Adult growth-hormone deficiency

Authors' reply Sir—We agree with D Devendra and colleagues that the diagnosis of GH deficiency in adults is complex, since several variables affect the outcome of GH-provocative tests. The advantage of the combined administration of GHRH-GHRP-6, which we propose as the new gold standard test for GH reserve in adults, is that in addition to its being devoid of side-effects, it is not affected by age, sex, adiposity, thyroid status, glucocorticoid status, diabetes mellitus, time of day, previous food intake, pretreatment with GH, or the prevous GH basal concentrations.1Casaneuva FF Dieguez C Growth hormone secretagogues, physiological studies and clinical utility.Trends Endocrinol Metab. 1999; 10: 30-38Summary Full Text Full Text PDF PubMed Scopus (151) Google Scholar Moreover, to have a test not affected by the assay used would be a bonus, since the assay is a powerful factor that confuses the diagnosis of GH deficiency. As proof of absence of interaction, the ITT cut-off of 3 ng/mL is valid only for polyclonal antibody-based assays,1Casaneuva FF Dieguez C Growth hormone secretagogues, physiological studies and clinical utility.Trends Endocrinol Metab. 1999; 10: 30-38Summary Full Text Full Text PDF PubMed Scopus (151) Google Scholar which have almost disappeared from current laboratory use. For the most commonly used test, therefore, there is no widely accepted valid cut-off value.2Growth Hormone Research Society (GRS)Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency.Porth Stephens workshop April 1997. J Clin Endocrinol Metab. 1998; 83: 379-381Google Scholar We are aware of the systematic bias introduced in the GH determination by the assay used, and we agree that we have not done a rigorous analysis of how the GH peaks produced by the combined test are altered by different assays, since this analysis was out of the scope of the study. However, in our preliminary data, not included in the report because of space constraints, we found that mean GH peaks in the different assays were similar (figure), although the number of patients in each group was too different to be sure. Second, when we took into account only the values provided by Delfia (timeresolved monoclonal-antibody-based fluoroimmunoassay), the result was identical. These data suggest that the noise introduced by use of seven different assays in the same study was not intense enough to alter the identification of healthy patients and those with GH deficiency. GHRH-GHRP-6 test does not act at the pituitary level. Although GH seretagogues were developed by their in-vitro GH-releasing capabilities, overwhelming evidence shows that compounds such as GHRP-6 and the combined GHRH-GHRP-6 act mainly at the hypothalamus.1Casaneuva FF Dieguez C Growth hormone secretagogues, physiological studies and clinical utility.Trends Endocrinol Metab. 1999; 10: 30-38Summary Full Text Full Text PDF PubMed Scopus (151) Google Scholar We, along with other groups, have reported that any organic alteration in the hypothalmus, the pituitary stalk, or the pituitary, blunts GHRH-GHRP-6-mediated GH release.3Popuvic V Damjanovic S Micic D et al.Blocked growth hormone-releasing peptide (GHRP-6)-induced GH secretion and absence of the synergic action of GHRP-6 plus GH-releasing hormone in patients with hypothalamopituitary disconnection: evidence that GHRP-6 main action is exerted at the hypothalmic level.J Clin Endocrinol Metab. 1995; 80: 942-947PubMed Google Scholar Therefore, the test explores the whole hypothalamopituitary unit, as does the ITT, identifying any organic or structural alteration. The efficacy of the test in the so-called functional, non-organic or idiopathic GH deficiencies has not yet been assessed. However, several groups agree that this syndrome, which is fairly rare in adults, is debatable or at least poorly defined. The GHRH-GHRP-6 test is scarcely affected by the GH assay used and detects organic lesions located at any level of the hypothalamopituitary somatotrope axis. We eagerly await the experience of other groups with this test in the clinical setting. Adult growth-hormone deficiencyV Popovic and colleagues (Sept 30, p 1137)1 claim to show a reliable test for adult growth-hormone (GH) deficiency and underscore inconsistencies in measuring insulin-like growth factor (IGF)-1, IGF binding protein 3 (IGFBP3), and a 24 h GH measurement in these patients.2 Full-Text PDF