Clinical trial NCT03083834: Salivary Free Cortisol Response to Cosyntropin Stimulation Test in Mitotane Treated Patients
Official title: Salivary Free Cortisol Response to Cosyntropin Stimulation Test in Mitotane Treated Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Adrenal Insufficiency
Adrenal Cancer
Keywords: cosyntropin
salivary free cortisol
mitotane
Lead sponsor: Bnai Zion Medical Center
Sponsor class: OTHER_GOV
First posted: 2017-03-20
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* mitotane treated
* known hypoadrenlism

Exclusion Criteria:

* pregnancy

Primary outcomes:
measure: Salivary free cortisol
timeFrame: 1 day
Secondary outcomes:
measure: serum cortisol
timeFrame: 1 day
Other outcomes:
Locations:
city: Haifa
country: Israel
facility: Bnai Zion MC
Study officials:
affiliation: Bnai Zion Medical Center
name: Leonard Saiegh, MD
role: PRINCIPAL_INVESTIGATOR
References: