Effect of thyroxine replacement on serum IGF-I, IGFBP-3 and the acid-labile subunit in patients with hypothyroidism and hypopituitarism.
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.
Schmid
Christoph
C
Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital of Zürich, Switzerland.
Zwimpfer
Cornelia
C
Brändle
Michael
M
Krayenbühl
Pierre-Alexandre
PA
Zapf
Jürgen
J
Wiesli
Peter
P
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*
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