Endocrine Abstracts

JOINT1520

Introduction: Cushing’s syndrome (CS) is a clinical condition due to exposure to high endogenous or exogenous glucocorticoids (GC). Chronic exposure to exogenous GC is generally associated with a more rapid onset of CS clinical signs as compared to endogenous hypercortisolism, but they share signs and symptoms. 10% of the total annual diagnoses of CS concerns children and the predominant cause are GC used to treat various clinical conditions. Indeed, the use of oral, inhaled, injected, or topical (e.g. creams and ointments) drugs containing GC is the most common cause of exogenous CS. In addition, some "unsuspected" natural formulations may contain GC or compounds with GC-like activity. Therefore, it is fundamental to investigate the use of these products in patients with CS. A 15-year-old girl referred to us for a suspected CS. Adrenocortical axis was suppressed but she denied any previous steroid consumption, and reported a 1-year head-application of an anti-lice spray. The clinical course showed a complete functional recovery after the product’s withdrawal. The purpose of this study is to investigate whether the anti-lice product contains compounds with GC-like activity. Anti-lice products are widely used in the pediatric population to treat and/or prevent head lice infestation.

Methods: LC-HRMS was performed to detect the spray components in patient’s serum, pyrethrins and piperonyl butoxide (PBO). To evaluate PBO effects, alone or combined with Mifepristone (Mif), we incubated the GloResponse 9XGAL4UAS-luc2P HEK293 cell line (GloHEK cell) using increasing compound concentrations (from 0,25 mM to 100 mM). The luminescence assay was performed using PBO 10 µM.

Results: PBO levels were high in patient’s serum during anti-lice product exposure (~ 50-fold vs. in control). Six months after stopping product application PBO levels were similar to control. PBO did not affect cell number at the concentration employed in the luciferase assay. To verify a possible PBO GC-like activity, we evaluated luminescence emission: PBO significantly increased baseline luminescence by >7-fold (P < 0.01). On the other hand, Mif enhanced baseline luminescence by ~2-fold (P < 0.01) and potently hampered PBO-induced luminescence (P < 0.05). ConclusionsPBO showed a GC-like activity, by a direct binding to the GR. The latter is demonstrated by the evidence that PBO effects are prevented by co-incubation with the GR antagonist. The prolonged exposure to the anti-lice spray was causing the CS-like appearance in this young girl.