Richard W. Nelson, DVM, Diplomate ACVIM
During the past decade, ultrasound has become a routine diagnostic tool for the evaluation of soft tissue structures in the abdominal cavity. One consequence of abdominal ultrasound is the unexpected finding of a seemingly incidental adrenal mass. There are many factors that determine how aggressive the diagnostic and therapeutic approach should be toward an adrenal mass, including the severity of concurrent problems, the original reason for performing abdominal ultrasound, the age of the dog or cat, the likelihood that the mass is hormonally active, the likelihood that the mass is a malignant or benign tumor, the size and invasiveness of the mass, and the owner's desires and willingness to pursue the problem. The first consideration is to be certain an adrenal mass exists. Abdominal ultrasound should always be repeated to confirm the mass is a repeatable finding. An adrenal mass is suspected when the maximum width of the adrenal gland exceeds 1.5 cm, there is loss of the typical 'kidney bean' shape of the gland, and there is asymmetry in shape and size between the affected adrenal gland and the contra lateral adrenal gland. Bulbous enlargement of the cranial or caudal pole of the adrenal gland is common in dogs with normal adrenal glands and can be misinterpreted as an adrenal mass.
The clinical relevance of an incidentally discovered adrenal mass is related to its malignant potential and functional status. Although an adrenal mass is not always neoplastic, the mass should be considered neoplastic until proven otherwise. Adrenalectomy is the treatment of choice if the mass is malignant and has not spread but adrenalectomy may not be indicated if the mass is benign, small, and hormonally inactive. Unfortunately, it is not easy to determine if an adrenal mass is malignant or benign prior to surgical removal and histopathologic evaluation. Guidelines to suggest malignancy include size of the mass, invasion of the mass into surrounding organs and blood vessels, and identification of additional mass lesions with abdominal ultrasound and thoracic radiographs. The bigger the mass the more likely it is malignant and the more likely metastasis has occurred, regardless of findings on abdominal ultrasound and thoracic radiographs. Cytologic evaluation of specimens obtained by ultrasound-guided fine needle aspiration of the adrenal mass may provide guidance regarding malignancy and origin of the mass, i.e., adrenal cortex versus medulla.
An adrenal tumor may be functional (i.e., producing and secreting a hormone) or nonfunctional. Excess secretion of cortisol, catecholamines, aldosterone, progesterone, and steroid hormone precursors has been documented. A cortisol-secreting adrenal mass causing hyperadrenocorticism is the most common functional adrenal tumor identified in dogs and cats. In addition to the typical clinical signs and clinicopathologic findings associated with hyperadrenocorticism, abdominal ultrasound should reveal a small or atrophied contra lateral adrenal gland; atrophy is a result of suppression of pituitary ACTH secretion. Tests of the pituitary-adrenocortical axis (i.e., ACTH stimulation test, low dose dexamethasone suppression test, endogenous ACTH concentration) are used to confirm adrenal-dependent hyperadrenocorticism.
Pheochromocytoma is a catecholamine-producing tumor derived from the chromaffin cells of the adrenal medulla that is relatively common in dogs but rare in cats. Pheochromocytoma should be considered malignant until proven otherwise. Invasion or extension of the tumor into the lumen of the adjacent vena cava and/or entrapment and compression of the caudal vena cava is common. Mural invasion and/or luminal narrowing of the aorta, renal vessels, adrenal vessels, and hepatic veins may also occur. Clinical signs and physical examination findings develop as a result of the space-occupying nature of the tumor and its metastases, or as a result of excessive secretion of catecholamines and their impact on blood pressure and cardiac function. The most common clinical manifestations are generalized weakness and episodic collapse, tachypnea, panting, tachycardia, and cardiac arrhythmias. A diagnosis of pheochromocytoma prior to surgery is usually one of exclusion. Unlike a cortisol-secreting adrenal tumor, the contra lateral adrenal gland should be normal in size and shape with a catecholamine-producing adrenal tumor. Catecholamine secretion by the tumor, and thus systemic hypertension, tends to be episodic; failure to document systemic hypertension does not rule out pheochromocytoma. Measurement of urinary catecholamine concentrations or their metabolites can strengthen the tentative diagnosis of pheochromocytoma but is not commonly performed in dogs. Because many of the clinical signs and blood pressure alterations are similar for pheochromocytoma and adrenal-dependent hyperadrenocorticism, it is important to rule out adrenal-dependent hyperadrenocorticism before focusing on pheochromocytoma.
Aldosterone-secreting adrenal tumors causing primary hyperaldosteronism (Conn's Syndrome) are rare in the dog and cat. Excessive secretion of aldosterone causes sodium retention and potassium depletion. The classic clinical manifestations of primary hyperaldosteronism are lethargy, weakness, mild hypernatremia, severe hypokalemia (usually < 3.0 mEq/L), and systemic hypertension. The contra lateral adrenal gland should be normal in size and shape on abdominal ultrasound. Documenting increased plasma aldosterone concentrations prior to and after ACTH administration is used to confirm the diagnosis.
Although a functional tumor arising from the zona reticularis of the adrenal cortex could secrete excessive amounts of estrogen, progesterone or testosterone, to date, only progesterone-secreting adrenocortical tumors in cats have been documented. Excessive progesterone secretion in affected cats caused diabetes mellitus and feline fragile skin syndrome, which was characterized by progressively worsening dermal and epidermal atrophy, patchy endocrine alopecia, and easily torn skin. The clinical features mimicked feline hyperadrenocorticism, which is the primary differential diagnosis. Results of tests of the pituitary-adrenocortical axis are normal to suppressed in cats with progesterone-secreting adrenal tumors and the contra lateral adrenal gland is normal in size and shape on abdominal ultrasound. Diagnosis requires documenting an increased plasma progesterone concentration.
Functional tumors producing excessive amounts of an intermediary in the biosynthetic pathway of adrenocortical steroids are rare in dogs and cats. A deoxycorticosterone-secreting adrenocortical carcinoma has been documented in a dog. Deoxycorticosterone is a precursor of aldosterone, has mineralocorticoid activity and acts on the same receptors as does aldosterone. The major clinical features were weakness, marked hypokalemia, and systemic hypertension. Increased plasma deoxycorticosterone and nondetectable plasma aldosterone concentrations were documented in the dog. Adrenal tumors secreting 17-OH-progesterone have also been documented in dogs. 17-OH-progesterone is a precursor of cortisol. Affected dogs had clinical signs and physical examination findings suggestive of hyperadrenocorticism, results of tests to assess the pituitary-adrenocortical axis were normal, and pre- and post-ACTH stimulation plasma 17-OH-progesterone concentrations were increased.
A thorough review of the clinical signs, physical examination findings, results of routine blood and urine tests and performance of appropriate hormonal tests should be done to determine the functional status of an incidental adrenal mass. Urine cortisol/creatinine ratio, ACTH stimulation test and low dose dexamethasone suppression test are used to rule out hyperadrenocorticism. If weakness and severe hypokalemia are present, plasma aldosterone concentrations can be measured in addition to plasma cortisol concentrations during the ACTH stimulation test. We do not routinely perform specific hormonal tests to identify pheochromocytoma. If hormonal tests for hyperadrenocorticism and serum electrolyte concentrations are normal and clinical signs suggestive of pheochromocytoma are present, we assume the adrenal mass is a pheochromocytoma and begin treatment with an alpha-adrenergic antagonist (e.g., phenoxybenzamine, 0.25 mg/kg orally every 12 hours initially) for at least 2 weeks to prevent severe clinical manifestations of hypertension and to promote a smooth anesthetic induction if adrenalectomy is planned. Adjustments in the dose are based on clinical response; an increase in the dose should be considered if clinical signs do not improve after 2 weeks of treatment. If hormonal tests for hyperadrenocorticism and serum electrolyte concentrations are normal, clinical signs suggestive of pheochromocytoma are not present, and adrenalectomy is planned, we still assume the adrenal mass is a pheochromocytoma and begin phenoxybenzamine treatment prior to adrenalectomy.
The biggest dilemma is whether to perform an adrenalectomy if hormonal tests for hyperadrenocorticism and serum electrolyte concentrations are normal and clinical signs and systemic hypertension suggestive of pheochromocytoma are not present. An aggressive approach (i.e., adrenalectomy) is based on the assumption that the mass is malignant and should be removed before metastasis has occurred. In theory, this approach offers the best chance for long-term survival of the dog or cat. However, when considering this approach the clinician should factor in the age of the dog or cat, the severity of concurrent illness, the size and invasive nature of the mass, and the probability for metastasis. Surgery is generally not indicated in old dogs and cats, especially if concurrent illness raises the anesthetic risk to an unacceptable level, when metastasis has been identified or if serious complications are likely because of the size or invasive nature of the mass. In addition, adrenalectomy may not be indicated when the mass is small (< 3 cm diameter) and nonfunctional, and the dog or cat is healthy. An alternative approach in these cases is to determine the rate of growth of the mass by repeating abdominal ultrasound initially at 2, 4 and 6 months. If the adrenal mass does not change in size, the time between ultrasound evaluations can be increased to every 4 to 6 months. However, if the adrenal mass is increasing in size, adrenalectomy should be considered.