A Report of Three Cases With Acquired Generalized Lipodystrophy With Distinct Autoimmune Conditions Treated With Metreleptin

J Clin Endocrinol Metab. 2015 Nov;100(11):3967-70. doi: 10.1210/jc.2015-2589. Epub 2015 Sep 21.


Context: Acquired generalized lipodystrophy (AGL) is associated with leptin deficiency as a result of adipose tissue loss and hypertriglyceridemia, insulin resistance, and hepatic steatosis. It may coexist with other autoimmune diseases such as Hashimoto's thyroiditis, rheumatoid arthritis, hemolytic anemia, and chronic active hepatitis. Metreleptin therapy has been shown to improve metabolic abnormalities in lipodystrophy, but the effect on AGL patients with active autoimmune disease is unknown.

Case description: We report 3 cases of pediatric patients with AGL and distinct active autoimmune diseases who were treated with metreleptin over a period of 4-6 years. Case 1 is a 9-year-old girl with active juvenile dermatomyositis, who was successfully treated with leptin with no worsening of her dermatomoysitis. Case 2 is a 16-year-old female with Graves' disease, who could discontinue all her antidiabetic medication completely with improved triglyceride levels. Case 3 is an 11-year-old boy with active autoimmune hepatitis and chronic urticaria, whose hyperphagia has resolved and his liver enzymes and hepatosplenomegaly have improved.

Conclusion: Metreleptin therapy is of considerable clinical benefit to reduce insulin resistance and hypertriglyceridemia and did not appear to alter the clinical course of autoimmune disease nor clinical efficacy of immunosuppressive treatments. Our observations suggest that risk or presence of autoimmune disease should not lead to withholding of metreleptin treatment from patients with AGL, but should prompt close clinical follow up in light of cautionary preclinical data.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Autoimmune Diseases / complications*
  • Autoimmune Diseases / physiopathology
  • Child
  • Compassionate Use Trials
  • Dermatomyositis / complications
  • Dermatomyositis / physiopathology
  • Female
  • Graves Disease / complications
  • Graves Disease / physiopathology
  • Hepatitis, Autoimmune / complications
  • Hepatitis, Autoimmune / physiopathology
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Leptin / adverse effects
  • Leptin / analogs & derivatives*
  • Leptin / therapeutic use
  • Lipodystrophy / complications
  • Lipodystrophy / drug therapy*
  • Lipodystrophy / immunology
  • Male
  • Severity of Illness Index
  • Treatment Outcome
  • Urticaria / complications
  • Urticaria / physiopathology


  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Leptin
  • metreleptin