4-Tube Cortisol Salivary
- Thread starter smithers
- Start date
Nelson Vergel
Founder, ExcelMale.com
You may have adrenal insufficiency. Are you not sleeping well? Too much stress and/or caffeine? Please elaborate. Thanks
Nelson Vergel
Founder, ExcelMale.com
This may be the second step if you cannot improve your cortisol profile with lifestyle changes.
ACTH stimulation test
ACTH stimulation test
Nelson Vergel
Founder, ExcelMale.com
ACTH Stimulation Test [Adrenal Insufficiency (AI) and Congenital Adrenal Hyperplasia (CAH); 1 mcg and 250 mcg]
Morning cortisol < 3 mcg/dl (83 nmol/L) is considered diagnostic of Adrenal Insufficiency. Whereas a random cortisol above 18 mcg/dl (500 nmol/L) rules it out. In all other cases a kind of a stimulation test is needed to confirm the suspicious of AI. Subnormal cortisol response in a stimulation test is consistent with either primary or secondary AI.
Insulin tolerance Test is considered to be the “Gold Standard” for evaluation of Hypothalamus- Pituitary- Adrenal (HPA) axis. In this test a severe stressful situation, i.e. symptomatic hypoglycemia, is used to stimulate the whole HPA axis. It is unpleasant and carries serious risks to patients, especially to elderly or severely sick patients, requires careful monitoring of the patient in presence of a physician. Moreover, it has a relatively poor reproducibility. For these reasons 250 mcg (High dose; HDT) and later 1 mcg (Low dose; LDT) ACTH stimulation tests have gained wider acceptance.
Original description of the test and corresponding diagnosis
ACTH stimulation test has been shown to be a useful tool in evaluation of HPA axis in patients suspicious of having hypocortisolism and also in evaluation of the patients with possible CAH. This test is a simple test, with no side effects and can be performed on an outpatient setting, at any time of the day, without presence of a physician and does not require fasting.
Indication for testing procedure
1) Screening procedure for Adrenal Insufficiency.
2) Diagnostic procedure for adrenal biosynthetic defects (e.g. CAH).
3) Monitoring recovery of adrenal function after cure from Cushing’s syndrome or glucocorticoid withdrawal.
Mechanics of how test is performed
If appropriate, exogenous glucocorticoids should be withheld for 24 hours prior to the testing.
A commercially available ACTH analogue, Cosyntropin (1 or 250 mcg) is given intravenously (IV) as a bolus. [This synthetic analogue has the 1-24 amino acid sequence of human ACTH 1-39 and possesses the full biologic activity of ACTH 1-39.]
Plasma samples are obtained at baseline and 30 and 60 minutes after the injection for measurement of cortisol or steroidogenesis precursors (17-Hydroxypregnenolone, 17-Hydroxyprogesterone and/or 11-Deoxycortisol).
Plasma ACTH can be measured in the basal sample.
In healthy individuals, the greatest cortisol response is seen in the morning, as oppose to the patients with AI, in whom the response is the same in the morning and afternoon. For this reason, although not essential, it is recommended that the test to be done in the morning to avoid misdiagnosing a normal individual.
Assay requirements
Most commonly assays used to measure cortisol or steroidogenesis precursors include:
1) Radioimmunoassay.
2) Immunoflurometric enzyme assays.
3) Isotope dilution gas chromatography- mass spectrometry.
4) Competitive protein-binding assays.
Proper interpretation of the test
The only parameter to be used is the peak cortisol not the delta cortisol level.
A plasma cortisol > 18 mcg/dl (500 nmol/L) at 30 minutes or > 20 mcg/dl (550 nmol/L) at 60 minutes, indicates normal HPA function and rules out AI.
Stimulated 17-hydroxypregnenolone > 2000 ng/dl indicates 3Β- Hydroxysteroid dehydrogenase deficiency.
Stimulated 17-hydroxyprogesterone (17-OHP) > 1500 ng/dl indicates 21-hydroxylase deficiency (most common cause of CAH).
Stimulated 11-deoxycortisol (11-DOC) > 1500 ng/dl indicates 11Β-hydroxylase.
In patients with primary AI, endogenous ACTH is already elevated and there is little or no response to exogenous ACTH. Thus elevated ACTH levels in the baseline plasma sample, in context of abnormal response to cosyntropin injection, make the diagnosis of primary AI more likely.
Statistics of test performance
In a meta-analysis of studies comparing LDT and HDT, it was shown that at a specificity of 95%, both tests have similar sensitivities for diagnosis of secondary AI (57% and 61% respectively) and a sensitivity of 97% for HDT for diagnosis of primary AI. (3)
Review of nine studies showed a significantly higher sensitivity and somewhat lower specificity for LDT, with a better accuracy of 90.1% (versus 83.9% for HDT). (2)
In their study Ambrosi et al. showed a 71% sensitivity, 93% specificity, and a positive predictive value (PPV) of 77% and a negative predictive value of 91% for 1 mcg ACTH stimulation test (LDT), assuming a 100% accuracy of insulin tolerance test (ITT). (1)
Giordano et al., in their study of comparing different provocative tests to assess HPA axis in patients with HPA disorders demonstrated that either HDT or LDT sensitivity approached 71·4% with a specificity of 82·4% or 73·3% with a specificity of 80% for cortisol cut-off of 582·1 or 477·3 nmol/l. (7)
Controversies in the literature
There have been some controversies regarding whether LDT is superior to HDT. 250 mcg ACTH stimulates the serum cortisol levels to supraphysiologic levels, whereas 1 mcg ACTH raises the cortisol levels to physiological levels. (4) LDT was thought to have the main advantages in diagnosing mild HPA suppression by glucocorticoid treatment and in partial primary adrenal failure. But it has been shown in a case report that the diagnosis of life-threatening Addison disease, which was missed by HDT, was established by LDT. (5) Ambrosi et al. demonstrated that LDT can induce a maximal adrenal response. (1) In their study Bayram et al. showed in the early post-operative period of pituitary surgery, the LDT results are more concordant than HDT in comparison with the ITT. (6)
References:
1) Ambrosi B, et al. “The one microgram adrenocorticotropin test in the assessment of hypothalamic-pituitary-adrenal function”. Euro J of Endocrinol 1998, 139: 575-579.
2) ****stein G, et al. “High-dose and low-dose cosyntropin stimulation tests for diagnosis of adrenal insufficiency”. Ann Intern Med 2004, 140: 312-313.
3) Dorin RI, et al. “Diagnosis of adrenal insufficiency”. Ann Intern Med 2003, Aug 5; 139(3):194-204.
4) Alia P, et al. “Profile, mean residence time of ACTH and cortisol response after low and standard ACTH tests in healthy volunteers”. Clin Endocrinol 2006, 65:346-351.
5) Okik K, et al. “A case of Addison disease confirmed with low dose cosyntropin stimulation test”. Endocrinol J 2007, 54: 765-769.
6) Bayram et al. “A comparison between the 1 microgram adrenocorticotropin (ACTH) test, the short ACTH (250 mcg) test, and the insulin tolerance test in the assessment of hypothlamo-pituitary-adrenal axis immediately after pituitary surgery”. J Clin Endocrinol Metab 2000, Oct; 85(10): 3713-19.
7) Giordano R, et al. “Hypothalamus-pituitary-adrenal axis evaluation in patients with hypothalamic-pituitary-adrenal disorders: Comparison of different provocative test”. Clin Endocrinol (Oxf) 2008, 68:935.
Morning cortisol < 3 mcg/dl (83 nmol/L) is considered diagnostic of Adrenal Insufficiency. Whereas a random cortisol above 18 mcg/dl (500 nmol/L) rules it out. In all other cases a kind of a stimulation test is needed to confirm the suspicious of AI. Subnormal cortisol response in a stimulation test is consistent with either primary or secondary AI.
Insulin tolerance Test is considered to be the “Gold Standard” for evaluation of Hypothalamus- Pituitary- Adrenal (HPA) axis. In this test a severe stressful situation, i.e. symptomatic hypoglycemia, is used to stimulate the whole HPA axis. It is unpleasant and carries serious risks to patients, especially to elderly or severely sick patients, requires careful monitoring of the patient in presence of a physician. Moreover, it has a relatively poor reproducibility. For these reasons 250 mcg (High dose; HDT) and later 1 mcg (Low dose; LDT) ACTH stimulation tests have gained wider acceptance.
Original description of the test and corresponding diagnosis
ACTH stimulation test has been shown to be a useful tool in evaluation of HPA axis in patients suspicious of having hypocortisolism and also in evaluation of the patients with possible CAH. This test is a simple test, with no side effects and can be performed on an outpatient setting, at any time of the day, without presence of a physician and does not require fasting.
Indication for testing procedure
1) Screening procedure for Adrenal Insufficiency.
2) Diagnostic procedure for adrenal biosynthetic defects (e.g. CAH).
3) Monitoring recovery of adrenal function after cure from Cushing’s syndrome or glucocorticoid withdrawal.
Mechanics of how test is performed
If appropriate, exogenous glucocorticoids should be withheld for 24 hours prior to the testing.
A commercially available ACTH analogue, Cosyntropin (1 or 250 mcg) is given intravenously (IV) as a bolus. [This synthetic analogue has the 1-24 amino acid sequence of human ACTH 1-39 and possesses the full biologic activity of ACTH 1-39.]
Plasma samples are obtained at baseline and 30 and 60 minutes after the injection for measurement of cortisol or steroidogenesis precursors (17-Hydroxypregnenolone, 17-Hydroxyprogesterone and/or 11-Deoxycortisol).
Plasma ACTH can be measured in the basal sample.
In healthy individuals, the greatest cortisol response is seen in the morning, as oppose to the patients with AI, in whom the response is the same in the morning and afternoon. For this reason, although not essential, it is recommended that the test to be done in the morning to avoid misdiagnosing a normal individual.
Assay requirements
Most commonly assays used to measure cortisol or steroidogenesis precursors include:
1) Radioimmunoassay.
2) Immunoflurometric enzyme assays.
3) Isotope dilution gas chromatography- mass spectrometry.
4) Competitive protein-binding assays.
Proper interpretation of the test
The only parameter to be used is the peak cortisol not the delta cortisol level.
A plasma cortisol > 18 mcg/dl (500 nmol/L) at 30 minutes or > 20 mcg/dl (550 nmol/L) at 60 minutes, indicates normal HPA function and rules out AI.
Stimulated 17-hydroxypregnenolone > 2000 ng/dl indicates 3Β- Hydroxysteroid dehydrogenase deficiency.
Stimulated 17-hydroxyprogesterone (17-OHP) > 1500 ng/dl indicates 21-hydroxylase deficiency (most common cause of CAH).
Stimulated 11-deoxycortisol (11-DOC) > 1500 ng/dl indicates 11Β-hydroxylase.
In patients with primary AI, endogenous ACTH is already elevated and there is little or no response to exogenous ACTH. Thus elevated ACTH levels in the baseline plasma sample, in context of abnormal response to cosyntropin injection, make the diagnosis of primary AI more likely.
Statistics of test performance
In a meta-analysis of studies comparing LDT and HDT, it was shown that at a specificity of 95%, both tests have similar sensitivities for diagnosis of secondary AI (57% and 61% respectively) and a sensitivity of 97% for HDT for diagnosis of primary AI. (3)
Review of nine studies showed a significantly higher sensitivity and somewhat lower specificity for LDT, with a better accuracy of 90.1% (versus 83.9% for HDT). (2)
In their study Ambrosi et al. showed a 71% sensitivity, 93% specificity, and a positive predictive value (PPV) of 77% and a negative predictive value of 91% for 1 mcg ACTH stimulation test (LDT), assuming a 100% accuracy of insulin tolerance test (ITT). (1)
Giordano et al., in their study of comparing different provocative tests to assess HPA axis in patients with HPA disorders demonstrated that either HDT or LDT sensitivity approached 71·4% with a specificity of 82·4% or 73·3% with a specificity of 80% for cortisol cut-off of 582·1 or 477·3 nmol/l. (7)
Controversies in the literature
There have been some controversies regarding whether LDT is superior to HDT. 250 mcg ACTH stimulates the serum cortisol levels to supraphysiologic levels, whereas 1 mcg ACTH raises the cortisol levels to physiological levels. (4) LDT was thought to have the main advantages in diagnosing mild HPA suppression by glucocorticoid treatment and in partial primary adrenal failure. But it has been shown in a case report that the diagnosis of life-threatening Addison disease, which was missed by HDT, was established by LDT. (5) Ambrosi et al. demonstrated that LDT can induce a maximal adrenal response. (1) In their study Bayram et al. showed in the early post-operative period of pituitary surgery, the LDT results are more concordant than HDT in comparison with the ITT. (6)
References:
1) Ambrosi B, et al. “The one microgram adrenocorticotropin test in the assessment of hypothalamic-pituitary-adrenal function”. Euro J of Endocrinol 1998, 139: 575-579.
2) ****stein G, et al. “High-dose and low-dose cosyntropin stimulation tests for diagnosis of adrenal insufficiency”. Ann Intern Med 2004, 140: 312-313.
3) Dorin RI, et al. “Diagnosis of adrenal insufficiency”. Ann Intern Med 2003, Aug 5; 139(3):194-204.
4) Alia P, et al. “Profile, mean residence time of ACTH and cortisol response after low and standard ACTH tests in healthy volunteers”. Clin Endocrinol 2006, 65:346-351.
5) Okik K, et al. “A case of Addison disease confirmed with low dose cosyntropin stimulation test”. Endocrinol J 2007, 54: 765-769.
6) Bayram et al. “A comparison between the 1 microgram adrenocorticotropin (ACTH) test, the short ACTH (250 mcg) test, and the insulin tolerance test in the assessment of hypothlamo-pituitary-adrenal axis immediately after pituitary surgery”. J Clin Endocrinol Metab 2000, Oct; 85(10): 3713-19.
7) Giordano R, et al. “Hypothalamus-pituitary-adrenal axis evaluation in patients with hypothalamic-pituitary-adrenal disorders: Comparison of different provocative test”. Clin Endocrinol (Oxf) 2008, 68:935.
Nelson Vergel
Founder, ExcelMale.com
Nelson Vergel
Founder, ExcelMale.com
Nelson,
No, I dont sleep well, I know that I snore, confirmed with the snorelab app. I struggle to get up out of bed, I don't have the motivation to get up and go that I would like. I beat myself up for not getting things done. I have coffee with breakfast, and an energy drink at work.
Nelson Vergel
Founder, ExcelMale.com
smithers
I would not waste time and money on an ACTH stimulation test but put that money on a sleep study (insurance pays if you have it). Resolving potential sleep apnea can improve your cortisol level.
What is your height, weight and neck size? Do you drink alcohol before bed? Tell me more.
I would not waste time and money on an ACTH stimulation test but put that money on a sleep study (insurance pays if you have it). Resolving potential sleep apnea can improve your cortisol level.
What is your height, weight and neck size? Do you drink alcohol before bed? Tell me more.
5'9 168lbs. 16.5" neck, no alcohol at all, cant remember the last time I had a drink
I got a sleep study appointment in October, the nurse said there's about 800 patients ahead of me, ouch.
Vince Carter
Banned
Knowing friends that go thru this and these masks and machines...I'd strongly suggest you look elsewhere for remedies. Supplementing DHEA and Pregnenolone can help, as well as dropping Hydrogenated oils. Read up on Adrenal Fatigue and delve in to those suggested areas. Sleep studies and CPAPs just give me the shivers, I want nothing to do with that stuff.
Yea, I've been reading about adrenal fatigue. My DHEA has always been on the high end of the reference range pre- and during TRT. I'm going to try Pregnenolone and see if that works for me, it sounds like the missing link.
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