Nausea, vomiting, and panic attacks in a 50-year-old woman
THE DIFFERENTIAL DIAGNOSIS
When considering a diagnosis of panic attack or panic disorder, the DSM-IV mandates that medical causes of the symptoms must be excluded. Common conditions causing a similar spectrum of symptoms include hyperthyroidism, caffeine and stimulant use or abuse, asthma, cardiac arrhythmias, alcohol withdrawal, and, more rarely, complex partial seizures and pheochromocytoma.2,4 Many of these conditions can be ruled out by the history alone in a reliable patient.
Our patient’s electrocardiogram showed no evidence of ischemia or arrhythmias. Also, her recent negative neurologic workup makes seizure activity less likely.
Many of this patient’s laboratory abnormalities are easily explained by her repeated bouts of vomiting. Specifically, her elevated hemoglobin level and hematocrit are likely secondary to volume contraction, while hypochloremia is seen following losses of HCl with emesis. Typically, however, patients with vomiting have a hypochloremic metabolic alkalosis, and her low serum bicarbonate level is inconsistent with the history.
Three factors might be contributing to this patient’s hypokalemia. First, in a volume-depleted state, the cortical collecting tubules secrete potassium in exchange for increased sodium reabsorption in an attempt to correct volume status. Second, the alkalotic state caused by losses of acid with vomiting results in a transcellular shift of potassium ions into cells in exchange for hydrogen ions. Third, increased levels of epinephrine also cause a shift of potassium ions into cells.5 Potassium is not lost directly through nausea and vomiting.
A state of catecholamine excess, such as during a severe panic attack or in the presence of a catecholamine-secreting tumor, could explain many of her abnormalities. In addition to causing hypokalemia, epinephrine has a gluconeogenic effect, whereas norepinephrine inhibits insulin release, providing a potential explanation for hyperglycemia in a patient with no risk factors for diabetes. Finally, catecholamine excess contributes to lactic acidosis, which could help to explain the low serum bicarbonate level and the elevated anion gap, but unless we take arterial blood gas measurements, the patient’s acid-base status cannot be determined.
While panic attacks do stimulate the sympathetic nervous system, certain elements of her history raise the clinical suspicion for another process. First, the severity of the electrolyte abnormalities is suspicious. Second, a typical panic attack peaks at 10 minutes and begins to subside, whereas this woman’s symptoms have persisted for 12 hours. Finally, the clinical history, in particular the prominence of headaches associated with the symptoms, is inconsistent with classic panic attack. Consequently, an alternative diagnosis, such as pheochromocytoma, deserves more careful evaluation.
Whenever laboratory results do not fit with the clinical scenario or patient, however, one final possibility should always be considered—laboratory error. Errors can be preanalytical (eg, patient misidentification), analytical, or postanalytical. In aggregate, the frequency of errors in laboratory results is 1 in 214 to 8,316.6 Given that even the more conservative estimates show an incidence higher than that of many of the rare diseases for which clinicians may be testing, laboratory error always deserves consideration.
COULD THIS BE PHEOCHROMOCYTOMA?
Pheochromocytoma is a neuroendocrine tumor most commonly arising from the chromaffin cells of the adrenal medulla. However, extra-adrenal pheochromocytoma, generally paraganglioma, accounts for 15% to 20% of these tumors. Although the condition is generally considered very rare, autopsy studies have demonstrated a prevalence of 0.05%, suggesting that many tumors are either missed or are not clinically significant.
The diagnosis is most often sought in hypertensive patients, a population in which pheochromocytoma has a prevalence of 0.1% to 0.6%.7
2. What is the most common presenting symptom of pheochromocytoma?
- Paroxysmal hypertension
- Sustained hypertension
- Nausea
- Cardiomyopathy
- Headache
- Hemorrhagic shock
- Psychological symptoms such as anxiety or panic
Although 50% to 60% of patients with pheochromocytoma have sustained hypertension, it may be absent in patients with primarily epinephrine-secreting tumors or large tumors that degrade catecholamines, leading to normal or low blood pressure.
Cardiomyopathy is a rare consequence of untreated pheochromocytoma, caused by the effects of excess circulating catecholamines over a long period of time.8 As seen in this patient, a prolonged QTc on ECG associated with elevated levels of norepinephrine and normetanephrine may be the only red flag.9
Pheochromocytoma is typically an extremely well-vascularized tumor, and rupture or hemorrhage is a rare but often fatal complication.
