SUN-188 A Case ofCongenital Combined Pituitary Hormone DeficiencyComplicated with Hyperinsulinism Caused by 20p11.21 Deletion that was Successfully Diagnosed by Array CGH

Abstract Disclosure: K. Miyako: None. K. Ishii: None. Background: The FOXA2 gene (formerly HNF-3β) is located on chromosome 20p11.21, which plays an important role during the development of the pituitary gland and pancreas. Array-based comparative genomic hybridization (array CGH) has often been used to diagnose congenital disorders without definite gene abnormalities. Clinical case: The patient was a 6-year-old boy. He was born by normal delivery to unconsanguineous parents after a 37-week uncomplicated pregnancy. There was no asphyxia. His birth weight was 2,788 g, and his body length was 49.0 cm. He had a microphallus and right cryptorchidism. Soon after birth, hypoglycemic convulsions and hypotension developed, and hydrocortisone was administered to improve his condition. Low levels of ACTH and cortisol were found during hypoglycemia, and ultrasonography revealed hypoplasia of the adrenal gland. A magnetic resonance imaging scan of the head showed a small pituitary gland and invisible pituitary stalk, leading to the diagnosis of adrenal insufficiency due to hypoplasia of the pituitary gland. Endocrinological stimulation tests revealed hypogonadotropic hypogonadism, central hypothyroidism, and severe growth hormone deficiency. No symptoms of diabetes insipidus were observed. The chromosomal karyotype was normal (46, XY). A genetic analysis revealed no significant pathogenic variants in genes involved in the pituitary function. Despite the replacement of pituitary hormones, hypoglycemia often occurred between meals or when a patient was sick. At four years of age, his IRI and CPR levels was 3.6 μIU/ml and 0.83 ng/ml, respectively, when his blood glucose level was 39 mg/dl. However, beta-hydroxybutyric acid and free fatty acid levels did not increase, suggesting hyperinsulinemic hypoglycemia. At six years of age, array CGH revealed a heterozygous microdeletion at 20p11.23-p11.21. As some patients with both hypopituitarism and hyperinsulinism are reported to be caused by a loss-of-function variant of the FOXA2 gene or deletion at chromosomal region 20p11.2, FOXA2 haploinsufficiency was considered a pathogenic mechanism of the conditions in this patient. Conclusion: FOXA2 haploinsufficiency is associated with both hypopituitarism and hyperinsulinism. Since some cases are caused by deletion at the chromosomal region 20p11.2, array CGH is a useful diagnostic tool for these patients. Presentation: Sunday, July 13, 2025