Corrtisol, as defined by the National Institutes of Health, "is a steroid hormone released from the adrenal gland in response to ACTH, a hormone from the pituitary gland in the brain." Cortisol levels naturally increase during emotional or physical stress, but chronically elevated levels of the hormone causes chronic stress and memory problems, and may also cause brain cell damage. Also, elevated cortisol levels may indicate Cushing's disease or tumours on the adrenal gland. Fortunately, research has shown promising results on the pharmacological reduction of cortisol levels and/or its effects.
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Drugs, such as ketoconazole, mitotane and trilostane result in the complete or partial inhibition of cortisol synthesis. Ketoconazole, for example, is believed to act directly on the secretion of ACTH in Cushing's patients and has shown a reduction of cortisol levels in their urine and plasma. According to a report in "Medscape Today," combinations of these drugs may create a synergistic or additive effect, which would allow for smaller doses of the drugs and the lessening of their side effects, which, depending on the drug, may include GI discomfort, neurological symptoms and oedema. Total blockade of the adrenal gland with glucocorticoid replacement is another approach being widely used. However, to maintain normal cortisol levels, use of these drugs would require frequent monitoring of cortisol in the patient's urine or plasma.
This approach to cortisol reduction involves the use of drugs, such as octreotide, bromocriptine, cyproheptadine, ritanserin and sodium valproate that act directly on the body's secretion of ACTH, the hormone that signals the adrenal gland to release cortisol. Octreotide and ketoconazole used in conjunction appeared to have an additive effect, normalising cortisol levels in patients with Nelson's syndrome--a condition caused by the surgical removal of Cushing's patients' adrenal glands. Serotonin antagonist, cyproheptadine, proved to normalise cortisol levels in three out of four Cushing's patients, though hypercortisolism recurred in some patients despite the drug's continued use. Bromocriptine acts as a dopamine receptor agonist. Studies have shown that the dopamine agonist bromocriptine directly suppresses ACTH. About 40 per cent of patients on a continued bromocriptine regimen "had normalised urine or plasma cortisol levels," the report states.
Mifepristone Treatment for Cushing's and Depression
According to clinical neuropsychologist Jennifer Kirkland, who was treated for adrenal Cushing's disease herself in 2007, studies have shown that the steroid mifepristone can reduce the effects of elevated cortisol levels without shutting down production of the hormone. This is significant because cortisol is necessary for the brain's ability to handle stress and anxiety. In addition, a 2004 article in "Neuropsychopharmacology," reported that 20 bipolar patients showed significant improvement in mood, memory and other cognitive functions after six weeks of treatment with mifepristone.
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