Dose-response relationship in the treatment of hypopituitary children with human growth hormone: a retrospective survey.

Abstract

During the past 15 years, dose-response studies of hGH have been limited to prepubertal patients with complete somatotrophic deficiency, who have usually been treated with hGH three times/week within a dose range of 10-40 IU/kg/year. In such studies a weak positive correlation has been found (r = 0.429, p less than 0.001) with marked important individual variations. Very few or no data have been published regarding the dose-response relationship after the first year of hGH treatment, or when the dose is increased because the growth rate is waning, or during puberty. The present paper reports some data on these issues. A group of 32 young hGH deficient children, whose bone age was 0-4 years, was followed up for at least 3 years with hGH given intramuscularly three times weekly at doses of 12-48 IU/kg/year (mean, 25 +/- 9 IU/kg/year - i.e. approximately 0.15 IU/kg/injection). A dose-response relationship existed during the first year but not during the following 2 years nor for the height gain obtained at the end of the third year of treatment. The results of an increase of the dose of hGH by 33-66% in 13 prepubertal hGH deficient children whose growth rate had decreased after 2-5 years of treatment were fair in 6, limited in 4 and absent in 3, and did not relate to the extent of dose increase. However, this series is too small to allow definite conclusions. The growth rate of 67 adolescents with complete hGH deficiency and normal spontaneous puberty was close to the normal mean in the 45 males but much less in the 22 females. Although the least favourable results came from cases with post-radiotherapy hypopituitarism, the mean total pubertal growth spurt in patients with idiopathic hGH deficiency was also below the average, mainly in the girls, and with a large range of individual variation. An important fact was that bone age increased more than height age or chronological age in these hypopituitary pubertal patients. No dose-response relationship was found in this group, within a limited range of doses (40 patients receiving 16-20 IU/kg/year injected three times weekly, 19 receiving less than 16 IU/kg/year and 8 receiving more than 20 IU/kg/year). It may be concluded that in prepubertal hypopituitary children, hGH at a dose of approximately 20 IU/kg/year at the onset of treatment is probably appropriate. The lack of a dose-response relationship after the first year of treatment suggests that higher initial doses should be avoided.(ABSTRACT TRUNCATED AT 400 WORDS)