Case Presentation: A 78 year old female with Type 2 diabetes, HTN, vitiligo, sacral decubitus ulcers, CHF, and atrial fibrillation presented with fevers and two weeks of malaise, dizziness, progressive somnolence, and altered mental status. Per her husband, she also had some episodes of sweating but had not complained of any headaches or palpitations. At the time of presentation, she was difficult to arouse and oriented only to self, with a temperature of 37.9°C, heart rate 100, respiratory rate 28, and oxygen saturation 93% on room air. CT and MRI brain demonstrated no acute intracranial process. Initial laboratory evaluation was notable for no apparent infection, elevated ESR (58 mm/hr) and CRP (22.11 mg/dL), increased LDH (987 U/L) with preserved haptoglobin (219 mg/dL), normal TSH (1.94 μIU/mL), and hypochromic microcytic anemia, with hemoglobin 9.7 g/dL and MCV 81 fL. Iron level was 30 μg/dL and ferritin was elevated at 1388 ng/mL. Further workup for the anemia uncovered undetectable serum vitamin C level. CT imaging – obtained due to the patient’s vague complaints of abdominal discomfort and concerning lab abnormalities – demonstrated a 6.4 cm right adrenal mass with metastatic lesions in the liver and lungs. Radiologic appearance and laboratory values were consistent with metastatic pheochromocytoma, with elevated plasma free normetanephrine (2278 pg/mL) and metanephrine (1318 pg/mL) and elevated 24-hour urinary normetanephrine (4615 mcg/24h) and metanephrine (5408 mcg/24h). Ultimately, given the patient’s poor prognosis and functional status, she was discharged home with comfort care.
Discussion: The classic presentation of pheochromocytoma includes episodic headache, tachycardia, and sweating. Paroxysmal hypertension may be seen, though essential hypertension, as our patient had, or normotension does not exclude the diagnosis. In patients not exhibiting the classic triad of symptoms, diagnosis of this rare tumor can be challenging, especially when more common disease processes (infection, autoimmune processes, etc.) are on the differential, as in our case. Interestingly, vitamin C is a required cofactor in the synthesis of norepinephrine via the hydroxylation of dopamine by the dopamine-beta-mono-oxygenase enzyme. Thus, laboratory evidence of depleted vitamin C and clinical symptoms of vitamin C deficiency, such as the anemia, weakness, and malaise seen in this patient, may help point to the diagnosis of pheochromocytoma even without the classic symptoms. In the absence of a dietary explanation for vitamin C deficiency, work-up for pheochromocytoma via imaging and/or catecholamine levels may be indicated in patients with low levels of vitamin C.
Conclusions: Given the role vitamin C plays in the synthesis of neurotransmitters, vitamin C deficiency and its accompanying clinical symptoms should raise the index of suspicion for pheochromocytoma in patients without an underlying alternative explanation for the deficiency.