Generic placeholder image

Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Research Article

Safety Assessment and Potential Risks of the Glucagon Stimulation Test in the Diagnosis of Secondary Adrenal Insufficiency

Author(s): Taieb Ach*, Asma Ben Abdelkrim , Yosra Hasni , Ghada Saad , Maha Kacem , Molka Chaieb , Monia Zaouali , Amel Maaroufi and Koussay Ach

Volume 17, Issue 1, 2022

Published on: 27 July, 2021

Page: [59 - 63] Pages: 5

DOI: 10.2174/1574886316666210727152000

Price: $65

Abstract

Background: Although it takes more time, the Glucagon Stimulation Test (GST) is a reliable measure for assessing growth hormone (GH) and Adrenocorticotropic Hormone (ACTH) secretion. The GST is considered to be a safe test; however, it still has mild side effects and potential risks.

Objectives: The objective of this study was to analyze the side effects of the GST while testing adrenal-insufficient patients.

Methods: This was a prospective study in which GST was performed in eighty-one patients (44 men, 37 women, mean age: 35.83A9.62 years) with the pituitary disorder. The GST consisted of an intramuscular injection of 1 mg of glucagon. Blood samples were collected at baseline, and 30, 60, 90, 120, 150, 180, and 210 min after glucagon injection for cortisol measurements. All patients were asked to report side effects associated with this test.

Results: The mean peak blood glucose level under GST was 9.01A.03 mmol/L, and the mean glycemic nadir was 4.34A.75 mmol/L most frequently found during the 30th minute (p <10-3). During the test, 35 subjects (43.2%) had side effects with a mean age of 42.89 A19.75 years. Frequent side effects included: nausea (29.62%), vomiting (27.16%), abdominal cramps (18.51%) and hunger (13.58%). All patients tolerated the test until the end. Adverse effects were significantly more prevalent in patients older than 50 years (p=0.012).

Conclusions: The GST is a reliable alternative to assess the hypothalamic pituitary adrenal axis but should be cautiously used especially in the elderly, despite minor side effects.

Keywords: Glucagon stimulation test, insulin tolerance test, aged, hypothalamic pituitary adrenal insufficiency, patients, side effects.

[1]
Yuen KC, Tritos NA, Samson SL, Hoffman AR, Katznelson L. American association of clinical endocrinologists and american college of endocrinology disease state clinical review: Update on growth hormone stimulation testing and proposed revised cut- point for the glucagon stimulation test in the diagnosis of adult growth hormone deficiency. Endocr Pract 2016; 22(10): 1235-44.
[http://dx.doi.org/10.4158/EP161407.DSCR]
[2]
Thomas N. Evaluation of the hypothalamo-pituitary-adrenal axis: The insulin tolerance test and beyond. Natl Med J India 1998; 11(3): 125-8.
[PMID: 9707703]
[3]
Kane KF, Emery P, Sheppard MC, Stewart PM. Assessing the hypothalamo-pituitary-adrenal axis in patients on long-term glucocorticoid therapy: The short synacthen versus the insulin tolerance test. QJM 1995; 88(4): 263-7.
[4]
Orme SM, Price A, Weetman AP, Ross RJ. Comparison of the diagnostic utility of the simplified and standard i.m. glucagon stimulation test (IMGST). Clin Endocrinol (Oxf) 1998; 49(6): 773-8.
[http://dx.doi.org/10.1046/j.1365-2265.1998.00610.x] [PMID: 10209565]
[5]
Tyberghein JM. The hyperglycemic action of glucagon as influenced by liver glycogen concentration, the pancreas, the adrenals and the pituitary in the baboon (Papio ursinus). Endocrinology 1961; 69(2): 312-8.
[http://dx.doi.org/10.1210/endo-69-2-312] [PMID: 13778852]
[6]
Takeda S, Inoue K. Glucagon-propranolol provocative test. Nihon Rinsho 1997; 55(Suppl. 2): 225-8.
[PMID: 9172512]
[7]
Kulina GR, Rayfield EJ. The role of glucagon in the pathophysiology and management of diabetes. Endocr Pract 2016; 22(5): 612-21.
[http://dx.doi.org/10.4158/EP15984.RA]
[8]
Zeugswetter FK, Schornsteiner E, Haimel G, Schwendenwein I. Metabolic and hormonal responses to subcutaneous glucagon in healthy beagles. J Vet Emerg Crit Care (San Antonio) 2012; 22(5): 558-63.
[http://dx.doi.org/10.1111/j.1476-4431.2012.00793.x] [PMID: 23110568]
[9]
Berg C, Meinel T, Lahner H, Yuece A, Mann K, Petersenn S. Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery.Eur J Endocrinol. European Federation of Endocrine Societies 2010; 162: pp. (3)477-82.
[http://dx.doi.org/10.1530/EJE-09-0824]
[10]
Kappy MS, Drake A, Gao D, Ratliff R. Assessing adrenal function in primary care settings with a single sample subcutaneous glucagon test. J Pediatr 2006; 149(5): 682-6.
[http://dx.doi.org/10.1016/j.jpeds.2006.07.033] [PMID: 17095343]
[11]
Simsek Y, Karaca Z, Tanriverdi F, Unluhizarci K, Selcuklu A, Kelestimur F. A comparison of low-dose ACTH, glucagon stimulation and insulin tolerance test in patients with pituitary disorders. Clin Endocrinol 2015; 82(1): 45-52.
[http://dx.doi.org/10.1111/cen.12528] [PMID: 24953859]
[12]
Tenenbaum A, Phillip M, de Vries L. The intramuscular glucagon stimulation test does not provide good discrimination between normal and inadequate ACTH reserve when used in the investigation of short healthy children. Horm Res Paediatr 2014; 82(3): 194-200.
[http://dx.doi.org/10.1159/000365190] [PMID: 25139316]
[13]
Tavares ABW, Seixas-da-Silva IA, Silvestre DHS, Paixão CM, Vaisman M, Conceição FL. Potential risks of glucagon stimulation test in elderly people. Growth Horn IGF Res 2015; 25(1): 53-6.
[http://dx.doi.org/10.1016/j.ghir.2014.11.002]
[14]
de Miguel Novoa P, Vela ET, Garcia NP, et al. Guidelines for the diagnosis and treatment of adrenal insufficiency in the adult. Endocrinologia y nutricion : Organo de la Sociedad Espanola de Endocrinologia y Nutricion 2014; 61(Suppl 1): 1-35.
[http://dx.doi.org/10.1016/S2173-5093(14)70069-8]
[15]
Karaca Z, Grossman A, Kelestimur F. Investigation of the Hypothalamo-pituitary-adrenal (HPA) axis: A contemporary synthesis. Rev Endocr Metab Disord 2021; 22(2): 179-204.
[http://dx.doi.org/10.1007/s11154-020-09611-3] [PMID: 33770352]
[16]
Abeillon-Du Payrat J, Raverot V, Simonet C, Borson-Chazot F, Raverot G. Évaluation du test au glucagon comme alternative à l’hypoglycémie insulinique chez les patients à risque de déficit antéhypophysaire. Ann Endocrinol (Paris) 2014; 75(5–6): 264.
[http://dx.doi.org/10.1016/j.ando.2014.07.048]
[17]
Hamrahian AH, Yuen KC, Gordon MB, Pulaski-Liebert KJ, Bena J, Biller BM. Revised GH and cortisol cut-points for the glucagon stimulation test in the evaluation of GH and hypothalamic-pituitary-adrenal axes in adults: Results from a prospective randomized multicenter study. Pituitary 2016; 19(3): 332-41.
[http://dx.doi.org/10.1007/s11102-016-0712-7] [PMID: 26897383]
[18]
Karaca Z, Lale A, Tanriverdi F, Kula M, Unluhizarci K, Kelestimur F. The comparison of low and standard dose ACTH and glucagon stimulation tests in the evaluation of hypothalamo-pituitary-adrenal axis in healthy adults. Pituitary 2011; 14(2): 134-40.
[http://dx.doi.org/10.1007/s11102-010-0270-3] [PMID: 21061072]
[19]
Leong KS, Walker AB, Martin I, Wile D, Wilding J, MacFarlane IA. An audit of 500 subcutaneous glucagon stimulation tests to assess growth hormone and ACTH secretion in patients with hypothalamic-pituitary disease. Clin Endocrinol (Oxf) 2001; 54(4): 463-8.
[http://dx.doi.org/10.1046/j.1365-2265.2001.01169.x] [PMID: 11318781]
[20]
Giuffrida FM, Berger K, Monte L, et al. Relationship between GH response and glycemic fluctuations in the glucagon stimulation test. Growth Horn IGF Res 2009; 19(1): 77-81.
[http://dx.doi.org/10.1016/j.ghir.2008.06.002]
[21]
Littley MD, Gibson S, White A, Shalet SM. Comparison of the ACTH and cortisol responses to provocative testing with glucagon and insulin hypoglycaemia in normal subjects. Clin Endocrinol (Oxf) 1989; 31(5): 527-33.
[http://dx.doi.org/10.1111/j.1365-2265.1989.tb01276.x] [PMID: 2560684]
[22]
Yuen KC, Biller BM, Katznelson L, et al. Clinical characteristics, timing of peak responses and safety aspects of two dosing regimens of the glucagon stimulation test in evaluating growth hormone and cortisol secretion in adults. Pituitary 2013; 16(2): 220-30.
[http://dx.doi.org/10.1007/s11102-012-0407-7] [PMID: 22806554]
[23]
di Iorgi N, Napoli F, Allegri A, et al. The accuracy of the glucagon test compared to the insulin tolerance test in the diagnosis of adrenal insufficiency in young children with growth hormone deficiency. J Clin Endocrinol Metab 2010; 95(5): 2132-9.
[http://dx.doi.org/10.1210/jc.2009-2697] [PMID: 20350939]
[24]
Rao RH, Spathis GS. Intramuscular glucagon as a provocative stimulus for the assessment of pituitary function: Growth hormone and cortisol responses. Metabolism 1987; 36(7): 658-63.
[http://dx.doi.org/10.1016/0026-0495(87)90150-8] [PMID: 3600280]
[25]
Goodwin PM, Capildeo R, Harrop JS, Marks V, Rose FC. The metabolic and hormonal response to glucagon. Part 1. Normal subjects. J Neurol Sci 1976; 27(3): 373-80.
[http://dx.doi.org/10.1016/0022-510X(76)90009-5] [PMID: 1262901]
[26]
Iranmanesh A, Lizarralde G, Veldhuis JD. Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 1991; 73(5): 1081-8.
[http://dx.doi.org/10.1210/jcem-73-5-1081] [PMID: 1939523]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy