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Based on the ATLAS study in heart failure patients, high doses (325 to 35 mg/day) did not significantly change overall mortality rate compared to low doses (25 to 5 mg/day PO); however, the high dose group had a lower hospitalization rate for heart failure.
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Since ACTH is made in the pituitary under the control of the part of the brain called the hypothalamus, diseases that destroy either the hypothalamus or pituitary can cause this lack of ACTH.