ALTERATIONS IN GROWTH-HORMONE SECRETION AND CLEARANCE IN PERIPUBERTALBOYS WITH CHRONIC-RENAL-FAILURE AND AFTER RENAL-TRANSPLANTATION

To elucidate the endocrine mechanisms underlying the pubertal growth f ailure observed in patients with chronic renal failure (CRF), we used deconvolution analysis to estimate the rates of GH secretion and elimi nation in nighttime plasma GH profiles of peripubertal boys with CRF a nd after renal transplantation (Tx). Forty-three boys with advanced CR F (conservative treatment with glomerular filtration rate <25 mL/min.1 .73 m(2) or dialysis; CT/D group), 38 boys after Tx, and 40 healthy co ntrol boys were studied. The estimated plasma GH half-life (mean +/- S EM) was significantly higher (P < 0.05) in CRF (25 +/- 1.8 min) than i n Tx patients (21 +/- 1.6 min) and controls (20 +/- 0.5 min). In the p re- and early pubertal CT/D boys, the calculated GH secretion rate was low normal or reduced when expressed in absolute numbers or normalize d per unit distribution volume or body surface. In late puberty, where as body surface-corrected GH secretion was double the prepubertal valu e in normal boys (389 +/- 56 vs. 868 +/- 113 mu g/m(2).11 h; P < 0.01) , it did not differ significantly from the prepubertal rate in CT/D bo ys (281 +/- 59 vs. 389 +/- 56 mu g/m(2).11 h). GH hyposecretion result ed from a decrease in the mass of GH released within each burst, where as burst frequency was unchanged. In the Tx group, GH secretion rates were significantly reduced in the prepubertal (221 +/- 39 mu g/m(2).11 h; P < 0.05) and late pubertal period (266 +/- 64 mu g/m(2).11 h; P < 0.01). The mass of hormone secreted per burst was significantly reduc ed 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 leve ls (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 t estosterone in both patient groups except CT/D boys with plasma testos terone below 0.9 nmol/L. In the Tx group, GH secretion rate was positi vely correlated with relative height (r = 0.31; P < 0.05). The dosage of corticosteroids administered for immunosuppression was negatively c orrelated with GH burst mass (r = -0.42; P < 0.01) and GH secretion ra te (r = -0.29; P = 0.08) and positively correlated with GH burst frequ ency (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 hyposoma totropism, which appears to be related to chronic corticosteroid treat ment. In both CT/D and Tx patients, GH hyposecretion is most accentuat ed in late puberty and is inadequate for the prevailing plasma testost erone levels. The failure to increase GH burst mass in response to ris ing 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.