ABSTRACT
The human monoclonal antibody denosumab inhibits osteoclast-mediated bone resorption by binding to receptor activator of nuclear factor κB ligand (RANKL), which is upregulated by tumor cells. Denosumab is indicated to prevent skeletal-related events (SREs) from osteoporosis and metastatic bone disease. We report a case of denosumab-induced hypocalcemia to highlight potential toxicity and treatment considerations. A 66-year-old man with prostate cancer, small cell lung cancer, and bone metastases presented with fatigue, weakness, and muscle spasm. Sixteen days prior, he received cycle 6 of cisplatin and etoposide, leuprolide, and denosumab (120 mg subcutaneously). His examination demonstrated a slight resting tremor, normal strength, and negative Chvostek sign. Laboratory analysis revealed hemoglobin, 8.0 g/dL; total calcium, 5.2 mg/dL (pre-denosumab, 8.9 mg/dL); and magnesium, 0.7 mg/dL. He initially received two units packed red blood cells, intravenous calcium and magnesium, and vitamin D. During his hospitalization, he required multiple doses of intravenous and oral calcium, magnesium, and vitamin D. Despite ongoing oral supplementation, his post-discharge serum calcium fluctuated significantly, requiring close monitoring and frequent dose adjustments. Denosumab's unique antiresorptive properties yield fewer SREs. The trade-off is increased hypocalcemia risk, which may be severe and require aggressive, prolonged supplementation and monitoring.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Density Conservation Agents/adverse effects , Bone Neoplasms/drug therapy , Denosumab/adverse effects , Hypocalcemia/chemically induced , Prostatic Neoplasms/drug therapy , Small Cell Lung Carcinoma/drug therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/blood , Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Combined Modality Therapy , Denosumab/therapeutic use , Humans , Hypocalcemia/therapy , Male , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/metabolism , Neoplasms, Second Primary/drug therapy , Prostatic Neoplasms/blood , Prostatic Neoplasms/metabolism , RANK Ligand/antagonists & inhibitors , RANK Ligand/metabolism , Small Cell Lung Carcinoma/blood , Small Cell Lung Carcinoma/metabolism , Treatment OutcomeABSTRACT
CONTEXT: Nearly pure caffeine is sold as a "dietary supplement," with instructions to ingest 1/64th to 1/16th of one teaspoon (50-200 mg). We report a patient with refractory cardiac dysrhythmias treated with defibrillation, beta-adrenergic blockade, and hemodialysis to highlight concentrated caffeine's dangers. CASE DETAILS: A 20-year-old woman presented with severe agitation, tremor, and vomiting approximately 1-2 h after suicidal ingestion of concentrated caffeine (powder and tablets). Within minutes, ventricular fibrillation commenced. Defibrillation, intubation, and amiodarone administration achieved return of spontaneous circulation (ROSC). Shortly thereafter, she developed pulseless ventricular tachycardia (VTach), with ROSC after defibrillation and lidocaine. She subsequently experienced 23 episodes of pulseless VTach, each responsive to defibrillation. Activated charcoal was administered via orogastric tube. An esmolol infusion was started. Hemodialysis was initiated once she was hemodynamically stable. She was extubated the following day, continued on oral metoprolol, and transferred to psychiatry on hospital day seven, achieving full neurological recovery. Serum caffeine concentrations performed approximately six and 18 h post-ingestion (pre/post-dialysis) were 240.8 mcg/mL and 150.7 mcg/mL. DISCUSSION: Severe caffeine toxicity can produce difficult to treat, life-threatening dysrhythmias. Concentrated caffeine, marketed for dietary supplementation, presents a substantial public health risk that demands action to limit consumer availability.