How can pheochromocytoma cause lactic acidosis?

Mechanisms of Lactic Acidosis in Pheochromocytoma

Pheochromocytoma can cause lactic acidosis through excessive catecholamine release, which leads to increased lactate production via enhanced glycolysis and decreased lactate clearance due to peripheral vasoconstriction.

Pathophysiological Mechanisms

• Catecholamine excess in pheochromocytoma causes direct metabolic effects that increase glycolysis and lactate production, even in the absence of tissue hypoxia 1, 2
• Epinephrine-secreting tumors are particularly associated with lactic acidosis due to epinephrine's potent glycogenolytic and glycolytic effects 1, 3
• Peripheral vasoconstriction from excessive catecholamines reduces tissue perfusion, creating localized hypoxia and anaerobic metabolism, further increasing lactate production 2, 3
• Catecholamine-induced vasoconstriction also impairs hepatic blood flow, reducing the liver's ability to clear lactate from circulation 3
• Catecholamine myocarditis, which occurs in pheochromocytoma patients, can contribute to reduced cardiac output and tissue hypoperfusion, exacerbating lactic acidosis 4

Clinical Presentation

• Lactic acidosis can be a presenting feature of pheochromocytoma even without severe hypertension, making diagnosis challenging 1, 3
• The American Heart Association notes that pheochromocytoma is characterized by increased blood pressure variability, which can contribute to intermittent tissue hypoperfusion and lactate production 4, 5
• Severe lactic acidosis may occur during pheochromocytoma crisis, which can be precipitated by steroid administration, even when administered intramuscularly 1

Diagnostic Considerations

• Pheochromocytoma should be included in the differential diagnosis of unexplained lactic acidosis, especially when accompanied by other suggestive features such as hypertension, headaches, or sweating 2, 3
• Plasma free metanephrines are the recommended initial diagnostic test for pheochromocytoma with 99% sensitivity and 89% specificity 5
• Despite improved diagnostic techniques, pheochromocytoma diagnosis is often delayed, with an average of 3 years between initial symptoms and final diagnosis 4, 5

Management Implications

• Recognition of lactic acidosis as a potential manifestation of pheochromocytoma is crucial, as undiagnosed pheochromocytoma can be fatal 4, 6
• Alpha-adrenergic blockade (with agents such as phenoxybenzamine or doxazosin) is essential before surgical resection to prevent hypertensive crisis and may help improve tissue perfusion and reduce lactate production 4, 6
• Complete surgical resection is the primary curative treatment for pheochromocytoma and should resolve the metabolic derangements including lactic acidosis 4, 5

Clinical Pitfalls and Caveats

• Lack of severe hypertension does not exclude pheochromocytoma as a cause of lactic acidosis, as demonstrated in case reports 1
• Noninvasive blood pressure measurements may be unreliable during pheochromocytoma crisis due to excessive peripheral vasoconstriction 1
• Many cases of pheochromocytoma are missed during life, with autopsy studies showing the tumor contributed to 55% of deaths and was not suspected in 75% of cases 4, 5
• Approximately 35% of pheochromocytomas are hereditary, warranting consideration of genetic testing, especially in patients with a family history, young age at diagnosis, bilateral tumors, or extra-adrenal location 5