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14-September-2008 18:02:45 - stimulation test Demonstration of how a blood draw is performed in the ACTH stimulation test Demonstration of how a blood draw is performed in the ACTH stimulation test The ACTH stimulation test also called the cosyntropin test or tetracosactide test is a medical test usually ordered and interpreted by endocrinologists to assess the functioning of the adrenal glands stress response by measuring the adrenal response to adrenocorticotropic hormone ACTH.12 ACTH is a hormone produced in the pituitary gland that stimulates the adrenal glands to release cortisol.2 During the test, a small amount of synthetic ACTH is injected, and the amount of cortisol, and sometimes aldosterone, that the adrenals produce in response is measured.3 This test may cause mild to moderate side effects in some individuals.45 This test is used to diagnose or exclude primary and secondary adrenal insufficiency, Addison's disease and related conditions.2 In addition to quantifying adrenal insufficiency, the test can distinguish whether the cause is adrenal low cortisol and aldosterone production or pituitary low ACTH production.1 The ACTH stimulation test is recognized by the medical community as the final say in whether or not an individual has a degree of adrenal insufficiency, although this test is primarily used to determine the presence of Addison's disease and pituitary impairment.6 If the test does not show Addison's, the test interpreter may see it as showing the adrenal glands are working, not recognizing any degree of adrenal insufficiency between frank Addison's the worst degree of adrenal insufficiency and healthy adrenal function.citation needed Secondary adrenal insufficiency is often missed by uninformed interpreters of this test.citation needed Adrenal insufficiency is a potentially life-threatening condition. Treatment should be initiated as soon as the diagnosis is confirmed, or sooner if the patient presents in adrenal crisis.7 Contents 1 Versions of the test 2 Preparation 3 Administration 4 Potential side effects 5 Interpretation of results 5.1 Cortisol stimulation 5.2 ACTH plasma test plus cortisol stimulation 5.3 Aldosterone stimulation 6 Other hormones and chemicals that will rise in the ACTH stimulation test 7 Simple diagnostic chart 8 See also 9 References 10 External links Versions of the test This test can be given as a low-dose short test, a conventional-dose short test, or as a prolonged-stimulation test. In the low-dose short test, 1 microgram of an ACTH drug is injected into the patient. In the conventional-dose short test, 250 µg of drug are injected. Both of these short tests last for about an hour and provide the same information. Studies have shown the measured stress response of the adrenals is the same for the low-dose and conventional-dose tests.8 The prolonged-stimulation test, which is also called a long conventional-dose test, can last up to 48 hours. This form of the test can differentiate between primary, secondary, and tertiary adrenal insufficiency. This form of the test is rarely performed because earlier testing of cortisol and ACTH levels in association with the short test may provide all the necessary information.7 Preparation The person must fast at least 8 hours before the test which should be started by 10 am, but as close to 7 am as possible.9 The test shouldn't be given if on glucocorticoids, pregnenolone, or adrenal extract supplement as these will affect test results. Stress and recently administered radioisotope scans can artificially increase levels and may invalidate test results. Spironolactone, contraceptives, licorice, estrogen, androgen including DHEA and progesterone therapy may also affect both aldosterone and cortisol stimulation test results.1011 If aldosterone is to be stimulated, salt and foods significant in sodium must be fasted for 24 hours prior to testing. This allows aldosterone to rise as far as possible. Women must test the first week of their cycle or aldosterone and occasionally cortisol results may appear ok in the last half of the cycle when progesterone is higher progesterone breaks down into aldosterone and cortisol.12 Administration Blood is drawn to get a starting or base cortisol plasma ACTH is also tested from this draw and or aldosterone level. Next, synthetic ACTH Synacthen aka Tetracosactide or Cortrosyn aka Cosyntropin is injected. Approximately 20 mL of heparinized venous blood is collected at 30 and 60 minutes after the synthetic ACTH injection.1314 All blood samples are kept on ice and sent immediately to the laboratory for testing.9 Potential side effects Normal reactions that should be reported are nausea, anxiety, sweating, dizziness, itchy skin, redness and or swelling of injection site, palpitations a fast of fluttering heart beat and facial flushing may also include arms and torso, but should disapear within a few hours.45 Rarely seen, but serious side effects include rash, fainting, headache, blurred vision, severe swelling, severe dizziness, trouble breathing, irregular heartbeat.5 Although uncommon, some people report feeling better or sense of well being after the test. Interpretation of results The adrenal glands sit atop the kidneys. The adrenal glands sit atop the kidneys. Cortisol stimulation In healthy individuals, the cortisol level should double from a value at least in the 20s within 60 minutes. If the cortisol level was a 25 before the stimulation base level, after the stimulation it should reach at least 50 ug/dl. Interpretation for primary adrenal insufficiency and Addison's disease The base cortisol level in people with adrenal insufficiency is usually in the mid teens. If the ACTH stimulation test raises cortisol level to 20 ug/dl, that is not doubling and supports the diagnosis of primary adrenal insufficiency. In Addison's, base cortisol is well below 10 ug/dl and rises no more than 25 percent. Interpretation for secondary adrenal insufficiency Cortisol stimulates by a factor doubling, tripling, quadrupling or more from a low base value. Other examples of multiple factoring reported include quintupling 5 stimulating to 25 ng/dl, 6 to 30, sextupling 4 ug/dl stimulating to 24, 4.1 to 26.9, 5 to 30, septupling 0.7 ug/dl stimulating to 4.9, decupling 2 ug/dl stimulating to 20, 2.7 to 27.6, tridecupling 1.25 ug/dl stimulating to 16, a factor of 12.8 and quadecupling 1.7 ug/dl stimulating to 24, after 1 1/2 hours reached 27.5 for sexdecupling. These examples illustrate how extreme the ACTH stimulation test result can be in secondary adrenal insufficiency, but most secondaries only double or triple and most start with a base cortisol value of at least 10. The lower the base cortisol value, the more likely the persons cortisol will stimulate by a high factor if they are secondary adrenal insufficient. The base cortisol can be very low because of the bodies lack of natural ACTH. When the synthetic ACTH is given to secondaries, the adrenals go hog wild because they can work, just not getting enough ACTH from the pituitary gland.9 In some instances, a second test performed later can suggest primary adrenal insufficiency cortisol value less than doubled. The diagnosis may be changed from secondary to primary adrenal insufficiency or to include primary adrenal insufficiency. In secondary adrenal insufficiency, if the adrenal glands lack ACTH for enough time, cortisol production can atrophy15 and fail to rise to a value at least double the base cortisol value. It is proper to continue with the diagnosis of secondary adrenal insufficiency. If secondary adrenal insufficiency is diagnosed, the insulin tolerance test ITT or the CRH Corticotropin-releasing hormone stimulation test can be used to distinguish between a hypothalamic tertiary and pituitary secondary cause, but is rarely used in clinical practice.15 ACTH plasma test plus cortisol stimulation Location of the pituitary gland. Location of the pituitary gland. An ACTH plasma test should always be given at the same time as the ACTH stimulation, although many doctors consider the test inaccurate. This test measures how much ACTH the pituitary gland is producing. A healthy ACTH value should be just into the upper third of the range assuming a range of 10-60 ng/L. The ACTH plasma and ACTH stimulation test together can give a clearer picture, especially for secondary adrenal insufficiency.13 Interpretation for primary adrenal insufficiency and Addison's disease ACTH will be high13 - either at the top or above range. In Addison's disease, ACTH may be way above range and may reach the hundreds. In very rare cases can reach the 1000s and 2000s. Interpretation for secondary adrenal insufficiency ACTH will be low13 - Usually below 35, but most people with secondary fall within the range limit. Although uncommon, values for ACTH can reach into the low 40s. 98% of people with secondary fall within range. In some cases, actual cause of low ACTH is from low CRH in the hypothalamus. It is possible to have separate ACTH and CRH impairment such as can happen in a head injury.16 Aldosterone stimulation The ACTH stimulation test is occasionally used to test adrenal production of aldosterone at the same time as cortisol to also help in determining if primary hyperreninemic or secondary hyporeninemic hypoaldosteronism is present.3 Human ACTH has a slight stimulatory effect on aldosterone17, but the amount of synthetic ACTH given in the stimulation is equivalent to more than a whole days production of natural ACTH, so the aldosterone response can be easily measured in blood serum.18 Same as cortisol, aldosterone should double from a respectable base value around 20 ng/dl, must fast salt 24 hours and sit upright for blood draw in a healthy individual. Interpretation for primary aldosterone deficiency The aldosterone response in the ACTH stimulation test is blunted or absent in patients with primary adrenal insufficiency including Addison's disease.3 The base value is usually in the mid teens or less and rise to less than double the base value thus indicating primary hypoaldosteronism sodium low, potassium and renin enzyme will be high and is an indicator of primary adrenal insufficiency or Addison's disease. Interpretation for secondary aldosterone deficiency Aldosterone response of several factors from a low base value. This factoring indicates secondary hypoaldosteronism sodium low, potassium and renin enzyme will be low. Usually doubling to quadrupling from a low base aldosterone value is what is seen in secondary adrenal insufficiency. Decupling of aldosterone in the ACTH stimulation test is possible ie 2 ng/dl stimming to 20.19 A result of doubling of more of aldosterone may help in tandem with a cortisol stimulation that doubled or more confirm a diagnosis of secondary adrenal insufficiency. In rare cases, an aldosterone stimulation which did not double, but with the presence of low potassium, low renin and low ACTH indicates atrophy of aldosterone production from the prolonged lack of renin. Similar to the cortisol stimulation in ACTH deficiency, the test interpreter may lack knowledge of how to properly interpret for secondary hypoaldosteronism and think a result of aldosterone doubling or more from a low base value is good. Other hormones and chemicals that will rise in the ACTH stimulation test Progesterone - precursor to cortisol and aldosterone20 Luteinizing hormone - a pituitary hormone that stimulates sex hormone production20 21-Hydroxylase21 DHEA and DHEA-S an androgen hormone produced in the adrenal glands Simple diagnostic chart Source of pathology CRH ACTH DHEA DHEA-S cortisol aldosterone renin Na K Causes5 hypothalamus tertiary1 low low low low low3 low low low low tumor of the hypothalamus adenoma, antibodies, environment, head injury pituitary secondary high2 low low low low3 low low low low tumor of the pituitary adenoma, antibodies, environment, head injury, surgical removal6, Sheehan's syndrome adrenal glands primary7 high high high high low4 low high low high tumor of the adrenal adenoma, stress, antibodies, environment, Addison's, injury, surgical removal 1 Automatically includes diagnosis of secondary hypopituitarism 2 Only if CRH production in the hypothalamus is intact 3 Value doubles or more in stimulation 4 Value less than doubles in stimulation 5 Most common, doesn't include all possible causes 6 Usually because of very large tumor macroadenoma 7 Includes Addison's disease See also Insulin tolerance test, another test used to identify sub-types of adrenal insufficiency Metyrapone, a drug used in the diagnosis of adrenal insufficiency Triple bolus test Renin, enzyme that converts Angiotensinogen to Angiotensin I, a precursor to Aldosterone Renin-angiotensin-aldosterone system HPA axis, explains the connections of the hypothalamus, pituitary and adrenal glands Hypopituitarism Pituitary adenoma adrenal adenoma References ^ a b Dorin RI, Qualls CR, Crapo LM 2003. Diagnosis of adrenal insufficiency PDF. Ann. Intern. Med. 139 3: 194-204. PMID 12899587. ^ a b c Elizabeth H. Holt, MD, PhD 2008. ACTH cosyntropin stimulation test. ^ a b c unknown. ACTH Stimulation Test. APPENDIX - Endocrinology. ^ a b unknown. Synacthen Test PDF. ^ a b c unknown. GENERIC NAME: COSYNTROPIN - INJECTABLE koe-sin-TROW-pin. ^ unknown 2006. ACTH Cortrosyn stimulation test. ^ a b Evangelia Charmandari, M.D., and George P. Chrousos, M.D.. ADRENAL INSUFFICIENCY Chapter 13. ^ Abdu TA; Elhadd TA; Neary R; Clayton RN 1999. Comparison of the low dose short synacthen test 1 microg, the conventional dose short synacthen test 250 microg, and the insulin tolerance test for assessment of the hypothalamic-pituitary-adrenal axis in patients with pituitary disease.. ^ a b c K. Pagana, PhD, RN and T. Pagana, MD, FACS. Mosby's Diagnostic and Laboratory Test Reference 2nd ed: Adrenocorticotropic hormone stimulation test: 17. ^ K. Pagana, PhD, RN and T. Pagana, MD, FACS. Mosby's Diagnostic and Lab Test Reference 2nd ed: Aldosterone, Cortisol: 29 and 260. ^ unknown 2006. Aldosterone in Blood. ^ Emily D. Szmuilowicz, Gail K. Adler, Jonathan S. Williams, Dina E.Green, Tham M. Yao, Paul N. Hopkins and Ellen W. Seely. Relationship between Aldosterone and Progesterone in the Human Menstrual Cycle: 3981-3987. ^ a b c d unknown. ACTH Rapid Stimulation Test Cortrosyn, Cosyntropin. ^ NIDDK's Office of Health Research Reports. Addison's disease. ^ a b Ashley B. Grossman, MD 2007. Addison's Disease. Endocrine and Metabolic Disorders. ^ Lynnette K Nieman, MD 2008. Corticotropin-releasing hormone stimulation test. ^ unknown. Role of ACTH in Regulation and Action of Adrenocorticoids: 7 of 52. ^ unknown. Aldosterone and Renin. ^ L.A. Cunningham and M.A. Holzwarth 1988. Vasoactive intestinal peptide stimulates adrenal aldosterone and corticosterone secretion. Endocrinology 122: 2090-2097. PMID 3359977. ^ a b Jardena J. Puder, Pamela U. Freda, Robin S. Goland, Michel Ferin,and Sharon L. Wardlaw. http://jcem.endojournals.org/cgi/reprint/85/6/2184.pdf Stimulatory Effects of Stress on Gonadotropin Secretion in Estrogen-Treated Women. The Journal of Clinical Endocrinology Metabolism 85: 2184-2188. ^ unknown. ACTH Stimulation Test for 21-Hydroxylase. External links ACTH cosyntropin stimulation test - based on information from Medline Plus Medical Encyclopedia ACTH stimulation test - Procedures/Diagnostic tests Warren Grant Magnuson Clinical Center National Institutes of Health. v d e Endocrine system: hormones/endocrine glands Peptide hormones, Steroid hormones Hypothalamic-pituitary Hypothalamus: TRH, CRH , GnRH, GHRH, somatostatin, dopamine - Posterior pituitary: vasopressin, oxytocin - Anterior pituitary: α FSH, LH, TSH, GH, prolactin, POMC ACTH, MSH, endorphins, lipotropin Adrenal axis Adrenal medulla: epinephrine, norepinephrine - Adrenal cortex: aldosterone, cortisol, DHEA Thyroid axis Thyroid: thyroid hormone T3 and T4 - calcitonin - Parathyroid: PTH Gonadal axis Testis: testosterone, AMH, inhibin - Ovary: estradiol, progesterone, inhibin/activin, relaxin pregnancy Other end. glands Pancreas: glucagon, insulin, somatostatin - Pineal gland: melatonin Non-end. glands Placenta: hCG, HPL, estrogen, progesterone - Kidney: renin, EPO, calcitriol, prostaglandin - Heart atrium: ANP - Stomach: gastrin, ghrelin - Duodenum: CCK, GIP, secretin, motilin, VIP - Ileum: enteroglucagon - Adipose tissue: leptin, adiponectin, resistin - Thymus: Thymosin - Thymopoietin - Thymulin - Skeleton: Osteocalcin - Liver/other: Insulin-like growth factor IGF-1, IGF-2 Target-derived NGF, BDNF, NT-3 v d e Endocrine pathology: endocrine diseases Hypothalamic/ pituitary axes Pituitary Hyperpituitarism Acromegaly, Hyperprolactinaemia, SIADH Hypopituitarism Sheehan's syndrome, Kallmann syndrome, Growth hormone deficiency, Diabetes insipidus Adiposogenital dystrophy - Empty sella syndrome - Pituitary apoplexy - ACTH deficiency Thyroid Hypothyroidism Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre, Myxedema Hyperthyroidism Graves disease, Toxic multinodular goitre, Teratoma with thyroid tissue or Struma ovarii Thyroiditis De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis Euthyroid sick syndrome - Thyroid hormone resistance - Thyroid nodule Adrenal Adrenocortical hyperfunction: Cushing's syndrome Nelson's syndrome, Pseudo-Cushing's syndrome - Hyperaldosteronism Conn syndrome, Bartter syndrome CAH Lipoid, 3β, 11β, 17α, 21α Adrenal insufficiency Addison's disease, Waterhouse-Friderichsen syndrome - Hypoaldosteronism Gonads ovarian Polycystic ovary syndrome, Premature ovarian failure testicular 5-alpha-reductase deficiency, 17-beta-hydroxysteroid dehydrogenase deficiency general Hypogonadism, Delayed puberty, Precocious puberty v d e Urinary system, physiology: renal physiology and acid base physiology Filtration Renal blood flow - Ultrafiltration - Countercurrent exchange Hormones affecting filtration Antidiuretic hormone ADH - Aldosterone - Atrial natriuretic peptide Secretion/clearance Pharmacokinetics - Clearance of medications Reabsorption Solvent drag - Na+ - Cl- - urea - glucose - oligopeptides - protein Endocrine Renin - Erythropoietin EPO - Calcitriol Active vitamin D - Prostaglandins Assessing Renal function/ Measures of dialysis Glomerular filtration rate - Creatinine clearance - Renal clearance ratio - Urea reduction ratio - Kt/V - Standardized Kt/V - Hemodialysis product - PAH clearance Effective renal plasma flow - Extraction ratio Acid base physiology Fluid balance - Darrow Yannet diagram - Body water - Interstitial fluid - Extracellular fluid - Intracellular fluid/Cytosol - Plasma - Transcellular fluid - Base excess - Davenport diagram - Anion gap - Arterial blood gas Buffering/compensation Bicarbonate buffering system - Respiratory compensation - Renal compensation Retrieved from http://en..org/wiki/ACTH_stimulation_test Categories: HPA axis | Medical tests | Blood tests | EndocrinologyHidden categories: All articles with statements | Articles with statements since September 2008 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Español Français This page was last modified on 11 September 2008, at 01:32
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