Adrenal Gland Tumors


Key Points

Adrenal gland tumors can secrete hormones that dramatically affect the well-being of the pet.  Surgery is frequently the best option.  Patients surviving the perioperative period have a good chance for long-term survival, providing that no evidence of spread is found.

 

Adrenal gland anatomy

The name “adrenal” is translated “near kidney”. The adrenal glands, therefore are glands that are located near the kidneys.

Adrenal glands are located adjacent to the left and right kidneys. The right adrenal gland is nestled between vena cava (largest vein that runs through the abdomen) and the muscles attached to the under side of the backbone. The draining vein of each adrenal gland joins directly onto the vena cava. A small artery branching directly off the abdominal aorta (great artery that runs through the abdomen) enters the top (dorsal) side of each adrenal gland.

The adrenal gland consists of an outer shell of tissue called the cortex and an inner core of glandular tissue called the medulla. The cortex has three layers called the zona reticularis, zona fasciculata, and zona glomerulosa and produce respectively, androgens, glucocorticoids, and mineralicorticoids. The cells in each layer have specific enzymes that will modify the steroid nucleus (originally cholesterol), thus producing their specific hormones. The adrenal gland is directly wired into the nervous system via a network of nerves.

 

Adrenal gland function

The adrenal glands are essential for life. They are needed for basic body regulation and to respond to stressful situations. They have five primary functions:

  1. Control blood pressure
  2. Water and salt balance
  3. Carbohydrate balance
  4. Immune system control
  5. Sex hormones (after menopause in humans or post neutering)

Androgens are precursors to sex hormones such as estrogen and testosterone. In neutered animals, these hormones are only produced by the adrenals.

Glucocorticoids are produced from the cortex of the adrenal gland and the most important form of this hormone is cortisone. This hormone is essential for the regulation of glucose (sugar) metabolism, increases the blood vessels to respond better to adrenalin (blood pressure control), suppresses inflammation and immune responses, and controls function of the nervous system. The release of this hormone is controlled by another hormone called ACTH.

Mineralicorticoids are also produced from the cortex and the most important hormone is called aldosterone. This hormone controls reabsorption of sodium and water by the kidney. Low blood pressure will increase the release of aldosterone from the adrenal gland (via the renin/angiotensin in the kidney).

 

Adrenal tumors

Adrenal gland tumors are uncommon in dogs and represent about 0.17 to 0.76% of all tumors in dogs. Tumors originating from the cortex are commonly adenomas or adenocarcinomas. These may produce sex hormones, cortisone, or aldosterone, which causes severe havoc to the body. Tumors originating from the medulla, called pheochromocytoma frequently secrete adrenalin, which causes episodic or continuous high blood pressure.

Malignant tumors can spread to other parts of the body with the liver, pancreas, and kidneys being most common. Metastasis to the lungs is relatively uncommon at the time of original diagnosis.

Adrenal tumors, especially pheochromocytomas, have a tendency to grow from the vein of the adrenal gland to the vena cava. This is called a tumor thrombus.

 

Signs

A nonfunctional (do not secrete hormones) tumor of the adrenal gland frequently does not cause the patient to have any clinical signs until it is sizable or has spread to another organ. Pheochromocytomas commonly have vague clinical signs such as panting, rapid heart rate, seizures and weakness. More dramatic signs may include bleeding into the abdomen and collapse.

Warning signs of an adrenal tumor that produces excessive cortisone includes excessive thirst, muscle wasting, abdominal enlargement, hair loss, and paper-thin skin especially on the abdomen.

 

Diagnosis

The diagnosis of cortisone secreting adrenal tumors is based on screening tests such as the urine cortisol creatinine ratio, low dose dexamethasone suppression test and the ACTH stimulation test. Abdominal ultrasound or CT scan can confirm the presence of the tumor in the adrenal gland. Pheochomocytomas frequently have nonspecific signs such as agitation and panting due to excessive production of adrenalin. Diagnosis of this type of tumor is based on finding high blood pressure and a mass in the adrenal gland. Abdominal ultrasound or CT scan can confirm the presence of an adrenal mass.

Other tests done prior to surgery may include a complete blood count, blood chemistry profile, and urinalysis to check internal organ health. Chest x-rays and abdominal ultrasound are used to identify visible spread of the cancer; however, microscopic spread of cancer to other organs cannot be detected with x-rays and ultrasound. Ultimately a definitive diagnosis of the type of adrenal tumor is based on microscopic analysis of the tumor (histopathology).

 

Preparation for surgery

The pet should be fasted prior to surgery, as instructed by the surgical team. Water is usually permitted up to the time of admission to the hospital. The surgical team should be informed of any medications that your pet is currently receiving. Just prior to surgery, your pet will receive a sedative, have an intravenous catheter placed for the administration of intravenous fluids and intravenous medications, be induced under general anesthesia with medication(s), and have a breathing tube (endotracheal tube) placed to allow delivery of oxygen and gaseous anesthesia. If a ventral bulla osteotomy is to be performed, the surgical site will be clipped and cleansed with an anti-septic solution in preparation for surgery. While under general anesthesia, the pet’s breathing will be assisted with a ventilator and vital parameters such as heart rate, respiratory rate, core body temperature, blood pressure, oxygenation of the blood (pulse oximetry), exhaled carbon dioxide (capnography), and heart rhythm (EKG) will be monitored to ensure the pet’s well being. Pain will be controlled both during and after surgery with analgesics (pain-controlling medication). Please note that each surgical and anesthesia team may elect to chose a different, but effective analgesia protocol. If a pheochromocytoma has been diagnosed or suspected, a medication called phenoxybenzamine may prescribed for 2 weeks prior to surgery. Some veterinarians will also attempt to reduce the cortisone levels with a mediation called Trilostane to help reduce the risk of blood clots during the perioperative period.

 

Surgery

An incision is typically made along the midline of the abdomen to expose the offending adrenal tumor. In some cases, the gland may be exposed with an incision made on the pet’s side. The blood supply to the tumor is tied off, the mass is dissected from its attachments and removed from the body; this is called an adrenalectomy. If the tumor has an extension (caval thrombus) into the great vessel called the vena cava, it is removed by opening this great vessel. This type of surgery is not to be taken lightly and should be done by experienced surgeons for optimal results. Complications may include anesthetic death, blood clots to the lungs, pneumonia, kidney failure, inflammation of the pancreas, wound infection and poor healing.

 

Results

In a study of 52 dogs that had surgical removal of adrenal tumors (Massari et al), factors found to negatively affect prognosis included size of the tumor being greater than 5 cm, metastasis (obviously), vein thrombosis and combining another abdominal procedure with adrenalectomy. The median survival time was 953 days with 65% of patients surviving greater than 1 year after surgery. The intraoperative mortality was 2% and the perioperative mortality rate was 13.5%. Dogs with large adrenal masses (>5 cm) had a median survival time of 156 days and had a more malignant in behavior. Although this study showed a poorer outcome with caval tumor thrombosis, two other studies did not show this to be a negative prognostic factor (Kyles and Schwartz). Caval tumor thrombus is also associated more commonly with pheochromocytomas, right-sided adrenal gland tumors and large tumor size are associated with an increase in the incidence of thrombosis (according to Massari).

In a study of 40 dogs by Kyles, the short-term mortality rate was evaluated in regards to the presence of caval tumor thrombus. Reportedly, tumor thrombus was seen in 25% of all dogs. Eleven percent of adenocarcinomas had tumor thrombus and 55% of pheochromocytomas had tumor thrombus. As mentioned, there was no difference in the perioperative death rate regardless of presence or absence of tumor thrombus. The perioperative death rate was 21% for adenocarcinomas and 18% for pheochromocytomas. However, the addition of phenoxybenzamine (as high as 2.5 mg/kg twice daily) starting 2 weeks prior to surgery reduced the death rate of patients with pheochromocytomas.

Swartz summarized the prognostic factors and survival of 41 patients undergoing adrenalectomy for adrenal tumors and she reported a 22% perioperative mortality rate. Overall, the median survival time was 690 days. Factors influencing shorter survival times included perioperative weakness, lethargy, decreased platelet count, increased BUN, increased clotting times (PTT), increased AST (liver enzyme), low potassium level, profuse bleeding during surgery, and the need to have a kidney removed at the time of surgery.

The bottom line:

  1. If the patient leaves the hospital, there is a very good chance for long-term survival.
  2. Of those patients that die while in the hospital do not die during surgery, rather from complications after surgery (like throwing a blood clot to the lungs).
  3. Adding medication a few weeks prior to surgery to stabilize blood pressure in patients that have pheochromocytomas will reduce the mortality rate from about 48% to 13% (Herrera).
  4. Adding medication about 1 month prior to surgery to lower cortisol production (trilostane) may help reduce the risk of blood clots in the lungs in patients that have functional adenomas or adenocarcinomas (most surgeons do not do this and there is no scientific proof in support of this, at the writing of this article – but that is what UC Davis surgeons are doing and they might be seeing a benefit).

 

References

  1. Assari F, Nicoli S, Romanelli G, et al. Adrenalectomy in dogs with adrenal gland tumors: 52 cases (2002-2008). J Am Vet Med Assoc 2011; 239:216-221.
  2. Kyles AE, Feldman EC, De Cock HE, et al. Surgical management of adrenal gland tumors with and without associated tumor thrombi in dogs: 40 cases (1994–2001). J Am Vet Med Assoc 2003;223:654–662.
  3. Schwartz P, Kovak JR, Koprowsky A, et al. Evaluation of prognostic factors in the surgical treatment of adrenal gland tumors in dogs: 41 cases (1999–2005). J Am Vet Med Assoc 2008;232:77–84.
  4. Herrera AM, Mehl PH, Kass, et al. Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing adrenalectomy for pheochromocytoma. J Vet Intern Med 2008;22:1333–1339.

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