Cut-off limits of the GH response to GHRH plus arginine test and IGF-I levels for the diagnosis of GH deficiency in late adolescents and young adults

Corneli, G.; Somma, Carolina Di; Prodam, Flavia; Bellone, J.; Bellone, Simonetta; Gasco, Valentina; Baldelli, Roberto; Rovere, Silvia; Schneider, Harald J.; Gargantini, L; Gastaldi, Roberto; Ghizzoni, Lucia; Valle, Domenico; Salerno, Mariacarolina; Colao, Annamaria; Bona, Gianni; Ghigo, Ezio; Maghnie, Mohamad; Aimaretti, Gianluca

doi:10.1530/eje-07-0384

Cited by 75 publications

(46 citation statements)

References 40 publications

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“…Thus, it should now be recognized that in late adolescent and early adulthood patients, a GH cut-off limit using the GHRHCARG test lower than 19.0 mg/l is able to distinguish between GHD and normal subjects. Interestingly, as anticipated by previous studies (29), the GH response to this test does not substantially vary from infancy to early adulthood.…”

Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younsupporting

confidence: 85%

“…On the other hand, the appropriate diagnostic cut-off limits for testing the GH response to GHRHCARG in the transition period have been defined very recently (29). For this maximal provocative test, the best pair of the highest Se (100%) and Sp (97%) was found choosing a peak GH of 19.0 mg/l (Fig.…”

Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younmentioning

confidence: 99%

“…Again, it has to be considered that the cut-off limits for provocative tests (either GHRHCARG or ITT) in the transition adolescent have been defined in lean subjects only; as anticipated, it would be preferable that these tests are validated also as a function of overweight and obesity (2,4,29).…”

Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younmentioning

confidence: 99%

“…Figure 2 Individual peak GH responses to both GHRHCARG and ITT tests in patients with a paediatric diagnosis of organic multiple hypopituitarism (nZ21) (left panel) and in patients with a paediatric diagnosis of isolated GHD (nZ47) (right panel). Dotted lines represent limits of normal GH response to GHRHCARG and ITT in the transition phase (28,29). Figure 3 Individual GH peak after GHRHC ARG test in subjects who had been treated with GH in childhood as having organic (defined as GH peak !10 mg/l after two classical tests and organic lesion on MRI) (left) or idiopathic (defined as GH peak !10 mg/l after two classical tests but without organic lesion on MRI) (middle) or GH neurosecretory dysfunction (defined as GH peak O10 mg/l after two classical tests but mean GH concentration over 24 h !3 mg/l) (right).…”

Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younmentioning

confidence: 99%

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Retesting the childhood-onset GH-deficient patient

Gasco¹,

Corneli

Beccuti³

et al. 2008

European Journal of Endocrinology

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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

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Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younsupporting

confidence: 85%

Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younmentioning

confidence: 99%

Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younmentioning

confidence: 99%

Section: Diagnosis Of Ghd In the Transition Period Adolescent-to-younmentioning

confidence: 99%

See 2 more Smart Citations

Retesting the childhood-onset GH-deficient patient

Gasco¹,

Corneli

Beccuti³

et al. 2008

European Journal of Endocrinology

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“…Following the publication of several validation studies 12,[15][16][17] and recommendations from current consensus guidelines, [7][8][9]11 the GHRH-ARG test was accepted as the most reliable alternative GH stimulation test to the ITT in diagnosing adult GHD. However, when EMD Serono, Inc decided to discontinue the manufacture of recombinant GHRH (Geref ® ) in the US 13 This analysis revealed striking regional variations in the approach to GH stimulation testing.…”

Section: Historical Perspective Of the Use Of Glucagon Stimulation Tementioning

confidence: 99%

Glucagon Stimulation Testing in Adult Growth Hormone Deficiency A 2014 Update

Yuen

2014

US Endocrinology

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Growth hormone deficiency (GHD) in adults is characterized by alterations in body composition, carbohydrate and lipid metabolism, bone mineral density, cardiovascular risk profile, and quality of life.1 Treatment with GH replacement has been shown to improve many, but not all, of these abnormalities. 2 By contrast, untreated GHD is associated with increased mortality and morbidity that was previously observed in adults with hypopituitarism. 3,4 These findings were substantiated in two large surveys based on national Danish registries, 5,6 where the morbidity of adults with GHD was found to be approximately threefold higher than that of a healthy population. This result was independent of gender and applied to patients with childhood-onset and adult-onset GHD, with mortality of childhoodonset GHD far exceeding that of adult-onset GH deficient patients. 6Current published consensus guidelines recommend the evaluation of adult GHD to be based on clinical findings, medical history and using the appropriate GH stimulation test for biochemical confirmation, 7-9 with the exception of patients with three or more pituitary hormone deficiencies and low serum insulin-like growth factor 1 (IGF-1) levels. 10 Serum IGF-1 levels should not be used alone to diagnose adult GHD and the maximum or peak GH secretion following GH stimulation testing is used as a surrogate of the capacity of the pituitary to release GH. The insulin tolerance test (ITT) is widely considered as the gold standard test for evaluation of GH deficiency and has been endorsed by several consensus guidelines. [7][8][9]11 However, this test is labor intensive, may be unpleasant for some patients, has potential risks, and is contraindicated in elderly patients and in patients with seizure disorders and ischemic heart disease. AbstractGrowth hormone deficiency (GHD) is a well-recognized clinical syndrome in adults, and its diagnosis is established through one or more GH stimulation tests. The decision to perform GH stimulation testing should be based on medical history and clinical findings, and using appropriate GH stimulation test/s for biochemical confirmation. The insulin tolerance test (ITT) remains the diagnostic test of choice; however, this test is labor intensive, contraindicated in the elderly and in adults with seizure disorders and ischemic heart disease, can be unpleasant for the patient, and is potentially hazardous. With the discontinuation of the growth hormone releasing hormone (GHRH) analog (Geref ® ) in the US in 2008, the glucagon stimulation test (GST) has gained increasing popularity as the alternative test to the ITT because of its availability, reproducibility, safety, lack of influence by gender and hypothalamic cause of GH deficiency (GHD), and relatively few contraindications. In this article, recommendations for performing this test, the potential drawbacks in conducting and caveats in interpreting this test, and its future perspectives are discussed.

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