Adrenal Crisis Induced by Zoledronic Acid in Two Patients With Hypopituitarism: A Case Report and Literature Review

Adrenal insufficiency (AI) is characterized by inadequate steroid hormone production and is frequently a consequence of hypopituitarism, which is also associated with increased risk of osteoporosis due to deficiencies in growth hormone, gonadotropins, and other pituitary hormones. Zoledronic acid (ZA), a widely used bisphosphonate, is associated with acute phase reaction (APR) that may trigger adrenal crisis in susceptible individuals. We describe two patients with hypopituitarism and osteoporosis who developed adrenal crisis shortly after their first ZA infusion, despite stable physiological steroid replacement and acetaminophen prophylaxis. One presented with hypotension and shock within 24 h, the other with hypotension, severe hyponatremia, and seizures at 48 h. Both recovered after high-dose glucocorticoids and were later switched to denosumab without complications. These cases highlight the potential for adrenal crisis in patients with central AI receiving ZA and suggest that standard prophylaxis may be insufficient. Alternative therapies and enhanced precautions may be warranted in this vulnerable population.