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Our objective was to assess the diagnostic accuracy of the Dex-CRH test and evaluate the potential impact of concomitant drugs. Patients were divided into two groups, depending on use of medications potentially interfering with dexamethasone metabolism: The latter group was further subdivided into patients taking one medication vs.
The specificity of a baseline post-low-dose-dexamethasone-suppressed test cortisol lower than 1. Sensitivity and specificity using a post-CRH cortisol cutoff of 1. The specificity of a cortisol lower than 1. Medications commonly prescribed in hypercortisolemic patients undergoing Dex-CRH testing may contribute to the variable diagnostic accuracy of this test.
Prospective studies to address this issue are needed. Patients with obesity, diabetes mellitus, hypertension, polycystic ovarian syndrome, or osteoporosis may have an underlying tumor 3 , 4. Therefore, it is essential to differentiate patients with true CS due to an underlying tumor from patients with PCS in these high-risk populations. The dexamethasone-suppressed CRH stimulation Dex-CRH test has been employed as such a diagnostic tool 5 , although some reports indicate it is less useful than previously described 6 — 9.
Its efficacy can be affected by several variables, including dexamethasone compliance, the type of CRH used, and patient comorbidities 2. An important potential confounder may be the effects of medications commonly used in these patients including antidepressants, antihypertensives, and lipid-lowering agents. Because some medications in these classes can potentially interfere with the CYP3A4 enzyme system, which regulates dexamethasone metabolism 11 , they could potentially alter test results and affect diagnostic accuracy 2.
To determine the diagnostic accuracy of the Dex-CRH test and define whether concomitant medications affect its reliability, we retrospectively reviewed test results in patients undergoing evaluation for possible CS. Dex-CRH testing was performed in patients with conflicting results on standard initial diagnostic evaluation for CS 2. All had clinical and biochemical features of hypercortisolism but needed an additional confirmatory test, due to a history of depression or alcoholism, or urinary free cortisol UFC from 1- to 3-fold above the upper limit of normal without classic physical features.
A single patient had pathologically confirmed adrenal Cushing without completely suppressed ACTH levels. Because all other CS patients clearly had a pituitary source, this group will be termed CD. The presumptive diagnosis of PCS was based on lack of conclusive biochemical testing at the initial evaluation, when results of first-line tests [UFC, late night salivary cortisol, overnight 1-mg dexamethasone suppression test DST or h 2-mg DST] were not all consistent with CD as described in consensus guidelines 2.
The diagnosis of PCS was confirmed by the improvement or the lack of progression of Cushingoid features during follow-up and absence of confirmation on repeated diagnostic testing. Hepatic and renal diseases were excluded. Detailed longitudinal records were available on 54 patients 30 CD; 24 PCS followed regularly at our center. Sixty-two patients without recent care at our center were contacted and asked to fill out a questionnaire and to provide more recent tests of adrenal function.
Of the 48 patients who did not respond, the results of 33 were included on the basis of available data obtained after their initial evaluation. The median follow-up in PCS patients who did not respond to the questionnaire was 12 months, with all patients except two being followed for 2—14 months after their test. Although we cannot rule out that some of them might have subsequently been diagnosed with CD, only two patients of 41 4. Fifteen patients had no further testing or follow-up after their initial Dex-CRH test and were excluded from the analysis because the final diagnosis was unknown.
Eight patients had the test performed more than once. Test results were categorized as Meds and No Meds, according to whether patients were receiving medications potentially interfering with dexamethasone metabolism 11 , and further subdivided based on type of medications as listed in Table 1. Drugs taken by the Meds group that may potentially interfere with dexamethasone metabolism Number of tests performed on each class of medication is indicated in parentheses.
Patients underwent initial hormonal evaluation for possible CD with measurement of serum cortisol 52 patients: UFC concentrations are expressed as the average of two measurements performed within 1 month before or after the Dex-CRH test. The overnight DST 1 mg was performed in 28 patients. The Dex-CRH test was performed as previously described 5.
Women taking oral estrogen discontinued it for approximately 8 wk before the test except two on conjugated estrogen. All tests were performed in an outpatient setting. They were instructed to return 2 d later at h. Salivary cortisol levels were not routinely measured during the first part of the decade, so the number available was inadequate for analysis. The intraassay variability was 6. Serum cortisol and UFC were measured using a chemiluminescent microparticle immunoassay Abbott Diagnostics, Chicago, IL , with a total coefficient of variation of 2.
Earlier measurements were performed by RIA; assay characteristics have been previously described The intraassay and interassay variabilities were 3. The effect of medication on diagnostic accuracy was examined by comparing the on- to off-medication sensitivity and specificity for each cutoff. All analyses were carried out using SAS version 9. Median follow-up for the entire group of patients was P values are CD vs. Data on bone status refer to 32 patients. IGT, Impaired glucose tolerance.
P value refers to comparison of females vs. PCS for each gender. The prevalence of depression was equal between groups; alcoholism was reported in two patients, both classified as PCS, and one of them had major depression with psychotic features Table 2. Units are micrograms per deciliter for cortisol, picograms per milliliter for ACTH, and nanograms per deciliter for dexamethasone.
Each P value refers to the comparison of the above two lines. Nine of 15 had a min post-CRH serum cortisol of less than the 1. The difference between sensitivities before and after CRH was not significant. Seven of 46 Another patient, who had an initially suppressed post-LDDST baseline cortisol, was just above the cutoff point at 1. Nine of these would have moved to the correct diagnosis of CD after CRH injection, but 25 remained misclassified after the combined test, because they showed serum cortisol levels below 1.
Using the cutoff proposed by Erickson et al. Using the cutoff proposed by Gatta et al. Both the sensitivity and specificity of the test in No Meds patients were higher than in the Meds group. Using a serum cortisol cutoff of 1. Using a serum cortisol threshold of 1. Units are micrograms per deciliter nanomoles per liter for cortisol and picograms per milliliter picomoles per liter for ACTH. The Meds group was divided into three subgroups according to whether patients were taking one group 1: The specificity of a post-CRH cortisol equal to 1.
No difference in specificity was observed between the two groups for any previously established threshold. Dexamethasone levels were comparable. The diagnostic accuracy of the recommended first-line screening tests was compared with the post-Dex-CRH 1. It can cause weight gain , skin problems , and other issues. Longer term, it can lead to conditions such as:. A tumor on your pituitary gland is the most common one that causes Cushing syndrome.
More ACTH means more cortisol. You can also get tumors on other organs where the tumor itself makes ACTH. This is called an ectopic ACTH-secreting hormone. Again, it leads to too much cortisol. Dexamethasone is a manmade version of cortisol. After you take a dose of it, your body should make less cortisol. Usually, the test is done overnight, but it can also be done over 2 days. There are two doses you can take for the test: The low-dose test helps you find out if you have Cushing syndrome or not.
You typically get 1 mg of dexamethasone. The high dose is typically 8 mg. Your doctor might also order this test if you have problems that aren't typical for your age but could mean you have Cushing syndrome: