L‐Arginine and insulin‐tolerance tests in the diagnosis of adult growth hormone deficiency: influence of confounding factors

Fisker, Sanne; Jørgensen, Jens Otto Lunde; Ørskov, Hans; Christiansen, Jens Sandahl

doi:10.1046/j.1365-2265.1998.00362.x

Cited by 38 publications

(20 citation statements)

References 36 publications

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“…The CV of the ITT is comparable to that found in the GHRHpyridostigmine test (13), and the CVs between GH response to test one and two comparable to those found in the GHRH-arginine test in different age groups (14). We have previously demonstrated that external factors such as physical activity prior to testing may confound the test result (15), and therefore the subjects in our study were admitted to hospital the night before testing. Pre-testing factors may thus explain some of the disagreement in peak GH variability in different studies.…”

Section: Discussionmentioning

confidence: 99%

GH stimulation tests: evaluation of GH responses to heat test versus insulin-tolerance test

Fisker

Jørgensen²,

Ørskov³

et al. 1998

European Journal of Endocrinology

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Objective: Heat exposure has been shown to stimulate GH release, but the specificity and the reproducibility have not been determined, and the test has not been compared with validated GH stimulation tests in adulthood. We therefore tested the specificity and the reproducibility of the heat exposure test in healthy subjects and compared the results with those obtained with the insulin-tolerance test (ITT). Design: Ten healthy non-obese men, aged 31.3 Ϯ 4.80 years, underwent four GH stimulation tests in random order: two ITTs and two heat exposure tests. In the heat test, subjects were placed in a hot bath with water temperature at 40.3 Ϯ 0.11 ЊC for 45 min, resulting in an identical (P ¼ 0.477) significant increase in tympanic temperature of 1.26 Ϯ 0.05 and 1.41 Ϯ 0.07 ЊC in the two tests. Results: Peak GH response to the heat exposure test was less than the peak GH response to ITT (5.25 Ϯ 1.72 vs 15.5 Ϯ 3.17 mg/l, P ¼ 0.006). Furthermore the specificity (arbitrary cut-off level ¼ 3 mg/l) of the heat test was lower than of the ITT (8/17 vs 18/20, P ¼ 0.006). The coefficient of variation did not differ between the two tests (heat test 0.31, ITT 0.36, P ¼ 0.77). Peak GH values in the individual tests were highly correlated (heat, r ¼ 0.908, P ¼ 0.002; ITT, r ¼ 0.815, P ¼ 0.004). Reproducible increments in the circulating levels of stress hormones were observed during ITT, but these hormones remained largely unchanged during heat exposure. Conclusions:The heat exposure test is not a reliable GH stimulation test compared with the ITT in adults. This study documents that the ITT has a high specificity and reproducibility in the diagnosis of GH deficiency in adulthood. We propose that the heat exposure test is not used in the diagnosis of this condition in adulthood.

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Section: Discussionmentioning

confidence: 99%

GH stimulation tests: evaluation of GH responses to heat test versus insulin-tolerance test

Fisker

Jørgensen²,

Ørskov³

et al. 1998

European Journal of Endocrinology

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“…Although the combined ARG plus GHRH test has been proposed to be the best alternative to the ITT with a peak GH cut-point of 9 g/liter (3,5), this test has been reported to be performed in fewer than 1% of patients in the United States (4). While the response to multiple pharmacologic agents in healthy adults has been evaluated in several studies (6 -12), comparison of diagnostic stimulation tests in patients with hypothalamic-pituitary disease has been limited to two or three tests in prior studies (5,(13)(14)(15)(16). Drawbacks of earlier studies included a lack of control subjects or matching control subjects to hypopituitary patients by age and sex alone.…”

Section: G H Deficiency (Ghd) In Adults Is Now a Well-recog-mentioning

confidence: 99%

Sensitivity and Specificity of Six Tests for the Diagnosis of Adult GH Deficiency

Biller

Samuels

Zagar

et al. 2002

The Journal of Clinical Endocrinology &Amp; Metabolism

325

156

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Although the use of the insulin tolerance test (ITT) for the diagnosis of adult GH deficiency is well established, diagnostic peak GH cut-points for other commonly used GH stimulation tests are less clearly established. Despite that fact, the majority of patients in the United States who are evaluated for GH deficiency do not undergo insulin tolerance testing. The aim of this study was to evaluate the relative utility of six different methods of testing for adult GH deficiency currently used in practice in the United States and to develop diagnostic cut-points for each of these tests. Thirty-nine patients (26 male, 13 female) with adult-onset hypothalamic-pituitary disease and multiple pituitary hormone deficiencies were studied in comparison with age-, sex-, estrogen status-, and body mass index-matched control subjects (n ‫؍‬ 34; 20 male, 14 female). A third group of patients (n ‫؍‬ 21) with adult-onset hypothalamic-pituitary disease and no more than one additional pituitary hormone deficiency was also studied. The primary end-point was peak serum GH response to five GH stimulation tests administered in random order at five separate visits: ITT, arginine (ARG), levodopa (L-DOPA), ARG plus L-DOPA, and ARG plus GHRH. Serum IGF-I concentrations were also measured on two occasions. For purposes of analysis, patients with multiple pituitary hormone deficiencies were assumed to be GH deficient. Three diagnostic cut-points were calculated for each test to provide optimal separation of multiple pituitary hormone deficient and control subjects according to three criteria: 1) to minimize misclassification of control subjects and deficient patients (balance between high sensitivity and high specificity); 2) to provide 95% sensitivity for GH deficiency; and 3) to provide 95% specificity for GH deficiency. The greatest diagnostic accuracy occurred with the ITT and the ARG plus GHRH test, although patients preferred the latter (P ‫؍‬ 0.001). Using peak serum GH cut-points of 5.1 g/liter for the ITT and 4.1 g/liter for the ARG plus GHRH test, high sensitivity (96 and 95%, respectively) and specificity (92 and 91%, respectively) for GH deficiency were achieved. To obtain 95% specificity, the peak serum GH cutpoints were lower at 3.3 g/liter and 1.5 g/liter for the ITT and ARG plus GHRH test, respectively. There was substantial overlap between patients and control subjects for the ARG plus L-DOPA, ARG, and L-DOPA tests, but test-specific cutpoints could be defined for all three tests to provide 95% sensitivity for GH deficiency (peak GH cut-points: 1.5, 1.4 and 0.64 g/liter, respectively). However, 95% specificity could be achieved with the ARG plus L-DOPA and ARG tests only with very low peak GH cut-points (0.25 and 0.21 g/liter, respectively) and not at all with the L-DOPA test. Although serum IGF-I levels provided less diagnostic discrimination than all five GH stimulation tests, a value below 77.2 g/liter was 95% specific for GH deficiency. In conclusion, the diagnosis of adult GH deficiency can be made without performing ...

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“…Although there was no gender difference in the GH response to the ITT, glucagon, or clonidine, women had a significantly higher peak response to arginine, thought to be due to an enhancing effect of oestrogens [27]. The arginine stimulation test has been shown to have a significantly lower specificity than the ITT [28]. …”

Section: Assessment Of Ghd In Adultsmentioning

confidence: 99%

Defining Growth Hormone Status in Adults with Hypopituitarism

Kaushal

Shalet²

2007

Horm Res Paediatr

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The identification of adults with severe growth hormone (GH) deficiency (GHD) is not straightforward. The insulin tolerance test remains the gold standard diagnostic test, although other stimuli such as GH-releasing hormone-arginine are gaining acceptance. Insulin-like growth factor-I has a poor diagnostic sensitivity in adult-onset GHD, but is more useful in the subgroup of adults with childhood-onset GHD. Therapeutic developments include increasing recognition of the need to continue GH therapy beyond final height in young adults with severe GHD on retesting. Consensus guidelines have provided a useful algorithm to identify individuals requiring retesting and the number of tests needed. The concept of partial GHD, recognized by paediatric endocrinologists for many years, is being examined in adults with hypothalamic-pituitary disease. Preliminary evidence suggests that this entity is associated with metabolic and anthropometric abnormalities intermediate between those in severe GHD and in healthy controls. It remains to be seen whether this subgroup will derive benefit from GH therapy. To date, therapeutic benefits of GH have been demonstrated only in adults with severe GHD. It is, therefore, imperative that these individuals are unequivocally identified; the diagnosis becomes more uncertain in the presence of obesity, increasing age, and in the absence of additional pituitary hormone deficits.

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L‐Arginine and insulin‐tolerance tests in the diagnosis of adult growth hormone deficiency: influence of confounding factors

Abstract: Since provocative GH responses are influenced by external factors, conditions should be standardized to optimize the reproductibility and specificity of the tests. Furthermore the higher specificity of the insulin-tolerance test as compared to the arginine stimulation test was confirmed.

Cited by 38 publications

References 36 publications

GH stimulation tests: evaluation of GH responses to heat test versus insulin-tolerance test

GH stimulation tests: evaluation of GH responses to heat test versus insulin-tolerance test

Sensitivity and Specificity of Six Tests for the Diagnosis of Adult GH Deficiency

Defining Growth Hormone Status in Adults with Hypopituitarism

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