scholarly journals Can the Gold Standard Be Beaten? How Reliable Are Various Modifications of the Synacthen Test Compared to the Insulin Tolerance Test

2017 ◽  
pp. S387-S395 ◽  
Author(s):  
M. KOSAK ◽  
M. DUSKOVA ◽  
L. STARKA ◽  
H. JANDIKOVA ◽  
H. POSPISILOVA ◽  
...  

Criteria for the evaluation of the insulin tolerance test (ITT) and Synacthen test are still a matter of debate. The objective of the study was to make a comparison of serum and salivary cortisol during four stimulation tests. Sixty four healthy volunteers underwent the ITT, the Synacthen test with 1 (LDST), 10 (MDST) and 250 (HDST) μg dose of ACTH. Maximum serum cortisol response was observed at the 90 min of the ITT (49 %), HDST (89 %) and MDST (56 %) and at the 40 min of the LDST (44 %). Results expressed as 95 % confidence intervals: 408.0-843.6 and 289.5-868.1 nmol/l in the IIT at 60 and 90 min. In the HDST and the MDST serum cortisol reached the maximum at 90 min 542.6-1245.5 and 444.2-871.3 nmol/l. Levels of salivary cortisol followed the same pattern as serum cortisol. Salivary cortisol reached the maximum response in the HDST and the MDST at 90 min and at 40 min in the LDST. We confirmed good reliability of all tests with respect to timing of response and maximum response compared to the ITT. We proved that the MDST test can provide the similar response in serum cortisol to the HDST. Measuring either salivary cortisol or ACTH levels did not provide any additional benefit then measuring serum cortisol by itself.

2015 ◽  
pp. S237-S246 ◽  
Author(s):  
K. SIMUNKOVA ◽  
M. DUSKOVA ◽  
M. KOSAK ◽  
M. KRSEK ◽  
V. HANA ◽  
...  

Determination of response of cortisol and its metabolites to different stimuli may be important for adrenal gland disorders. To date, only one metabolite, cortisone, has been followed in stimulation tests of the adrenal gland. We aimed to describe a response of cortisol metabolites to the standard short Synacthen test (HDST), insulin tolerance test (ITT), low dose Synacthen test (LDST) and medium dose Synacthen test (MDST). Sixty healthy subjects were investigated: 30 men and 30 women. Plasma for measurements of cortisol and its metabolites was obtained before and 30th and 60th min after Synacthen and insulin administration. The cut-off 500 nmol/l of cortisol was reached after stimulation in all of tests, the maximal stimulation level was reached in 60th min in all of the tests except for LDST. The response of cortisol and its metabolites at 30th and 60th min strongly correlated in all of the tests except for LDST. Cortisol and its metabolites increased after stimulation; in contrast, cortisone and its metabolites decreased. We showed that the response of the cortisol metabolites during the Synacthen tests and ITT well correlated, and the MDST showed similar response compared to HDST. The decrease in cortisone metabolites may correspond to the regeneration of cortisol from cortisone in response to stimulation test.


2009 ◽  
Vol 160 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Timo Deutschbein ◽  
Nicole Unger ◽  
Klaus Mann ◽  
Stephan Petersenn

ObjectiveAccurate assessment of adrenal function is essential in patients with hypothalamic–pituitary–adrenal (HPA) disease. The measurement of salivary cortisol (SaC) instead of serum cortisol (SeC) offers several advantages, such as the determination of the free hormone. We evaluated the diagnostic value of SeC and SaC both unstimulated and during a high-dose short synacthen test (HDT) in comparison to the insulin tolerance test (ITT).DesignComparative study between 2005 and 2007.MethodsFifty-five patients with HPA impairment and 21 healthy controls were enrolled. Samples were collected in the early morning and over 120 min during the HDT. Receiver operating characteristic analysis revealed individual thresholds for four HDT periods (0–30, 0–60, 0–90, and 0–120 min).ResultsThe ITT identified 30 subjects as adrenal insufficient. With respect to the four HDT periods, sensitivity and specificity were 67–79% and 71–88% for SeC, compared with 63–72% and 72–86% for SaC. If upper and lower thresholds (with specificities >95%) were applied, patients were diagnosed in 40–45% by SeC and in 25–31% by SaC. The combination of basal cortisol and HDT allowed a diagnosis in 47–49% (SeC) and in 42–45% (SaC) respectively.ConclusionWe suggest the determination of basal SeC or SaC as first-line test. In comparison to the ITT, the HDT has only limited value in screening for alterations of the HPA axis. If the HDT is performed, sampling may be limited to 30 min post-synacthen, using either SeC or SaC. Due to the ease of collection and the independence of binding proteins, SaC may be preferable.


2021 ◽  
Author(s):  
Valentina Gasco ◽  
Chiara Bima ◽  
Alice Geranzani ◽  
Jacopo Giannelli ◽  
Lorenzo Marinelli ◽  
...  

Introduction According to guidelines, a morning serum cortisol level <83 nmol/L is diagnostic for central adrenal insufficiency (CAI), a value >414 nmol/L excludes CAI, while values between 83 and 414 nmol/L require stimulation tests. However, there are no currently reliable data on morning serum cortisol for prediction of cortisol response to insulin tolerance test (ITT). Objective Using the receiver operating characteristic curve analysis, the purpose of this study was to detect the morning serum cortisol cut-off with a specificity (SP) or a sensitivity (SE) above 95% that identify those patients who should not be tested with ITT. Methods We included 141 adult patients (83 males) aged 42.7+/-12.3 (mean +/- SD) years old. Based on serum cortisol response to ITT, patients have been divided in two groups: subjects with CAI (peak serum cortisol <500 nmol/L; 65 patients) and subjects with preserved adrenocortical function (peak cortisol >500 nmol/L; 76 patients). Results The best morning cortisol cut-off, in terms of SE (87.7%) and SP (46.1%), was ≤323.3 nmol/L. The cut-off of morning serum cortisol concentration that best predicted a deficient response to ITT was ≤126.4 nmol/L (SE 13.8%, SP 98.7%). The cut-off of morning serum cortisol concentration that best predicted a normal response to ITT was >444.7 nmol/L (SE 96.9%, SP 14.5%). Conclusions This is the first study that identifies a morning serum cortisol cut-off that best predict the response to ITT in order to simplify the diagnostic process in patients with suspected CAI. A new diagnostic flow chart for CAI is proposed.


2016 ◽  
Vol 117 (1) ◽  
pp. 18-33 ◽  
Author(s):  
Michaela Dušková ◽  
Kateřina Šimůnková ◽  
Jana Vítků ◽  
Lucie Sosvorová ◽  
Hana Jandíková ◽  
...  

Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis). The gold standard is still considered the insulin tolerance test (ITT), but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD ±4.8) years, and mean/median BMI (body mass index) 25.38/24.82 (SD ±3.2) kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 μg, 10 μg, and 250 μg Synacthen (ACTH) tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone) were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 μg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results.


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