| Location: | Adrenal gland, on top of the kidney |
| Behaviour: | Mostly malignant |
| Diagnostics: | Endocrine lab tests and diagnostic imaging: ultrasonography, CT or MRI |
| Treatment: | Surgery, drugs (that inhibit hormone production and/or affect tumour growth), radiotherapy |
| Prognosis: | Depends on the presence of metastasis and tumour size |
This tumour type originates in the adrenal gland. There are two adrenal glands, and they are situated on the top of both kidneys. The adrenal gland consists of two parts: the cortex (outer part) and medulla (inner part).
Adrenocortical tumours originate in the adrenal cortex and most commonly secrete excessive amounts of the hormone cortisol, but -although less common- they can also excessively secrete other hormones such as aldosterone, or secrete no hormones at all.
Most cortisol-secreting adrenocortical tumours (75%) are malignant (adrenocortical carcinoma), 25% are benign (adrenocortical adenoma). These tumours’ size can vary from few millimetres to up to 10 centimetres. Large tumours often invade blood vessels (20% of adrenocortical carcinomas) and neighbouring tissues. Metastasis was identified in approximately 50% of dogs with adrenocortical carcinomas and occurs mostly in the liver, lungs and lymph nodes. Functional cortisol-secreting adrenocortical tumours usually occur in only one of the adrenal glands (unilateral). Concurrent adrenocortical and pituitary tumours are reported in 5-10% of cases.
The prevalence of adrenocortical tumours is largely unknown. Cortisol-secreting tumours resulting in adrenal-dependent hypercortisolism (ADH) are most common and the estimated prevalence is 1 in every 5000 dogs.
In general: largely unknown, for ADH: see pituitary tumours.
The most common clinical signs in dogs with ADH include excessive eating and drinking, increased urination, muscle weakness, accumulation of fat in the abdomen, panting, progressive bilateral hair loss, thinning of the skin, and poor wound healing. When the adrenocortical tumour invades blood vessels, hemorrhage around the kidneys, anemia and abdominal pain can occur, or it can cause the formation of a tumour clot that leads to free fluid in the abdomen (ascites) or rear limb partial paralysis. A rupture of an adrenocortical tumour or major vessel can result in an acute, life-threatening illness.
Aldosterone-secreting adrenocortical tumours usually present with hypertension and similar clinical signs as cortisol-secreting tumours.
Hormonally silent adrenocortical tumours are usually an incidental finding on the diagnostic imaging. Clinical signs, if any, are associated with mass-effects and can include among other abdominal pain, bleedings, ascites.
The suspicion of ADH is based on the dog’s medical history, clinical signs, and laboratory analyses such as blood and urine tests. While the diagnosis of hypercortisolism is confirmed with one of the endocrine tests, described under pituitary tumours, the diagnosis of ADH can be made only when endogenous ACTH concentration is suppressed and when an adrenal mass is visualized on diagnostic imaging.
With abdominal ultrasonography the symmetry, size, shape of the adrenal gland, as well as vascular or local soft tissue invasion of an adrenal tumour can be described.
The preferred diagnostic imaging option is a CT scan and should include the abdomen for both adrenal glands, thorax to investigate the presence of metastasis and also the head to screen for the possible involvement of the concurrent pituitary tumour.
Dogs with cortisol-secreting adrenocortical tumours can be treated with surgery, radiotherapy, and/or pharmacotherapy.
Surgery (adrenalectomy) is the preferred treatment because it eliminates the tumour and thus the cause of the cortisol excess with its associated side effects. There is no need for lifelong medication after surgery when the tumour is limited to one adrenal gland. In unilateral cases, because of the atrophy of the cortex of the non-cancerous contralateral adrenal gland, glucocorticoid substitution is needed temporarily for 6 to 8 weeks after surgery. When both adrenal glands need to be removed, the dog will need a lifelong supplementation of the hormones normally produced by the adrenal glands (glucocorticoids and mineralocorticoids).
The surgical removal of the adrenal gland can be performed via a classic “open abdomen” surgery or via laparoscopy (“closed abdomen”, i.e. surgery via small incisions and guided via an intra-abdominal camera). The advantages of the laparascopy include shorter hospital stays, and a faster recovery period. When tumours exceed 5 cm in diameter and/or when there is an invasion of a large blood vessel, the “open abdomen” technique is preferred.
Hypofractionated stereotactic volumetric-modulated radiotherapy was reported recently in 9 dogs with invasive cortisol-secreting adrenocortical tumours. The treatment resulted in a reduction of the tumour volume and a median survival time of 1030 days. These results are very encouraging; however, this modality is available in only few institutions in Europe (non-exhaustive list).
Among pharmacotherapy, ADH can be treated with trilostane or mitotane. Mitotane or trilostane therapy for ADH are used when surgery is not a good option for the dog or before surgery to stabilize the dog’s hypercortisolism.
In dogs with a cortisol-secreting adrenocortical tumour trilostane will only reduce the clinical signs and not affect the growth of the tumour and development of metastasis. The treatment is only palliative. More information about trilostane therapy is described in the section on ‘pituitary tumours’.
Another medical treatment option is mitotane. The advantage of mitotane is that it can destroy adrenocortical tumour cells and even metastases. Because the goal of mitotane therapy in cortisol-secreting adrenocortical tumours is not only to reduce cortisol production but also to destroy the neoplastic cells, a non-selective treatment protocol that affects the entire adrenal cortex should be considered. Each daily dose should be divided into three or four portions (every six-eight hours, with food). Because of this treatment the adrenal cortex no longer produces hormones, therefore these must be administered (substitution therapy). Substitution therapy starts at the third day and consists of daily glucocorticoids, mineralocorticoids, and salt. After the initial course of mitotane has been administered, the glucocorticoid dose is reduced, but doubled for one or two days in the event of injury, severe physical stress, or anesthesia. To prevent recurrence, an adapted mitotane dose should be administered once weekly for at least 6 months, or even lifelong. Adverse effects of mitotane include anorexia, lethargy, weakness and diarrhea. If they develop, the mitotane treatment must be temporarily discontinued, but the substitution therapy should always be maintained.
Aldosterone-secreting adrenocortical tumours can be surgically removed or treated via pharmacotherapy (with an aldosterone secretion blocker).
For hormonally silent adrenocortical tumours, the most optimal treatment is surgical removal, when the adrenal mass diameter exceeds 2 cm. There is no pharmacotherapy available so far.
The prognosis of ADH depends greatly on the adrenal tumour size and the presence of metastasis.
Median survival times for dogs with ADH undergoing adrenalectomy range from 778 days to 953 days. Among clinical parameters, the tumour diameter is significantly associated with survival, while blood vessel invasion, adrenal gland capsule rupture, surgery duration and medical treatment before surgery had no influence on survival. Dogs with a tumour diameter of <3 cm had significantly better survival times after adrenalectomy than those with a diameter of ≥3 cm.
Stereotactic radiotherapy has been reported in a small number of dogs with adrenocortical tumours with blood vessel invasion (9 dogs). The median survival time was 1030 days, tumour size was reduced and no dogs experienced severe radiotoxicity. Of note, six of the nine dogs had an hormonally silent tumour and more studies involving a greater number of dogs are necessary to further evaluate this mode of therapy.
The reported median survival times of dogs with a cortisol secreting tumour treated with trilostane range from 353 to 596 days.
The median survival times of dogs treated with mitotane range from 102 to 476 days and did not differ significantly from the survival times for dogs treated with trilostane in both studies. However, these studies did not use the mitotane protocol aimed at complete adrenocortical destruction, which might generate different results. Furthermore, the dogs within the mitotane group had more severe disease including metastases compared with the dogs in the trilostane group, which might affect the results as well.
So far, there are no data on survival of dogs with aldosterone-secreting and hormonally-silent adrenocortical tumours.
