Background Ketamine has garnered increased interest for its promising applications in chronic pain treatment, particularly in cases where conventional therapies have proven insufficient. Nevertheless, despite its potential advantages, ketamine remains classified as a third-line medication for pain management. While there are well-documented reactions to ketamine such as hypertension and tachycardia, not much is known about its relationship to cortisol. In this case report, we explicate the administration of ketamine in a patient presenting with atypical facial pain, examining its multifaceted effects on cortisol levels and concurrent pain management.

Case presentation A patient with a history of Cushing’s disease underwent multiple resections of a pituitary tumor. Afterwards, the patient began experiencing a burning-like pain on the left side of the face. The discomfort was initially treated with a variety of neuromodulatory and anti-inflammatory medications, which caused intolerable side effects and were not effective for pain. As a final recourse, we initiated a regimen of oral compounded ketamine at 5–10 mg three times daily as needed. The patient exhibited marked amelioration in their pain symptoms; however, there was an elevation in their baseline cortisol. In view of the potential risk of inducing Cushing’s syndrome, the administration of daily ketamine was discontinued.

Conclusion While ketamine is primarily known to control pain through the antagonization of N-methyl-D-aspartate receptors, its effects on cortisol may also contribute to its analgesic properties. Physicians should be aware of the potential for these interactions, particularly when treating patients with a predisposition to hormonal imbalances.