Large dopamine-secreting pheochromocytoma: case report.

Abstract: Pheochromocytomas are rare tumors that typically present with catecholamine-stimulated symptoms. Some pheochromocytomas secrete dopamine in addition to or in the absence of other catecholamines. Patients with these tumors are frequently normotensive. We describe a normotensive 26-year-old woman with a large pheochromocytoma that secreted multiple catecholamines, including dopamine.

Key Words: dopamine, pheochromocytoma

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Physicians frequently face patients with common, nonspecific complaints that can produce a large differential diagnosis. We report the case of a previously healthy young woman who presented with the primary symptoms of palpitations, chest pain, dyspnea, and paresthesias.

Case Report

A 26-year-old, previously healthy white woman presented to the emergency department (ED) with multiple complaints. She reported palpitations, chest pain, paresthesias, and progressive dyspnea of several weeks' duration. She described marital difficulties, claiming the stress may have been the cause of her symptoms.

In the ED, the patient's temperature was 36.8[degrees]C, her blood pressure was 122/80 mm Hg, her pulse was 102 beats/min, and her oxygen saturation was 98% on room air. The patient seemed slightly anxious. She had an obese body habitus and was of short stature. The physical examination of the head, eyes, ears, nose, and throat was unremarkable, and the lungs were clear to auscultation bilaterally. A cardiovascular examination revealed tachycardia, normal rhythm, and no murmurs, rubs, or gallops. The abdomen was soft and nontender on examination, and normoactive bowel sounds were present with no masses. Radial, femoral, and dorsalis pedis pulses were present and symmetric bilaterally. Extremities were without edema, tenderness, cyanosis, or clubbing. Integument was normal without striae, hyperpigmentation, or color changes. Neurologic assessments of the cranial nerves, motor system, and deep tendon reflexes, as well as the sensory examination, were unremarkable.

The electrocardiogram (ECG), chest radiograph, and blood glucose level were normal, except for tachycardia present on the ECG. The patient was administered one dose of oral atenolol for tachycardia. The patient was discharged to follow-up with the cardiology service. The next day, the patient was returned by the emergency squad with worsening symptoms of chest pain, palpitations, dyspnea, and paresthesias. She had developed new-onset emesis accompanied by severe headaches. In the ED, her temperature was 37.1 [degrees]C, her blood pressure was 115/80 mm Hg, her pulse was 76 beats/min, and her pulse oximetry was 91% on room air. Arterial blood gas analysis revealed a widened alveolar-arterial gradient of 26. The patient's chest radiograph, ECG, troponin level, complete blood count, coagulation studies, D-dimer, metabolic panel, and venous Doppler sonography of the lower extremities were normal. A spiral computed tomographic (CT) scan of the chest was negative for pulmonary embolism. However, CT images extending through the thoracoabdominal region revealed an 11 x 10 x 9-cm mass in the right upper quadrant. A magnetic resonance imaging scan was ordered to better visualize the mass (Fig. 1).

[FIGURE 1 OMITTED]

The patient was admitted for evaluation of an adrenal mass. Serum aldosterone, adrenocorticotropic hormone, cortisol, total testosterone, dehydroepiandrosterone, thyroid-stimulating hormone, and thyroxine were normal. An overnight 1-mg dexamethasone suppression test was normal. Twenty-four-hour urine collection revealed profound elevation of urinary catecholamines, metanephrines, and dopamine (Table 1), with dopamine being one of the predominant hormones. The laboratory tests, together with the radiologic findings, fulfilled the criteria for pheochromocytoma. Medical management was initiated with phenoxybenzamine followed by propanolol to reduce the risk of a hypertensive crisis. A mutation within the ret protooncogene was not identified lot multiple endocrine neoplasia Types 2A and 2B.

The patient underwent surgical removal of the adrenal mass. Intraoperative photographs demonstrate the location of the abdominal mass before surgical removal (Fig. 2). Tumor removal was successful without complications. She followed an uncomplicated course to discharge, with normalization of all previously abnormal laboratory values.

[FIGURE 2 OMITTED]

Cut surface of the tumor (Fig. 3) demonstrated multiple cysts with large necrotic centers. The histologic examination demonstrated a lobulated or islet pattern typical of pheochromocytoma (Fig. 4). Rare S-100-positivc sustentacular cells were present, which confirmed the tissue diagnosis of pheochromocytoma (Fig. 5).

[FIGURE 3-5 OMITTED]

Discussion

There are several laboratory tests that are used to uncover the presence of a pheochromocytoma: however, the best biochemical marker is a plasma-free metanephrine test. This test is 99% sensitive in detecting pheochromocytomas. (1) If a patient has a positive laboratory test suggesting pheochromocytoma, a CT or magnetic resonance imaging scan of the adrenals is usually successful in identifying intra-adrenal lesions. In addition, (131) I-metaiodobenzylguanidine scans may be needed to characterize lesions when biochemical confirmation is indeterminate, or to localize extra-adrenal pheochromocytomas known to be metastatic, recurrent, or multiple.

There are several types of pheochromocytomas, depending on the hormones they secrete. The majority of pheochromocytomas secrete mixed catecholamines without dopamine, a few tumors secrete mixed catecholamines including dopamine, and very rarely, a pheochromocytoma can secrete exclusively dopamine. Proye et al (2) reported in a case series of 50 pheochromocytomas that 12 of the 50 secreted both dopamine and other catecholamines, and that 3 of the 50 were sole secretors of dopamine. Ten of these 15 patients whose tumor secreted partial or entirely dopamine were normotensive. Proye et al hypothesized that the absence of hypertension was related to the ratio of dopamine to other catecholamines. They reported the dopamine-to-catecholamine ratio at 0.380 [+ or -] 0.274 for hypertensives and 5.470 [+ or -] 4.840 for normotensives. Our normotensive patient had a ratio of 6.05.

In the central nervous system, dopamine causes hypotension, whereas in the kidney it possesses vasodilatory effects, increasing natriuresis and renal blood flow. In our patient, the dopaminergic response offset the vasoconstrictive properties of other catecholamines, resulting in normotension. In addition, high levels of dopamine can cause nausea and may have been the cause of our patient's vomiting. Dopamine-secreting pheochromocytomas are also reported to cause diarrhea. (3)

Hypertension is the most common manifestation of a pheochromocytoma. In 60% of cases, the hypertension is sustained, although significant blood pressure lability is common, including episodes of hypertensive crisis. The 40% of patients without sustained hypertension have blood pressure elevations only during an attack. (4) The hypertension is often severe and is associated with headaches, diaphoresis, and palpitations.

Our patient's adrenal tumor was identified during a workup for suspected pulmonary embolus. Adrenal masses smaller than 4 cm require further study and close follow-up, and any tumor larger than 5 cm warrants removal. Adrenal tumors with the following profile are at high risk for malignancy: 1) CT scan attenuation coefficient >10 Hounsfield units, 2) >5 cm diameter or increase in size at reevaluation, and 3) intratumoral necrosis or evidence of capsular invasion. (5) In the past decade, with readily available imaging modalities, an increased incidence of pheochromocytomas has been reported. Mannelli et al, (6) in a case series, found that among 284 patients with pheochromocytomas, 40% were diagnosed from 1978 to 1992 and 60% were diagnosed from 1993 to 1997. This is a 50% increase in the incidence of pheochromocytomas in one-third of the period.

Currently, there are no histologic methods available to establish whether a pheochromocytoma is benign or malignant. Malignancy is normally determined by evidence of infiltration of surrounding tissues or by the spread of disease to distant sites, particularly those where chromaffin cells are not usually found (eg, lymph nodes, bone). (131) I-metaiodobenzyl-guanidine imaging is normally performed preoperatively to search for such metastases. Lack of malignancy is determined only by the absence of spread of the tumor to nonchromaffin tissues over time.

Key Points

* Some pheochromocytomas secrete dopamine in addition to or in the absence of other catecholamines.

* Individuals with dopamine-secreting pheochromocytomas are frequently normotensive.

* The best biochemical marker for detecting pheochromocytomas is a plasma-free metanephrine.

Table 1. 24-h collection of urinary catecholamines and
metabolites

                                          Normal
Laboratory test                           values     Results

Creatinine, urine (g/24 h)               0.63-2.5         1.3
Urine epinephrine ([micro]g/24 h)           2-24        395
Urine norepinephnne ([micro]g/24 h)        15-100       281
Urine dopamine ([micro]g/24 h)             52-480     4,095
Urine normetanephrine ([micro]g/24 h)      52-310    10,649
Urine metanephrine ([micro]g/24 h)         19-140    36,310

References

(1.) Lenders JW, Pacak K, Walther MM, et al. Biochemical diagnosis of pheochromocytoma: Which test is best? JAMA 2002; 287:1427-01434.

(2.) Proye C, Fossati P, Fontaine P, et al. Dopamine-secreting pheochromocytoma: An unrecognized entity? Classification of pheochromocytomas according to their type of secretion. Surgery 1986; 100:1154-1162.

(3.) Kashyap AS, Varadarajulu R, Kashyap S. A young woman with intractable diarrhoea. Postgrad Med J 2001; 77:124-125, 133.

(4.) Young WF Jr. Pheochromocytoma and primary aldosteronism. Endocrin Hypertens 2000; 21: 1-11.

(5.) Mosnier-Pudar H, Luton JP. Adrenal incidentalomas [in French]. Rev Prat 1998; 48:754 759.

(6.) Mannelli M, Ianni L, Cilotti A, et al. Pheochromocytoma in Italy: A multicentric retrospective study. Eur J Endocrinol 1999; 141:619-624.

From the Bethesda Family Medicine Residency Program and the Good Samaritan General Surgery Residency Program, Cincinnati, OH.

Reprint requests to Scott E. Woods, MD, MPH, MEd, Bethesda Family Medicine Residency Program, 4411 Montgomery Road, Suite 200, Cincinnati, OH 45212. Email: [e-mail]

Accepted April 10, 2003. Copyright [c] 2003 by The Southern Medical Association 0038-4348/03/9609-0914