Dealing With Incidental Adrenal Tumours

Dr Frank Kettner  BVSc MMedVet(Med), DipECVIM(CA),

Tygerberg Animal Hospital – Bellville, Cape Town

medicine@tah.co.za, Tel (021) 919 1191

An adrenal “incidentaloma” is an adrenal mass, found as an incidental finding during ultrasound or CT examination of the abdomen, where adrenal pathology is not initially suspected In humans the incidence varies from <1% to 7%, and increases with the age of the population

In canine and feline veterinary patients, most incidentally discovered adrenal masses, in otherwise healthy patients, are non-functional benign tumours or non-neoplastic lesions. Most functional adrenal masses are either cortisol secreting tumours or pheochromocytomas. In veterinary medicine there is no consensus on the best approach to an incidentaloma. Deciding upon an appropriate treatment plan requires classification of the incidentaloma as malignant or benign and functional or non-functional.

Normal adrenal gland anatomy and physiology

The adrenal gland consists of an outer cortex and an inner medulla. The latter is the site of catecholamine production. The cortex has 3 zones: from the outside to the inside these are the zona glomerulosa, the zona fasciculata and the zona reticularis. The zona glomerulosa is responsible for the production of mineralocorticoids (aldosterone). Glucocorticoids (cortisol) and androgens are synthesized in both the zona fasciculata and reticularis.

In human medicine the causes for adrenal masses include:

  1. Functional masses (up to 15%):  adenoma (aldosterone or cortisol); carcinoma (any adrenal hormone); pheochromocytoma; congenital adrenal hyperplasia; massive macro nodular adrenal disease; nodular variant of Cushing’s disease
  2. Non-functional masses: adenoma; myelolipoma; neuroblastoma; ganglioneuroma; haemangioma; carcinoma; metastasis; cyst; haemorrhage; granuloma; amyloidosis; infiltrative disease

Hormones that are released from functional masses include: cortisol or one of the precursors (Cushing’s disease); aldosterone (Conn’s syndrome); sex hormones and adrenalin (pheochromocytoma).

The canine patient may be completely asymptomatic, as would be expected in a non-functional, small benign adrenal adenoma. Patients with functional adrenal masses may present with signs of the underlying hormone excess. Animals with malignant tumours (functional or non-functional), may show non-specific signs such as decreased appetite, weight loss, lethargy and nausea. Should metastasis be present, clinical signs will further depend on the organ/s which have been affected.

Surgical removed of functional or malignant adrenal masses would be ideal. However, not every mass needs to be removed and surgery holds significant risks to the patient, either due to age related anaesthetic issues, co-existing morbidity or due to surgical complications. On the other hand, surgically removing a pre-metastatic adrenal malignancy may be lifesaving.

General guidelines for surgical removal include masses that are larger than 3cm, show signs of malignancy, are functional or show invasion of the surrounding blood vessels. It may not be easy however, to determine the malignancy of a mass without cytological or histological evaluation. The larger the mass the greater the likelihood of it being malignant. Both CT scanning and abdominal ultrasound have been shown to be sensitive for the detection of invasion of blood vessels.

Although ultrasound was sensitive for the detection of thrombi in the caudal vena cava, it was only 75% sensitive for detecting all forms of invasion. In one study, invasion of the surrounding blood vessel was shown to occur via the phrenico-abdominal vein as opposed to the erosion of blood vessel walls.  Pheochromocytomas seem to have predilection for invasion of blood vessels. Between 36-70% of all adrenal masses (benign or malignant) are seen to invade the surrounding blood vessels.

In humans, CT scanning is an additional factor that is used to decide on adrenalectomy. Benign masses tend to have a Hounsfield unit of <10% and a >50% contrast washout. Inhomogeneous masses with an irregular border are less likely to be benign, especially if the HU is > 20. In those cases that warrant surgical removal, pre-operative investigations for metastasis should be done.

A CT scan of the thorax and abdomen has a higher sensitivity for detecting metastatic lesions than thoracic radiographs and abdominal ultrasound. As discussed previously, in human medicine, the CT density of the adrenal mass has diagnostic significance.

Masses that are <3cm in size, those that are not producing hormones and those that show no invasion of the surrounding blood vessels may be left for careful observation. The size of the adrenal mass is reassessed at 1, 2, 4 and 6 months after initial diagnosis. Those masses increasing in size should be considered for adrenalectomy. The non-enlarging, stable mass should continue to be observed at 4-6 month intervals.

Pre-operative attempts to diagnose the etiological cause for the adrenal mass are essential. Surgical excision of an undiagnosed pheochromocytoma carries a significant risk for peri-anaesthetic / operative morbidly and mortality. These can be significantly lowered by medically managing this endocrine disorder pre-operatively. Functional adrenal testing is therefore essential prior to surgical removal – especially to detect the presence of a pheochromocytoma.

 

Adrenal functional testing 

Pheochromocytoma: Tachycardia and hypertension are the hallmarks of catecholamine release, but hormone release may be episodic. Patients may, therefore, be completely normal during the physical examination – and be normotensive. A wide variety of clinical signs may be noticed by the owner, including: collapse/weakness; panting, tachycardia/arrhythmias, restlessness, inappetence/anorexia, nonspecific lethargy, exercise intolerance, polyuria/polydipsia, and weakness.

Testing for the presence of a pheochromocytoma in dogs has centred on the measurement of adrenalin metabolites in the urine, either absolute amounts per 24hrs or as measured by a ratio to creatinine. Ideally, a first morning urine sample is collected and a small amount of acid is added to the prevent degradation of the metabolites. Metanephrine and normetanephrine to creatinine ratios are readily available to veterinarians in South Africa through use of the human clinical pathology laboratories. Pheochromocytomas should always be considered malignant in dogs, with metastasis occurring in up to 40% of affected dogs.

Hyperaldosteronism: (Conn’s syndrome). This condition is suspected in patients with hypokalaemia, hypernatremia and hypertension. All findings are not consistently present in all patients. So, while identifying these electrolyte disturbances in a patient with an adrenal mass is supportive for this diagnosis, the absence of these findings do not exclude a case of Conn’s syndrome.

The condition is rare in dogs and cats. Low renin and high aldosterone serum concentrations are useful in diagnosing those suspected patients with unremarkable serum electrolyte concentrations. Aldosterone levels are easily tested for, renin requires special collection practices.

Hyperadrenocorticalism: (Cushing’s disease) Both the ACTH stimulation test and low dose dexamethasone may be used to diagnose Cushing’s disease. Most patients should have clinical signs consistent with Cushing’s disease. In some cases it may be more appropriate to exclude hyperadrenocorticism as a differential. The urine cortisol to creatinine ratio is a highly sensitively test, but not very specific. Therefore it has a high negative predictive value. Patients with a negative result are unlikely to have Cushing’s; while a dog that tests positive may or may not have hyperadrenocorticism.

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