Growth of Short Normal Children in Puberty Treated for 3 Years with Growth Hormone Alone or in Association with Gonadotropin-Releasing Hormone Agonist

Abstract

GH, 0.1 IU/kg/day 6 days/week, was given to 30 early pubertal short patients for 3 years. There were 16 males, aged 14.4 ± 0.8 years, and 14 females, aged 12.2 ± 1.2 years, at pubertal stage 2 or 3 with slow growth (4.2 ± 1.2 cm/year) and no detected GH insufficiency or other cause for short stature. They were randomized in 2 groups: group A with GH alone, and group B with GH and a gonadotropin-releasing hormone agonist during the first 2 years. 28 of the 30 patients completed 3 years of treatment. The annual growth rate increased during the 1st year in both groups and sexes, the increase being significant (p < 0.01) in group A only. Patients of group A kept an improved growth velocity in the 2nd year, then returned to pretreatment growth rate in the 3rd year, while completing their sexual development and bone maturation. Their height, expressed as standard deviation score (SDS) for bone age, improved in the first 2 years, but decreased thereafter. Group B patients returned to pretreatment growth velocity in the 2nd year, and had no significant improvement in growth rate in the 3rd year with GH alone. Their bone maturation, slow when on the GnRH agonist, accelerated when sexual development resumed. At the end of the 3 years, height, expressed as SDS for age, improved in group A from -2.5 ± 0.6 to -1.5 ± 0.4 in males (p < 0.05) and from -2.8 ± 0.5 to -2.1 ± 0.9 in females (NS). In group B there was no significant progress in height for age at any time. Mean height SDS for bone age slightly improved in males (NS) but not in females. In both groups, the mean predicted height according to Bayley and Pinneau was slightly, nonsignificantly increased at the end of 3 years on GH, with a gain of 2-5 cm on average, depending on the group. There was a wide interindividual variability in these results within each group. Looking for possible correlations of results with pretreatment characteristics of the patients did not account for such differences. The only correlations found were within group A, one negative between total height gain in 3 years and the patient’s height at the onset of treatment, and one positive between growth rates in years 2-3 and year 1 of the study. The annual measurement of plasma IGF₁ showed different degrees of increase, not correlated with the growth changes. The most certain conclusion of this study is that inhibiting sexual development in constitutionally short pubertal subjects has no advantage and must be avoided. The other possible conclusion is that GH alone can accelerate growth for 2 years, and slightly improve the predicted height in relation to the result of the first year of treatment. The expected results cannot be overestimated. The present data cannot be considered as an opening for the possible routine use of GH in endocrinologically normal short adolescents.

IGF-I, IGFBP-2 and -3 but not GH concentrations are different in normal and poor growing piglets

“…This hypothesis is still controversial; some authors [24] reported that GH deficiency does not appear to explain normally occurring short stature in children and studies using high and /or prolonged dosages of GH do not suggest a problem with limited endogenous GH in the young pig [10,16]. On the other hand, several studies proposed a GH involvement in cause and therapy of slow growth [11,18,20,23]. In farm animals the diagnostic trials applied to the identification of GHD are even much more limited by factors like breed, management and social or behavioural stress.…”

Catch-up growth after prolonged hypothyroidism

“…This approach of gonadal suppression in combination with growth hormone therapy in order to improve final height is sometimes also applied in conditions such as idiopathic short stature [6,14], idio pathic growth hormone deficiency [5,17] and precocious puberty [10,15]. It is tempting to speculate that the out come of catch-up growth in the first three of the herein described patients might have been better if they had been treated according to this new therapeutic strategy.…”

A Randomized Controlled Trial of Three Years Growth Hormone and Gonadotropin-Releasing Hormone Agonist Treatment in Children with Idiopathic Short Stature and Intrauterine Growth Retardation

“…The study population, however, was very heterogeneous, and, therefore, the results are difficult to interpret (12). More recent studies, using the combined treatment of GH and GnRHa in children with ISS or IUGR, report a gain in final height prediction between Ϫ0.5 to 10 cm (1,(13)(14)(15)(16)(17), but none of these studies used randomized controls.…”