Iatrogenic Cushing's syndrome as a consequence of nasal use of Betamethasone spray during pregnancy

Glucocorticoids (GC) are largely used for their anti-inflammatory and immunosuppressive effects. Until recently "local" administration (inhalation, topical, intra-articular, ocular and nasal) was considered devoid of important systemic side effects, but there is no administration form, dosing or treatment duration for which the risk of iatrogenic Cushing's syndrome (CS) and consequent adrenal insufficiency (AI) can be excluded with certainty. We present the case of a pregnant woman who developed overt CS with secondary AI in the second trimester of pregnancy. She had low morning plasma cortisol 6.95 nmol/L (normal non-pregnant range 166 - 507) and low ACTH level 1.54 pg/mL (normal range 7.2 - 63.3), suggestive for iatrogenic CS. A thorough anamnesis revealed chronic sinusitis long-term treated with high doses of intranasal betamethasone spray (6 - 10 applications/day, approximately 10 mg betamethasone/week, for 5 months). After decreasing the dose and switching to an alpha-1 adrenergic agonist spray, the adrenal function recovered in a few weeks without manifestations of AI. The patient underwent an uneventful delivery of a normal baby. A review of the literature showed that only a few cases with exogenous CS and consequent AI caused by intranasal GC administration were described, mostly in children, but none during pregnancy. Long-term high doses of intranasal GC may induce iatrogenic CS and should be avoided. Low levels of ACTH and cortisol should prompt a detailed anamnesis looking for various types of glucocorticoid administration.