Salivary Free Cortisol Response to Cosyntropin Stimulation Test in Mitotane Treated Patients

Study Overview
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Brief Summary
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In mitotane treated patients, serum cortisol cannot be used to diagnose hypoadrenalism, since mitotane increases cortisol binding globulin levels (CBG), artificially raising total cortisol. Salivary free cortisol (SC) is not affected by CBG alterations, and reflects the free serum cortisol. In the current study, investigators will assess serum and SC responses during low-dose cosyntropin stimulation test in healthy volunteers, mitotane-induced hypoadrenal patients on steroid replacement therapy and in patients who suffer from hypoadrenlism caused from other etiology. Investigators will compare results between groups and try to demonstrate the superiority of SC in assessing adrenal function in mitotane treated patients.

Detailed Description
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80-90% of circulating cortisol is bound to cortisol binding globulin (CBG) or transcortin, whereas only 3-10% is in the free state. Salivary free cortisol (SC) is an index of plasma free cortisol. In previous studies it was shown that in low-dose cosyntropin stimulation test, SC increases significantly in normal but not in hypoadrenal patients. It was suggested that dynamic assessment of the SC response to ACTH may be particularly helpful whenever the measurement of serum cortisol is complicated by increased or decreased CBG levels. Adrenocortical carcinoma (ACC) is a rare malignancy with a heterogeneous presentation and a variable but generally poor prognosis. Mitotane is the main drug for ACC treatment and it plays a role both in adjuvant treatment after complete resection and in recurrent, inoperable and/or metastatic ACC. Mitotane blocks adrenocortical steroid synthesis and also exerts a specific cytotoxic effect on adrenocortical cells. Mitotane induces adrenal insufficiency, requiring hydrocortisone replacement therapy. In mitotane treated patients, serum cortisol cannot be used to diagnose hypoadrenalism, since mitotane increases CBG levels, artificially raising total cortisol. SC is not affected by CBG alterations, and reflects the free serum cortisol and may be more accurate in diagnosing hypoadrenalism in mitotane treated patients. In the current study, investigators will assess serum and SC responses during low-dose cosyntropin stimulation test in healthy volunteers, mitotane-induced hypoadrenal patients on steroid replacement therapy and in patients who suffer from hypoadrenlism caused from any other etiology. Investigators will compare results between groups and try to demonstrate the superiority of SC in assessing adrenal function in mitotane treated patients.

Official Title
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Salivary Free Cortisol Response to Cosyntropin Stimulation Test in Mitotane Treated Patients

Conditions
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Adrenal Insufficiency, Adrenal Cancer

Intervention / Treatment
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* Diagnostic Test: Cosyntropin stimulation test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: mitotane treated known hypoadrenlism Exclusion Criteria: pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: healthy subjects<br>low-dose cosyntropin stimulation test | Diagnostic Test: Cosyntropin stimulation test<br>* At 0800h to 0900h, a 25 mm plastic intravenous line will be inserted in an antecubital vein. Then, 1 μg/ml ACTH aliquot stock solution will be pushed through, followed by 5 ml physiologic saline (0.9%). Serum cortisol and salivary free cortisol will measured just before ACTH administration and 30 minutes later.<br>|
| Experimental: hypoadrenal mitotane treated patients<br>low-dose cosyntropin stimulation test | Diagnostic Test: Cosyntropin stimulation test<br>* At 0800h to 0900h, a 25 mm plastic intravenous line will be inserted in an antecubital vein. Then, 1 μg/ml ACTH aliquot stock solution will be pushed through, followed by 5 ml physiologic saline (0.9%). Serum cortisol and salivary free cortisol will measured just before ACTH administration and 30 minutes later.<br>|
| Experimental: hypoadrenal no-mitotane treated patients<br>low-dose cosyntropin stimulation test | Diagnostic Test: Cosyntropin stimulation test<br>* At 0800h to 0900h, a 25 mm plastic intravenous line will be inserted in an antecubital vein. Then, 1 μg/ml ACTH aliquot stock solution will be pushed through, followed by 5 ml physiologic saline (0.9%). Serum cortisol and salivary free cortisol will measured just before ACTH administration and 30 minutes later.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Salivary free cortisol | Salivary free cortisol concentrations during intravenous low dose cosyntropin stimulation test.. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum cortisol | Serum cortisol concentrations during intravenous low dose cosyntropin stimulation test. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cosyntropin, salivary free cortisol, mitotane