Background: General anaesthesia and surgical intervention in humans are known to affect the function of the hypothalamicpituitaryadrenal axis (HPA). In the literature there are conflicting reports about the effect of propofol, a commonly used intravenous anaesthetic agent, on HPA function.
Case reports: We report two males (11 and 12 years) with ACTH-dependent Cushing syndrome (CS) who underwent inferior petrosal sinus sampling (IPSS) with general anaesthesia. ACTH was measured from bilateral petrosal and peripheral sites at baseline and after administration of corticotrophin releasing hormone (CRH). Anaesthetic agents used included: propofol infusion (pt A: 7.8 mg/kg; pt B: 29 mg/kg), fentanyl, and midazolam. ACTH results from IPSS were atypical for both patients (i.e. no stimulation of ACTH (peripherally) and overall low values of ACTH). Since the ACTH results precluded scheduling of transsphenoidal surgery, the IPSS procedures were repeated. Results of the 2nd IPSS showed appropriate stimulation of peripheral and central ACTH levels and peripheral to central ratios consistent with Cushing disease (CD) in both patients. Anaesthetic agents used included single dose propofol at induction (~50 min prior to sampling) (pt A: 1.8 mg/kg; pt B: 1.4 mg/kg), fentanyl, and midazolam. Subsequently, both patients underwent TSS for removal of corticotropinoma which was confirmed at histology; they remain in remission of hypercortisolemia to date.
Conclusion: Historically, propofol has been shown to have direct antisteroidogenic effects on adrenal cells and to be a weak inhibitor of adrenal steroidgenesis, compared to etomidate. However, the two cases presented provide a novel insight about a possible interaction of propofol and ACTH. These cases suggest a possible short-term inhibition of ACTH secretion by propofol and highlight the importance of future research. A better understanding of the interaction of propofol with ACTH may be of vital importance in the intra- and post-operative management of patients as well as in diagnostic endocrine testing that involves anaesthesia.