Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation

Franz Schaefer, Johannes D Veldhuis, Richard Stanhope, Jenny Jones, Karl Schärer, G. Offner, T. M. Barratt, G. Hamill, S. Lederman, R. S. Trompeter, F. Perfumo, L. Rees, R. N. Fine, S. Rigden, D. Geary, R. Postlethwaithe, D. Michalk, S. Devaux, R. M. Blizzard, A. D. RogolP. M. Martha

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1298-1306
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume78
Issue number6
DOIs
StatePublished - Jun 1994
Externally publishedYes

Fingerprint

Kidney Transplantation
Growth Hormone
Chronic Kidney Failure
Plasmas
Testosterone
Puberty
Adrenal Cortex Hormones
Dialysis
Half-Life
Deconvolution
Steroids
Hormones
Growth
Glomerular Filtration Rate
Scanning electron microscopy
Immunosuppression
Reference Values

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation. / Schaefer, Franz; Veldhuis, Johannes D; Stanhope, Richard; Jones, Jenny; Schärer, Karl; Offner, G.; Barratt, T. M.; Hamill, G.; Lederman, S.; Trompeter, R. S.; Perfumo, F.; Rees, L.; Fine, R. N.; Rigden, S.; Geary, D.; Postlethwaithe, R.; Michalk, D.; Devaux, S.; Blizzard, R. M.; Rogol, A. D.; Martha, P. M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 78, No. 6, 06.1994, p. 1298-1306.

Research output: Contribution to journalArticle

Schaefer, F, Veldhuis, JD, Stanhope, R, Jones, J, Schärer, K, Offner, G, Barratt, TM, Hamill, G, Lederman, S, Trompeter, RS, Perfumo, F, Rees, L, Fine, RN, Rigden, S, Geary, D, Postlethwaithe, R, Michalk, D, Devaux, S, Blizzard, RM, Rogol, AD & Martha, PM 1994, 'Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation', Journal of Clinical Endocrinology and Metabolism, vol. 78, no. 6, pp. 1298-1306. https://doi.org/10.1210/jc.78.6.1298
Schaefer, Franz ; Veldhuis, Johannes D ; Stanhope, Richard ; Jones, Jenny ; Schärer, Karl ; Offner, G. ; Barratt, T. M. ; Hamill, G. ; Lederman, S. ; Trompeter, R. S. ; Perfumo, F. ; Rees, L. ; Fine, R. N. ; Rigden, S. ; Geary, D. ; Postlethwaithe, R. ; Michalk, D. ; Devaux, S. ; Blizzard, R. M. ; Rogol, A. D. ; Martha, P. M. / Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation. In: Journal of Clinical Endocrinology and Metabolism. 1994 ; Vol. 78, No. 6. pp. 1298-1306.
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abstract = "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.",
author = "Franz Schaefer and Veldhuis, {Johannes D} and Richard Stanhope and Jenny Jones and Karl Sch{\"a}rer and G. Offner and Barratt, {T. M.} and G. Hamill and S. Lederman and Trompeter, {R. S.} and F. Perfumo and L. Rees and Fine, {R. N.} and S. Rigden and D. Geary and R. Postlethwaithe and D. Michalk and S. Devaux and Blizzard, {R. M.} and Rogol, {A. D.} and Martha, {P. M.}",
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T1 - Alterations in growth hormone secretion and clearance in peripubertal boys with chronic renal failure and after renal transplantation

AU - Schaefer, Franz

AU - Veldhuis, Johannes D

AU - Stanhope, Richard

AU - Jones, Jenny

AU - Schärer, Karl

AU - Offner, G.

AU - Barratt, T. M.

AU - Hamill, G.

AU - Lederman, S.

AU - Trompeter, R. S.

AU - Perfumo, F.

AU - Rees, L.

AU - Fine, R. N.

AU - Rigden, S.

AU - Geary, D.

AU - Postlethwaithe, R.

AU - Michalk, D.

AU - Devaux, S.

AU - Blizzard, R. M.

AU - Rogol, A. D.

AU - Martha, P. M.

PY - 1994/6

Y1 - 1994/6

N2 - 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.

AB - 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.

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