Assessment of Growth Hormone Reserve: Comparison of Intravenous Arginine and Subcutaneous Glucagon Stimulation Tests<sup>1</sup>

Podolsky, Stephen; Sivaprasad, R.

doi:10.1210/jcem-35-4-580

Cited by 33 publications

(5 citation statements)

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“…Clonidine alone is clearly not adequate, as many normal individuals have no detectable GH response, or show the same response as to placebo (12,47). Glucagon injection im is considered a useful alternative to ITT by some investigators, but reported by others as being less effective than ARG (7,12,55). A number of agents have been used in combination with GHRH.…”

Section: Discussionmentioning

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

320

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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Section: Discussionmentioning

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

320

156

View full text Add to dashboard Cite

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“…A decrease in somatostatin secretion [29] or in free fatty acid concentrations [29, 30] have been proposed as potential explanations. Sustained hyperglycemia [31] and absence of hyperglycemic response to glucagon following prolonged fasting [32] obliterate the GH response to glucagon, suggesting that hyperglycemia followed by a decrease in blood sugar towards normal values is necessary to elicit GH response. Consistent with this latter hypothesis, we observed a significant correlation between GH AUC and changes in glucose concentrations, after controlling for the dose of glucagon or for insulin response to glucagon.…”

Section: Discussionmentioning

confidence: 99%

Ghrelin Is Suppressed by Glucagon and Does Not Mediate Glucagon-Related Growth Hormone Release

Hirsh

Heinrichs²,

Leenders³

et al. 2005

Horm Res Paediatr

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Background:Glucagon stimulation is routinely used as a provocative test to assess growth hormone (GH) sufficiency in pediatrics. Ghrelin also markedly stimulates GH secretion. Because glucagon stimulates the promoter of the ghrelin gene in vitro as well as ghrelin secretion by the perfused rat stomach, we sought todetermine whether ghrelin mediates glucagon-induced GH secretion. Methods: We compared ghrelin, GH, insulin and glucose responses following administration of 0.03 mg/kg intravenously (iv; max. 1 mg) and 0.1 mg/kg intramuscularly (im; max. 2 mg) of glucagon in two groups (n = 10–11/group) of GH-sufficient children. We also measured ghrelin before and 6 min after iv administration of 1 mg glucagon in 21 adult subjects. Results: In children, glucagon caused a 26% decrease in ghrelin and a 72% increase in glucose concentrations that were independent of the dose or administration route of glucagon. In contrast, the insulin response was 2–3 times higher following administration of 0.1 mg/kg im compared to 0.03 mg/kg of glucagon iv. There was a significant correlation between the maximum decrease in ghrelin and increases in glucose (p = 0.03) but not in insulin. There was a significant correlation between ghrelin and GH area under the curve after controlling for the dose of glucagon (p = 0.03) but not for the maximum increase in glucose.In normal adults, glucagon administration caused a 7% decrease in ghrelin concentrations after 6 min (p = 0.0002). Conclusion: Ghrelin does not play a causal role in the GH response to pharmacological glucagon administration, which suppresses ghrelin levels starting a few minutes after injection.

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“…(1 97 1) studied nineteen normal children and reported consistent increases of GH. On the other hand, Eddy et al (1970) reportedwithout giving detailed figures-that only three out of eight normal subjects showed a definite GH response to subcutaneous glucagon, and Podolsky & Sivaprasad (1972) obtained an increase of G H of 6 ng/ml or more in only six out of ten normal subjects given subcutaneous glucagon. Our results agree with those of Mitchell et al (1971) andCain et al (1972); in fourteen out of fifteen normal subjects or patients with unrelated disease the peak growth hormone level was more than 5 ng/ml.…”

Section: Side Ejectsmentioning

confidence: 99%

“…3e and 3f) also indicate the independence of hormonal response and blood sugar change. However, Podolsky & Sivaprasad (1972) performed glucagon tests after 48 and 72 hr fasts in eighteen normal subjects and in only four was a GH response obtained. An increase of G H concentration may follow a slow and gradual fall of blood sugar, but an ACTH-cortisol response usually requiles a fall of blood sugar to 40 mg/100 ml or less and we do not believe that the fall of blood sugar is the explanation of the hormonal changes that follow subcutaneous glucagon.…”

Section: Side Ejectsmentioning

confidence: 99%

Subcutaneous Glucagon as a Test of the Ability of the Pituitary to Secrete Gh and Acth

Spathis

Bloom

Jeffcoate

et al. 1974

Clinical Endocrinology

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SUMMARY The response to the subcutaneous injection of glucagon (1 mg) has been studied as a test of the ability of the pituitary to secrete ACTH and growth hormone (GH). Tests have been performed on fifteen normal subjects or patients with unrelated conditions, nine patients with pituitary tumours and seventeen with acromegaly. It is suggested that a normal response is a peak level of 5 ng/ml or more of GH (standard NIH GH 1216C) and either a rise of plasma cortisol measured by competitive protein binding of at least 4 μg/100 ml or a peak level of 7 μg/100 ml. In seventeen patients the responses were compared with those obtained in the insulin hypoglycaemia test and there was good agreement. Measurement of plasma ACTH showed that the response is at pituitary and not adrenal cortical level. Peak responses of ACTH and GH were obtrained at 150 min and of cortisol at 180 min. Plasma glucagon concentrations were falling steadily by this time although still above the control level. The mechanism of action of glucagon is not clear but does not appear to be related to fall of blood sugar. The subcutaneous injection of glucagon is not without side effects; about half the patients were nauseated and nine vomited. Nevertheless we believe that a subcutaneous glucagon test is of value for testing the pituitary reserve of ACTH and GH in situations where insulin hypoglycaemia cannot be used.

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Assessment of Growth Hormone Reserve: Comparison of Intravenous Arginine and Subcutaneous Glucagon Stimulation Tests¹

Cited by 33 publications

References 0 publications

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

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

Ghrelin Is Suppressed by Glucagon and Does Not Mediate Glucagon-Related Growth Hormone Release

Subcutaneous Glucagon as a Test of the Ability of the Pituitary to Secrete Gh and Acth

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Assessment of Growth Hormone Reserve: Comparison of Intravenous Arginine and Subcutaneous Glucagon Stimulation Tests1

Cited by 33 publications

References 0 publications

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

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

Ghrelin Is Suppressed by Glucagon and Does Not Mediate Glucagon-Related Growth Hormone Release

Subcutaneous Glucagon as a Test of the Ability of the Pituitary to Secrete Gh and Acth

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Assessment of Growth Hormone Reserve: Comparison of Intravenous Arginine and Subcutaneous Glucagon Stimulation Tests¹