The aim of the study was to evaluate serum acid-labile subunit (ALS) concentrations and their relationship with other parameters of the human ternary IGF-I-binding protein (IGFBP) complex in girls with central precocious puberty (CPP) before and after pharmacological arrest of puberty. We studied serum ALS, free IGF-I, total IGF-I, IGFBP-3 levels and IGFBP-3 protease activity in 13 girls, aged 1.6-7.8 yr (mean, 5.9 +/- 2.2), diagnosed as having CPP before and after 6 and 12 months of GnRH analog (GnRHa) therapy. The ALS SD score before treatment was high (1.4 +/- 0.72) and decreased significantly after 6 and 12 months of GnRHa therapy [0.4 +/- 0.54 (P < 0.01) and -0.4 +/- 0.61 (P < 0.01), respectively]. Serum IGF-I and IGFBP-3 were also increased before treatment, but both of these factors remained elevated after 6 and 12 months of GnRH-A therapy [IGF-I SD score, 3.20 +/- 1.64, 2.92 +/- 1.82, and 3.68 +/- 1.94 (P = NS), respectively; IGFBP-3 SD score, 1.02 +/- 0.53, 0.94 +/- 0.68, and 1.22 +/- 0.87 (P = NS), respectively]. Serum free IGF-I levels and IGFBP-3 proteolytic activity did not vary significantly from their pretreatment values during GnRHa therapy. In conclusion, serum ALS levels were elevated in girls with CPP and decreased significantly during the first year of GnRHa therapy. Serum IGF-I and IGFBP-3 levels were also increased before therapy, but their levels were not influenced by treatment. The ALS decrease seems to be the sole GH-dependent factor that parallels the decreases in steroid levels and growth velocity during GnRHa therapy.

Serum GH levels were measured in 9 prepubertal children with growth hormone (GH) deficiency using an immunofluorometric assay (IFMA) and a Nb2 cell bioassay, prior to and 2, 4, 6 and 12 hours after the first hGH subcutaneous injection (sc) (0.1 IU/Kg). After this first acute phase, hGH treatment was continued regularly at a dose of 0.1 IU/kg per day at bedtime. The acute pharmacokinetic profile was similar in the patients irrespectively of the assay used: serum GH usually starts to rise after 2 hours, peaks by 4 or 6 hours and drops back to near baseline levels 12 hours after s.c. GH administration. A great variation in the amplitude of peak levels was observed among the patients. The assays significantly (p<0.0001) correlate with each other in all subjects. An increase in serum GH values as evaluated by the Nb2 bioassay was observed in most children after s.c. GH injection, suggesting that the administered hormone preserves its biological activity. The individual variations in GH bioactivity in our GH-deficient children could be due to different mechanisms of the drug's degradation at the site of injection or in circulation. Pre-treatment height velocity calculated as standard deviation scores (SDS) significantly increased (p<0.001) from -2.77+/-0.42 to 1.22+/-0.87 SDS after a 12-month period of GH treatment in 8 patients who had already completed the first year of therapy, although it varied considerably among subjects. A higher serum GH peak value evaluated by both assays corresponded to a higher growth response during the 1st year, but not in the 2nd year of GH therapy. In conclusion, the degree of GH bioactivity released into circulation after sc GH injection may vary considerably among GHD patients and correlates with the growth response observed during the 1st year of GH therapy.