Pheochromocytomas Most Commonly Present As Adrenal Incidentalomas: A Large Tertiary Center Experience

Abstract

Context: Pheochromocytomas are increasingly diagnosed in incidentally detected adrenal masses. However, the characteristics of incidental pheochromocytomas are unclear.

Objective: We aimed to assess the proportion and clinical, biochemical, radiological, genetic, histopathological, and follow-up characteristics of incidental pheochromocytomas.

Methods: A retrospective review was conducted of patients with pheochromocytoma seen between January 2010 and October 2022 at a large UK tertiary care center. The diagnosis was confirmed histologically or by the combined presence of increased plasma and/or urinary metanephrines (MN), indeterminate adrenal mass on cross-sectional imaging, and metaiodobenzylguanidine avidity.

Results: We identified 167 patients with pheochromocytoma; 144 (86.2%) underwent adrenalectomy, for 23 (13.8%) surgery was either awaited, deemed unsuitable due to frailty or other metastatic malignancy, or declined by the patients. Excluding pheochromocytomas diagnosed via screening genetically predisposed individuals (N = 20), 37 of 132 (28.0%) presented with adrenergic symptoms and/or uncontrolled hypertension, while 91 of 132 (69.0%) patients presented with an incidentally detected adrenal mass. Incidentally detected patients were older (median age 62 years) than those detected due to clinical suspicion (aged 42 years) or after genetic screening (aged 33 years) (all P < .05). Incidentally detected pheochromocytomas were smaller (median 42 mm) than tumors detected due to adrenergic symptoms/uncontrolled hypertension (60 mm), but larger than tumors identified by genetic screening (30 mm) (all P < .05). Increased MN excretion showed a similar pattern (symptomatic/uncontrolled hypertension > incidental > genetic screening) (all P < .05). Hereditary predisposition was detected in 20.4% of patients (incidental, 15.3%; symptomatic/uncontrolled hypertension, 42.9%).

Conclusion: The majority of pheochromocytomas are diagnosed incidentally and have distinct clinical, radiological, biochemical, and genetic features. Their detection at older age but smaller size may point to a different underlying tumor biology.

Keywords: adrenal incidentaloma; catecholamines; metanephrines; normetanephrines; pheochromocytoma.

Figure 1.

Clinical characteristics of patients with pheochromocytoma. A, Patients divided by pheochromocytoma mode of discovery after excluding those diagnosed on screening for genetic susceptibility (N = 20) and those with unknown mode of discovery (N = 15). B, Spread of patients’ age, divided by mode of discovery of pheochromocytoma. C, Prevalence of adrenergic symptoms and an underlying diagnosis of hypertension in patients with pheochromocytoma who presented as adrenal incidentaloma. D, Spread of age of onset of hypertension, divided by mode of discovery of pheochromocytoma. The horizontal lines represent the median of each group. Statistical significance was set at P less than .05.

Figure 2.

Radiological characteristics. Spread of pheochromocytoma tumor size, divided by mode of discovery. The horizontal lines represent the median of each group. Statistical significance was set at P less than .05.

Figure 3.

Biochemical characteristics. A, Spread of metanephrines increase, divided by mode of discovery of pheochromocytoma. B, Increase in metanephrines levels in patients with pheochromocytoma who presented as adrenal incidentaloma, divided into 4 tumor size groups. The horizontal lines represent the median of each group. Statistical significance was set at P less than .05.

Figure 4.

Preoperative α-blockade. Total daily dose of doxazosin immediately preoperatively (or at last follow-up if a patient did not undergo surgery), divided by mode of discovery of pheochromocytoma. The horizontal lines represent the median of each group. Statistical significance was set at P less than .05.