To elucidate the endocrine mechanisms underlying the pubertal growth failure observed in patients with chronic renal failure (CRF), we used deconvolution analysis to estimate the rates of GH secretion and elimination in nighttime plasma GH profiles of peripubertal boys with CRF and after renal transplantation (Tx). Forty-three boys with advanced CRF (conservative treatment with glomerular filtration rate <25 mL/min · 1.73 m2 or dialysis; CT/D group), 38 boys after Tx, and 40 healthy control boys were studied. The estimated plasma GH half-life (mean ± SEM) was significantly higher (P < 0.05) in CRF (25 ± 1.8 min) than in Tx patients (21 ± 1.6 min) and controls (20 ± 0.5 min). In the pre- and early pubertal CT/D boys, the calculated GH secretion rate was low normal or reduced when expressed in absolute numbers or normalized per unit distribution volume or body surface. In late puberty, whereas body surface-corrected GH secretion was double the prepubertal value in normal boys (389 ± 56 vs. 868 ± 113 μg/m2 · 11 h; P < 0.01), it did not differ significantly from the prepubertal rate in CT/D boys (281 ± 59 vs. 389 ± 56 μg/m2 · 11 h). GH hyposecretion resulted from a decrease in the mass of GH released within each burst, whereas burst frequency was unchanged. In the Tx group, GH secretion rates were significantly reduced in the prepubertal (221 ± 39 μg/m2 · 11 h; P < 0.05) and late pubertal period (266 ± 64 μg/m2 · 11 h; P < 0.01). The mass of hormone secreted per burst was significantly reduced at each pubertal stage, whereas GH secretory burst frequency tended to be increased (significant in prepubertal group, P < 0.05). The GH secretion rate was positively correlated with plasma testosterone levels (r = 0.58; P < 0.0001) in controls, but not in CT/D or Tx patients. GH secretion rates were lower than expected at each level of plasma testosterone in both patient groups except CT/D boys with plasma testosterone below 0.9 nmol/L. In the Tx group, GH secretion rate was positively correlated with relative height (r = 0.31; P < 0.05). The dosage of corticosteroids administered for immunosuppression was negatively correlated with GH burst mass (r = -0.42; P < 0.01) and GH secretion rate (r = -0.29; P = 0.08) and positively correlated with GH burst frequency (r = 0.49; P < 0.01). We conclude that in peripubertal boys with CRF, a state of GH hyposecretion is associated with an increase in the apparent plasma half- life of GH. Boys after Tx exhibit overt hyposomatotropism, which appears to be related to chronic corticosteroid treatment. In both CT/D and Tx patients, GH hyposecretion is most accentuated in late puberty and is inadequate for the prevailing plasma testosterone levels. The failure to increase GH burst mass in response to rising sex steroid levels in late puberty may be a key abnormality in the pathophysiology of pubertal growth failure in boys with CRF and after Tx.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical