In a minority of cases, TSH deficiency is isolated and may occur as a result of defects in genes controlling the TSH biosynthetic pathway, eg mutations in the thyrotropin-releasing hormone receptor (TRHR), thyroid stimulating hormone β subunit (TSHB) and the more recently-described immunoglobulin superfamily member 1 gene (IGSF1) (Garcia et al. 2014). Here, IGSF1 is linked to hyperinsulinemic hypoglycemia, familial, 4.