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 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.

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.

scholarly journals Response of Cortisol Metabolites in the Insulin Tolerance Test and Synacthen Tests

2015 ◽  
pp. S237-S246 ◽  
Author(s):  
K. SIMUNKOVA ◽  
M. DUSKOVA ◽  
M. KOSAK ◽  
M. KRSEK ◽  
V. HANA ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Similar Response ◽  
Strongly Correlated ◽  
Insulin Tolerance ◽  
Stimulation Tests ◽  
Synacthen Test ◽  
Short Synacthen Test ◽  
Cortisol Metabolites

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.

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.

Delayed peak response of cortisol to insulin tolerance test in patients with Prader-Willi syndrome

2018 ◽  
Vol 176 (6) ◽  
pp. 1369-1374 ◽  
Author(s):  
Yuji Oto ◽  
Keiko Matsubara ◽  
Tadayuki Ayabe ◽  
Masahisa Shiraishi ◽  
Nobuyuki Murakami ◽  
...  
Keyword(s):  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Prader Willi Syndrome ◽  
Peak Response ◽  
Insulin Tolerance
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