title: Effect of thyroxine replacement on serum IGF-I, IGFBP-3 and the acid-labile subunit in patients with hypothyroidism and hypopituitarism.
abstract: OBJECTIVE
  To describe the effect of T4 replacement in patients with primary and central hypothyroidism on components of the IGF binding protein complex: IGF-I, the acid-labile subunit (ALS) and IGFBP-3.
  
  
  METHODS
  We determined IGF-I, ALS and IGFBP-3 (by 125I-IGF-II ligand blots and immunoblots) in serum of 19 patients with primary and 11 patients with central hypothyroidism.
  
  
  RESULTS
  Mean (+/- SD) free T4 (fT4) increased from 4.4 +/- 2.4 pmol/l at baseline to 18.6 +/- 5.2 pmol/l following T4 therapy. In patients with primary hypothyroidism, IGF-I concentrations increased from 101 +/- 57 to 158 +/- 60 microg/l (P < 0.001) and ALS from 12.6 +/- 4.7 to 15.6 +/- 5.2 mg/l (P = 0.001). IGFBP-3 levels (in arbitrary units, AU), assessed by 125I-IGF-II ligand blot and by Western blot (the intensity of the 45/42-kDa doublet following T4 replacement defined as 1 AU) increased from 0.74 +/- 0.47 to 1 (P = 0.029) and from 0.76 +/- 0.42 to 1 (P = 0.018), respectively. In patients with hypopituitarism, IGF-I and ALS concentrations increased on T4 therapy from 49 +/- 23 to 97 +/- 36 microg/l (P < 0.001) and from 7.8 +/- 4.1 to 11.0 +/- 2.7 mg/l (P = 0.010), respectively. IGFBP-3 remained unchanged during T4 replacement.
  
  
  CONCLUSIONS
  T4 replacement increases the serum levels of IGF-I and ALS in patients with primary as well as central hypothyroidism. IGFBP-3 levels increase in response to T4 replacement in patients with primary hypothyroidism but not in those with central hypothyroidism, suggesting that thyroid hormones increase IGF-I and ALS but not IGFBP-3 in patients with GH deficiency.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital of Zürich, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmid
authors.forename: Cornelia
authors.initials: C
authors.lastname: Zwimpfer
authors.forename: Michael
authors.initials: M
authors.lastname: Brändle
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Krayenbühl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Zapf
authors.forename: Peter
authors.initials: P
authors.lastname: Wiesli
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000150:complications / Q000188:drug therapy; D000328:Adult; D001327:Autoimmune Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy; D002352:Carrier Proteins / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D007018:Hypopituitarism / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D007037:Hypothyroidism / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D015151:Immunoblotting; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008107:Liver Diseases / Q000097:blood / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011863:Radioimmunoassay; D011869:Radioligand Assay; D018709:Statistics, Nonparametric; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use*
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I; D013972:Thyrotropin; D013006:Growth Hormone; D013974:Thyroxine