July 7, 2020
Glucagon Test of the Hypothalamo-pituitary Axis Minimize

Glucagon test of the hypothalamo-pituitary axis


Assessment of pituitary-adrenal axis (GH and ACTH/cortisol). It is particularly useful when insulin-induced hypoglycaemia is contraindicated.


The test should not be performed in subjects with hypothyroidism or marked adrenal failure ie 0900h cortisol < 100 nmol/L. This test is unreliable in patients with diabetes mellitus.

Hypoglycaemia may occur in: phaeochromocytoma, insulinoma, after prolonged starvation (> 48 hours) or glycogen storage diseases (inability to mobilise glycogen may result in hypoglycaemia).

Principle of test

Glucagon stimulates the release of GH and ACTH by a hypothalamic mechanism and therefore indirectly stimulates cortisol. Simultaneous administration of TRH and LHRH does not interfere with the effect of glucagon.

Intra-muscular administration is essential as absorption via the subcutaneous route is unreliable.

Side effects

Some subjects generally feel unwell and a proportion develop nausea and vomiting.


Fasting from midnight but may drink water. The patient does not need to be continuously observed as hypoglycaemia is not provoked. Systemic steroids should be stopped 24 hours before the test.


  • Glucagon dose 1mg for adults (1.5mg if > 90kg)
  • Indwelling cannula gauge 19
  • 3 plain tubes


For children see alternative protocol

0 min

take 2 mL blood into plain tube for cortisol & GH
immediately give Glucagon intra-muscularly.

150 min

take 2 mL blood into plain tube for cortisol & GH

180 min

take 2 mL blood into plain tube for cortisol & GH


An adequate cortisol response is defined as a rise of greater than 200 nmol/L to above 600 nmol/L. The value of 600 nmol/L is used to exclude adrenal insufficiency in view of variation between analytical methods. An adequate GH response is a rise to a value greater than 20 mU/L (7µg/L).

There is probably a blunted response in hypothyroidism and obesity.

Sensitivity and Specificity

This test is generally considered to be a slightly less reliable test of the ability of the pituitary to secrete GH and ACTH than the insulin stress test, but its diagnostic efficacy is defined by the response to the ITT. It is an excellent alternative in patients who cannot tolerate hypoglycaemia because of epilepsy, ischaemic heart disease or hypopituitarism.

Glucagon is a good secretagogue for GH in children. However, there is some suggestion it is unreliable for testing the pituitary-adrenal axis in older children.


  • Böttner A, Kratzsch J, Liebermann S, Keller A, Pfaffle RW, Kiess W, Keller E. Comparison of adrenal function tests in children--the glucagon stimulation test allows the simultaneous assessment of adrenal function and growth hormone response in children. J Pediatr Endocrinol Metab. 2005;18:433-42.
  • Johnstone HC, Cheetham TD. GH and cortisol response to glucagon administration in short children. Horm Res 2004;62:27-32.
  • Mitchell ML, Byrne MJ, Sanchez Y, Sawin CT. Detection of growth-hormone deficiency: the glucagon stimulation test. N Eng J Med 1970;282:539-41.
  • Orme SM, Peacey SR, Barth JH, Belchetz PE. Comparison of tests of stress-released cortisol secretion in pituitary disease. Clin Endocrinol 1996;45:135-140.
  • Rao RAH, Spathis GS. Intramuscular glucagon as a provocative stimulus for the assessment of pituitary function: growth hormone and cortisol responses. Metabolism 1987;36:658-63.

 JHB 22 Sept 2011


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