Relationship between GH response and glycemic fluctuations in the glucagon stimulation test

Giuffrida, Fernando de Mello Almada; Berger, Karina; Monte, Lia; Oliveira, Cláudia H.M.C.; Hoff, Ana O.; Maciel, Rui M. B.; Vieira, José Gilberto H.

doi:10.1016/j.ghir.2008.06.002

Cited by 26 publications

(27 citation statements)

References 18 publications

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“…The detailed physiological mechanisms by which glucagon induces both GH and cortisol release are unclear. Some of the hypothesized mechanisms include the glycemic fluctuations during the test where blood glucose levels increase initially before decreasing later in the test (23), the generation of a peptidyl fragment associated with the GH-and ACTH-releasing activity (20), and the induction of norepinephrine secretion in stimulating GH and ACTH release via a-receptors (10).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery

Berg

Meinel

Lahner

et al. 2010

European Journal of Endocrinology

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Objective: The glucagon stimulation test (GST) like the insulin tolerance test (ITT) stimulates both ACTH and GH secretion. However, there are limited data with modern assays on sensitivity and specificity for GST in comparison to ITT. The aim of this study was to evaluate the diagnostic utility of the GST for GH deficiency (GHD) and adrenal insufficiency (AI) in patients following pituitary surgery. Design and patients: ITT and GST were performed within 7 days in 49 patients at least 3 months after transsphenoidal surgery. Serum GH and cortisol were measured by Immulite 2000 assay (Siemens AG). Receiver-operating characteristic (ROC) analysis was performed to identify the thresholds for GST. Results: In ITT, 18/49 cases were classified as AI. ROC analysis revealed a peak cortisol value O599 nmol/l in GST for adrenal sufficiency with 100% specificity and 32% sensitivity, and a peak cortisol !277 nmol/l with O95% specificity and 72% sensitivity for AI. Of the 49 subjects, 25 (51%) demonstrated levels between these cut-offs and could not be diagnosed by GST alone with sufficient accuracy. Regarding GHD, 21/49 cases were classified as insufficient by ITT. ROC analysis revealed a cut-off of 2.5 ng/ml with 95% sensitivity and 79% specificity. Of the 49 cases, seven (14%) were discordant in terms of defining GHD, with six subjects being treated for GHD according to GST although being sufficient in ITT. Conclusion: In our prospective series of patients with pituitary disease, GST is a potential alternative test for the assessment of GH reserve, but is a poor test for ACTH reserve. Test-specific cut-offs should be applied to avoid misinterpretation.

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Section: Discussionmentioning

confidence: 99%

Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery

Berg

Meinel

Lahner

et al. 2010

European Journal of Endocrinology

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“…Another possible mechanism is via noradrenergic stimulation, since it has been shown that glucagon induces noradrenalin release [35]. The stimulatory effects are unrelated to glucose variations and stress-mediated actions [36], as well as GHRH-and SRIF-mediated actions [15]. GH secretion via SRIF because of low basal serum GH levels in this subject.…”

Section: Acknowledgmentsmentioning

confidence: 83%

Is there an undiscovered neurocircuit for regulating GH secretion? -Pitfalls of GHRP-2 and ITT as GH provocative tests-

Kamoi

Shimatsu

Kobayashi³

2010

Endocr J

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“…Glucagon appears to be well-tolerated and is only relatively contraindicated in patients with malnourishment or have not eaten for more than 48 hours due to concern of prolonged hypoglycemia and those with pheochromocytoma in whom a significant exacerbation of blood pressure may be observed. 25 The GST was initially described as a 4-hour test in older studies, 33 31 Accordingly, the authors proposed that the diagnostic utility of the simplified GST could be improved further by drawing an additional blood sample at 210 minutes when assessing GH deficiency. The audit by Leong et al 27 reported that the GST could be shortened by omitting the 240-minute blood sample.…”

Section: Discussionmentioning

confidence: 99%

“…[20][21][22][23][24] The true mechanism by which glucagon induces GH release is still a mystery. Some of the hypothesized mechanisms include the glycemic fluctuations during the test where blood glucose levels increase initially before decreasing later in the test, 25 the generation of a peptidyl fragment associated with the GH-and adrenocorticotropic hormone (ACTH)-releasing activity, 26 and the induction of norepinephrine secretion in stimulating GH release via a-receptors. 27 It has also been previously demonstrated that glucagon stimulates GH release more effectively when administered intramuscularly or subcutaneously compared with the intravenous route.…”

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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Relationship between GH response and glycemic fluctuations in the glucagon stimulation test

Cited by 26 publications

References 18 publications

Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery

Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery

Is there an undiscovered neurocircuit for regulating GH secretion? -Pitfalls of GHRP-2 and ITT as GH provocative tests-

Glucagon Stimulation Testing in Adult Growth Hormone Deficiency A 2014 Update

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Relationship between GH response and glycemic fluctuations in the glucagon stimulation test

Cited by 26 publications

References 18 publications

Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery

Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery

Is there an undiscovered neurocircuit for regulating GH secretion? -Pitfalls of GHRP-2 and ITT as GH provocative tests-

Glucagon Stimulation Testing in Adult Growth Hormone Deficiency A 2014 Update

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Glucagon Stimulation Testing in Adult Growth Hormone Deficiency A 2014 Update