Dose‐response Relationship in the Treatment of Hypopituitary Children with Human Growth Hormone: a Retrospective Survey
Authors: JOB JEAN‐CLAUDE , CHAUSSAIN JEAN‐LOUIS , GARNIER PHILIPE , ROLLAND ANNE , JOAB NADINE 
Published: January 2008

Job, J.‐C., Chaussain, J.‐L., Garnier, P., Rolland, A. and Joah N. (Hôpital Saint‐Vincent‐de‐Paul, Paris, France). Dose‐response relationship in the treatment of hypopituitary children with human growth hormone: a retrospective survey. Acta Paediatr Scand [Suppl] 337:93, 1987.

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 < 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 hone 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 hut 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 hut much less in the 22 females. Although the least favourable results came from cases with post‐radiotherapy hypopituitaryism, 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 hone 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 he 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 he avoided. The usefulness of increasing doses when the growth rate decreases after 2 years or more of treatment, and the optimal size of dose increase, are still uncertain. At puberty, higher doses could be tried, mainly in females, with the hope of improving the pubertal height gain. Probably an earlier start of treatment in hGH deficient children, and changing the usual frequency of administration from three to six injection/week, would be a better way of improving the final results than using high doses of hGH. Prospective studies must be organized to allow the long‐term evaluation of the dose‐response relationship and the cost‐effectiveness of dose increases.