ESPE Abstracts

Background: The Dutch HYPOthalamic and PITuitary gene (HYPOPIT) study investigates the genetic and non-genetic causes of isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). Former projects within the HYPOPIT study showed that only a small minority of the Dutch IGHD and CPHD cases could be explained by mutations in GH1, GHRHR, HMGA2 and CDK6 in IGHD patients and PROP1, HESX1, POU1F1, LHX3, LHX4, OTX2, SHH and HHIP in CPHD patients.

Aims and objectives: In the current project, we chose to study immunoglobulin superfamily gene 1 (IGSF1, highly expressed in pituitary and testis) as a new candidate gene. Mutations in IGSF1 have recently been associated with central hypothyroidism. Initially, IGSF1-related central hypothyroidism was only described in combination with macro-orchidism. Later on, IGSF1 mutations were also reported in patients with central hypothyroidism without macro-orchidism, with or without additional pituitary hormone deficiencies. Therefore, we chose to study IGSF1 as a new candidate gene for patients with the rare combination of central hypothyroidism and growth hormone deficiency.

Methods: We screened 80 males and 14 females patients with the combination of central hypothyroidism and GH deficiency for genetic defects in exons 10–17, encoding the extracellular region of IGSF1.

Results: A total of six SNPs, one known mutation and one known deletion were identified in the extracellular regions of IGSF1. We will present the genotypic and phenotypic data of the patients with variants in IGSF1.

Conclusion: Central hypothyroidism combined with growth hormone deficiency is explained by IGSF1 defects in a small minority of the patients.