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

Adrenal Insufficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03083834
• Other study ID #: 0006-17-BNZ
• Status: Recruiting
• Phase: N/A
• Start date: March 14, 2017
• Est. completion date: December 31, 2019

Study information

• Verified date: January 2019
• Source: Bnai Zion Medical Center
• Contact: Leonard Saiegh, MD
• Phone: +972506267262
• Email: leonard.saiegh[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• mitotane treated

• known hypoadrenlism

Exclusion Criteria:

• pregnancy

Related Conditions & MeSH terms

• Adrenal Cancer
• Adrenal Gland Neoplasms
• Adrenal Insufficiency

Intervention

Diagnostic Test:
• Cosyntropin stimulation test
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.

Locations

Country	Name	City	State
Israel	Bnai Zion MC	Haifa

Sponsors (1)

Lead Sponsor	Collaborator
Bnai Zion Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Salivary free cortisol	Salivary free cortisol concentrations during intravenous low dose cosyntropin stimulation test..	1 day
Secondary	serum cortisol	Serum cortisol concentrations during intravenous low dose cosyntropin stimulation test.	1 day