Pheochromocytoma

Pheochromocytoma
Name	Pheochromocytoma
Field	Endocrinology
Symptoms	Paroxysmal hypertension, headache, sweating, palpitations
Complications	Cardiomyopathy, stroke, hypertensive crisis
Onset	Any age, peak 30–50 years
Duration	Variable
Causes	Chromaffin cell tumor of adrenal medulla
Treatment	Alpha blockade, surgical adrenalectomy

Pheochromocytoma Pheochromocytoma is a catecholamine-secreting chromaffin cell tumor of the adrenal medulla that produces episodic sympathetic hyperactivity. It presents variably with paroxysmal hypertension and adrenergic symptoms and is associated with several hereditary syndromes and multisystem complications. Diagnosis commonly uses biochemical assays, cross-sectional imaging, and functional nuclear medicine techniques; definitive management is surgical resection after medical optimization.

Introduction

Pheochromocytoma arises from adrenal medullary chromaffin cells and is classically described by the "rule of tens" in older literature, though modern genetics has revised epidemiology. It occurs sporadically and as part of hereditary conditions including multiple endocrine neoplasia type 2 linked to Medullary thyroid carcinoma, von Hippel–Lindau disease linked to Renal cell carcinoma, and hereditary paraganglioma–pheochromocytoma syndromes associated with Succinate dehydrogenase. Historical surgical series and contemporary cohort studies from centers such as Mayo Clinic and Johns Hopkins Hospital have informed perioperative protocols and outcomes.

Signs and symptoms

Clinical features are dominated by catecholamine excess: episodic or sustained hypertension, severe headache, diaphoresis, palpitations, tremor, and pallor. Presentations may mimic acute coronary syndromes evaluated at institutions like Massachusetts General Hospital or Cleveland Clinic, and can precipitate cardiogenic shock described in case reports from Mount Sinai Hospital and Karolinska University Hospital. Other manifestations include anxiety-like states encountered in psychiatric consultations at places such as McLean Hospital and neurovascular events managed at stroke centers like Royal London Hospital.

Causes and pathophysiology

Tumors derive from neural crest–derived chromaffin cells with catecholamine biosynthesis involving tyrosine hydroxylase; molecular drivers include RET proto-oncogene mutations identified in Harvard Medical School research, VHL mutations characterized by investigators at University of Oxford, and SDH subunit mutations elucidated by teams at University of Cambridge. Pathophysiology links excess epinephrine and norepinephrine to alpha- and beta-adrenergic receptor activation with downstream effects observed in studies from Stanford University and University of California, San Francisco. Paragangliomas at head and neck sites seen in reports from Guy's Hospital contrast biochemically with adrenal tumors described in surgical series from Toronto General Hospital.

Diagnosis

Biochemical confirmation uses plasma free metanephrines or 24-hour urinary fractionated metanephrines measured in laboratories at institutions like Mayo Clinic Laboratories and Quest Diagnostics. Imaging localization employs computed tomography at centers such as Royal Prince Alfred Hospital or magnetic resonance imaging protocols developed at Imperial College London. Functional imaging with 123I-MIBG scintigraphy and 68Ga-DOTATATE PET/CT is performed in nuclear medicine units at Memorial Sloan Kettering Cancer Center and Johns Hopkins Hospital. Genetic testing for RET, VHL, NF1, and SDHx is routinely offered through genetics clinics at Sheffield Teaching Hospitals and University of Pennsylvania.

Treatment and management

Preoperative medical optimization emphasizes alpha-adrenergic blockade with phenoxybenzamine or selective agents used in practice at Cleveland Clinic and Mayo Clinic, often followed by beta-blockade to control tachycardia according to protocols from National Institutes of Health. Laparoscopic adrenalectomy is the preferred surgical approach at high-volume centers such as Addenbrooke's Hospital and Mount Sinai Hospital, with open surgery reserved for locally invasive disease as managed at Royal Marsden Hospital. In metastatic or unresectable disease, options include systemic therapies reported by MD Anderson Cancer Center and radionuclide therapy with 131I-MIBG used at specialist centers like Gustave Roussy.

Prognosis and complications

Prognosis depends on tumor genetics, size, and presence of metastases; survival data from cohort studies at Karolinska University Hospital and Mayo Clinic inform risk stratification. Acute complications include hypertensive emergency, myocardial infarction, arrhythmia, and stroke described in case series from St Thomas' Hospital and Royal Infirmary of Edinburgh. Long-term follow-up recommendations from endocrine societies and outcome registries at European Society of Endocrinology and Endocrine Society emphasize lifelong surveillance for recurrence, secondary neoplasms such as Medullary thyroid carcinoma in MEN2, and counseling through genetics services at centers like University College London Hospitals.

Category:Endocrine neoplasia