The level of bioavailable growth hormone (GH) after the first GH injection predicts the first year’s growth response in GH-deficient children

Abstract

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.

High Serum Levels of Growth Hormone (GH) and Insulin-Like Growth Factor-I (IGF-I) during High-Dose GH Treatment in Short Children Born Small for Gestational Age

“…We found great interindividual variations in mean serum GH levels among the short SGA children in both GH dosage groups. Comparable individual variations in GH levels after sc GH injection have previously been reported in GH-deficient children and were attributed to different mechanisms of the degradation of GH at the site of injection or in the circulation (22). Two children in group A and one child in group B had extremely high GH levels compared with the other children in the groups.…”

Inhaled Growth Hormone (GH) Compared with Subcutaneous GH in Children with GH Deficiency: Pharmacokinetics, Pharmacodynamics, and Safety

“…PK data on injected GH in GHD children are surprisingly sparse (24 -27). One study of only nine prepubertal GHD children found that serum GH levels peaked 4 -6 h after sc administration, returned to baseline values by 12 h, and demonstrated significant variations in peak GH levels (24). A larger study of 25 non-GHD children detected a 4-fold rise in GH levels after injection with return to preinjection levels by 12 h (27).…”

Growth Hormone Immunoreactivity Does Not Reflect Bioactivity

“…A limitation of this assay is that it measures lactogenic, and not somatogenic GH bioactivity. However, lactogenic GH bioactivity, evaluated after s.c. GH administration, shows a good correlation with the growth response during the first year of GH therapy (17), and thus can be used as an indirect measurement of somatogenic activity.…”