Mechanism of constitutional growth delay

University Of Michigan At Ann Arbor, Ann Arbor MI

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Abstract

At least 25% of all children referred to pediatric endocrinologists with growth concerns have constitutional growth delay (CGD). Children with CGD have appropriate growth through early infancy, exhibit a marked deceleration in growth velocity between 6 to 9 months and 3 years of age, grow at a normal velocity in the mid childhood years despite their relative short stature, and have delayed onset of pubertal development. These children often achieve a normal final height but have short stature during childhood compared to age-matched peers. The purpose of this research is to determine why growth deceleration occurs in constitutional growth delay (CGD) during infancy. Since adolescents with CGD respond well to sex steroid treatment and since delay in adolescent development is a prominent part of CGD, we hypothesize that an early onset of quiescence of the reproductive axis in infancy results in premature reduction of sex steroid concentrations and slow growth. To test this hypothesis we will relate gonadotropin-releasing hormone agonist (GnRHa) stimulation of gonadotropin and sex steroid concentrations to stimulated GH concentrations in normally growing infant girls and in girls with slow growth. In this pilot study 3 girls with precocious thelarche and 3 girls with growth deceleration between the ages of 6 months and 3 years will be studied. All girls will have determination of gonadotropin secretion in response to the GnRH analogue, Lupron, with serial blood sampling for LH, FSH, and estradiol for 24 h following administration. All girls will also have determination of GH response to clonidine before and during Lupron therapy. Lupron should increase estradiol concentrations thereby increasing GH release in response to clonidine. The relative difference in GH release with Lupron therapy may prove useful in differentiating CGD to GH deficiency. The GH response to clonidine after Lupron will be expected to be greater in children with CGD than in children with GH deficiency. In addition, to examine the role of early decrease of gonadotropin secretion in children with CGD, the gonadotropin and GH responses will be correlated in the girls with CGD and the girls with precocious thelarche. It is expected that girls with precocious thelarche will have greater GH and gonadotropin responses to stimulation than will girls with CGD. A better understanding of why CGD occurs should facilitate diagnosis and reassurance of family.