The Wide Variation in Urinary Excretion of Human Growth Hormone in Normal Growing and Growth Hormone-Deficient Children Limits Its Clinical Usefulness

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Abstract
We measured urinary growth hormone (U-GH) excretion to estimate the spontaneous growth hormone (GH) production in normal children according to age, sex, height, body mass index, serum insulin-like growth factor-1 (IGF-1), and pubertal status. To assess the clinical usefulness of this parameter, U-GH excretion measurements were obtained in children with GH deficiency (GHD). One hundred and forty-nine prepubertal and 105 pubertal (Tanner stage 2-5) normal children, aged 3-17 years, were studied. They had heights and weights within 2 SD of age-corresponding normal measures. Two consecutive 24-hour urine collections were performed for all of them. Blood sampling for IGF-1 measurement was performed for 54 consented normal subjects. Forty-one children aged 1.8-13.8 years with classical GHD with at least two subnormal GH responses to provocative test were also evaluated. Nocturnal serum GH profile was also performed in 26 of them. GHD children were investigated for U-GH excretion just before human GH therapy. U-GH was measured by a two-step immunoradiometric method that we have developed using two monoclonal antibodies. Despite a wide intra- and interindividual variation, no difference was found related to age or sex in prepubertal normal children. U-GH excretion values were significantly dependent on the pubertal stage with 3.4-fold increased values compared to prepubertal stage in both sexes. In normal children, the U-GH excretion was related to serum IGF-1 values, but no relation was found with the height or the body mass index expressed as standard deviation score. U-GH excretion values were significantly lower in GHD children compared to those with normal stature (p < 0.0001) with an overlap between the two groups. No relation was found between the physiological GH concentration by serum measurement and urinary excretion in children diagnosed as GHD by the pharmacological GH test. In conclusion, U-GH excretion determination offers an evaluation of the endogenous growth hormone secretion. Unfortunately, the wide variation of U-GH excretion makes this measurement unreliable for individual assessment of GH secretion. Therefore, it is not a real alternative to GH stimulation testing.

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