Hypoadrenalism secondary to topical corticosteroid-containing skin-lightening cream: danger of over-the-counter cosmetic agents

A 26-year-old Sudanese woman was referred to the endocrinology clinic for investigation of low serum cortisol detected during investigations for fertility difficulties. There were no symptoms or signs to suggest adrenal insufficiency, nor did she have any overt Cushingoid features to suggest exogenous glucocorticoid exposure. Her blood pressure was 120/84 mmHg without postural drop. Although she had a generalised dark complexion, her face was a lighter shade compared with the rest of her body.

On further questioning, she admitted to using two “skin-lightening” creams for many years. These contained fluocinonide 0.075% and hydrocortisone acetate 1% and were purchased over the counter from a suburban store selling African goods in Sydney.

Repeat pathology (Box) confirmed the low cortisol on several separate mornings — 62 nmol/L, 116 nmol/L, < 28 nmol/L (reference interval [RI], 200–600 nmol/L), with a low-normal adrenocorticotropic hormone (ACTH) level of 3.1 pmol/L (RI, <10 pmol/L) and low 24-hour urine cortisol of 33 nmol (RI, 50–250 nmol/24 hours). These were consistent with the corticosteroid-containing creams causing suppression of her hypothalamic–pituitary–adrenal (HPA) axis. Cream usage was carefully weaned over a few weeks, with no symptoms of adrenal insufficiency. ACTH stimulation test performed a month later showed recovery of adrenal gland cortisol reserve.

Systemic absorption of the corticosteroid-containing creams resulted in suppression of the HPA axis in our patient. Studies have found a linear relationship between use of topical clobetasol propionate, which is used in skin-lightening creams, and the development of HPA axis suppression, occurring as early as a few days after commencement.1

Despite use of exogenous corticosteroids, the patient’s serum and urine cortisol levels were low. Routine cortisol immunoassays are most specific for cortisol (hydrocortisone), with significant cross-reactivity to prednisolone, methylprednisolone and prednisone. There is less cross-reactivity with other steroids, including cortisone and dexamethasone.2 Reduced cross-reactivity of the other synthetic corticosteroids in the creams used by this patient is the most likely reason for the low cortisol levels measured. This underscores the need for clinicians to be aware of possible falsely low cortisol results due to limitations of currently available immunoassays for measuring synthetic steroids.

The use of skin-lightening creams in women with dark skin tone is a common practice in some countries, with 67% prevalence in parts of Africa.3 While the prevalence is not known in Australia, it is possible that it is becoming more common with increasing migrant populations.4 Use of these corticosteroid-containing creams can cause unrecognised glucocorticoid excess syndromes and secondary adrenal insufficiency.1 Symptoms of hypoadrenalism can occur after cream cessation.1 Increased awareness of the potentially harmful consequences of these seemingly harmless “cosmetic agents” in our increasingly multicultural population will help minimise complications.