Pit-1 Mutation and Lipoedema in a Family

Abstract

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

Key words

estrogens - hypopituitarism - leptin - obesity

References

• 1 Hines EA, Allen EV. Lipoedema of the legs: a syndrome characterised by fat legs and orthostatic edema.  Proceedings of the Staff Meetings of the Mayo Clinic. 1940;  15 184-187
• 2 Harwood CA, Bull RH, Evans J. et al . Lymphatic and venous function in lipoedema.  Br J Dermatol. 1996;  134 1-6
• 3 Fofanova OV, Takamura N, Kinoshita E. et al . Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency.  Am J Med Genet. 1998;  77 360-365
• 4 Bastard JP, Pieroni L. Plasma plasminogen activator inhibitor 1, insulin resistance and android obesity.  Biomedicine and Pharmacotherapy. 1999;  53 455-460
• 5 Ohta K, Nobukuni Y, Mitsubuchi H. et al . Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency.  Biochem Biophys Res Commun. 1992;  189 851-855
• 6 Quentien MH, Barlier A, Franc JL. et al . Pituitary transcription factors: from congenital deficiencies to gene therapy.  J Neuroendocrinol. 2006;  18 633-642
• 7 Rudkin GH, Miller TA. Lipedema: a clinical entity distinct from lymphedema, Plast Reconstr.  Surg. 1994;  94 841-847
• 8 Schmeller W, Meier-Vollrath I. Tumescent liposuction: a new and successful therapy for lipedema.  J Cutan Med Surg. 2006;  10 7-10
• 9 Mauras N, O’Brien KO, Welch S. et al . Insulin-like growth factor 1 and growth hormone (GH) treatment in GH-deficient humans: differential effects on protein, glucose, lipid, and calcium metabolism.  J Clin Endocrinol Metab. 2002;  85 1686-1629
• 10 Moran A, Jacobs Jr DR, Steinberger J. et al . Insulin resistance during puberty: results from clamp studies in 357 children.  Diabetes. 1999;  48 2039-2044
• 11 Roemmich JN, Rogol AD. Evidence supporting an adipose leptin GHaxis in obesity-related hyposomatotropism.  Endocrinologist. 1999;  9 424-430
• 12 Fors H, Matsuoka H, Boseous I. Serum leptin levels correlated with GH secretion and body fat in children.  J Clin Endocrinol Metab. 1999;  84 586-3590
• 13 Span JP, Pieters GF, Sweep CG. et al . Gender difference in insulin-like growth factor I response to growth hormone (GH) treatment in GH-deficient adults: role of sex hormone replacement.  J Clin Endocrinol Metab. 2000;  85 1121-1125
• 14 Meinhardt UJ, Ho KK. Regulation of growth hormone action by gonadal steroids.  Endocrinol Metab Clin North Am. 2007;  36 57-73
• 15 Földi E, Földi M. Lipedema. In Textbook of lymphology edited by M. Földi, E. Földi and S. Kubik, pp. Germany Urban & Fischer 2003: 395-403
• 16 Macdonald JM, Sims N, Mayrovitz N. Lymphedema, lipedema, and the open wound: the role of compression therapy.  Surg Clin North Am. 2003;  83 639-658

Correspondence