Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) suppression and/or manifestations of Cushing's syndrome in some patients. Clobetasol propionate has been shown to suppress the HPA axis at doses as low as 2 g/day. Conditions which increase systemic absorption include application of high-potency corticosteroids, use over large surface areas, prolonged use, use in areas where the epidermal barrier is disrupted (., skin abrasion), use in pediatric patients, use in patients with hepatic disease, and the use of an occlusive dressing. Clobetasol propionate preparations should not be used with occlusive dressings. Patients receiving large doses of a potent topical corticosteroid like clobetasol should be evaluated periodically for evidence of HPA axis suppression and manifestations of Cushing's syndrome. If these effects are noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent corticosteroid. Recovery of HPA axis function is generally prompt and complete upon discontinuation. Infrequently, signs and symptoms of withdrawal may occur, requiring supplemental systemic corticosteroids. It is recommended that the administration of clobetasol creams, ointments, gels, or topical solutions be limited to no more than 14 days duration, in order to limit the risk of systemic effects. Clobetasol propionate emollient creams may be administered for up to 4 weeks duration if applied to no more than 5—10% of body surface area. The total weekly dose limit of 50 g or 50 mL of a % preparation should not be exceeded for any clobetasol preparation.
Metyrapone is used for the medical control of hypercortisolism in Cushing's syndrome (ACTH dependent or independent). The aim for medical treatment is to achieve pre-operative control of hypercortisolism, or for control of residual disease persisting post-operatively (TSS, adrenalectomy). It is not for long term definitive treatment/cure, only as an adjunct (surgery is the aim for cure in most causes of Cushing's syndrome). Metyrapone hence acts by inhibiting adrenal steroidogenesis. One side effect is hirsutism (in women) because of the excess androgen precursors created. The other commonly used agent for medical treatment of Cushing's is ketoconazole (an anti-fungal agent). This does not exhibit the side effect of hirsutism.