Corticotropin-releasing hormone stimulation test
- Lynnette K Nieman, MD
Lynnette K Nieman, MD
- Section Editor — Adrenal Disease
- Senior Investigator
- Bethesda, MD
Corticotropin-releasing hormone (CRH) is a 41-amino acid peptide that is the major physiologic corticotropin (ACTH) secretagogue . There is considerable sequence homology of CRH among species, particularly in the amino-terminal region, which is required for biologic activity. As a result, both ovine and human sequences are used in endocrine testing to:
●Evaluate the cause of ACTH-dependent Cushing's syndrome (with or without vasopressin analogs).
●Discriminate between pseudo-Cushing's and Cushing's syndrome.
●Discriminate between pituitary or hypothalamic localization of central adrenal insufficiency.
●To assess ACTH suppression in patients suspected of primary adrenal mild Cushing's syndrome when basal ACTH levels are incompletely suppressed between 5 and 15 pg/mL [1.1 to 3.3 pmol/L]. (See "Cushing's syndrome due to primary bilateral macronodular adrenal hyperplasia".)
- Vale W, Rivier C, Brown MR, et al. Chemical and biological characterization of corticotropin releasing factor. Recent Prog Horm Res 1983; 39:245.
- Nieman LK, Oldfield EH, Wesley R, et al. A simplified morning ovine corticotropin-releasing hormone stimulation test for the differential diagnosis of adrenocorticotropin-dependent Cushing's syndrome. J Clin Endocrinol Metab 1993; 77:1308.
- Sheldon WR Jr, DeBold CR, Evans WS, et al. Rapid sequential intravenous administration of four hypothalamic releasing hormones as a combined anterior pituitary function test in normal subjects. J Clin Endocrinol Metab 1985; 60:623.
- Nicholson WE, DeCherney GS, Jackson RV, et al. Plasma distribution, disappearance half-time, metabolic clearance rate, and degradation of synthetic ovine corticotropin-releasing factor in man. J Clin Endocrinol Metab 1983; 57:1263.
- Schürmeyer TH, Avgerinos PC, Gold PW, et al. Human corticotropin-releasing factor in man: pharmacokinetic properties and dose-response of plasma adrenocorticotropin and cortisol secretion. J Clin Endocrinol Metab 1984; 59:1103.
- DeBold CR, DeCherney GS, Jackson RV, et al. Effect of synthetic ovine corticotropin-releasing factor: prolonged duration of action and biphasic response of plasma adrenocorticotropin and cortisol. J Clin Endocrinol Metab 1983; 57:294.
- Orth DN, Jackson RV, DeCherney GS, et al. Effect of synthetic ovine corticotropin-releasing factor. Dose response of plasma adrenocorticotropin and cortisol. J Clin Invest 1983; 71:587.
- Nieman LK, Cutler GB Jr, Oldfield EH, et al. The ovine corticotropin-releasing hormone (CRH) stimulation test is superior to the human CRH stimulation test for the diagnosis of Cushing's disease. J Clin Endocrinol Metab 1989; 69:165.
- Chrousos GP, Schulte HM, Oldfield EH, et al. The corticotropin-releasing factor stimulation test. An aid in the evaluation of patients with Cushing's syndrome. N Engl J Med 1984; 310:622.
- Kaye TB, Crapo L. The Cushing syndrome: an update on diagnostic tests. Ann Intern Med 1990; 112:434.
- DeCherney GS, DeBold CR, Jackson RV, et al. Diurnal variation in the response of plasma adrenocorticotropin and cortisol to intravenous ovine corticotropin-releasing hormone. J Clin Endocrinol Metab 1985; 61:273.
- Valassi E, Swearingen B, Lee H, et al. Concomitant medication use can confound interpretation of the combined dexamethasone-corticotropin releasing hormone test in Cushing's syndrome. J Clin Endocrinol Metab 2009; 94:4851.
- Jakobsdóttir S, Twisk JW, Drent ML. The impact of blood glucose levels on stimulated adrenocorticotropin hormone and growth hormone release in healthy subjects. Clin Endocrinol (Oxf) 2009; 71:853.
- Liu JH, Muse K, Contreras P, et al. Augmentation of ACTH-releasing activity of synthetic corticotropin releasing factor (CRF) by vasopressin in women. J Clin Endocrinol Metab 1983; 57:1087.
- DeBold CR, Sheldon WR, DeCherney GS, et al. Arginine vasopressin potentiates adrenocorticotropin release induced by ovine corticotropin-releasing factor. J Clin Invest 1984; 73:533.
- Gaillard RC, Riondel AM, Ling N, Muller AF. Corticotropin releasing factor activity of CRF 41 in normal man is potentiated by angiotensin II and vasopressin but not by desmopressin. Life Sci 1988; 43:1935.
- Malerbi DA, Mendonça BB, Liberman B, et al. The desmopressin stimulation test in the differential diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf) 1993; 38:463.
- Malerbi DA, Fragoso MC, Vieira Filho AH, et al. Cortisol and adrenocorticotropin response to desmopressin in women with Cushing's disease compared with depressive illness. J Clin Endocrinol Metab 1996; 81:2233.
- Scott LV, Medbak S, Dinan TG. Desmopressin augments pituitary-adrenal responsivity to corticotropin-releasing hormone in subjects with chronic fatigue syndrome and in healthy volunteers. Biol Psychiatry 1999; 45:1447.
- Orth DN, DeBold CR, DeCherney GS, et al. Pituitary microadenomas causing Cushing's disease respond to corticotropin-releasing factor. J Clin Endocrinol Metab 1982; 55:1017.
- Reimondo G, Paccotti P, Minetto M, et al. The corticotrophin-releasing hormone test is the most reliable noninvasive method to differentiate pituitary from ectopic ACTH secretion in Cushing's syndrome. Clin Endocrinol (Oxf) 2003; 58:718.
- Tsagarakis S, Tsigos C, Vasiliou V, et al. The desmopressin and combined CRH-desmopressin tests in the differential diagnosis of ACTH-dependent Cushing's syndrome: constraints imposed by the expression of V2 vasopressin receptors in tumors with ectopic ACTH secretion. J Clin Endocrinol Metab 2002; 87:1646.
- Newell-Price J, Morris DG, Drake WM, et al. Optimal response criteria for the human CRH test in the differential diagnosis of ACTH-dependent Cushing's syndrome. J Clin Endocrinol Metab 2002; 87:1640.
- Pecori Giraldi F, Invitti C, Cavagnini F, Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-pituitary-adrenal axis. The corticotropin-releasing hormone test in the diagnosis of ACTH-dependent Cushing's syndrome: a reappraisal. Clin Endocrinol (Oxf) 2001; 54:601.
- Dickstein G, DeBold CR, Gaitan D, et al. Plasma corticotropin and cortisol responses to ovine corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), CRH plus AVP, and CRH plus metyrapone in patients with Cushing's disease. J Clin Endocrinol Metab 1996; 81:2934.
- Newell-Price J, Perry L, Medbak S, et al. A combined test using desmopressin and corticotropin-releasing hormone in the differential diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 1997; 82:176.
- Nakahara M, Shibasaki T, Shizume K, et al. Corticotropin-releasing factor test in normal subjects and patients with hypothalamic-pituitary-adrenal disorders. J Clin Endocrinol Metab 1983; 57:963.
- Lytras N, Grossman A, Perry L, et al. Corticotrophin releasing factor: responses in normal subjects and patients with disorders of the hypothalamus and pituitary. Clin Endocrinol (Oxf) 1984; 20:71.
- Müller OA, Stalla GK, von Werder K. Corticotropin releasing factor: a new tool for the differential diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 1983; 57:227.
- Pieters GF, Hermus AR, Smals AG, et al. Responsiveness of the hypophyseal-adrenocortical axis to corticotropin-releasing factor in pituitary-dependent Cushing's disease. J Clin Endocrinol Metab 1983; 57:513.
- Oldfield EH, Doppman JL, Nieman LK, et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing's syndrome. N Engl J Med 1991; 325:897.
- Arlt W, Dahia PL, Callies F, et al. Ectopic ACTH production by a bronchial carcinoid tumour responsive to desmopressin in vivo and in vitro. Clin Endocrinol (Oxf) 1997; 47:623.
- Baid SK, Rubino D, Sinaii N, et al. Specificity of screening tests for Cushing's syndrome in an overweight and obese population. J Clin Endocrinol Metab 2009; 94:3857.
- Michelson D, Galliven E, Hill L, et al. Chronic imipramine is associated with diminished hypothalamic-pituitary-adrenal axis responsivity in healthy humans. J Clin Endocrinol Metab 1997; 82:2601.
- Lindsay JR, Oldfield EH, Stratakis CA, Nieman LK. The postoperative basal cortisol and CRH tests for prediction of long-term remission from Cushing's disease after transsphenoidal surgery. J Clin Endocrinol Metab 2011; 96:2057.
- Romanholi DJ, Machado MC, Pereira CC, et al. Role for postoperative cortisol response to desmopressin in predicting the risk for recurrent Cushing's disease. Clin Endocrinol (Oxf) 2008; 69:117.
- Yanovski JA, Cutler GB Jr, Chrousos GP, Nieman LK. Corticotropin-releasing hormone stimulation following low-dose dexamethasone administration. A new test to distinguish Cushing's syndrome from pseudo-Cushing's states. JAMA 1993; 269:2232.
- Nieman L. Editorial: The dexamethasone-suppressed corticotropin-releasing hormone test for the diagnosis of Cushing's syndrome: what have we learned in 14 years? J Clin Endocrinol Metab 2007; 92:2876.
- Erickson D, Natt N, Nippoldt T, et al. Dexamethasone-suppressed corticotropin-releasing hormone stimulation test for diagnosis of mild hypercortisolism. J Clin Endocrinol Metab 2007; 92:2972.
- Martin NM, Dhillo WS, Banerjee A, et al. Comparison of the dexamethasone-suppressed corticotropin-releasing hormone test and low-dose dexamethasone suppression test in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 2006; 91:2582.
- Pecori Giraldi F, Pivonello R, Ambrogio AG, et al. The dexamethasone-suppressed corticotropin-releasing hormone stimulation test and the desmopressin test to distinguish Cushing's syndrome from pseudo-Cushing's states. Clin Endocrinol (Oxf) 2007; 66:251.
- Gatta B, Chabre O, Cortet C, et al. Reevaluation of the combined dexamethasone suppression-corticotropin-releasing hormone test for differentiation of mild cushing's disease from pseudo-Cushing's syndrome. J Clin Endocrinol Metab 2007; 92:4290.
- Newell-Price J, Trainer P, Perry L, et al. A single sleeping midnight cortisol has 100% sensitivity for the diagnosis of Cushing's syndrome. Clin Endocrinol (Oxf) 1995; 43:545.
- Raff H, Raff JL, Findling JW. Late-night salivary cortisol as a screening test for Cushing's syndrome. J Clin Endocrinol Metab 1998; 83:2681.
- Papanicolaou DA, Mullen N, Kyrou I, Nieman LK. Nighttime salivary cortisol: a useful test for the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 2002; 87:4515.
- 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.
- Karlsson R, Kallio J, Irjala K, et al. Adrenocorticotropin and corticotropin-releasing hormone tests in preterm infants. J Clin Endocrinol Metab 2000; 85:4592.
- Schlaghecke R, Kornely E, Santen RT, Ridderskamp P. The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. N Engl J Med 1992; 326:226.
- Schmidt IL, Lahner H, Mann K, Petersenn S. Diagnosis of adrenal insufficiency: Evaluation of the corticotropin-releasing hormone test and Basal serum cortisol in comparison to the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease. J Clin Endocrinol Metab 2003; 88:4193.
- CORTICOTROPIN-RELEASING HORMONE STIMULATION TEST
- Normal values
- CRH PLUS ARGININE VASOPRESSIN OR DESMOPRESSIN
- DIAGNOSIS OF THE CAUSE OF CUSHING'S SYNDROME
- CRH stimulation test
- CRH plus arginine vasopressin stimulation test
- CRH plus desmopressin stimulation test
- Caveats to the use of CRH, AVP or desmopressin in Cushing's syndrome
- CRH AFTER TRANSSPHENOIDAL SURGERY TO PREDICT RECURRENCE
- CRH AFTER LOW-DOSE DEXAMETHASONE TEST
- ADRENAL INSUFFICIENCY
- SOCIETY GUIDELINE LINKS