Epinephrine-secreting pheochromocytoma in a normotensive woman with adrenal incidentaloma.

Abstract: Pheochromocytomas are rare neuroendocrine tumors that produce, metabolize, and usually secrete catecholamines. Although hypertension is a common presenting feature of pheochromocytoma, the tumors occur (or are present) in only 0.1% of patients with hypertension. The variability of symptoms and rarity of occurrence render these tumors difficult to diagnose; many are discovered incidentally during radiological examination or at autopsy. A patient is presented with a pheochromocytoma that was discovered incidentally when she presented with abdominal pain and a normal blood pressure.

Key Words: pheochromocytoma, normotensive, adrenal incidentaloma

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Pheochromocytomas are rare neuroendocrine tumors that produce, metabolize, and usually, but not always, secrete catecholamines. Although hypertension is a common presenting feature of pheochromocytoma, the tumors occur (or are present) in only 0.1% of patients with hypertension. The wide variability of symptoms and rarity of occurrence render these tumors difficult to diagnose; many are discovered incidentally during radiological examination or at autopsy. We describe a patient with pheochromocytoma that was discovered incidentally when she presented with abdominal pain and normal blood pressure.

Case Report

A 72-year-old lady was referred to our institution for further management of an incidental adrenal mass. She presented with a history of abdominal pain of six months' duration. There was neither alteration in bowel habit nor any other gastrointestinal symptom. There was no loss of appetite or weight and she denied symptoms of headache, palpitation or sweating. She was not hypertensive, but had a 5-year history of diabetes.

Her blood pressure was 132/62 mm Hg with no postural drop and her pulse rate was 86/min and regular. There was no fluctuation in the blood pressure and the cardiovascular and respiratory examinations were unremarkable. The abdomen was soft and nontender with no masses palpable.

In view of the prolonged abdominal pain, an upper endoscopy was performed and showed normal findings. A CT scan of the abdomen revealed a 4.1 X 3.4 cm well-defined, enhancing left adrenal mass. Her serum concentrations of renin, aldosterone and cortisol were normal. An overnight 1 mg dexamethasone suppression test was normal. The 24-hour urinary catecholamines revealed a profound elevation of urinary epinephrine excretion of 1518 nmol/24 hours (normal 5-80). The urinary norepinephrine and dopamine excretions were within normal range, at 293 nmol/24 hours (40-780) and 1227 nmol/24 hours (200-3500) respectively. The electrocardiogram did not reveal any tachycardia or evidence of left ventricular hypertrophy.

A laparoscopic left adrenalectomy was performed. It was uneventful and there was no fluctuation of blood pressure intra- or postoperatively. The 24-hour urinary catecholamines were normal postoperatively. Histopathological examination confirmed the presence of a pheochromocytoma.

Discussion

Adrenal incidentaloma refers to an adrenal mass discovered by imaging techniques unrelated to adrenal disease. (1) Pheochromocytoma is a frequent cause of adrenal incidentaloma, accounting for 1.5 to 23% of these masses. (2) Most hormonally active pheochromocytomas produce a combination of norepinephrine and epinephrine, although many exclusively produce norepinephrine, and a much smaller proportion produce only epinephrine. These differences in catecholamine production reflect variations in expression of phenylethanolamine-N-methyltransferase, (3) the enzyme in the catecholamine biosynthetic cascade that converts norepinephrine to epinephrine.

The hypertension that accompanies pheochromocytoma has generally been ascribed to the excessive circulating catecholamines released from the tumor. Epinephrine and norepinephrine are the main catecholamines released and cause sustained or paroxysmal hypertension. Norepinephrine principally has [alpha]-excitatory effects and hypertensive manifestations which parallel its circulating level. Epinephrine has both [alpha]- and [beta]-excitatory effects. Its action at the level of the [alpha]-2 presynaptic receptors is perhaps responsible for the occasional functional dysautonomia with postural hypotension and collapse. (4)

Another explanation for normotension in pheochromocytoma is the fact that apart from catecholamine, these tumors secrete more than 10 other substances: calcitonin, somatostatin, neurotensin, adrenocorticotropin, [beta]-endorphin, lipotropin, metenkephalin, dopamine, neuropeptide Y and occasionally, vasoactive intestinal peptide (VIP). Calcitonin gene-related peptide and VIP are potent vasodilators and these may contribute to the normal blood pressure. (5,6)

In a retrospective multicentric study done by Mannelli et al (7) on 284 patients with pheochromocytoma, normal blood pressure (systolic and diastolic) was present both in the supine and upright positions in 21.1% of patients. When only one plasma catecholamine was elevated, normotension was more frequent in patients with an epinephrine-secreting pheochromocytoma, than in a norepinephrine-secreting tumor.

Our patient remained normotensive due perhaps to the predominantly secreted epinephrine from the tumor. Without hypertension, the clinical investigation was a diagnostic challenge. The diagnostic difficulties may be due both to the clinical silence and to the atypical clinical expressions of the neoplasm as in this case, where a pheochromocytoma shows nonspecific abdominal symptoms rather than the typical signs of catecholamine overproduction. According to the current literature, abdominal symptoms occur in about 7% of all suprarenal pheochromocytomas. (8) Although most of these tumors predominantly secrete dopamine, in our patient, the predominant catecholamine was epinephrine.

Treatment for pheochromocytoma requires surgery, and when managed appropriately, the prognosis is excellent with a disease-free survival rate of 92% and 80% at 5 and 10 years respectively. (1)

Conclusion

Every adrenal incidentaloma should be screened for pheochromocytoma since it can account for up to 20% of cases. Epinephrine-producing pheochromocytoma is often asymptomatic.

References

1. Porcaro AB, Novella G, Ficarra V, et al. Incidental adrenal pheochromocytoma: report on 5 operated patients and update of the literature. Arch Ital Urol Androl 2003;75:217-225.

2. Mansmann G, Lau J, Balk E, et al. the clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev 2004;25:309-340.

3. Feldman JM, Blalock JA, Zern RT, et al. The relationship between enzyme activity and the catecholamine content and secretion of pheochromocytomas. J Clin Endocrinol Metab 1979;49:445-451.

4. 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.

5. Ito Y, Fujimoto Y, Obara T. The role of epinephrine, norepinephrine, and dopamine in blood pressure disturbances in patients with pheochromocytoma. World J Surg 1992;16:759-764.

6. Viale G, Dellorto P, Moro E, et al. Vasoactive intestinal polypeptide, somatostatin, and calcitonin-producing adrenal pheochromocytoma associated with the watery diarrhea (WDHH) syndrome: first case report with immunohistochemical findings. Cancer 1985;55:1099-1106.

7. Mannelli M, lanni L, Cilotti A, et al. Pheochromocytoma in Italy: a multicentric retrospective study. Eur J Endocrinol 1999;141:619-624.

8. Bartolacci M, Bartolacci S, Leombruni E, et al. Adrenal incidentaloma: a dopamine-secreting pheochromocytoma with an atypical clinical picture: a case report and review of the literature. Ann Ital Chir 1998;69:805-814.

Norlela Sukor, MD, MMed, Rashidi Saidin, MBBS, MMed, and Nor Azmi Kamaruddin, MBBS, MMed

From the Department of Medicine, Hospital Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

Reprint requests to Dr. Norlela Sukor, Medical Department, Hospital Universiti Kebangsaan Malaysia, Jalan Yaakob Latiff, 56000 Cheras, Kuala Lumpur, Malaysia. Email: [e-mail]

Accepted April 4, 2006.

RELATED ARTICLE: Key Points

* Every adrenal incidentaloma should be screened for pheochromocytoma since it can account for up to 20% of cases.

* The hypertension that accompanies pheochromocytoma has generally been ascribed to the excessive circulating catecholamines released from the tumor.

* Epinephrine producing pheochromocytoma is more often asymptomatic.