scholarly journals A Comparison of Salivary Steroid Levels during Diagnostic Tests for Adrenal Insufficiency

2016 ◽  
Vol 117 (1) ◽  
pp. 18-33 ◽  
Author(s):  
Michaela Dušková ◽  
Kateřina Šimůnková ◽  
Jana Vítků ◽  
Lucie Sosvorová ◽  
Hana Jandíková ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Salivary Cortisol ◽  
Diagnostic Tests ◽  
False Negative ◽  
Cost Effective ◽  
Tolerance Test ◽  
Insulin Tolerance ◽  
Liquid Chromatography Tandem Mass ◽  
Synacthen Test ◽  
Cortisol Levels

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.

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 ◽  
...  
Keyword(s):  
Salivary Cortisol ◽  
Serum Cortisol ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Maximum Response ◽  
Similar Response ◽  
Good Reliability ◽  
Maximum Serum ◽  
Insulin Tolerance ◽  
Synacthen Test

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.

scholarly journals Normal Cortisol Response to High-Dose Synacthen and Insulin Tolerance Test in Children and Adults with Prader-Willi Syndrome

2011 ◽  
Vol 96 (1) ◽  
pp. E173-E180 ◽  
Author(s):  
Stense Farholt ◽  
Rasmus Sode-Carlsen ◽  
Jens Sandahl Christiansen ◽  
John R. Østergaard ◽  
Charlotte Høybye
Keyword(s):  
Hpa Axis ◽  
Genetic Diagnosis ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
High Dose ◽  
Prader Willi Syndrome ◽  
University Hospitals ◽  
Insulin Tolerance ◽  
Synacthen Test ◽  
Clinically Significant

Context: Prader-Willi syndrome (PWS) is a genetic disease associated with hypogonadism and partial GH insufficiency, possibly explained in part by a hypothalamic dysfunction. Partial insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis has recently been suggested. Objective: The objective of the study was to further explore the HPA axis in PWS by use of routine tests. Design: Nonselected PWS patients were examined with a standard high-dose synacthen test or the insulin tolerance test (ITT). A random serum (s) cortisol was measured in case of acute illness. Setting: The study was conducted at university hospitals in Denmark and Sweden. Patients: Sixty-five PWS patients with a confirmed genetic diagnosis participated in the study. Main Outcome Measures: A s-cortisol value above 500 nmol/liter as well as an increase of 250 nmol/liter or greater was considered a normal response. Results: Fifty-seven PWS patients (median age 22 yr, total range 0.5–48 yr) were examined with the high-dose synacthen test. The median s-cortisol at the time of 30 min was 699 (474–1578) nmol/liter. Only one patient had a s-cortisol level below 500 nmol/liter but an increase of 359 nmol/liter. This patient subsequently showed a normal ITT response. Two patients had increases less than 250 nmol/liter but a time of 30-min s-cortisol values of 600 nmol/liter or greater. These three patients were interpreted as normal responders. Eight patients [aged 26 (16–36) yr] examined with the ITT had a median peak s-cortisol of 668 (502–822) nmol/liter. Four children admitted for acute illnesses had s-cortisol values ranging from 680 to 1372 nmol/liter. Conclusion: In this PWS cohort, the function of the HPA axis was normal, suggesting that clinically significant adrenal insufficiency in PWS is rare.

scholarly journals Adverse childhood experiences, daytime salivary cortisol, and depressive symptoms in early adulthood: a longitudinal genetically informed twin study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eleonora Iob ◽  
Jessie R. Baldwin ◽  
Robert Plomin ◽  
Andrew Steptoe
Keyword(s):  
Depressive Symptoms ◽  
Hpa Axis ◽  
Salivary Cortisol ◽  
Adverse Childhood Experiences ◽  
Emotional Abuse ◽  
Early Adulthood ◽  
Cumulative Exposure ◽  
Childhood Experiences ◽  
Adverse Childhood ◽  
Cortisol Levels

AbstractDysregulated hypothalamic–pituitary–adrenal (HPA)-axis function might underlie the relationship between adverse childhood experiences (ACEs) and depression. However, limited research has examined the possible mediating role of the HPA-axis among young people using longitudinal data. Moreover, it remains unclear whether genetic influences could contribute to these associations. Participants were 290 children from the Twins Early Development Study. ACEs were assessed from age 3–11 years. We calculated a cumulative risk score and also derived different ACEs clusters using factor analysis and latent class analysis. HPA-axis activity was indexed by daytime salivary cortisol at age 11. Depressive symptoms were ascertained at age 21. Genetic liability to altered cortisol levels and elevated depressive symptoms was measured using a twin-based method. We performed causal mediation analysis with mixed-effects regression models. The results showed that ACEs cumulative exposure (b = −0.20, p = 0.03), bullying (b = −0.61, p = 0.01), and emotional abuse (b = −0.84, p = 0.02) were associated with lower cortisol levels at age 11. Among participants exposed to multiple ACEs, lower cortisol was related to higher depressive symptoms at age 21 (b = −0.56, p = 0.05). Lower cortisol levels mediated around 10–20% of the total associations of ACEs cumulative exposure, bullying, and dysfunctional parenting/emotional abuse with higher depressive symptoms. Genetic factors contributed to these associations, but the mediation effects of cortisol in the associations of ACEs cumulative exposure (b = 0.16 [0.02–0.34]) and bullying (b = 0.18 [0.01–0.43]) remained when genetic confounding was accounted for. In conclusion, ACEs were linked to elevated depressive symptoms in early adulthood partly through lower cortisol levels in early adolescence, and these relationships were independent of genetic confounding.

scholarly journals The Role of Very Low Calorie Ketogenic Diet in Sympathetic Activation through Cortisol Secretion in Male Obese Population

2021 ◽  
Vol 10 (18) ◽  
pp. 4230
Author(s):  
Rita Polito ◽  
Giovanni Messina ◽  
Anna Valenzano ◽  
Alessia Scarinci ◽  
Ines Villano ◽  
...  
Keyword(s):  
Body Composition ◽  
Adipose Tissue ◽  
Ketogenic Diet ◽  
Hpa Axis ◽  
Salivary Cortisol ◽  
Acute Stress ◽  
Stress Factors ◽  
Therapeutic Interventions ◽  
Low Calorie ◽  
Cortisol Levels

Adipose tissue is considered an endocrine organ, and its excess compromises the immune response and metabolism of hormones and nutrients. Furthermore, the accumulation of visceral fat helps to increase the synthesis of cortisol. The hypothalamus-pituitary-adrenal (HPA) axis is a neuroendocrine system involved in maintaining homeostasis in humans under physiological conditions and stress, and cortisol is the main hormone of the HPA axis. It is known that a stress-induced diet and cortisol reactivity to acute stress factors may be related to dietary behavior. In obesity, to reduce visceral adipose tissue, caloric restriction is a valid strategy. In light of this fact, the aim of this study was to assess the effects of a commercial dietary ketosis program for weight loss on the sympathetic nervous system and HPA axis, through evaluation of salivary cortisol and GSR levels. Thirty obese subjects were recruited and assessed before and after 8 weeks of Very Low Calorie Ketogenic Diet (VLCKD) intervention to evaluate body composition and biochemical parameters. Salivary cortisol levels and GSR significantly decreased after dietary treatment; in addition, body composition and biochemical features were ameliorated. The VLCKD had a short-term positive effect on the SNS and HPA axes regulating salivary cortisol levels. Finally, the effects of the VLCKD on the SNS and HPA axis may lead to more individualized treatment strategies that integrate obesity and stress and support the usefulness of such therapeutic interventions in promoting the reduction of the individual disease burden.

scholarly journals Central Adrenal Insufficiency Is Rare in Adults With Prader–Willi Syndrome

2020 ◽  
Vol 105 (7) ◽  
pp. e2563-e2571 ◽  
Author(s):  
Anna G W Rosenberg ◽  
Karlijn Pellikaan ◽  
Christine Poitou ◽  
Anthony P Goldstone ◽  
Charlotte Høybye ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Outcome Measure ◽  
Tolerance Test ◽  
Pituitary Hormone ◽  
Prader Willi Syndrome ◽  
Insulin Tolerance ◽  
Synacthen Test ◽  
Central Adrenal Insufficiency ◽  
Stress Dose ◽  
Hydrocortisone Treatment

Abstract Context Prader–Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. In some countries, it is general practice to prescribe stress-dose hydrocortisone during physical or psychological stress in patients with PWS. Side effects of frequent hydrocortisone use are weight gain, osteoporosis, diabetes mellitus, and hypertension—already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity—or even mortality. Objective To prevent both over- and undertreatment with hydrocortisone, we assessed the prevalence of CAI in a large international cohort of adults with PWS. As the synacthen test shows variable results in PWS, we only use the metyrapone test (MTP) and insulin tolerance test (ITT). Design Metyrapone test or ITT in adults with PWS (N = 82) and review of medical files for symptoms of hypocortisolism related to surgery (N = 645). Setting Outpatient clinic. Patients or Other Participants Eighty-two adults with genetically confirmed PWS. Main Outcome Measure For MTP, 11-deoxycortisol > 230 nmol/L was considered sufficient. For ITT, cortisol > 500 nmol/L (Dutch, French, and Swedish patients) or > 450 nmol/L (British patients) was considered sufficient. Results Central adrenal insufficiency was excluded in 81 of 82 patients. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative hydrocortisone treatment. None of them had displayed any features of hypocortisolism. Conclusions Central adrenal insufficiency is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing hydrocortisone stress-doses in adults with PWS.

scholarly journals Diagnosis of secondary adrenal insufficiency in patients with hypothalamic–pituitary disease: comparison between serum and salivary cortisol during the high-dose short synacthen test

2009 ◽  
Vol 160 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Timo Deutschbein ◽  
Nicole Unger ◽  
Klaus Mann ◽  
Stephan Petersenn
Keyword(s):  
Salivary Cortisol ◽  
Serum Cortisol ◽  
Early Morning ◽  
Diagnostic Value ◽  
Tolerance Test ◽  
High Dose ◽  
Characteristic Analysis ◽  
Synacthen Test ◽  
Short Synacthen Test

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.

The Use of the Short Tetracosactrin Test for the Investigation of Suspected Pituitary Hypofunction

1996 ◽  
Vol 33 (2) ◽  
pp. 112-118 ◽  
Author(s):  
T W M Wang ◽  
M S Wong ◽  
J Falconer Smith ◽  
T A Howlett
Keyword(s):  
Hpa Axis ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Cortisol Response ◽  
Established Method ◽  
Time Points ◽  
Routes Of Administration ◽  
Insulin Tolerance ◽  
Significant Difference ◽  
Cortisol Responses

The short Synacthen (tetracosactrin) test (SST) is an established method of assessing adrenocortical reserve, and is increasingly replacing the insulin tolerance test (ITT) for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis. However, there is no consensus on how the test is performed, and various time points and routes of administration are used. The present study was done, first, to determine whether there was any difference in cortisol responses when Synacthen was administered intramuscularly compared with intravenously and, secondly, to compare cortisol responses at 30 and 60 min. We found no significant difference between the two routes of administration. However, cortisol responses at 60 min were significantly higher than at 30 min ( P < 0·05). Previous validations for the use of the SST in place of the ITT have used cortisol responses 30 min after Synacthen. We conclude that where the SST is used to assess the HPA axis, cortisol response at 30 min after intravenous Synacthen should be used.

scholarly journals Is the plasma ACTH concentration a reliable parameter in the insulin tolerance test?

2003 ◽  
pp. 535-541 ◽  
Author(s):  
K Borm ◽  
M Slawik ◽  
L Seiler ◽  
F Flohr ◽  
M Petrick ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Healthy Subjects ◽  
Peak Plasma ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Cortisol Concentration ◽  
Plasma Acth ◽  
Hypothalamic Pituitary Adrenal ◽  
Insulin Tolerance ◽  
Acth Concentration

OBJECTIVE: The insulin tolerance test (ITT) is an established standardized test for the evaluation of the hypothalamic-pituitary-adrenal axis. While a peak cortisol value of >18 microg/dl is usually interpreted as a sufficient response to the ITT, the plasma ACTH response has not yet been standardized. METHODS: We evaluated retrospectively the peak plasma ACTH concentrations during 140 ITTs in 125 patients with suspected pituitary insufficiency and prospectively in 15 healthy subjects. RESULTS: All healthy subjects had a peak cortisol concentration >/=18 microg/dl; 32 of 125 tests in the patients showed an insufficient cortisol response (peak cortisol concentration <18 microg/dl). The peak stimulated ACTH concentration in patients with secondary adrenal insufficiency (SAI) was 49.2+/-37.2 pg/ml (mean+/-s.d.) vs 130.9+/-89.3 pg/ml in patients without SAI, and 110.9+/-55.4 pg/ml in normal subjects (P<0.001). There was a weak, but significantly positive correlation between the peak ACTH and peak cortisol concentrations (rho=0.446, P<0.001), but there was also a very wide spread of the values. Defining a cut-off value for the peak plasma ACTH concentration with a sufficient sensitivity and specificity to identify patients with an impaired hypothalamic-pituitary-adrenal (HPA) axis was not possible. A peak plasma ACTH <20 pg/ml as a cut-off value had a sensitivity of 25% and a specificity of 98% for SAI. A cut-off value of a peak plasma ACTH <140 pg/ml had a sensitivity of 97% but a low specificity of 39%. CONCLUSIONS: Although there is a significant positive correlation between the peak ACTH and the peak cortisol concentrations, we conclude that there is no additional benefit in determining the ACTH concentrations during an ITT. Because of the strong variations of the values, the peak ACTH concentration is a poor parameter for the evaluation of the HPA axis.

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