ACTH stimulation test: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Bot: Automated text replacement (-{{SIB}} + & -{{EH}} + & -{{EJ}} + & -{{Editor Help}} + & -{{Editor Join}} +))
 
No edit summary
Line 1: Line 1:
__NOTOC__
{{Diagnostic infobox |
  Name        = {{PAGENAME}} |
  Image      = |
  Caption    = |
  ICD10      = |
  ICD9        = |
  MeshID      = |
  OPS301      = {{OPS301|1-797}} |
  OtherCodes  = |
}}
{{SI}}
{{SI}}
{{CMG}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}
__NOTOC__
 
'''Associate Editor-In-Chief:''' {{CZ}}
==Overview==
The '''ACTH stimulation test''' (also called the '''[[cosyntropin]] test''', '''[[tetracosactide]] test''' or '''Synacthen test''') is a [[medical test]] usually ordered and interpreted by [[endocrinologist]]s to assess the functioning of the [[adrenal gland]]s stress response by measuring the adrenal response to [[adrenocorticotropic hormone]] (ACTH).<ref name="pmid12899587">{{cite journal |author=Dorin RI, Qualls CR, Crapo LM |title=Diagnosis of adrenal insufficiency |journal=[[Ann. Intern. Med.]] |volume=139 |issue=3 |pages=194–204 |year=2003 |pmid=12899587 |url=http://www.annals.org/cgi/reprint/139/3/194.pdf|format=PDF}}</ref><ref name="003696.htm">{{cite journal | author=Elizabeth H. Holt, MD, PhD | title=ACTH (cosyntropin) stimulation test |year=2008|url=http://www.nlm.nih.gov/medlineplus/ency/article/003696.htm}}</ref> [[ACTH]] is a hormone produced in the [[pituitary gland]] that stimulates the adrenal glands to release [[cortisol]], dehydroepiandrosterone (DHEAS) and [[aldosterone]].<ref name="pmid7581984">{{Cite journal  | last1 = Hanukoglu | first1 = A. | last2 = Fried | first2 = D. | last3 = Nakash | first3 = I. | last4 = Hanukoglu | first4 = I. | title = Selective increases in adrenal steroidogenic capacity during acute respiratory disease in infants. | journal = Eur J Endocrinol | volume = 133 | issue = 5 | pages = 552-6 | month = Nov | year = 1995 | doi = 10.1530/eje.0.1330552 | PMID = 7581984 }}</ref>
 
During the test, a small amount of synthetic ACTH is injected, and the amount of cortisol, and sometimes [[aldosterone]], the adrenals produce in response is measured.<ref name="Appendix09_ACTHa.pdf">{{cite journal| author=unknown | title=ACTH Stimulation Test| journal=APPENDIX – Endocrinology|url=http://www.wardelab.com/Appendix09_ACTHa.pdf|format=PDF}}{{dead link|date=May 2012}}</ref>  This test may cause mild to moderate side effects in some individuals.<ref name>{{cite journal | author=unknown | title= Synacthen Test|url=http://www.stgeorges.nhs.uk/docs/leaflets/synacthen.pdf | format=PDF}}{{dead link|date=May 2012}}</ref><ref name="article.htm">{{cite journal | author=unknown | title=GENERIC NAME: COSYNTROPIN - INJECTABLE (koe-sin-TROW-pin) |url=http://www.medicinenet.com/cosyntropin-injectable/article.htm}}</ref>
 
This test is used to diagnose or exclude primary and secondary [[adrenal insufficiency]], [[Addison's disease]] and related conditions.<ref name="003696.htm" />  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).<ref name="pmid12899587">{{cite journal |author=Dorin RI, Qualls CR, Crapo LM |title=Diagnosis of adrenal insufficiency |journal=Ann. Intern. Med. |volume=139 |issue=3 |pages=194–204 |year=2003 |pmid=12899587 |url=http://www.annals.org/cgi/reprint/139/3/194.pdf|format=PDF}}</ref>  The ACTH stimulation test is recognized as the gold standard assay of adrenal insufficiency, although this test is primarily used to determine the presence of Addison's disease and pituitary impairment.<ref name="ACTH-Cortrosyn-stimulation-test.htm">{{cite journal| author=unknown | title=ACTH (Cortrosyn) stimulation test| sect=Why the test is performed | year=2006 | url=http://adam.about.com/encyclopedia/ACTH-Cortrosyn-stimulation-test.htm| page=1}}</ref>  The test is extremely sensitive (97% at 95% specificity) to primary adrenal insufficiency, but less so to secondary adrenal insufficiency (57-61% at 95% specificity); while secondary adrenal insufficiency may thus be dismissed by some interpreters on the basis of the test, additional testing may be called for if probability of secondary adrenal insufficiency is particularly high.<ref name="pmid12899587" />
 
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 apparent adrenal crisis.<ref name="adrenalframe13.htm">{{cite journal| author=Evangelia Charmandari, M.D., and George P. Chrousos, M.D. | title=ADRENAL INSUFFICIENCY Chapter 13|url=http://www.endotext.org/adrenal/adrenal13/adrenalframe13.htm}}</ref>
 
==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&nbsp;µg of an ACTH drug is injected into the patient.  In the conventional-dose short test, 250&nbsp;µg of drug are injected.  Both of these short tests last for about an hour and provide the same information.  Studies have shown the cortisol response of the adrenals is the same for the low-dose and conventional-dose tests.<ref name="emed_ckb_ref_0">{{cite journal | author=Abdu TA; Elhadd TA; Neary R; Clayton RN | title=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|journal=Journal of Clinical Endocrinology and Metabolism | year=1999 | url=http://www.medscape.com/medline/abstract/10084558?src=emed_ckb_ref_0 | doi=10.1210/jc.84.3.838 | volume=84 | pages=838–43 | issue=3 | pmid=10084558}}</ref><ref name="pmid20626639">{{cite journal | author = Cemeroglu AP, Kleis L, Postellon DC, Wood MA | title = COMPARISON OF LOW AND HIGH DOSE COSYNTROPIN STIMULATION TESTING IN CHILDREN | journal = [[Pediatrics International : Official Journal of the Japan Pediatric Society]] | volume = 53| issue = 2| pages = 175–80| year = 2010 | month = July | pmid = 20626639 | doi = 10.1111/j.1442-200X.2010.03203.x | url =  }}</ref>
 
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.<ref name="adrenalframe13.htm"/>
 
== 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. The test shouldn't be given if on [[glucocorticoids]], 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 <citation needed for radioisotope scans>.  [[Spironolactone]], [[contraceptives]], [[licorice]], [[estrogen]], [[androgen]] (including [[DHEA]]) and [[progesterone]] therapy may also affect both aldosterone and cortisol stimulation test results. To stimulate aldosterone, added salt and foods significant in sodium must be avoided for 24 hours prior to testing.  Women should ideally undergo testing during the first week of their menstrual cycle as aldosterone (and occasionally cortisol) may be falsely elevated in the luteal cycle secondary to progesterone inhibition, leading to a compensatory rise in aldosterone levels.<ref name = "91/10/3981">{{cite journal| author=Emily D. Szmuilowicz, Gail K. Adler, Jonathan S. Williams, Dina E.Green, Tham M. Yao, Paul N. Hopkins and Ellen W. Seely | journal=Journal of Clinical Endocrinology & Metabolism|title=Relationship between Aldosterone and Progesterone in the Human Menstrual Cycle|pages=3981–3987|url=http://jcem.endojournals.org/cgi/content/full/91/10/3981|volume=91| doi=10.1210/jc.2006-1154| year=2006|issue=10| pmid=16868049}}</ref>
 
== Administration ==
Traditionally, cortisol and ACTH levels (separate lavender top tube) are drawn at baseline (time = 0).  Next, synthetic ACTH (Synacthen aka [[Tetracosactide]] or Cortrosyn aka [[Cosyntropin]]) is injected IM or IV depending on the agent<ref>{{cite web|title=Drugs.com Citation|url=http://www.drugs.com/ppa/cosyntropin-synthetic-corticotropin-synthetic-acth.html}}</ref> .  Approximately 20 mL of heparinized venous blood is collected at 30 and 60 minutes after the synthetic ACTH injection to measure cortisol levels.<ref name="ACTHRapidStimulationTest.html">{{cite journal| author=unknown | title=ACTH Rapid Stimulation Test (Cortrosyn, Cosyntropin)|url=http://www.clinlabnavigator.com/Tests/ACTHRapidStimulationTest.html}} {{dead link|date=July 2010}}</ref><ref name="addison.htm">{{cite journal| author=NIDDK's Office of Health Research Reports | title=Addison's disease |url=http://endocrine.niddk.nih.gov/pubs/addison/addison.htm}}</ref>
 
All blood samples are kept on ice and sent immediately to the laboratory for testing.<ref name="Mosby's Diagnostic and Laboratory Test Reference 2nd ed.">{{cite journal |author=K. Pagana, PhD, RN and T. Pagana, MD, FACS | title=Mosby's Diagnostic and Laboratory Test Reference 2nd ed.: Adrenocorticotropic hormone stimulation test| pages = 17–18}}</ref>
 
==Potential side effects==
 
Commonly reported reactions are nausea, anxious sweating, dizziness, itchy skin, redness and or swelling of injection site, palpitations (a fast or fluttering heart beat) and facial flushing (may also include arms and torso), but should disappear within a few hours.<ref name>{{cite journal | author=unknown | title= Synacthen Test|url=http://www.stgeorges.nhs.uk/docs/leaflets/synacthen.pdf | format=PDF}}</ref><ref name="article.htm"/>  Rarely seen, but serious side effects include rash, fainting, headache, blurred vision, severe swelling, severe dizziness, trouble breathing, irregular heartbeat.<ref name="article.htm"/>
 
Although uncommon, some people report feeling better or sense of well being after the test.{{cn|date=May 2011}}
 
==Interpretation of results==
 
[[Image:Illu adrenal gland.jpg|thumb|right||200px|The [[adrenal glands]] sit atop the kidneys.]]


===Cortisol stimulation===
In healthy individuals, the cortisol level should double from a baseline of 20-30&nbsp;µg/dl within 60 minutes. For example, if the serum cortisol level was 25&nbsp;ug/dl before the stimulation, it should reach at least 50&nbsp;µg/dl.


;Interpretation for primary adrenal insufficiency and Addison's disease
The baseline cortisol level in people with adrenal insufficiency is usually near 15&nbsp;µg/dl.  An ACTH stimulation test that raises the cortisol concentration to 20&nbsp;µg/dl would support the diagnosis of primary [[adrenal insufficiency]].  In Addison's disease, baseline cortisol is well below 10&nbsp;µg/dl and rises no more than 25 percent.


==Overview==
;Interpretation for secondary adrenal insufficiency
ACTH may dramatically stimulate cortisol from the low baseline value encountered in patients suffering from secondary adrenal insufficiency.  Stimulation resulting in a greater than 14-fold increase in serum concentration over 30 minutes has been reported, although more typically serum cortisol levels will double or triple from baseline.  The lower the baseline cortisol, the more likely it is that the patient's cortisol will increase by a large amount.<ref name="Mosby's Diagnostic and Laboratory Test Reference 2nd ed."/>


The '''ACTH stimulation test''' (also called the '''short Synacthen test''') is a [[medical test]] performed to assess the functioning of the [[adrenal gland]]s. Specifically, it is used to diagnose or exclude [[adrenal insufficiency]], [[Addison's disease]] and related conditions. It involves the injection of synthetic [[adrenocorticotropic hormone]] (ACTH) and measuring the amount of [[cortisol]] and sometimes [[aldosterone]] the adrenals produce in response.  Apart from objectivating adrenal insufficiency, it can also distinguish the various causes.<ref name="pmid12899587">{{cite journal |author=Dorin RI, Qualls CR, Crapo LM |title=Diagnosis of adrenal insufficiency |journal=Ann. Intern. Med. |volume=139 |issue=3 |pages=194–204 |year=2003 |pmid=12899587 |url=http://www.annals.org/cgi/reprint/139/3/194.pdf|format=PDF}}</ref>
In some instances, a second test 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 [[atrophy]]<ref name="ch153b.html">{{cite journal | author=Ashley B. Grossman, MD | title=Addison's Disease | journal=Endocrine and Metabolic Disorders|sect=Testing|year=2007|url=http://www.merck.com/mmpe/print/sec12/ch153/ch153b.html|page=4}}</ref> 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.


==Method of preparation and administration==
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.<ref name="ch153b.html"/>
The patient should fast 12 hours before the test which should be done before 10 am, but as close to 7 am as possible.<ref name="Mosby's Diagnostic and Laboratory Test Reference 2nd ed.">{{cite journal |author=K. Pagana, PhD, RN and T. Pagana, MD, FACS | title=Mosby's Diagnostic and Laboratory Test Reference 2nd ed: Adrenocorticotropic hormone stimulation test| pages = 17}}</ref>  If the patient is already on a glucocorticoid, DHEA, pregnenolone or adrenal extract supplement, they should be off of these for at least 2 weeks after safely weaning.  Stress and recently administered radioisotope scans can artificially increase levels and may invalidate test results.  Spironolactone, contraceptives, estrogen, androgen and progesterone therapy may also affect both aldosterone and cortisol stimulation test results.<ref name="Mosby's Diagnostic and Lab Test Reference 2nd ed.">{{cite journal |author=K. Pagana, PhD, RN and T. Pagana, MD, FACS |title=Mosby's Diagnostic and Lab Test Reference 2nd ed: Aldosterone, Cortisol| pages = 29 and 260}}</ref> If aldosterone is to be stimulated, salt and foods significant in sodium must be fasted for 24 hours prior to the test.  This is to allow aldosterone to rise as far as possible.  Women must test aldosterone in the first week of their cycle.  The test procedure should be explained to the patient well before the test is performed. 


The patients blood is drawn to get a starting or base [[cortisol]] level (serum [[ACTH]] should also be tested), next synthetic ACTH (Synacthen aka [[Tetracosactide]] or Cortrosyn aka [[Cosyntropin]]) is injected. Approximately 20 mg of heparinized venous blood is collected (in a red top tube to be chilled after last blood draw and shipped on ice to the lab immediately) is drawn 30 min, sometimes 45 min, and at 60 minutes after the synthetic ACTH has been injected.<ref name="Mosby's Diagnostic and Laboratory Test Reference 2nd ed.">{{cite journal |author=K. Pagana, PhD, RN and T. Pagana, MD, FACS | title=Mosby's Diagnostic and Laboratory Test Reference 2nd ed.: Adrenocorticotropic hormone stimulation test| pages = 17-18}}</ref> The test must be done for at least 60 minutes.  In healthy adrenal function, the cortisol level should double within 60 minutes.  If the cortisol level was a 25 before the stimulation (base level), after the stimulation should reach at least 50.  Most patients feel nothing during or after the test, but flushed skin, anxiety and nausea and even an increased sense of well being are possible.
===ACTH plasma test plus cortisol stimulation===
[[Image:Pituitary gland.png‎|thumb|right|200px|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&nbsp;ng/L).  The ACTH plasma and ACTH stimulation test together can give a clearer picture, especially for secondary adrenal insufficiency.<ref name="ACTHRapidStimulationTest.html"/>


==Method and interpretation for cortisol stimulation==
;Interpretation for primary adrenal insufficiency and Addison's disease
In primary adrenal insufficiency, the base [[cortisol]] level usually starts at least a little lower, such as 15 (can be much lower).  If the [[ACTH]] stimulation test raises cortisol level to 20, that would not be doubling and support the diagnosis of primary [[adrenal insufficiency]].
ACTH will be high<ref name="ACTHRapidStimulationTest.html"/> - 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.


In secondary adrenal insufficiency, the base [[cortisol]] can double, triple, quadruple or more from a low base value.  Other examples reported include quintupling (5 stimming to 25 ng/dl, 6 stimming to 30), sextupling (4 stimming to 24, 5 stimming to 30), septupling (0.7 stimming to 4.9) and decupling (2 stimming to 20, 2.7 stimming to 27.6) and recently a stim that almost tridecupled (1.25 - 16 went up 12.8 times) and a stimulation that quadecupled (went up 14 times 1.7 stimming to 24, after 1 1/2 hours reached 27.5 for sexdecupling).  These examples illustrate how extreme secondaries ACTH stimulation test can be.  Most secondaries only double or triple and usually start with a base cortisol value of at least 10.  The base cortisol can be very low because of the bodies lack of natural [[ACTH]].  When the synthetic ACTH is given in the test, the patients adrenals go hog wild because they can work, just not getting enough ACTH from the pituitary gland.<ref name="Mosby's Diagnostic and Laboratory Test Reference 2nd ed.">{{cite journal |author=K. Pagana, PhD, RN and T. Pagana, MD, FACS | title=Mosby's Diagnostic and Laboratory Test Reference 2nd ed.: Adrenocorticotropic hormone stimulation test| pages = 17-18}}</ref>
;Interpretation for secondary adrenal insufficiency
ACTH will be low<ref name="ACTHRapidStimulationTest.html"/> - Usually below 35, but most people with secondary fall within the range limit. Although uncommon, values for ACTH can reach into the low 40s.


Some have reported their first [[ACTH]] stimulation test doubled or more from a low base [[cortisol]] value, but another test done later suggested they are really primary adrenal insufficient (cortisol value less than doubled).  Many have reported their doctor changed their diagnosis from secondary to primary adrenal insufficiency "I guess you were primary the whole time". In secondary adrenal insufficiency, if the adrenals lack ACTH for enough time, adrenal cortisol production can [[atrophy]], thus no longer rise in an ACTH stimulation with serum ACTH being in the lower half of the range. It is proper to continue with the secondary diagnosis.
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.<ref name="L8psmoE71_MEP">{{cite journal| author=Lynnette K Nieman, MD | title=Corticotropin-releasing hormone stimulation test| year=2008 |url=http://www.uptodate.com/patients/content/topic.do?topicKey=~L8psmoE71_MEP}}</ref>


The [[ACTH]] test is usually the final say in whether you have [[adrenal insufficiency]], but most doctors are only looking for [[Addison's disease]].  If the test does not show Addison's (for example, in true Addison's, the stimulation may start at 3 and rise to 4 or 6 rising to 8), then doctors see the stimulation as showing the adrenals are working. They fail to recognize any degree of adrenal insufficiency between Addison's and healthy adrenal function.  Many patients with secondary adrenal insufficiency are missed because most doctors see doubling or more even from a low base [[cortisol]] value with low acth being ok, not recognizing this indicates low ACTH production.
===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.<ref name="Appendix09_ACTHa.pdf"/>  Human ACTH has a slight stimulatory effect on aldosterone,<ref name="s5ch7_7.htm">{{cite journal |author=unknown | title=Role of ACTH in Regulation and Action of Adrenocorticoids | pages = 7 of 52|url=http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch7/s5ch7_7.htm}}</ref> 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.<ref name="test.html">{{cite journal| author=unknown | title=Aldosterone and Renin | url=http://www.labtestsonline.org/understanding/analytes/aldosterone/test.html}}</ref> Same as cortisol, aldosterone should double from a respectable base value (around 20&nbsp;ng/dl, must fast salt 24 hours and sit upright for blood draw) in a healthy individual.


The [[ACTH]] serum test should always be given at the same time as the ACTH stimulation.  This test measures how much ACTH the pituitary is making.  ACTH serum and ACTH stimulation test together can give a clearer picture, especially if one is secondary adrenal insufficient.  
;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.<ref name="Appendix09_ACTHa.pdf"/> 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.


In primary adrenal insufficiency (including Addison's), [[ACTH]] serum will be at the top of the range or above range.  Sometimes in Addison's disease, ACTH will be way above range as high as the hundreds and even 1000's and 2000's.
;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 (i.e. 2&nbsp;ng/dl stimming to 20).<ref name="abstract/122/5/2090">{{cite journal | author=L.A. Cunningham and M.A. Holzwarth | title=Vasoactive intestinal peptide stimulates adrenal aldosterone and corticosterone secretion | journal=[[Endocrinology (journal)|Endocrinology]] | volume=122|pages=2090–2097|year=1988|url=http://endo.endojournals.org/cgi/content/abstract/122/5/2090 | pmid=3359977 | doi=10.1210/endo-122-5-2090 | issue=5}}</ref>  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.


In secondary adrenal insufficiency, serum [[ACTH]] will usually be in the bottom half of the range to the very bottom, but not usually below the range, but values can reach into the low 40's (98% of secondaries are in range on the serum ACTH).  A healthy serum ACTH value should be just into the upper third of the range (assuming a range of 10 - 60 as they almost always were until about 3 years ago).
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.


==Method and interpretation for aldosterone stimulation==
==Other hormones and chemicals that will rise in the ACTH stimulation test==
The [[ACTH]] stimulation test is occasionally used to stimulate the production of [[aldosterone]] at the same time as [[cortisol]] to also help in determining if primary (hyperreninemic) or secondary (hyporeninemic) hypoaldosteronism in [[adrenal insufficiency]] is present.  Natural human ACTH has a small effect on aldosterone<ref name="s5ch7_7.htm">{{cite journal |author=unknown | title=Role of ACTH in Regulation and Action of Adrenocorticoids | pages = 7 of 52|
* [[Progesterone]] - precursor to cortisol and aldosterone<ref name="2184.pdf">{{cite journal| author=Jardena J. Puder, Pamela U. Freda, Robin S. Goland, Michel Ferin,and Sharon L. Wardlaw | title=Stimulatory Effects of Stress on Gonadotropin Secretion in Estrogen-Treated Women*| journal=The Journal of Clinical Endocrinology & Metabolism|volume=85|pages=2184–2188|url=http://jcem.endojournals.org/cgi/reprint/85/6/2184.pdf|format=PDF| issue=6| doi=10.1210/jc.85.6.2184| year=2000}}</ref>
url=http://www.lib.mcg.edu/edu/eshuphysio/program/section5/5ch7/s5ch7_7.htm}}</ref>, but the amount of synthetic ACTH given in stimulation is equivalent to more than a whole days production of natural ACTH, so the aldosterone response can be easily measured. 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). 
*[[Luteinizing hormone]] - a pituitary hormone that stimulates sex hormone production<ref name="2184.pdf">{{cite journal| author=Jardena J. Puder, Pamela U. Freda, Robin S. Goland, Michel Ferin,and Sharon L. Wardlaw | title=Stimulatory Effects of Stress on Gonadotropin Secretionin Estrogen-Treated Women*| journal=The [[Journal of Clinical Endocrinology & Metabolism]]|volume=85|pages=2184–2188|url=http://jcem.endojournals.org/cgi/reprint/85/6/2184.pdf|format=PDF| issue=6| doi=10.1210/jc.85.6.2184| year=2000}}</ref>
*[[21-Hydroxylase]]<ref name="TestDetail.asp?ID=2025">{{cite journal| author=unknown | title=ACTH Stimulation Test for 21-Hydroxylase|url=http://referencelab.clevelandclinic.org/DBSearch/TestDetail.asp?ID=2025}}</ref>
*[[DHEA]] and DHEA-S (an androgen hormone produced in the adrenal glands)


In primary adrenal insufficiency, the aldosterone base value will be lower (low teens or less) and rise to less than double the base value.  If aldosterone does double or more from a low base value, that suggests secondary hypoaldosteronism and along side the cortisol stimulation can help support the diagnosis of secondary adrenal insufficiency. 
==Simple diagnostic chart==


In secondary adrenal insufficiency, aldosterone production can go up by several factors from a low base value. Decupling of aldosterone in the ACTH stimulation test is possible (ie 2 ng/dl stimming to 20).<ref name="abstract/122/5/2090">{{cite journal | author=L.A. Cunningham and M.A. Holzwarth | title=Vasoactive intestinal peptide stimulates adrenal aldosterone and corticosterone secretion | Journal=Endocrinology | volume=122 |pages=2090-2097|year=1988|url=http://endo.endojournals.org/cgi/content/abstract/122/5/2090}}</ref> Like the cortisol stimulation, many doctors lack knowledge of how to properly interpret for secondary hypoaldosteronism and think this result is fantastic.  Usually doubling to quadrupling from a low base aldosterone value is what is seen in secondary adrenal insufficiency.
{| border="4" cellspacing="1" cellpadding="4" style="text-align:center; margin:10px;"
|-----
| style="background:#ddcef2" | '''Source of pathology'''
| style="background:#cef2e0" | '''CRH'''
| style="background:#cef2e0" | '''ACTH'''
| style="background:#cef2e0" | '''DHEA'''
| style="background:#cef2e0" | '''DHEA-S'''
| style="background:#cef2e0" | '''cortisol'''
| td style="background:#cef2e0" | '''aldosterone'''
| style="background:#cef2e0" | '''renin
| style="background:#cef2e0" | '''Na'''
| style="background:#cef2e0" | '''K'''
| style="background:#f2e0ce" | '''Causes'''<sup>5</sup>
|-----
| style="background:#cedff2" | '''hypothalamus'''<br>(tertiary)<sup>1</sup>
| style="background:#F8F8F8" | low  || style="background:#F8F8F8" | low
| style="background:#F8F8F8" | low || style="background:#F8F8F8" | low
| style="background:#F8F8F8" | low<sup>3</sup>
| style="background:#F8F8F8" | low || style="background:#F8F8F8" | low
| style="background:#F8F8F8" | low || style="background:#F8F8F8" | low
| style="background:#F8F8F8" | tumor of the hypothalamus (adenoma), antibodies, environment, head injury
|-----
| style="background:#cedff2" | '''pituitary'''<br>(secondary)
| style="background:#F8F8F8" | high<sup>2</sup>
| style="background:#F8F8F8" | low || style="background:#F8F8F8" | low
| style="background:#F8F8F8" | low
| style="background:#F8F8F8" | low<sup>3</sup>
| style="background:#F8F8F8" | low || style="background:#F8F8F8" | low
| style="background:#F8F8F8" | low || style="background:#F8F8F8" | low
| style="background:#F8F8F8" | tumor of the pituitary (adenoma), antibodies, environment, head injury,<br>'''surgical removal'''<sup>6</sup>, Sheehan's syndrome
|-----
| style="background:#cedff2" | '''adrenal glands'''<br>(primary)<sup>7</sup>
| style="background:#F8F8F8" | high || style="background:#F8F8F8" | high
| style="background:#F8F8F8" | high || style="background:#F8F8F8" | high
| style="background:#F8F8F8" | low<sup>4</sup>
| style="background:#F8F8F8" | low || style="background:#F8F8F8" | high
| style="background:#F8F8F8" | low || style="background:#F8F8F8" | high
| style="background:#F8F8F8" | tumor of the adrenal (adenoma), stress, antibodies, environment, Addison's, injury, surgical removal
|}


==References==
{| border="2" cellspacing="1" cellpadding="2" style="margin:10px;"
{{reflist|2}}
|-----
| ''' 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 ==
== See also ==
* [[ACTH]]
* [[Insulin tolerance test]], another test used to identify sub-types of adrenal insufficiency
* [[Corticotropin-releasing hormone]]
* [[Metyrapone]], a drug used in the diagnosis of adrenal insufficiency
* [[Aldosterone]]
* [[Triple bolus test]]
* [[Cortisol]]
* [[Renin]], enzyme that converts Angiotensinogen to Angiotensin I, a precursor to Aldosterone
* [[Addison's disease]]
* [[Renin-angiotensin-aldosterone system]]
* [[HPA axis]]
* [[HPA axis]], explains the connections of the hypothalamus, pituitary and adrenal glands
* [[Hypopituitarism]]
* [[Hypopituitarism]]
* [[Pituitary adenoma]]
* [[adrenal adenoma]]
* [[corticorelin]]
==References==
{{Reflist|2}}
==External links==
<!-- BEFORE inserting new links here you should first post it to the talk page, otherwise your edit may be reverted-->
* [http://www.nlm.nih.gov/medlineplus/ency/article/003696.htm ACTH (cosyntropin) stimulation test] - based on information from [[Medline Plus]] Medical Encyclopedia
* [http://www.cc.nih.gov/ccc/patient_education/procdiag/acth.pdf ACTH stimulation test] - Procedures/Diagnostic tests  Warren Grant Magnuson Clinical Center [[National Institutes of Health]].


==Additional Links==
{{Endocrine system procedures}}
* [http://es.wikipedia.org/wiki/Prueba_de_estimulaci%C3%B3n_con_ACTH Prueba de estimulación con ACTH]
* [http://fr.wikipedia.org/wiki/Test_de_stimulation_de_l%E2%80%99ACTH Test de stimulation à l’ACTH]


[[Category:HPA axis]]
[[Category:Medical tests]]
[[Category:Blood tests]]
[[Category:Blood tests]]
[[Category:Endocrinology]]
[[Category:Endocrine procedures]]
[[Category:Hormones of the hypothalamus-pituitary-adrenal axis]]


{{WikiDoc Help Menu}}
[[es:Prueba de estimulación con ACTH]]
{{WikiDoc Sources}}
[[fr:Test de stimulation à l’ACTH]]

Revision as of 00:04, 13 August 2012

Template:Diagnostic infobox

WikiDoc Resources for ACTH stimulation test

Articles

Most recent articles on ACTH stimulation test

Most cited articles on ACTH stimulation test

Review articles on ACTH stimulation test

Articles on ACTH stimulation test in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on ACTH stimulation test

Images of ACTH stimulation test

Photos of ACTH stimulation test

Podcasts & MP3s on ACTH stimulation test

Videos on ACTH stimulation test

Evidence Based Medicine

Cochrane Collaboration on ACTH stimulation test

Bandolier on ACTH stimulation test

TRIP on ACTH stimulation test

Clinical Trials

Ongoing Trials on ACTH stimulation test at Clinical Trials.gov

Trial results on ACTH stimulation test

Clinical Trials on ACTH stimulation test at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on ACTH stimulation test

NICE Guidance on ACTH stimulation test

NHS PRODIGY Guidance

FDA on ACTH stimulation test

CDC on ACTH stimulation test

Books

Books on ACTH stimulation test

News

ACTH stimulation test in the news

Be alerted to news on ACTH stimulation test

News trends on ACTH stimulation test

Commentary

Blogs on ACTH stimulation test

Definitions

Definitions of ACTH stimulation test

Patient Resources / Community

Patient resources on ACTH stimulation test

Discussion groups on ACTH stimulation test

Patient Handouts on ACTH stimulation test

Directions to Hospitals Treating ACTH stimulation test

Risk calculators and risk factors for ACTH stimulation test

Healthcare Provider Resources

Symptoms of ACTH stimulation test

Causes & Risk Factors for ACTH stimulation test

Diagnostic studies for ACTH stimulation test

Treatment of ACTH stimulation test

Continuing Medical Education (CME)

CME Programs on ACTH stimulation test

International

ACTH stimulation test en Espanol

ACTH stimulation test en Francais

Business

ACTH stimulation test in the Marketplace

Patents on ACTH stimulation test

Experimental / Informatics

List of terms related to ACTH stimulation test

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

The ACTH stimulation test (also called the cosyntropin test, tetracosactide test or Synacthen 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).[1][2] ACTH is a hormone produced in the pituitary gland that stimulates the adrenal glands to release cortisol, dehydroepiandrosterone (DHEAS) and aldosterone.[3]

During the test, a small amount of synthetic ACTH is injected, and the amount of cortisol, and sometimes aldosterone, the adrenals produce in response is measured.[4] This test may cause mild to moderate side effects in some individuals.[5][6]

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 as the gold standard assay of adrenal insufficiency, although this test is primarily used to determine the presence of Addison's disease and pituitary impairment.[7] The test is extremely sensitive (97% at 95% specificity) to primary adrenal insufficiency, but less so to secondary adrenal insufficiency (57-61% at 95% specificity); while secondary adrenal insufficiency may thus be dismissed by some interpreters on the basis of the test, additional testing may be called for if probability of secondary adrenal insufficiency is particularly high.[1]

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 apparent adrenal crisis.[8]

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 µg 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 cortisol response of the adrenals is the same for the low-dose and conventional-dose tests.[9][10]

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.[8]

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. The test shouldn't be given if on glucocorticoids, 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 <citation needed for radioisotope scans>. Spironolactone, contraceptives, licorice, estrogen, androgen (including DHEA) and progesterone therapy may also affect both aldosterone and cortisol stimulation test results. To stimulate aldosterone, added salt and foods significant in sodium must be avoided for 24 hours prior to testing. Women should ideally undergo testing during the first week of their menstrual cycle as aldosterone (and occasionally cortisol) may be falsely elevated in the luteal cycle secondary to progesterone inhibition, leading to a compensatory rise in aldosterone levels.[11]

Administration

Traditionally, cortisol and ACTH levels (separate lavender top tube) are drawn at baseline (time = 0). Next, synthetic ACTH (Synacthen aka Tetracosactide or Cortrosyn aka Cosyntropin) is injected IM or IV depending on the agent[12] . Approximately 20 mL of heparinized venous blood is collected at 30 and 60 minutes after the synthetic ACTH injection to measure cortisol levels.[13][14]

All blood samples are kept on ice and sent immediately to the laboratory for testing.[15]

Potential side effects

Commonly reported reactions are nausea, anxious sweating, dizziness, itchy skin, redness and or swelling of injection site, palpitations (a fast or fluttering heart beat) and facial flushing (may also include arms and torso), but should disappear within a few hours.[16][6] Rarely seen, but serious side effects include rash, fainting, headache, blurred vision, severe swelling, severe dizziness, trouble breathing, irregular heartbeat.[6]

Although uncommon, some people report feeling better or sense of well being after the test.[citation needed]

Interpretation of results

The adrenal glands sit atop the kidneys.

Cortisol stimulation

In healthy individuals, the cortisol level should double from a baseline of 20-30 µg/dl within 60 minutes. For example, if the serum cortisol level was 25 ug/dl before the stimulation, it should reach at least 50 µg/dl.

Interpretation for primary adrenal insufficiency and Addison's disease

The baseline cortisol level in people with adrenal insufficiency is usually near 15 µg/dl. An ACTH stimulation test that raises the cortisol concentration to 20 µg/dl would support the diagnosis of primary adrenal insufficiency. In Addison's disease, baseline cortisol is well below 10 µg/dl and rises no more than 25 percent.

Interpretation for secondary adrenal insufficiency

ACTH may dramatically stimulate cortisol from the low baseline value encountered in patients suffering from secondary adrenal insufficiency. Stimulation resulting in a greater than 14-fold increase in serum concentration over 30 minutes has been reported, although more typically serum cortisol levels will double or triple from baseline. The lower the baseline cortisol, the more likely it is that the patient's cortisol will increase by a large amount.[15]

In some instances, a second test 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 atrophy[17] 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.[17]

ACTH plasma test plus cortisol stimulation

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 high[13] - 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 low[13] - Usually below 35, but most people with secondary fall within the range limit. Although uncommon, values for ACTH can reach into the low 40s.

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.[18]

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.[4] Human ACTH has a slight stimulatory effect on aldosterone,[19] 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.[20] 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.[4] 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 (i.e. 2 ng/dl stimming to 20).[21] 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

Simple diagnostic chart

Source of pathology CRH ACTH DHEA DHEA-S cortisol aldosterone renin Na K Causes5
hypothalamus
(tertiary)1 		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
(primary)7 		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

References

  1. ↑ 1.0 1.1 1.2 Dorin RI, Qualls CR, Crapo LM (2003). "Diagnosis of adrenal insufficiency" (PDF). Ann. Intern. Med. 139 (3): 194–204. PMID 12899587.
  2. ↑ 2.0 2.1 Elizabeth H. Holt, MD, PhD (2008). "ACTH (cosyntropin) stimulation test".
  3. ↑ Hanukoglu, A.; Fried, D.; Nakash, I.; Hanukoglu, I. (1995). "Selective increases in adrenal steroidogenic capacity during acute respiratory disease in infants". Eur J Endocrinol. 133 (5): 552–6. doi:10.1530/eje.0.1330552. PMID 7581984. Unknown parameter |month= ignored (help)
  4. ↑ 4.0 4.1 4.2 unknown. "ACTH Stimulation Test" (PDF). APPENDIX – Endocrinology.[dead link]
  5. ↑ unknown. "Synacthen Test" (PDF).[dead link]
  6. ↑ 6.0 6.1 6.2 unknown. "GENERIC NAME: COSYNTROPIN - INJECTABLE (koe-sin-TROW-pin)".
  7. ↑ unknown (2006). "ACTH (Cortrosyn) stimulation test": 1. Unknown parameter |sect= ignored (help)
  8. ↑ 8.0 8.1 Evangelia Charmandari, M.D., and George P. Chrousos, M.D. "ADRENAL INSUFFICIENCY Chapter 13".
  9. ↑ 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". Journal of Clinical Endocrinology and Metabolism. 84 (3): 838–43. doi:10.1210/jc.84.3.838. PMID 10084558.
  10. ↑ Cemeroglu AP, Kleis L, Postellon DC, Wood MA (2010). "COMPARISON OF LOW AND HIGH DOSE COSYNTROPIN STIMULATION TESTING IN CHILDREN". Pediatrics International : Official Journal of the Japan Pediatric Society. 53 (2): 175–80. doi:10.1111/j.1442-200X.2010.03203.x. PMID 20626639. Unknown parameter |month= ignored (help)
  11. ↑ Emily D. Szmuilowicz, Gail K. Adler, Jonathan S. Williams, Dina E.Green, Tham M. Yao, Paul N. Hopkins and Ellen W. Seely (2006). "Relationship between Aldosterone and Progesterone in the Human Menstrual Cycle". Journal of Clinical Endocrinology & Metabolism. 91 (10): 3981–3987. doi:10.1210/jc.2006-1154. PMID 16868049.
  12. ↑ "Drugs.com Citation".
  13. ↑ 13.0 13.1 13.2 13.3 unknown. "ACTH Rapid Stimulation Test (Cortrosyn, Cosyntropin)".[dead link]
  14. ↑ NIDDK's Office of Health Research Reports. "Addison's disease".
  15. ↑ 15.0 15.1 K. Pagana, PhD, RN and T. Pagana, MD, FACS. "Mosby's Diagnostic and Laboratory Test Reference 2nd ed.: Adrenocorticotropic hormone stimulation test": 17–18.
  16. ↑ unknown. "Synacthen Test" (PDF).
  17. ↑ 17.0 17.1 Ashley B. Grossman, MD (2007). "Addison's Disease". Endocrine and Metabolic Disorders: 4. Unknown parameter |sect= ignored (help)
  18. ↑ Lynnette K Nieman, MD (2008). "Corticotropin-releasing hormone stimulation test".
  19. ↑ unknown. "Role of ACTH in Regulation and Action of Adrenocorticoids": 7 of 52.
  20. ↑ unknown. "Aldosterone and Renin".
  21. ↑ L.A. Cunningham and M.A. Holzwarth (1988). "Vasoactive intestinal peptide stimulates adrenal aldosterone and corticosterone secretion". Endocrinology. 122 (5): 2090–2097. doi:10.1210/endo-122-5-2090. PMID 3359977.
  22. ↑ 22.0 22.1 Jardena J. Puder, Pamela U. Freda, Robin S. Goland, Michel Ferin,and Sharon L. Wardlaw (2000). "Stimulatory Effects of Stress on Gonadotropin Secretion in Estrogen-Treated Women*" (PDF). The Journal of Clinical Endocrinology & Metabolism. 85 (6): 2184–2188. doi:10.1210/jc.85.6.2184.
  23. ↑ unknown. "ACTH Stimulation Test for 21-Hydroxylase".

External links

Retrieved from "https://www.wikidoc.org/index.php?title=ACTH_stimulation_test&oldid=682399"