An Adrenal Crisis After Denosumab Use in a Patient With Addison's Disease: A Case Report

Primary adrenal insufficiency (Addison's disease) requires lifelong glucocorticoid and mineralocorticoid replacement, and patients are vulnerable to adrenal crisis during physiologic stress or medication-related perturbations. Denosumab, a monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), is widely used for osteoporosis treatment and is generally well tolerated. However, to our knowledge, an adrenal crisis temporally associated with denosumab administration has not been previously documented. A 69-year-old female patient with a 35-year history of primary adrenal insufficiency was on stable replacement therapy with 5 mg of oral prednisolone daily. Due to chronic kidney disease, denosumab was selected as an alternative antiresorptive therapy for severe postmenopausal osteoporosis. Approximately 24 hours after receiving 60 mg of subcutaneous denosumab, she developed profound fatigue, vomiting, dizziness, and hypotension. Laboratory evaluation revealed hyponatremia, elevated creatinine, and low morning cortisol with elevated adrenocorticotropic hormone (ACTH), confirming adrenal crisis. Infectious, cardiac, gastrointestinal, and pharmacokinetic triggers - including medications known to accelerate glucocorticoid metabolism - were excluded. She was successfully treated with intravenous hydrocortisone and fluid resuscitation, with full clinical recovery. To our knowledge, this is the first reported case of adrenal crisis temporally linked to denosumab use in a female patient with Addison's disease, suggesting a possible association rather than definite causality, particularly when stress-dose glucocorticoids are not provided. Clinicians should be aware of this potential association and consider individualized risk assessment, pre-treatment glucocorticoid dose adjustments, and close monitoring in patients with adrenal insufficiency receiving denosumab.