Monitoring of growth hormone replacement therapy in adults, based on measurement of serum markers

被引:138
作者
deBoer, H
Blok, GJ
PoppSnijders, C
Stuurman, L
Baxter, RC
vanderVeen, E
机构
[1] FREE UNIV AMSTERDAM HOSP, DEPT CLIN CHEM, AMSTERDAM, NETHERLANDS
[2] ROYAL N SHORE HOSP, KOLLING INST MED RES, ST LEONARDS, NSW 2065, AUSTRALIA
关键词
D O I
10.1210/jc.81.4.1371
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The optimal dose for GH replacement therapy in GH-deficient (GHD) adults is not known, nor is there a consensus as to which method is the most appropriate for the monitoring of treatment. To establish a general guideline for GH replacement therapy in adults, we evaluated the relationship between the administered GH dose and the achieved serum levels of three GH-dependent serum markers. Serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and the acid-labile subunit (ALS) were measured in 46 GKD men participating in a 1-yr, double blind, and placebo-controlled dose-response study. The doses of recombinant human GH ranged from 0.33-3.0 IU/m(2) . day. During GH treatment, dose reduction was necessary because of side-effects in 18 of 46 patients, i.e. in 18% of the patients receiving a maintenance dose of 1 IU/m(2) . day, in 35% of the patients receiving a dose of 2 IU/m(2) . day, and in 67% of the patients receiving a dose of 3 IU/m(2) . day. In the untreated state, serum levels of all three markers were below the normal range in 90% of the patients. The rise in serum marker concentrations during the first month of treatment was dose dependent. Significant increases in IGF-I, IGFBP-3, and ALS levels were observed with a dose as low as 0.33 IU/m2 . day. The minimal GH dose required for normalization of the serum IGF-I concentration was 0.66 IU/m(2) . day, and it was 1.0 IU/m(2) . day for ALS and IGFBP-3. In patients receiving 2.0 IU/m(2) . day, the mean serum IGF-I concentration rose to an abnormally high level, whereas at this dose, the mean IGFBP-3 and ALS levels were not different from normal. The lower sensitivity of IGFBP-3 and ALS to GH doses in the high range was also apparent during long term treatment. The number of patients who developed IGFBP-3 or ALS levels that exceeded the upper normal limit was substantially smaller than the number of patients with elevated IGF-I concentrations (2, 8, and 19 of 46 patients, respectively). In conclusion, serum IGF-I appears to be the preferred biochemical marker for the detection of GH excess in adults receiving GH replacement therapy, because it is more sensitive than IGFBP-3 and ALS to GH doses in the high range. If normalization of the serum IGF-I concentration is taken as the criterion for optimal GH replacement therapy, the predicted optimal GH dose for GHD men 20-40 yr old is 1.4 IU/m(2) . day, and the 95% confidence interval is 1.2-1.6 IU/m(2) . day.
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页码:1371 / 1377
页数:7
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