ESPE Abstracts

The Ig superfamily member 1 (IGSF1) gene encodes a plasma membrane immunoglobulin superfamily glycoprotein, that is highly expressed in Rathke’s pouch and the adult pituitary gland and testis. It is now known that a loss-of-function mutation in this gene causes X-linked syndromic disorders including congenital central hypothyroidism, macroorchidism, prolactin deficiency, partial and transient growth hormone (GH) deficiency, disharmonious pubertal development and overweight. We report a case of congenital central hypothyroidism due to a novel nonsense mutation in the IGSF1 gene complicated with complete GH deficiency. The male patient was incidentally diagnosed with central hypothyroidism during the newborn period when he was referred for neonatal seizure, and levothyroxine was started. At 6 years of age, a genetic test revealed a novel hemizygous nonsense mutation c.2548C>T (p.R850*) in IGSF1 gene and the diagnosis was confirmed. Due to decreased growth velocity, his pituitary function was examined at 10 years of age. His height was 126.0 cm (-1.81SD) and his body weight was 33.9kg (body mass index, 21.4 kg/m²; 91.4 percentile). The patient’s Tanner stages were G1 and PH1, and the volume of each testicle was 2 ml. His thyroid function was normal on levothyroxine (FT₄, 0.96 ng/dl; TSH, <0.01 µIU/ml). His insulin-like growth factor-1 value was 148 ng/ml, which was within normal range for his age. His adrenal function was normal and his gonadal function was at the prepubertal stage. His hypothalamic-pituitary function was more examined by stimulation tests. GH stimulation tests showed extremely poor responses; the peak levels of GH were 0.68 ng/ml with arginine and 2.19 ng/ml with l-dopa, indicating complete GH deficiency. The peak levels of TSH and PRL on a TRH test were 0.01 µIU/ml and 8.08 ng/ml, respectively, which were consistent with the genetic diagnosis. An LHRH test showed prepubertal LH and FSH responses; the peak levels of LH and FSH were 2.01 mIU/ml and 18.89 mIU/ml, respectively. The pituitary-adrenal axis was normal on a CRH test. The present case differed from previous reports, in that the patient’s GH deficiency was not partial, but complete. Because his growth velocity had been gradually decreased since the young infant period, complete GH deficiency might be one of features of IGSF1 deficiency. From the viewpoint of GH therapy in adult life, long-term follow-up is needed to know whether his GH deficiency is transient or persistent.