Is cortisol elevated in pheochromocytoma?

Cortisol Elevation in Pheochromocytoma

Yes, cortisol levels can be elevated in patients with pheochromocytoma due to adrenal cortical-medullary interactions involving the influence of catecholamines on adrenal steroid production. 1

Mechanism and Evidence

• Patients with pheochromocytoma have higher circulating concentrations of cortisol, 11-deoxycortisol, 11-deoxycorticosterone, and corticosterone compared to patients with primary hypertension 1
• These elevated steroids correlate positively with plasma and urinary metanephrines and catecholamines specifically in patients with pheochromocytoma (but not in paraganglioma) 1
• After adrenalectomy for pheochromocytoma, significant decreases in cortisol, 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, aldosterone, and 18-oxocortisol are observed 1

Clinical Significance

• The bidirectional relationship between adrenal steroids and catecholamines can contribute to the cardiovascular complications seen in pheochromocytoma 1
• Some patients with pheochromocytoma may experience symptoms secondary to increased adrenocortical steroid levels, including hypertension, hyperglycemia, hypokalemia, and muscle atrophy 2
• These elevated cortisol levels can complicate the clinical presentation and management of patients with pheochromocytoma 1

Special Cases: ACTH-Producing Pheochromocytomas

• In rare cases, pheochromocytomas can directly produce ACTH, leading to severe Cushing syndrome 3
• ACTH-producing pheochromocytomas represent an exception where both catecholamine excess and severe cortisol elevation occur simultaneously 4
• These cases present with findings of both adrenocorticoid and catecholamine excess, as well as elevated levels of plasma ACTH, urinary metanephrines, and urinary free cortisol 4
• Preoperative control of hypertension and hypokalemia can be very challenging in these patients 3
• Unilateral adrenalectomy is typically curative for ACTH-producing pheochromocytomas, resolving both hormone excess syndromes 4

Diagnostic Considerations

• When evaluating patients with resistant hypertension, screening for pheochromocytoma involves measuring circulating catecholamine metabolites 2
• The screening test of choice is measurement of plasma free metanephrines (sensitivity 96%-100%, specificity 89%-98%) or urinary fractionated metanephrines (sensitivity 86%-97%, specificity 86%-95%) 2
• If cortisol levels are also elevated, a 24-hour urine cortisol test is recommended to evaluate for Cushing syndrome 2
• Imaging should only be pursued after biochemical evidence for a pheochromocytoma has been obtained 2

Clinical Implications

• The presence of elevated cortisol in pheochromocytoma may contribute to the metabolic derangements seen in these patients 1
• Physicians should be aware that some pheochromocytomas can present with features mimicking metabolic syndrome due to cortisol excess 2
• Early recognition of this relationship is crucial to decrease morbidity and mortality 3
• After surgical removal of pheochromocytoma, patients may require corticosteroid supplementation until recovery of the hypothalamus-pituitary-adrenal axis 2

Pitfalls and Caveats

• Hypertensive patients frequently have elevated levels of catecholamine metabolites, especially with obesity and obstructive sleep apnea, usually <4 times the upper limit of normal 2
• The presence of rare comorbidities should be considered if clinical findings cannot be explained by the pathophysiology of pheochromocytoma alone 5
• In cases of suspected ectopic ACTH production from pheochromocytoma, dexamethasone suppression tests may demonstrate suppressed serum cortisol and altered catecholamine levels 5
• The average 3-year delay in diagnosis of pheochromocytoma highlights the importance of considering this diagnosis in resistant hypertension 2