Endocrine Abstracts

Background: Abiraterone, a CYP17A1 inhibitor for metastatic prostate cancer, suppresses adrenal cortisol and androgen synthesis. Adrenal insufficiency may occur despite steroid supplementation, presenting with fatigue, dizziness, hypotension, particularly in those with pre-existing autonomic dysfunction.

Case: A 54-year-old man with metastatic prostate cancer, chronic postural hypotension and depression presented with generalized pain, dizziness and breathlessness three weeks after initiating Abiraterone with Prednisolone. Profound postural hypotension persisted despite Abiraterone discontinuation. Short Synacthen test off Prednisolone confirmed adrenal insufficiency (cortisol <28 nmol/l). Prednisolone was restarted and Fludrocortisone commenced, but despite dose escalation (Fludrocortisone 300 µg/day) and addition of Midodrine (10 mg three times a day) systolic blood pressure dropped >40 mmHg on standing. Ivabradine 5 mg BD was added to control symptomatic tachycardia. Historical asthma diagnosis was challenged and excluded following pulmonary function testing. Pyridostigmine was introduced, reducing postural drop and dramatically improving function, allowing the patient to tolerate 90 minutes sitting upright and walk indoors with a frame.

Discussion: Abiraterone may precipitate clinically significant adrenal insufficiency despite glucocorticoid supplementation, aggravating pre-existing autonomic dysfunction. Recognition is essential as conventional therapy with Fludrocortisone and Midodrine may be inadequate. Pyridostigmine, an acetylcholinesterase inhibitor that enhances ganglionic transmission without worsening supine hypertension, proved highly effective in this refractory case. This highlights the importance of considering adrenal insufficiency in Abiraterone-treated patients and suggests a potential adjunctive role for Pyridostigmine in severe postural hypotension unresponsive to standard measures. To our knowledge, no prior reports describe pyridostigmine for adrenal-insufficiency-related postural hypotension, making this a novel demonstration of its therapeutic potential.

Conclusion: Clinicians should recognise Abiraterone-induced adrenal insufficiency causing refractory postural hypotension. Pyridostigmine can achieve functional recovery when conventional therapy is insufficient, representing a novel adjunctive approach.