Dr. Tanju YILDÖN & Tıp Bilim Eğitimi

Cushing hastalığında medikal tedavi


Drug treatment in Cushing's disease

I-Act on the corticotrope tumor

1-Cabergoline; is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth. Cabergoline is an ergot derivative and a potent dopamine D2 receptor agonist.

2-Pasireotide;  is a somatostatin analog with a 40-fold increased affinity to somatostatin receptor 5 compared to other somatostatin analogs

II-Steroidogenesis inhibitors

Ketoconazole; "operates through at least two mechanisms of action. First, and most notably, high oral doses of ketoconazole (e.g. 400 mg three times per day) block both testicular and adrenal androgen biosynthesis, leading to a reduction in circulating testosterone levels. It produces this effect through inhibition of 17α-hydroxylase and 17,20-lyase, which are involved in the synthesis and degradation of steroids, including the precursors of testosterone. Due to its efficacy at reducing systemic androgen levels, ketoconazole has been used with some success as a treatment for androgen-dependent prostate cancer. Second, ketoconazole is an androgen receptor antagonist, competing with androgens such as testosterone and dihydrotestosterone (DHT) for binding to the androgen receptor. This effect is thought to be quite weak however, even with high oral doses of ketoconazole

Metyrapone; "blocks cortisol steroidogenesis by acting as a reversible inhibitor of 11β-hydroxylase. This stimulates adrenocorticotropic hormone (ACTH) secretion, which in turn increases plasma 11-deoxycortisol levels."

Etomidate; " use as an anesthetic, etomidate has also been found to directly inhibit the enzymatic biosynthesis of steroid hormones, including corticosteroids in the adrenal gland. As the only adrenal steroidogenesis inhibitor available for intravenous or parenteral administration, it is useful in situations in which rapid control of hypercortisolism is necessary or in which oral administration is unfeasible"

Mitotane; "is a steroidogenesis inhibitor and cytostatic antineoplastic medication which is used in the treatment of adrenocortical carcinoma and Cushing's syndrome"

III-Cortisol receptor antagonist

Mifepristone; " antiprogestogen agent, competitive progesterone receptor antagonist"

IV-Combination therapies

Ketoconazole + metyrapone

Mitotane + metyrapone + ketoconazole

Cabergoline + ketoconazole         

Pasireotide + cabergoline + ketoconazole