Rapid Development of Iatrogenic Cushing Syndrome In A Patient On Ritonavir: The Adverse Metabolic Consequence of Topical Steroid Use

ABSTRACT Objective Topical steroid use is common, but its association with Cushing syndrome is rare. We report the rapid development of iatrogenic Cushing syndrome in a patient on ritonavir who applied a moderate-potency topical steroid cream, triamcinolone, on his genital mucosa for treatment of phimosis. Methods Clinical and diagnostic challenges associated with topical steroid use are presented and discussed. Results A 41-year-old man with human immunodeficiency virus infection on stable antiretroviral therapy that included ritonavir, a cytochrome P450 3A4 inhibitor, presented with new onset diabetes and development of overt cushingoid features over a 4-week period. He reported no known history of steroid use. A midnight salivary cortisol using a quantitative enzyme immunoassay was obtained and reported at >15.0 μg/dL (normal, <0.112 μg/dL). However, free cortisol in a 24-hour urine collection was undetectable by high-performance liquid chromatography and morning plasma cortisol was also unexpectedly low at 1.1 μg/dL (normal, 4.5 to 23.0 μg/dL). Further investigation revealed that the patient had been applying a topical cream with triamcinolone acetonide (0.1%) on the glans penis for treatment of phimosis. The salivary enzyme immunoassay for cortisol appears to have detected the absorbed triamcinolone, a compound known to cross-react with cortisol in this assay. Conclusion This case raises awareness on the severe metabolic consequence resulting from the seemingly benign use of a topical steroid medication when applied to the genital mucosa in the setting of stable therapy with ritonavir and illustrates the limitations of salivary cortisol enzyme immunoassays for the evaluation of Cushing syndrome in this setting. Abbreviations ART antiretroviral therapy; CYP3A4 cytochrome P450 3A4; HIV human immunodeficiency virus; LC/TMS liquid chromatography/tandem mass spectrametry