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The term adrenal tumour can refer to one of several benign and malignant neoplasms of the adrenal gland, several of which are notable for their tendency to overproduce endocrine hormones. Adrenal cancer specifically refers to malignant adrenal tumors, which include neuroblastoma, adrenocortical carcinoma, and a minority of adrenal pheochromocytomas. Most adrenal pheochromocytomas and all adrenocortical adenomas are benign tumors, which do not metastasize or invade nearby tissues, but which may still cause significant health problems by giving rise to hormonal imbalances.

Adrenocortical adenomas are benign tumors of the adrenal cortex which are relatively finding at autopsy. They should not be confused with adrenocortical nodules, which are not true neoplasms. A minority (about 15%) of adrenocortical adenomas are 'functional', meaning that they produce glucocorticoids, mineralocorticoids, and/or sex steroids, resulting in endocrine disorders such as Cushing's syndrome, Conn's syndrome (hyperaldosteronism), virilization of females, or feminization of males. Functional adrenocortical adenomas are surgically curable.

Size and weight of the adrenal cortical tumors are no longer considered to be a reliable sign of benignity or malignancy. Grossly, adrenocortical adenomas are encapsulated, well-circumscribed, solitary tumors with solid, homogeneous yellow-cut surface. Necrosis and haemorrhage are rare findings.

Adrenocortical carcinoma (ACC) is a rare, highly aggressive cancer of adrenal cortical cells. ACC's may be functional, producing steroid hormones and consequent endocrine dysfunction similar to that seen in many adrenocortical adenomas, but many are not. Due to their location deep in the retroperitoneum, most adrenocortical carcinomas are not diagnosed until they have grown quite large. They frequently invade large vessels, such as the renal vein and inferior vena cava, as well as metastasizing via the lymphatics and through the blood to the lungs and other organs.

In the cat, the most common functional adrenocortical carcinoma is a progesterone-secreting tumour, and one cat was reported to have an estradiol- and testosterone-secreting tumour. The few cats reported were middle-aged to older cats (aged 7-14 years). In humans and dogs, progesterone binds to cortisol-binding proteins displacing cortisol and resulting in increased concentrations of free cortisol. Progesterone is also a potent insulin antagonist. Cats with progesterone-secreting tumours have clinical signs indistinguishable from hyperadrenocorticism, including concurrent diabetes mellitus.

In cats with a progesterone-secreting tumour,l skin and hair coat changes are the most common signs. Thin, fragile skin that is easily burised, an unkempt greasy hair coat, non-pruritic symmetrical alopecia, and skin infections including demidicosis were the most common signs reported.

Polyuria and polydipsia is typical and in the majority of cats was attributable to poorly controlled diabetes mellitus. Weight loss occurs as a result of poorly controlled diabetes.

One cat with an estradiol- and testosterone-secreting tumour developed behavioural changes including aggression, had vulval hyperplasia, urine with a strong 'tom-cat' smell and an unkempt hair coat.

Diagnosis of a progesterone-secreting tumour is based on consistent clinical signs, an abnormal dexamethasone suppression test (0.1 mg/kg), i.e. basal cortisol concentrations are low-normal, but there is failure of cortisol to suppress below 41 nmol/L (1.5 μg/dl) at both 4 and 8 hr after IV dexamethasone, increased basal progesterone concentrations and evidence of an adrenal mass on ultrasound. Alternatively, as with dogs, basal cortisol may be low-normal and suppress normally following dexamethasone. Cortisol concentrations were below the reference range after ACTH stimulation, but that occurs in 50% of cats with hyperadrenocorticism.

The cat with an estradiol- and testosterone-secreting tumour has bilaterally enlarged adrnal glands and basal estradiol and testosterone concentrations were markedly elevated.

Hyperadrenocorticism is the most likely differential diagnosis and may appear identical clinically and on hormonal testing to a progesterone-secreting tumour, except for the absence of markedly increased basal progesterone concentrations.

Other causes of poorly controlled diabetes need to be considered, e.g. excessive insulin dose, too short a duration of action of insulin, hyperthyroidism and acromegaly. Other causes of a poor hair coat need to be considered.

Aminoglutethimide (AGT; approximately 6 mg/kg q 12 hrs PO) was used successfully for 1-2 months in some cats to control signs prior to surgery. Aminoglutethimide inhibits the enzyme which converts cholesterol to pregnenolone during synthesis of adrenocortical steroids. Mammary gland enlargement following treatment has been reported in a male cat.

Trilostane resulted in a temporary improvement in the cat with the estradiol- and testosterone-secreting tumour.

The most effective treatment is surgery, although this is not feasible for many patients, and the overall prognosis of the disease is poor. Chemotherapy, radiation therapy, and hormonal therapy may also be employed in the treatment of this disease.

Neuroblastoma is an aggressive cancer of immature neuroblastic cells (precursors of neurons), and is one of the most common pediatric cancers, with a median age at diagnosis of two years. Adrenal neuroblastoma typically presents with a rapidly enlarging abdominal mass. Although the tumor has often spread to distant parts of the body at the time of diagnosis, this cancer is unusual in that many cases are highly curable when the spread is limited to the liver, skin, and/or bone marrow (stage IVS). Related, but less aggressive tumors composed of more mature neural cells include ganglioneuroblastoma and ganglioneuroma. Neuroblastic tumors often produce elevated levels of catecholamine hormone precursors, such as vanillylmandelic acid (VMA) and homovanillic acid, and may produce severe watery diarrhea through production of vasoactive intestinal peptide. Treatment of neuroblastoma includes surgery and radiation therapy for localized disease, and chemotherapy for metastatic disease.

Phaeochromocytomas are the most common tumours in the adrenal medulla of animals; they develop most often in cattle, laboratory rats, and dogs, and are infrequent in cats. In bulls and rats, pheochromocytomas develop concurrently with calcitonin-secreting C-cell tumours of the thyroid gland, possibly as a neoplastic transformation of multiple types of endocrine cells of neuroectodermal origin in the same individual. 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. Functional pheochromocytomas are reported infrequently in animals; however, several dogs and horses with pheochromocytomas have had tachycardia, oedema, and cardiac hypertrophy attributed to excess catecholamine secretion. It appears that horses may have a syndrome similar to the multiple endocrine neoplasia noted in humans with concurrent adrenal and thyroid disease.

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.


Normal anatomy of the adrenal gland	Appearance of a phaeochromocytoma (located at 11-12 o'clock, within the adrenal gland)

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.

In humans, noteworthy symptoms include: Elevated heart rate; Elevated blood pressure, including paroxysmal (sporadic, episodic) high blood pressure, which sometimes can be more difficult to detect; another clue to the presence of pheochromocytoma is orthostatic hypotension, a fall in systolic blood pressure greater than 20 mmHg or a fall in diastolic blood pressure greater than 10 mmHg on making the patient stand; Palpitations Anxiety often resembling that of a panic attack; Diaphoresis (excessive sweating); Headaches; Pallor; Weight loss; Localized amyloid deposits found microscopically; Elevated blood glucose level (due primarily to catecholamine stimulation of lipolysis (breakdown of stored fat) leading to high levels of free fatty acids and the subsequent inhibition of glucose uptake by muscle cells. Further, stimulation of beta-adrenergic receptors leads to glycogenolysis and gluconeogenesis and thus elevation of blood glucose levels).

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 renal disease. Hyperadrenocorticism 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.

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.

Usually the best treatment is to remove the pheochromocytoma. 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. Phenoxybenzamine, an alpha-adrenergic antagonist.

If the pheochromocytoma is cancerous and has spread, chemotherapy with cyclophosphamide, vincristine and dacarbazine may 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.