Pit-1 mutation and lipoedema in a family

BACKGROUND: A 23-year-old male was referred to our clinic with diagnosis of idiopathic isolated growth hormone deficiency. A detailed family history revealed short stature and swelling of legs which only affected females in four generations of his family. METHODS: Combined pituitary function tests revealed growth hormone deficiency, secondary hypothyroidism and hypoprolactinemia in the proband. His mother had hypoprolactinemia and growth hormone deficiency. A diagnosis of inherited combined pituitary deficiency due to a PIT-1 mutation was suspected in view of the short stature with associated multiple pituitary hormone deficiencies. RESULTS: A mutation was identified in PIT-1 (POU1F1), 196C>T, which produces the amino acid change P24L in exon 1. The mutation was also found in the mother of the proband but not in his phenotypically normal half-sister. CONCLUSION: The case shows a novel association of two rare conditions Pit-1 mutation and lipoedema in a family that has not been described before. It also allows formulation of hypothesis on the interaction of growth hormone and sex steroids resulting in abnormal fat distribution in predisposed subjects at the time of puberty.