Pulsatile, nyctohemeral and entropic characteristics of GH secretion in adult GH-deficient patients: Selectively decreased pulsatile release and increased secretory disorderliness with preservation of diurnal timing and gender distinctions

Ferdinand Roelfsema, Nienke R. Biermasz, Johannes D. Veldhuis

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

INTRODUCTION: The present clinical investigation uses a high-precision GH immunofluorometric assay to examine the postulate that principally the amplitude mode of GH secretory control is disrupted in adults with GH deficiency. PATIENTS AND METHODS: To this end, we investigated GH secretory dynamics in a cohort of 19 adult GH-deficient (GHD) patients and 19 age-, gender- and body mass index-matched controls. GHD was established by blunted (< 7 mU/l) GH release during insulin-induced hypoglycaemia. Twenty-four-hour serum GH concentration profiles obtained by 10-min sampling were analysed by deconvolution, cosinor analysis and approximate entropy to appraise pulsatile, diurnally rhythmic, and pattern-dependent GH secretion, respectively. RESULTS: Deconvolution analysis revealed that pulsatile GH release was decreased by threefold, due to amplitude-specific damping, detectable GH secretory burst frequency was paradoxically increased by twofold, but basal non-pulsatile GH release was fully preserved. GH half-life in patients and controls was similar, thus excluding major kinetic differences. The acrophase (time of maximum) of the 24-h GH rhythm was unchanged. The regularity of the GH release process, as measured by ApEn, was decreased profoundly in GHD patients (P < 10-8). The changes in GH secretion were similar in irradiated and nonirradiated patients. Daily GH secretion was also comparable in male and female GHD patients, but plasma IGF-I concentrations were higher in male than female patients (P = 0.031). Furthermore, the gender-specific GH ApEn difference, evident in controls, was still demonstrable in patients (P = 0.017). The ratio of plasma IGF-I and pulsatile GH production was increased threefold in patients (P = 0.004), pointing to increased sensitivity to GH in GH deficiency and/or non-GH-dependent IGF-I production. CONCLUSIONS: The present detailed analyses of daily GH secretory dynamics in patients with (moderate) GH deficiency document an amplitude-specific decrease in pulsatile GH secretion, which is partly compensated for by increased GH pulse frequency. The remarkably disorderly patterns of GH secretion in patients identify other major alterations in GH neuroregulation in such individuals, reflecting withdrawal of expected GH and/or IGF-I repression of pulsatile GH secretion. Preservation of the nyctohemeral timing of GH release and the gender contrast in GH ApEn in GHD patients would also be consistent with partial retention of central neuroregulation and GH/IGF-I feedback-dependent control in hypopituitary subjects.

Original languageEnglish (US)
Pages (from-to)79-87
Number of pages9
JournalClinical Endocrinology
Volume56
Issue number1
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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