Pheochromocytomas and paragangliomas (PPGLs)

Pheochromocytomas and paragangliomas (PPGLs) are closely related neuroendocrine tumours arising from chromaffin/paraganglial tissue. Pheochromocytomas arise in the adrenal medulla, whereas paragangliomas arise outside the adrenal gland and may be sympathetic or parasympathetic in origin. Sympathetic paragangliomas, like pheochromocytomas, may secrete catecholamines and produce systemic manifestations of catecholamine excess; in contrast, most parasympathetic paragangliomas, particularly head-and-neck tumours, are non-secretory and present predominantly with local mass effects. The psychiatric manifestations described below are therefore primarily relevant to catecholamine-secreting PPGLs (pheochromocytomas and sympathetic paragangliomas).

It can present with psychiatric features such as episodic anxiety, panic-like episodes, marked apprehension, agitation, emotional lability, and a subjective sense of impending doom, and, less commonly, psychotic symptoms. Psychotic symptoms have been reported both as transient episodes and as more persistent or relapsing phenomena; their temporal relationship to catecholamine secretion remains incompletely understood. Reported phenomenology includes paranoid and schizophreniform psychosis occurring outside the context of delirium, with psychotic symptoms improving following tumour removal in some cases.

Other characteristic features include episodic or sustained hypertension; paroxysmal headache; diaphoresis; palpitations or tachycardia; tremor; pallor; and heat intolerance. The traditional triad of headache, sweating, and palpitations is characteristic but lacks sufficient sensitivity to exclude PPGL when absent. Symptoms may be spontaneous or precipitated by physical exertion, emotional stress, certain medications, anaesthesia, procedures, or other stimuli that provoke catecholamine release. Neurologic manifestations may include severe headache, dizziness, visual disturbance, and, in severe catecholamine crises, cerebrovascular complications.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

• Cardiovascular: sustained or paroxysmal hypertension; tachycardia and palpitations; orthostatic hypotension; arrhythmias; myocardial ischaemia or infarction; catecholamine-mediated cardiomyopathy, including stress/Takotsubo-like cardiomyopathy; and, in severe cases, acute heart failure or hypertensive crisis. Cardiovascular morbidity is a major source of the acute and chronic complications of catecholamine-secreting PPGLs.

• Endocrine: increased metabolic rate, weight loss, heat intolerance, hyperglycaemia, and diabetes mellitus. Rare functional tumours may have additional hormone secretion, producing an endocrine phenotype beyond catecholamine excess.

• Dermatologic: prominent diaphoresis and episodic pallor are characteristic autonomic manifestations.

Early diagnosis is important to reduce the risk of potentially life-threatening cardiovascular and cerebrovascular complications and catecholamine crises; facilitate appropriate preoperative management and definitive treatment; identify tumours with metastatic potential; and prompt assessment for an underlying hereditary syndrome and appropriate surveillance of affected individuals and at-risk relatives. PPGLs may be hereditary and may have metastatic potential, making recognition and appropriate long-term follow-up particularly important.