxine treatment. Prolactin levels were elevated, while adrenal function and gonadotropin levels were normal. GH stimulation tests showed GH deficiency. MRI showed a small stalk with normal pituitary gland. Despite excellent growth, clinical and laboratory findings suggested combined pituitary deficiency. Hormonal replacement therapy with L-thyroxine and GH was started. Exome sequencing is currently in progress.

Conclusion: The paradox of normal growth in patients with confirmed growth hormone and L-T4 deficiency remains enigmatic. Similar cases have been documented in obese individuals. One hypothesized mechanism involves hyperinsulinism, given the high homology between insulin receptors and IGF-1 receptors. Furthermore, hyperprolactinemia, hyperleptinemia and GH variants have been proposed as contributing factors in this phenomenon. The intricate interplay between these hormonal imbalances and growth regulation warrants further investigation to elucidate the underlying mechanisms. Additionally, cases of normal growth despite GHD have been described in patients with mutations in the HESX1 gene, associated with combined pituitary hormone deficiency. Ongoing genetic analyses in our patients will advance our understanding.