Adrenal Suppression With Chronic Topical Corticosteroid Use in Psoriasis Patients

Cortisol is an endogenous glucocorticoid produced in the adrenal gland under physiological stress conditions (eg infection, tissue injury, trauma) and is required for normal cellular function, including immune function, metabolism and vascular tone.^1,2 Its production is regulated by the hypothalamic-pituitary-adrenal (HPA) axis.³ Exogenous sources of corticosteroids may affect regulation of the HPA axis by inhibiting upstream pathways involved in cortisol production.¹

Topical corticosteroids (TCS) are used for a variety of skin conditions, including psoriasis.⁴ As psoriasis is a chronic disease, TCS are typically used for extended periods of time, often beyond recommendations in the prescribing information.⁴ Because of potential systemic absorption,⁵ chronic TCS use may result in side effects similar to those of systemic corticosteroids, such as adrenal suppression, Cushing’s syndrome, uncontrolled blood sugar levels, and neurological changes.^6-12 Adrenal suppression occurs when the adrenal glands are unable to produce a sufficient amount of cortisol secondary to exogenous sources of glucocorticoids, which would lead to adrenal insufficiency (AI).¹³ The most common method of diagnosing adrenal suppression is with the Cortrosyn® stimulation test. The patient is injected with cosyntropin, a synthetic adrenocorticotropic hormone,⁴ and adrenal suppression is confirmed if the post-cosyntropin cortisol level is less than 18 mcg/dL.^14,15

Patients using TCS are not routinely screened for adrenal suppression, and it is often not a factor that many physicians consider when prescribing TCS. However, studies have demonstrated that adrenal suppression may occur as early as one week following TCS use.⁹ Nineteen percent of subjects using a super-high potency TCS over greater than 20% of body surface area (BSA) for just 2 weeks developed evidence of HPA suppression.¹⁶ Twenty-two percent of patients using a TCS of high to super-high potency over greater than 15% of BSA developed evidence of HPA suppression in 4 weeks.¹⁷ The degree of suppression and the resulting health effects arising from long-term use are unknown. There are no signs or symptoms of adrenal suppression until clinical signs of Cushing’s syndrome occur.^11,18 Patients using TCS chronically are likely unaware of these risks. The potential systemic absorption from long term topical application especially over a significant BSA may result in “silent” HPA axis disruption, leading to secondary AI.¹⁸ This may result in atrophy of adrenal glands¹⁹ and if patients suddenly discontinue the corticosteroid therapy or experience physiological stress, the adrenal glands may not be able to produce adequate amounts of glucocorticoids to respond.^13,20 For these reasons, we sought to investigate the real world effects of chronic TCS use and its effects on the HPA axis in a chronic disease such as psoriasis.

Data for this study were obtained from screening visits from a psoriasis clinical trial evaluating the efficacy of a potent TCS combination in subjects with moderate to severe psoriasis.¹⁰ This