Insulin-induced hypoglycemia test
- Lynnette K Nieman, MD
Lynnette K Nieman, MD
- Section Editor — Adrenal Disease
- Senior Investigator
- Bethesda, MD
The diagnosis of adrenal insufficiency can be made by the finding of low morning serum cortisol concentration and low 24-hour urinary cortisol excretion, often with a subnormal response to corticotropin (ACTH). In some circumstances, however, other tests, such as insulin-induced hypoglycemia, are utilized to evaluate the response to stress, particularly when ACTH deficiency is suspected as the cause. This stress test also is used to establish a diagnosis of growth hormone deficiency. It has been used in patients with suspected Cushing's syndrome, but is not recommended as a diagnostic test in this setting.
Details of the insulin-induced hypoglycemia test in adults will be reviewed here. Additional information on the diagnoses of adrenal insufficiency, growth hormone deficiency, and Cushing's syndrome in adults is reviewed separately. (See "Diagnosis of adrenal insufficiency in adults" and "Growth hormone deficiency in adults" and "Establishing the diagnosis of Cushing's syndrome".)
INSULIN-INDUCED HYPOGLYCEMIA TEST
Stress response — Stress is difficult to define, let alone to reproduce. However, hypoglycemia causes a major stress response, with increases in plasma corticotropin (ACTH) and serum cortisol, growth hormone, and prolactin, and activation of the sympathetic nervous system. (See "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus".)
Advantages/disadvantages — As a stress test, insulin-induced hypoglycemia has certain advantages:
●This test evaluates the integrity of the full hypothalamic-pituitary-adrenal axis as hypoglycemia acts centrally to stimulate hypothalamic corticotropin-releasing hormone (CRH) release and, therefore, ACTH release
- Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016; 101:364.
- Dökmetaş HS, Colak R, Keleştimur F, et al. A comparison between the 1-microg adrenocorticotropin (ACTH) test, the short ACTH (250 microg) test, and the insulin tolerance test in the assessment of hypothalamo-pituitary-adrenal axis immediately after pituitary surgery. J Clin Endocrinol Metab 2000; 85:3713.
- Courtney CH, McAllister AS, McCance DR, et al. The insulin hypoglycaemia and overnight metyrapone tests in the assessment of the hypothalamic-pituitary-adrenal axis following pituitary surgery. Clin Endocrinol (Oxf) 2000; 53:309.
- Berg C, Meinel T, Lahner H, et al. Recovery of pituitary function in the late-postoperative phase after pituitary surgery: results of dynamic testing in patients with pituitary disease by insulin tolerance test 3 and 12 months after surgery. Eur J Endocrinol 2010; 162:853.
- Klose M, Lange M, Kosteljanetz M, et al. Adrenocortical insufficiency after pituitary surgery: an audit of the reliability of the conventional short synacthen test. Clin Endocrinol (Oxf) 2005; 63:499.
- Agha A, Tomlinson JW, Clark PM, et al. The long-term predictive accuracy of the short synacthen (corticotropin) stimulation test for assessment of the hypothalamic-pituitary-adrenal axis. J Clin Endocrinol Metab 2006; 91:43.
- Jayasena CN, Gadhvi KA, Gohel B, et al. Day 5 morning serum cortisol predicts hypothalamic-pituitary-adrenal function after transsphenoidal surgery for pituitary tumors. Clin Chem 2009; 55:972.
- Watts NB, Tindall GT. Rapid assessment of corticotropin reserve after pituitary surgery. JAMA 1988; 259:708.
- Auchus RJ, Shewbridge RK, Shepherd MD. Which patients benefit from provocative adrenal testing after transsphenoidal pituitary surgery? Clin Endocrinol (Oxf) 1997; 46:21.
- Long TD, Ellingrod VL, Kathol RG, et al. Lack of menstrual cycle effects on hypothalamic-pituitary-adrenal axis response to insulin-induced hypoglycaemia. Clin Endocrinol (Oxf) 2000; 52:781.
- Streeten DH, Anderson GH Jr, Dalakos TG, et al. Normal and abnormal function of the hypothalamic-pituitary-adrenocortical system in man. Endocr Rev 1984; 5:371.
- Erturk E, Jaffe CA, Barkan AL. Evaluation of the integrity of the hypothalamic-pituitary-adrenal axis by insulin hypoglycemia test. J Clin Endocrinol Metab 1998; 83:2350.
- Borm K, Slawik M, Beuschlein F, et al. Low-dose glucose infusion after achieving critical hypoglycemia during insulin tolerance testing: effects on time of hypoglycemia, neuroendocrine stress response and patient's discomfort in a pilot study. Eur J Endocrinol 2005; 153:521.
- Nieman LK. Dynamic evaluation of adrenal hypofunction. J Endocrinol Invest 2003; 26:74.
- Staub JJ, Jenkins JS, Ratcliffe JG, Landon J. Comparison of corticotrophin and corticosteroid response to lysine vasopressin, insulin, and pyrogen in man. Br Med J 1973; 1:267.
- Fleisher MR, Glass D, Bitensky L, et al. Plasma corticotrophin levels during insulin-hypoglycaemia: comparison of radioimmunoassay and cytochemical bioassay. Clin Endocrinol (Oxf) 1974; 3:203.
- Donald RA. Plasma immunoreactive corticotrophin and cortisol response to insulin hypoglycemia in normal subjects and patients with pituitary disease. J Clin Endocrinol Metab 1971; 32:225.
- Krieger DT, Liotta AS, Suda T, et al. Human plasma immunoreactive lipotropin and adrenocorticotropin in normal subjects and in patients with pituitary-adrenal disease. J Clin Endocrinol Metab 1979; 48:566.
- DeCherney GS, DeBold CR, Jackson RV, et al. Effect of ovine corticotropin-releasing hormone administered during insulin-induced hypoglycemia on plasma adrenocorticotropin and cortisol. J Clin Endocrinol Metab 1987; 64:1211.
- Perogamvros I, Owen LJ, Keevil BG, et al. Measurement of salivary cortisol with liquid chromatography-tandem mass spectrometry in patients undergoing dynamic endocrine testing. Clin Endocrinol (Oxf) 2010; 72:17.
- Deutschbein T, Unger N, Mann K, Petersenn S. Diagnosis of secondary adrenal insufficiency in patients with hypothalamic-pituitary disease: comparison between serum and salivary cortisol during the high-dose short synacthen test. Eur J Endocrinol 2009; 160:9.
- James VH, Landon J, Wynn V, Greenwood FC. A fundamental defect of adrenocortical control in Cushing's disease. J Endocrinol 1968; 40:15.
- Tyrrell JB, Wiener-Kronish J, Lorenzi M, et al. Cushing's disease: growth hormone response to hypoglycemia after correction of hypercortisolism. J Clin Endocrinol Metab 1977; 44:218.
- Berman JD, Cook DM, Buchman M, Keith LD. Diminished adrenocorticotropin response to insulin-induced hypoglycemia in nondepressed, actively drinking male alcoholics. J Clin Endocrinol Metab 1990; 71:712.
- Gruen PH, Sachar EJ, Altman N, Sassin J. Growth hormone responses to hypoglycemia in postmenopausal depressed women. Arch Gen Psychiatry 1975; 32:31.