Retesting the childhood-onset GH-deficient patient

Abstract

GH deficiency (GHD) in adults has to be shown by a single provocative test, provided that it is validated. Insulin tolerance test (ITT) has been indicated as the test of choice; now also glucagon test is validated and represents an alternative. The GHRH plus arginine (ARG) test and testing with GHRH plus a GH secretagogue are equally reliable diagnostic tools, and are now considered as 'golden' standards as ITT. Childhood-onset (CO) GHD needs retesting in late adolescence or young adulthood; this is a major clinical challenge and raises questions about the most appropriate method and cut-off value. Appropriate re-evaluation of GH status is represented by simple measurement of IGF1 concentration off rhGH treatment. Clearly, low IGF1 levels are evidence of persistent severe GHD in subjects with genetic GHD or panhypopituitarism. However, normal IGF1 levels never rule out severe GHD and CO-GHD with normal IGF1 levels must undergo a provocative test. The appropriate GH cut-off limit is specific for each provocative test. As shown by the ROC curve analysis, in late adolescents and young adults, the lowest normal GH peak response to ITT is 6.1 mg/l while that to GHRHCARG test is 19.0 mg/l. These cut-off limits, however, are just indicative as being variable as a function of the assay used. No other test is validated for retesting. As GHRHCARG test mostly explores the GH-releasable pool, normal GH response would be verified by a second ITT in order to rule out subtle hypothalamic defect. European Journal of Endocrinology 159 S45-S52

Częstość i czynniki prognostyczne trwałego niedoboru hormonu wzrostu u pacjentów z rozpoznaną w dzieciństwie izolowaną somatotropinową niedoczynnością przysadki

“…Similar was the statement of Quigley et al [8] who performed a single GH stimulation test to reassess the patients with multiple pituitary hormone deficiency, and two tests to confirm persistent isolated GHD. Moreover, our findings point at the possibility of using the test with clonidine in transition period, although that test has not been recommended in adults [6,9,17]. It seems worth mentioning that -in our study -almost half of the patients with decreased GH peak in ITT had a normal GH peak in the test with clonidine.…”

“…According to the current recommendations [1,3,6,17], in order to confirm GHD after the completion of growth-promoting therapy, it is sufficient to prove decreased GH peak in only one stimulation test. However, it has also been recently suggested that two stimulation tests should be used in order to diagnose isolated GHD in adults (due to a significant falsepositive error rate in GH response in a single test) [7].…”

“…Nevertheless, in current recommendations, the statement that -in adults -normal IGF-I concentration does not exclude GHD has been strongly emphasised [1,3,[6][7][8][9], as an overlap in IGF-I levels between patients with GHD and normal controls has been reported [2]. On the other hand, it has been suggested in the same studies [2,7,9] that a very low IGF-I concentration might be diagnostic of GHD in the transition phase.…”

Growth Hormone Deficiency and Lysinuric Protein Intolerance: Case Report and Review of the Literature

“…Niinikoski et al (2011) observed in four LPI children very low IGF-1 concentrations (5-13 nmol/L), despite arginineinsulin GH provocative test revealed an abnormal GH peak level (< 10 ug/L) in only one of the patients. Nevertheless, a normal GH response to provocative tests in patients with auxology suggestive of GHD does not definitively rule out GHD because they may have a low spontaneous GH secretion over 24 h, likely reflecting GH neurosecretory dysfunction (Gasco et al 2008). Moreover, today, there is no gold standard for estimating GH secretion in LPI Reference range is also indicated Reference range is also indicated patients.…”

Growth hormone deficiency: diagnosis and therapy in children

“…Serum samples for the GH analysis are obtained at 0, 15, 30, 45, 60, 90 and 120 minutes. The cut-of for this test is 20 ng/ml for the GH peak in childhood and 19.0 ng/ml in late adolescent and early adulthood [43]. Furthermore, the GHRH plus arginine test is useful for identifying false positive GHD in children showing a blunted GH response to classic stimuli in contrast with a normal growth rate [44].…”