Kelly N. Monaghan, DVM, DACVIM
Internal Medicine Specialist
Adrenal tumors represent approximately 1% of all neoplasias in dogs. Of these, about 10-30% are pheochromocytomas. Pheochromocytomas are catecholamine-producing tumors of the adrenal medullary chromaffin cells and are usually malignant. They can be highly invasive and have an unpredictable growth pattern. However, about half of these tumors are found incidentally and cause no clinical signs. When clinical signs are noted, they may include weakness, collapse, tachyarrhythmias, hypertension, and polyuria/polydipsia.
Once an adrenal tumor is suspected or has been identified incidentally on abdominal ultrasound, it is important to try to determine whether the tumor is a pheochromocytoma versus the more common adrenocortical tumor. Historically, pheochromocytomas have been difficult to definitively diagnose, particularly in asymptomatic patients. However, there are now diagnostic tests that may be considered to identify an adrenal tumor as a pheochromocytoma.
Naturally, evaluation of catecholamine levels has been investigated as a means to diagnose them. In the past 5 years there have been a few studies investigating urinary and plasma catecholamines and they have found that urinary normetanephrine levels can be useful in diagnosing pheochromocytomas. In fact, one study by Quante et al. found that using a cut-off ratio of 4 times the higher normetanephrine:crea measured in controls is associated with a nearly 100% probability of pheochromocytoma. Unfortunately, this test requires special handling and 20% hydrochloric acid must be added to the urine after collection. Additionally, in people, this test can show a false positive result in patients on phenoxybenzamine, a commonly used medication in pheochromocytoma patients. Another study by Gostelow et al. found that assessing the catecholamine metabolite, free normetanehprine in plasma has a sensitivity of 100% and specificity of 97.6% for the diagnosis of pheochromocytoma. However, the usefulness of this test is also limited due to difficulties with sample stability and availability of the assay.
Fortunately, a newer assay has become available in the past few years that is both useful diagnostically and avoids sampling challenges. Inhibin is a glycoprotein synthesized in ovarian granulosa and testicular sertoli cells; adrenal glands are an extragonadal source of inhibin in people. It is secreted in the highest rates in cortisol-secreting adrenocortical tumors and as such, it can be used to differentiate between adrenocortical tumors and pheochromocytomas in patients with a known adrenal tumor. In a 2013 study by Bromel, et al., inhibin levels in neutered dogs with pheochromocytomas were undetectable and were similar to that of healthy neutered dogs. They found that the sensitivity, specificity, and accuracy of an undetectable serum inhibin concentration for identifying an adrenal gland tumor as a pheochromocytoma are 100%, 88.9%, and 93.6%, respectively when used in neutered dogs with adrenal tumors. Therefore, inhibin is useful for differentiating adrenocortical tumors from pheochromocytomas in neutered dogs. However, this test should not be used in sexually intact dogs with adrenal tumors. Conveniently, this assay requires a single blood sample, no special handling, and no injections for additional pituitary-adrenal function testing and can be performed at the University of California-Davis.
In addition to the diagnostic investigation to determine the tumor type of a dog with an adrenal tumor, testing should be performed to assess for potential complications of a pheochromocytoma—namely, blood pressure measurement and electrocardiography. Computed tomography (CT) may also be useful to assess for vascular invasion of the tumor if this cannot be determined ultrasonographically.
Surgery is the treatment of choice for pheochromocytomas and unfortunately, there is no medical alternative aside from palliation if surgery is not pursued. Palliative therapies (and pre-operative stabilization) are aimed at controlling hypertension and tachyarrhythmias.
Interestingly, a 2008 study by Herrera et al. found that treatment with phenoxybenzamine, a non-specific alpha antagonist may be beneficial in dogs with pheochromocytomas undergoing surgery even when they are normotensive. In fact, the mortality of these dogs was only 13% as compared to 48% in the non-treated group. Theoretically, this medication may help to reverse vasoconstriction and control fluctuations in blood pressure and heart rate and is recommended for 2-3 weeks pre-operatively.
In patients with tachyarrhythmias, propranolol may also be beneficial. However, this medication should never be used without concurrent alpha-blockade as it could promote severe hypertension by blocking vasodilation. Additionally, prednisone and metoclopramide should be avoided in these patients as they could contribute to a catecholamine crisis.
The prognosis for patients that undergo surgical resection of a pheochromocytoma is up to a few years if they survive the perioperative period. However, it should be noted that adrenalectomy is associated with a relatively high morbidity and mortality. Mortality rate for all types of adrenal tumors is 12-38% in the short term.
There are a few potential prognostic indicators worthy of consideration in these patients. Multiple studies have shown that vena caval invasion is more common with pheochromocytomas than with other adrenal tumors. Interestingly, there is some debate regarding the prognostic significance of such a finding. However, it does seem that dogs that have extensive vascular invasion (to the level of the hepatic hilus) are at greater risk for intraoperative mortality and any vascular invasion may contribute to shorter survival times although this point is still in question. Two studies have shown that larger adrenal tumors are associated with an increase in perioperative mortality and adrenal tumors that measure greater than 5cm in length are associated with an 85% shorter survival time. A need for concurrent nephrectomy has been shown to increase mortality to 75%. While there is some debate as to the effect that metastasis may have on survival, this would have an obvious impact on decision making for pet owners. Pheochromocytomas have a metastatic potential of 18-30% and most commonly metastasize to the lungs and liver.