When no evidence of vena cava involvement is found, laparoscopic adrenalectomy may be an option (Pelaez et al, 2008; Mayhew, 2009). Laparoscopic adrenalectomy (LA) has been described in veterinary patients; however, the procedure is challenging and requires careful patient selection. Removal of the right adrenal gland in dogs is especially challenging because the gland capsule can be continuous with the tunica externa of the caudal vena cava. Preoperative diagnostic imaging is important in the work-up for adrenal masses and is the basis for deciding whether a laparoscopic approach might be feasible. The dimensions of the mass are vital, as are relationships to surrounding organs and vascular structures. Approximately 25% of adrenal neoplasms invade the vena cava, phrenicoabdominal veins, or renal vasculature; pheochromocytomas are more likely to invade than adrenocortical tumors. Vascular invasion is an indication for an “open” surgical approach. Ultrasonography and computed tomography are used most often for preoperative imaging. Ultrasonography has a sensitivity and a specificity of 80% and 90%, respectively, for detection of tumor thrombus. The sensitivity and specificity of CT or MRI for detection of vascular invasion are currently unknown, but recent experience with CT suggests that it is excellent for detection and delineation of tumor thrombus. Animals with functional tumors causing clinical signs and with those measuring more than 3 to 4 cm that do not exhibit vascular invasion should be considered for LA. Animals that are systemically unstable and those that have uncontrolled metabolic or acid-base disturbance, uncontrolled coagulopathies, untreated severe arrhythmias, or hypertension should not undergo LA. Animals that may be poorly tolerant of pneumoperitoneum (e.g., severe cardiorespiratory disease, diaphragmatic herniation) are poor candidates. Vascular invasion of the mass into surrounding vessels and large masses (>6 cm) are indications for open adrenalectomy; however, the effect of tumor size on morbidity during LA has not been evaluated in small animals. Inadequate training is an important contraindication for LA. For a description of LA, see the articles by Pelaez and associates (2008) and Mayhew (2009).

Healing of the Adrenal and Pituitary Glands

Because adrenal or pituitary biopsies are rarely performed, little information is available about the healing of these glands after surgery.

Suture Materials and Special Instruments

HAC may cause delayed wound healing; therefore abdominal closure should be performed with strong, slowly absorbed, or nonabsorbable suture material (e.g., polydioxanone, polyglyconate, polypropylene, nylon). Self-retaining retractors, such as Balfour abdominal retractors, are recommended to improve abdominal visualization. Malleable retractors covered with moistened sponges are used to retract viscera from the adrenal glands. Hemostasis is easier to achieve with electrocautery and hemoclips than with suture ligation of vessels.

Postoperative Care and Assessment

After adrenalectomy, the patient’s hydration status and electrolyte balance should be monitored carefully and corrected as necessary. Bilateral adrenalectomy causes permanent adrenal insufficiency, and these animals require lifelong glucocorticoid (prednisone or prednisolone) and/or mineralocorticoid (deoxycorticosterone or fludrocortisone) replacement (Box 23-3). Animals should be closely monitored for hypoadrenocortical collapse. They are most likely to have an Addisonian crisis after they have been released to the owner’s care. Owners must be advised to watch for malaise, inappetence, vomiting, weakness, and other clinical signs suggesting decompensation. Temporary adrenal insufficiency occurs after unilateral removal of functional adrenal tumors because the tumor has suppressed the function of the contralateral adrenal. Glucocorticoids should be supplemented postoperatively (see Box 23-3) but may be discontinued when the remaining adrenal begins to function normally, as determined by the results of an ACTH stimulation test.

Box 23-3 Postoperative Drug Therapy After Adrenalectomy in Dogs

Pulmonary thromboembolism is a potentially life-threatening complication of adrenal surgery, particularly in dogs with adrenal neoplasia. Sudden, severe postoperative respiratory distress may indicate pulmonary thromboembolism. Lung perfusion scans may help identify lung regions that are underperfused. Treatment with strict cage rest, oxygen, anticoagulants (e.g., aspirin, heparin), and thrombolytic agents (e.g., streptokinase) may be beneficial (see Box 23-3). Animals treated for pulmonary thromboembolism should be assessed frequently for signs of hemorrhage, and the hematocrit should be checked every 2 hours. If the packed cell volume (PCV) drops or hemorrhage is noted, the streptokinase infusion should be discontinued.

Complications

The main complications of adrenalectomy are hemorrhage, fluid and electrolyte imbalance, pancreatitis, wound infection, delayed wound healing, and thromboembolism. Postoperative hemorrhage usually is associated with incomplete occlusion of small vessels surrounding an enlarged, highly vascular tumor. Judicious use of electrocautery and hemoclips helps prevent this complication. The Ligasure cautery device (Tyco Healthcare Group LP, Boulder, Colo.) has been useful for controlling hemorrhage from small vessels surrounding the adrenal gland during adrenalectomy. For prevention of thromboembolism, animals may be started on heparin during surgery and continued on it postoperatively (see Box 23-3). Delayed wound healing often is encountered in animals with HAC because of the adverse effect of steroids on wound healing; therefore, care should be taken with abdominal closure in these animals (see previous discussion). Strong monofilament absorbable (i.e., polydioxanone or polyglyconate) or nonabsorbable (i.e., polypropylene) suture should be used.

Special Age Considerations

Animals with adrenal neoplasia usually are old and often have concurrent abnormalities such as hypertension or cardiovascular abnormalities; therefore, extreme care should be exercised during anesthesia. These animals also require extensive postoperative monitoring. If the animal is debilitated, anorexic, or vomiting, placement of an enteral feeding tube during surgery (see p. 110) or parenteral nutrition (see p. 99) is advised.

References

Mayhew, PD. Advanced laparoscopic procedures (hepatobiliary, endocrine) in dogs and cats. Vet Clin North Am Small Anim Pract. 2009;39:925.

Pelaez, MJ, Bouvy, BM, Dupre, GP. Laparoscopic adrenalectomy for treatment of unilateral adrenocortical carcinomas: technique, complications, and results in seven dogs. Vet Surg. 2008;37:444.

Specific Diseases

Adrenal Neoplasia

Definitions

Adrenal carcinomas are autonomously functioning, malignant tumors of the adrenal cortex; adrenal adenomas are benign adrenocortical tumors. Pheochromocytomas are catecholamine-secreting tumors of the chromaffin tissue, which usually arise in adrenal medullary tissue. Pheochromocytomas are also known as paragangliomas.

General Considerations and Clinically Relevant Pathophysiology

Adrenal gland tumors are adrenal adenomas, carcinomas, and pheochromocytomas. Most adrenal tumors are nonfunctional and clinical signs are caused by local invasion of the tumor into surrounding tissue, distant metastases, or both. Functional tumors secrete excessive amounts of cortisol, which inhibits pituitary ACTH secretion and causes atrophy of the contralateral adrenal. Adrenocortical adenomas and carcinomas appear to occur with equal frequency. They usually are unilateral, although bilateral adrenocortical neoplasia rarely occurs. History, physical examination, and laboratory findings do not differentiate between bilateral and unilateral adrenal neoplasia. Ultrasonographic evaluation of the adrenals often identifies adrenomegaly on one side and adrenal atrophy on the other; this localizes the tumor. Colonic perforation is a rare sequela of excessive glucocorticoid secretion. Corticosteroids may inhibit collagen synthesis and increase collagen breakdown. They also may cause breakdown of the mucosal barrier and inhibit normal immune responses.

NOTE • Most animals with HAC have pituitary (rather than adrenal) tumors.

Adrenal adenomas and carcinomas have been diagnosed in cats. Adrenal gland carcinomas in cats have been reported to secrete cortisol, progesterone, aldosterone, and testosterone (DeClue et al, 2005). Feline adrenal tumors may be unilateral or bilateral. Bilateral tumors may be of more than one tumor type. Progressive polyuria, polydipsia, polyphagia, aggression, and weight gain have been reported in a cat with adrenocortical adenoma in one adrenal gland and pheochromocytoma in the other (Calsyn et al, 2010). Primary hyperaldosteronism secondary to adrenal adenoma or carcinoma occurs in middle-aged and older cats with hypokalemic polymyopathy and/or systemic hypertension (Ash et al, 2005).

Pheochromocytomas are tumors of the adrenal medulla that secrete excessive amounts of catecholamines (primarily norepinephrine, but also epinephrine and dopamine) and other vasoactive peptides (e.g., vasoactive intestinal polypeptide, somatostatin, enkephalin, corticotropin). Excessive catecholamine and vasoactive peptide levels may manifest as cardiovascular, respiratory, or central nervous system (CNS) disease. Although these tumors classically have been reported as benign, recent reports suggest that regional invasion and distant metastases (liver, regional lymph nodes, lungs, spleen, ovaries, diaphragm, and vertebrae) occur in as many as 50% of affected dogs. Invasion of the caudal vena cava, phrenicoabdominal (cranial abdominal) artery or vein, renal artery or vein, or hepatic vein may cause signs of ascites, edema, or venous distention. Pheochromocytomas usually are unilateral, although bilateral tumors occur. These masses usually are reddish tan, multilobulated, firm, or friable, and may be completely or partly encapsulated. Occasionally, pheochromocytomas may be associated with neoplastic transformation of multiple endocrine tissues of neuroectoderm origin (e.g., pituitary, adrenocortical, or thyroid adenomas; or pancreatic islet cell tumors). Extra-adrenal pheochromocytomas have been reported in dogs and cats. Other tumors rarely arising from the adrenal medulla include neuroblastoma and ganglioneuroma.

Diagnosis

Clinical Presentation

Signalment

Adrenocortical tumors usually occur in older, large-breed dogs and appear to be diagnosed more commonly in females. A definitive breed predisposition has not been identified. Pheochromocytomas usually occur in older dogs but have been reported in dogs as young as 1 year of age. Both genders appear to be equally affected, and Boxers may be predisposed to this tumor.

History

It is critical to understand that HAC can be diagnosed only in animals with clinical signs clearly consistent with HAC. To diagnose HAC, one must see polyuria-polydipsia, polyphagia, pendulous abdomen (i.e., “pot belly”), endocrine alopecia, hyperpigmentation, and/or calcinosis cutis. One might also see muscle wasting, weakness, lethargy, and/or panting in some patients, but these are not strongly suggestive of HAC. No imaging or laboratory findings (including adrenal gland function tests) allow diagnosis of HAC in the absence of obvious clinical signs. Pheochromocytoma and nonfunctional tumors will not have these signs.

Vomiting has been associated with intestinal perforation in a dog with adrenocortical adenoma, but this is rare. High circulating levels of glucocorticoids may make diagnosis of intestinal perforation difficult because signs of peritonitis (abdominal discomfort, restlessness, panting, weakness, and/or dyspnea) initially are obscured. Cats reported with primary hyperaldosteronism present with a history of vomiting, inappetence, dehydration, weakness, diarrhea, and cervical ventroflexion (Ash et al, 2005; Rose et al, 2007; Renschler and Dean, 2009). Spraying urine with a strong odor and aggressive behavior were included in the history of a cat with functional (elevated sex hormones androstenedione and testosterone) adrenal cortical adenoma (Millard et al, 2009).

Pheochromocytomas may cause vague, intermittent signs of weakness or panting due to episodic hypertension and tachycardia. Many times they are incidental findings of ultrasonography or necropsy. Signs of nonfunctional adrenocortical tumors may include anorexia, abdominal enlargement, abdominal pain, diarrhea, vomiting, and lethargy; however, they too may be incidental findings of ultrasonography or necropsy.

Physical Examination Findings

Clinical findings in animals with adrenocortical tumors depend on whether the tumors are functional. Dogs with ADH should have obvious signs of HAC (see previous discussion). Ascites, abdominal pain, edema, diarrhea, and vomiting are more common with nonfunctional tumors, although many are asymptomatic. Aggression has been associated with a cat with adrenocortical adenoma and pheochromocytoma (Millard et al, 2009; Calsyn et al, 2010) and blindness secondary to systemic hypertension (retinal detachment) and weakness may be seen in cats with primary aldosteronism (Ash et al, 2005).

Clinical findings in animals with pheochromocytomas may include tachycardia or cardiac arrhythmia, acute collapse, polypnea, panting, cough, lethargy, anorexia, dyspnea, weakness, abdominal distention, congestive heart failure, ataxia, incoordination, polyuria-polydipsia, and alopecia. Hypertension (paroxysmal or sustained) also is frequently present. However, pheochromocytomas are often incidental findings in dogs that have no clinical signs associated with the tumor.

Diagnostic Imaging

Adrenal tumors are difficult to detect radiographically unless they are associated with significant adrenal enlargement (20 mm or larger) or calcification. Food should be withheld for 24 hours before radiography to allow the gastrointestinal tract to empty. In some dogs, mineralization of tissue cranial to the kidney may be seen on survey radiographs and may or may not be associated with obvious adrenal enlargement. This finding is suggestive of adrenocortical neoplasia (adenoma or carcinoma). Nonneoplastic mineralization of adrenal glands is rare in dogs; however, bilateral adrenal calcification may occur with PDH. Conversely, adrenal gland mineralization is considered an incidental finding in cats (Fig. 23-5). Hepatomegaly, calcinosis cutis, or osteoporosis may be seen with PDH and ADH. Enhanced abdominal contrast caused by increased abdominal fat may occur. Dogs with HAC are more likely to have calcium-containing uroliths than dogs without clinical evidence of HAC. Although pheochromocytomas may be detected radiographically if sufficiently large, ultrasonography is more sensitive.

FIG 23-5 Lateral abdominal radiograph of a cat with a mineralized adrenal gland. (Courtesy L. Homco, Ithaca, N.Y.)

NOTE • If you note mineralization of an adrenal gland radiographically in a dog, consider the possibility of neoplasia.

Ultrasonography is useful for assessing the adrenal size, echogenicity, and shape of the gland and whether invasion into adjacent structures has occurred. The normal canine adrenal gland size in mature dogs is dependent on body size. Several methods can be used to ultrasonographically assess the size of the adrenal gland. One method is to compare the maximal width versus the length of the gland, which should be less than approximately 30%. Alternatively, the width of the gland should not be larger in diameter than the diameter of the adjacent aorta. Absolute measurements have also been reported (e.g., the canine adrenal should be less than 7.4 mm; the feline adrenal should be less than 4.3 mm).

Both adrenals should be routinely imaged in dogs with HAC because one normal adrenal gland does not exclude the existence of a contralateral functional adrenocortical tumor. Bilateral adrenocortical tumors are rare. Pheochromocytomas have been reported to have mixed echo patterns and cannot be definitively differentiated from adrenocortical tumors. Although bilateral adrenal enlargement is suggestive of PDH, atrophy of the contralateral adrenal gland in dogs with functional adrenocortical tumors may not be apparent ultrasonographically. Adrenal metastasis may be diagnosed ultrasonographically. In cats, unilateral or bilateral adrenal masses may be identified by abdominal ultrasound.

NOTE • It is not possible to definitively differentiate between benign and malignant adrenal lesions using ultrasonographic criteria alone unless invasion of the vena cava has occurred.

CT and MRI allow accurate localization of adrenal neoplasia, but they do not allow differentiation of tumor type. Adrenal carcinomas may appear as well-demarcated, homogeneous masses, or they may be poorly demarcated, with irregular texture and contrast enhancement. Masses that are poorly demarcated, irregularly shaped, and nonhomogeneous with mineralization usually are carcinomas. Ultrasound can detect caudal vena cava invasion, but contrast-enhanced CT is more sensitive. Administration of contrast agents in patients with pheochromocytoma may produce severe hypertension; thus, it should be done cautiously. If contrast-enhanced CT and ultrasound are not performed, caudal vena caval angiography (note precautions in previous discussion) may be considered before surgery if caudal vena caval thrombosis is suspected (Fig. 23-6). Excretory urography may help identify tumor invasion requiring nephrectomy (i.e., ureteral obstruction or renal invasion).

FIG 23-6 Color Doppler evaluation of the caudal vena cava. A hyperechoic mass is seen within the lumen of the cava from invasion of an adrenal tumor. Note the disruption of blood flow around the mass (blue).

NOTE • CT and MRI do not differentiate adrenal adenomas, carcinomas, or pheochromocytomas. Clinical signs, biochemical testing, and a tissue sample are necessary for a definitive diagnosis.

Laboratory Findings

No laboratory changes are reliably seen in all animals with HAC; however, common laboratory abnormalities include substantially increased serum alkaline phosphatase, neutrophilic leukocytosis, lymphopenia, eosinopenia, mild polycythemia, modestly increased alanine aminotransferase, and hypercholesterolemia. Urinary tract abnormalities may include hyposthenuria (urine specific gravity below 1.007) or isosthenuria (1.008 to 1.012). Urinary tract infections are common, even when bacteriuria and pyuria are absent.

Diagnosis of HAC requires clinical signs consistent with the disease. Abnormal adrenal function test results in the absence of clinical signs are not diagnostic of HAC. The ACTH stimulation test (Box 23-4) and the low-dose dexamethasone suppression (LDDS) test are the primary adrenal function tests used. The ACTH stimulation test is easy and quick to perform, and is the best test to look for iatrogenic HAC (Box 23-5). However, the ACTH stimulation test has disadvantages. Dogs with ADH can have almost any response (i.e., normal, exaggerated, or diminished) to ACTH, and many dogs without HAC have exaggerated test results that mimic HAC. Classically, one measures cortisol concentrations before and after administration of ACTH, but one may also measure sex steroids (e.g., 17-hydroxyprogesterone). However, the sensitivity and specificity of measuring sex steroids are still being determined at the time of this writing, and some evidence suggests that increased 17-hydroxyprogesterone concentrations post ACTH administration may not be as specific for HAC as was originally thought. The LDDS test requires 8 hours to perform, but it is a better test to look for spontaneous HAC. Furthermore, the LDDS test often permits differentiation of PDH and ADH.

Box 23-4 ACTH Stimulation Test in Dogs