Hydrocortisone Aminoglutethimide

Aminoglutethimide 250 mg orally twice daily and hydrocortisone 20 mg twice daily Fatigue, mild nausea Skin rash, adrenal insufficiency, myelosuppression... 

Aminoglutethimide blocks even earlier, preventing the conversion of cholesterol to pregnenolone. It therefore blocks synthesis of aU steroids, hydrocortisone, aldosterone and sex hormones (including the conversion of androgens to oestrogens) it has a use in breast cancer. 

Precautions Aminoglutethimide administered with adrenal replacement doses of hydrocortisone. Hypercalcemia may occur in patients with bone metastases. Use in combination with IHRH agonist. ... 

Aminoglutethimide (Cytadren AG), a first-generation type 2 AI, originally was developed as an anticonvulsant but was subsequently found to inhibit the synthesis of adrenocortical steroids. AG is a nonspecific weak AI, administered as a 250-mg dose four times daily with hydrocortisone supplementation because of unwanted adrenal suppression. Because of significant toxicides related to its anticonvulsant structure and its relatively weak inhibition of aromatase, its use has declined considerably with the advent of newer AIs. 

Santen, R.J., T.J. Worgul, E. Samojlik, A. Interrante, A.E. Boucher, A. Lipton et al. (1981). A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer. Engl. J. Med. 305, 545-551. 

The effects of dexamethasone, but not hydrocortisone, can be reduced or abolished by aminoglutethimide. 

One study found that aminoglutethimide did not affect the response to hydrocortisone, and that hydrocortisone 40 mg was adequate replacement therapy in patients taking aminoglutethimide 1 g daily. In this study, aminoglutethimide did not affect the half-life of H-cortisol, which suggests that it does not affect hydrocortisone metabolism. Hydrocortisone 30 mg daily is normally adequate replacement in patients taking aminoglutethimide. ... 

Information is limited but the interaction between dexamethasone and aminoglutethimide is established. The reduction in the serum corticosteroid levels can be enough to reduce or even abolish the effects of corticosteroid replacement therapy or to cause loss of control of a disease condition. This has been successfully accommodated by increasing the dosage of the dexamethasone. Hydrocortisone is routinely used with aminoglutethimide as replacement therapy, and would seem to be a suitable alternative to dexamethasone, where clinically appropriate. Other synthetic corticosteroids are predicted to interact in the same way as dexamethasone, but this needs confirmation. 

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