title: Clinical evidence that hyperinsulinaemia independent of gonadotropins stimulates ovarian growth.
abstract: OBJECTIVE
  Ovarian enlargement is a constant feature of syndromes of extreme insulin resistance. The objective of this study is to show the role of insulin on ovarian growth in the presence of low gonadotropin levels.
  
  
  METHODS
  Seven young patients with syndromes of extreme insulin resistance (five with lipodystrophy, one with Type B syndrome and one with Rabson-Mendenhall syndrome) were studied.
  
  
  METHODS
  Baseline LH concentrations and luteinizing hormone releasing hormone (LHRH) tests were performed. Total testosterone, insulin and C-peptide values were measured. Pelvic ultrasounds were performed.
  
  
  RESULTS
  Four patients were prepubertal (age range 7-10 years old) and had prepubertal gonadotropin levels, and 2 of the 4 who were tested did not respond to LHRH (NIH 10 and RM-PAL). Three patients were Tanner stage 4 (age range 13-17 years old) and had low gonadotropins that did not respond to LHRH stimulation test. All seven patients had marked hyperinsulinaemia and 6 of 7 had at least one enlarged ovary. Testosterone values were increased in 4 of 7 patients.
  
  
  CONCLUSIONS
  This represents the first example of the pathologic role of insulin to stimulate ovarian growth with low circulating gonadotropins. Thus, while ovarian growth and steroidogenesis are normally stimulated by gonadotropins at puberty, hyperinsulinaemia stimulates pathologic growth of the ovary and an androgenic steroid profile that is active at all ages. We suggest that these patients constitute a model to separate the effect of insulin from gonadotropin in stimulating ovarian growth and/or steroidogenesis.
authors.affiliation: Clinical Endocrinology Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892-1770, USA. carlam@intra.niddk.nih.gov
authors.forename: Carla
authors.initials: C
authors.lastname: Musso
authors.forename: Thomas
authors.initials: T
authors.lastname: Shawker
authors.forename: Elaine
authors.initials: E
authors.lastname: Cochran
authors.forename: Edward D
authors.initials: ED
authors.lastname: Javor
authors.forename: Janice
authors.initials: J
authors.lastname: Young
authors.forename: Phillip
authors.initials: P
authors.lastname: Gorden
mesh_terms: D000293:Adolescent; D002096:C-Peptide / Q000097:blood; D002648:Child; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000097:blood / Q000502:physiology; D006062:Gonadotropins / Q000097:blood*; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000031:analogs & derivatives / Q000627:therapeutic use; D008060:Lipodystrophy / Q000097:blood / Q000503:physiopathology; D007986:Luteinizing Hormone / Q000097:blood; D010053:Ovary / Q000000981:diagnostic imaging / Q000254:growth & development*; D011627:Puberty / Q000502:physiology; D013739:Testosterone / Q000097:blood; D014463:Ultrasonography
chemical_list: D002096:C-Peptide; D006062:Gonadotropins; D007328:Insulin; D020738:Leptin; C122136:recombinant methionyl human leptin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone