A pheochromocytoma is a neuroendocrine tumour of the medulla of the adrenal glands (originating in the chromaffin cells) or extra-adrenal chromaffin tissue which failed to involute after birth, which secretes excessive amounts of catecholamines, usually epinephrine and norepinephrine. Extra-adrenal paragangliomas (often described as extra-adrenal pheochromocytomas) are closely related, though less common, tumors that originate in the ganglia of the sympathetic nervous system and are named based upon the primary anatomical site of origin.
Traditionally it is known as the '10% tumour':
- approximately 10% of tumours are bilateral
- approximately 10% of tumours are malignant
- approximately 10% are located in chromaffin tissue outside of the adrenal gland
- approximately 10% arise in infancy
- approximately 10% are genetic/familial
- approximately 10% recur after being resected.
Phaeochromocytomas are the most common tumours in the adrenal medulla, but still a rare disease in cats. Malignant pheochromocytoma designates a medullary tumour that invades through the adrenal capsule into adjacent structures (eg, posterior vena cava) or metastasizes to distant sites (eg, liver, regional lymph nodes, or lungs), or both.
Although size varies considerably, pheochromocytomas may be large (≥10 cm in diameter) and incorporate most of the affected adrenal. A small remnant of the adrenal gland often can be found at one pole. Smaller tumours are well encapsulated by a thin, compressed rim of adrenal cortex. Large pheochromocytomas are multilobular and variegated, and they may exert pressure on and invade adjacent tissues, particularly the vena cava and aorta. In dogs, ~50% of pheochromocytomas metastasize to the liver, regional lymph nodes, spleen, and lungs.
Pheochromocytoma should be considered malignant until proven otherwise. A diagnosis of pheochromocytoma prior to surgery is usually one of exclusion. Unlike a cortisol-secreting adrenal tumour, the contra lateral adrenal gland should be normal in size and shape with a catecholamine-producing adrenal tumour. Catecholamine secretion by the tumour, 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.
The signs and symptoms of a pheochromocytoma are those of sympathetic nervous system hyperactivity. Affected cats are typically old, ranging from 10-20 years. Clinical signs are usually vague and diagnosis pre-mortem is rare. Signs include hypertension, polyuria and/or polydipsia. In diabetic cats, phaeochromocytoma may result in poor glycaemic control associated with insulin resistance. Sudden blindness with evidence of retinal haemorrhage and detachment has been reported as well as congestive heart failure.
A pheochromocytoma can also cause resistant arterial hypertension. A pheochromocytoma can be fatal if it causes malignant hypertension, or severely high blood pressure. Not all patients experience all of the signs and symptoms listed.
Primary hyperaldosteronism (Conn's syndrome) may also cause hypertension in an elderly cat and be associated with an adrenal mass. Typically there is hypokalemia due to chronically stimulated adrenergic receptors and consequent secondary hyperaldosteronism. The hypokalemia is difficult to control.
Other causes of hypertension in elderly cats include hyperthyroidism and chronic renal disease. Hyperadrenocorticism (Cushing's syndrome) may be associated with an adrenal mass and PU/PD, but can be ruled out based on clinical signs and a low-dose dexamethasone-suppression test. Concurrent Cushing's syndrome and phaochromocytomas in cats have been reported, with clinical signs of polyuria, polydipsia, polyphagia, aggression, and weight gain.
An index of suspicion is required to make a presumptive diagnosis. Systemic hypertension together with an adrenal mass, in the absence of signs of hyperadrenocorticism or hypokalemia are suggestive of phaeochromocytoma. The mass can be imaged with ultrasound, MRI or CT. Biopsy may establish a definitive diagnosis. A definitive diagnosis based on demonstration of increased plasma or 24-hour urinary catecholamine excretion is rarely performed. A recent study has shown that many cats with phaochromocytoma have elevated levels of plasma normetanephrine.
Usually the best treatment is to remove the pheochromocytoma via adrenalectomy. Surgery is often delayed, however, until the tumour's secretion of catecholamines is under control with drugs, because having high levels of catecholamines can be dangerous during surgery. Clinical signs can be improved with the use of adrenergic drugs, e.g. Phenoxybenzamine, an alpha-adrenergic antagonist.
If the pheochromocytoma is cancerous and has spread, chemotherapy with cyclophosphamide, vincristine and dacarbazinemay help slow the tumour's growth. Treatment with a radioisotope known as MIBG that targets the tumour tissue can also be highly effective. The dangerous effects of the excess catecholamines secreted by the tumour can almost always be blocked by continuing to take phenoxybenzamine or a similar drug and beta-blockers.
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