A 45-year-old man with episodic headache, palpitations, and sweating, and elevated plasma metanephrines is most likely to have:

The patient’s episodes of headache, palpitations, and sweating alongside elevated plasma metanephrines strongly indicate pheochromocytoma, a catecholamine-secreting tumor of the adrenal medulla. Plasma metanephrines are the most sensitive diagnostic markers for pheochromocytoma. Key management involves preoperative alpha-adrenergic blockade to control hypertension and prevent intraoperative hypertensive crises, followed by surgical resection of the tumor. Early diagnosis and careful perioperative management are crucial to avoid life-threatening cardiovascular complications.

Reference: Harrison's Principles of Internal Medicine, Jameson et al., 20th Edition.