title: Consequences of stopping and restarting leptin in an adolescent with lipodystrophy.
abstract: OBJECTIVE
  Lipodystrophy encompasses a group of rare disorders characterized by deficiency of adipose tissue resulting in hypoleptinemia, and metabolic abnormalities including insulin resistance, diabetes, dyslipidemia, and nonalcoholic steatohepatitis. Leptin replacement effectively ameliorates these metabolic derangements. We report effects of leptin discontinuation and resumption in a child with acquired generalized lipodystrophy.
  
  
  METHODS
  Intermittent treatment with leptin with follow-up over 5 years.
  
  
  RESULTS
  Pretreatment metabolic abnormalities included insulin resistance, hypertriglyceridemia and steatohepatitis. Leptin was started at the age of 10 years. After 2 years, the family requested discontinuation of leptin due to lack of visible physical changes. Nine months later, worsened metabolic abnormalities and arrest of pubertal development were observed. Leptin was restarted, followed by improvements in metabolic parameters. Laboratory changes (before vs. 6 months after restarting leptin) were: fasting glucose from 232 to 85 mg/dl, insulin from 232 to 38.9 µU/ml, HbA(1c) from 7.5 to 4.8%, triglycerides from 622 to 96 mg/dl, ALT from 229 to 61 U/l, AST from 91 to 18 U/l, and urine protein:creatinine ratio from 5.4 to 0.3. Progression of puberty was observed 1 year after restarting leptin.
  
  
  CONCLUSIONS
  Initial leptin therapy likely prevented progression of metabolic abnormalities. Treatment discontinuation led to rapid metabolic decomposition and pubertal arrest. Reintroduction of leptin reversed metabolic abnormalities and allowed normal pubertal progression.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: F
authors.initials: F
authors.lastname: Kamran
authors.forename: K I
authors.initials: KI
authors.lastname: Rother
authors.forename: E
authors.initials: E
authors.lastname: Cochran
authors.forename: E
authors.initials: E
authors.lastname: Safar Zadeh
authors.forename: P
authors.initials: P
authors.lastname: Gorden
authors.forename: R J
authors.initials: RJ
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000410:Alanine Transaminase; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D005234:Fatty Liver; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000008:administration & dosage*; D008060:Lipodystrophy / Q000188:drug therapy*; D065626:Non-alcoholic Fatty Liver Disease; D011627:Puberty / Q000187:drug effects; D014280:Triglycerides
chemical_list: D000410:Alanine Transaminase; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D020738:Leptin; D014280:Triglycerides