Chapter 26. Tumors of the Endocrine System
SECTION A Adrenal and Pituitary Tumors in Dogs and Cats
Amy E. DeClue and Jeffrey N. Bryan
Tumors involving the adrenal gland may arise from the adrenal cortex or medulla or may be due to metastatic disease. It is important to note that metastatic lesions represent 26.7% of canine and 60% of feline adrenal neoplasms. 1 Metastatic disease should be considered in any patient with an adrenal mass.
ADRENAL CORTICAL TUMORS IN DOGS
Incidence/Etiology and Risk Factors
Tumors of the adrenal cortex may be adenomas or carcinomas. Although some adrenal cortical tumors are hormonally silent, a myriad of hormones either singly or in combination can be produced, with cortisol being the most common ( Table 26-1 ).
| ALP, Alkaline phosphatase; ALT, alanine transaminase; CK, creatine kinase. | |||||
| ∗ References 2,5,9,11,14,16,64-68. | |||||
| † References 29,33,36,37,69-72. | |||||
| ‡ Most common findings. | |||||
| Tumor Type | Hormone Produced | Clinical Findings | Clinicopathologic Abnormalities | ||
|---|---|---|---|---|---|
| Dogs ∗ | Cats † | Dogs ∗ | Cats † | ||
| Adrenal cortical adenoma/carcinoma | Cortisol Progesterone 17-OH progesterone Corticosterone Testosterone Estradiol Androstenedione | ||||
| Aldosterone | Rare, similar to cats | Rare, similar to cats | Hypokalemia ‡ Mild hypernatremia Metabolic alkalosis Hypophosphatemia Hypomagnesemia Azotemia Increased CK | ||
| Pheochromocytoma | Norepinephrine Epinephrine | Asymptomatic ‡ Syncope, weakness Anxiety, panting Hypertension Seizure Cardiac arrhythmia Polyuria/polydipsia | Rare, similar to dogs | Mild thrombocytopenia Mild anemia Increased ALT Hypoalbuminemia Hypercholesterolemia Azotemia Proteinuria | Unknown |
Signalment and Clinical Features
Adrenal tumors are most commonly recognized in middle-aged to older (median age, 11–12 years), large breed (median weight, 20 kg), female dogs. 2,3 Clinical signs and clinicopathologic abnormalities are related to the type of hormone produced (see Table 26-1 ).
Diagnosis and Staging
Definitive diagnosis of an adrenal tumor requires histopathologic evaluation, although a presumptive diagnosis can be made based on clinical signs, endocrinologic testing, and the presence of an adrenal mass. Radiographic evidence of adrenal calcification is present in about half of cases but fails to differentiate benign from malignant lesions. 4,5 Ultrasound or CT are the most commonly used imaging modalities for the detection of adrenal tumors and abdominal metastases. Atrophy of the contralateral adrenal gland is inconsistent and, therefore, a lack of atrophy does not rule out a functional cortical tumor. 4 Any animal with a suspected adrenal tumor should undergo thorough endocrinologic evaluation to determine functionality ( Table 26-2 ).
| ACTH, Adrenocorticotropic hormone; AT , adrenal tumor; HAC , hyperadrenocorticism; LDDST , low-dose dexamethasone suppression test; PDH , pituitary dependent hyperadrenocorticism; UCC, urine cortisol:creatinine. | ||||
| ∗ Androgens include androstenedione, estradiol, progesterone, testosterone, and 17-hydroxyprogesterone. | ||||
| Diagnostic Test | Sensitivity | Specificity | Interpretation | Comments |
|---|---|---|---|---|
| LDDST | Excellent | Good | Failure to suppress at 8 hr is consistent with HAC; suppression at 4 hr is consistent with PDH, not AT | Diagnostic test of choice to diagnose HAC because of the high sensitivity in dogs and cats |
| ACTH stimulation test: Cortisol | Poor | Good | Hyperstimulation is consistent with HAC | Poor sensitivity makes this test less desirable; cannot differentiate PDH from AT. This test is not recommended in cats. |
| ACTH stimulation test: Androgens ∗ | Unknown | Unknown | Hyperstimulation is consistent with an androgen-secreting AT | Consider in patients with adrenal tumors and negative LDDST |
| UCC | ~100% | Poor | UCC ≤ the reference range is inconsistent with HAC | Because of poor specificity, this test cannot be used to diagnose HAC |
| Aldosterone | Unknown | Unknown | Elevation may be consistent with an aldosterone secreting tumor | Evaluate prior to starting antihypertensive medications, potassium supplementation, or fluid therapy |
Biological Behavior/Metastasis
Tumors of the adrenal glands occur with equal frequency in the left and right gland with 14 to 30% of dogs having bilateral tumors. 2,4 Approximately 56% to 83% of adrenal cortical tumors are carcinomas. 2,6 Tumor size > 2 cm in diameter is associated with adrenal cortical carcinomas. 7 Metastatic lesions are recognized in 14% to 28% of dogs with adrenal neoplasia, with the lungs, liver, and lymph nodes being the most common sites. 2,8
Therapy and Prognosis
Adrenalectomy is the treatment of choice for any hormonally functional adrenal cortical tumor or any adrenal cortical tumor > 2 cm. Although reported post-operative mortality is high (19%–30%), patients that survive 2 weeks after adrenalectomy have a good long-term prognosis (mean survival, 778 days). 2,6,9 It is important to note that tumor size, patient age, histopathologic diagnosis, and presence of tumor thrombi of the vena cava are not prognostic. 2,9 For patients that are poor surgical candidates, medical management is possible ( Table 26-3 ). 10-13 Since it is adrenolytic, mitotane is the preferred medical treatment for adrenocortical tumors with a median survival of 11.5 months. 10 In addition, mitotane may be administered to control cortisol- or androgen-related clinical signs associated with metastatic disease.
| AT , Adrenal tumor; PDH , pituitary-dependent hyperadrenocorticism. | ||||
| ∗ Androgens: androstenedione, estradiol, progesterone, testosterone, and 17-hydroxyprogesterone. | ||||
| Drug | Mechanism of Action | Side Effects | Efficacy | Comments |
|---|---|---|---|---|
| Mitotane | Adrenal cortical lysis, enzyme inhibitor | Hypoadrenocorticism Gastrointestinal | Good | Dogs with AT typically require higher doses than dogs with PDH |
| Trilostane | Enzyme inhibitor | Hypoadrenocorticism | Good | FDA approved for the treatment of hypoadrenocorticism secondary to AT; no effect on tumor growth or metastasis |
| Ketoconazole | Enzyme inhibitor | Gastrointestinal Hepatic toxicity Hypoadrenocorticism Thrombocytopenia Lightening of haircoat | Fair | Typically used for pre-operative rather than long-term management; no effect on tumor growth or metastasis |
PHEOCHROMOCYTOMA IN DOGS
Incidence/Etiology and Risk Factors
Signalment/Clinical Features
Pheochromocytomas are most commonly found in middle-aged to older dogs. 14,15 Clinical findings are variable (see Table 26-1 ) and 60% of dogs are asymptomatic. 14-16 Aortic thromboembolism and retroperitoneal hemorrhage are unique sequelae. 17,18
Diagnosis and Staging
A presumptive diagnosis of pheochromocytoma can be made on the bases of appropriate clinical signs and the presence of an adrenal mass. Diagnostic assessment should include blood pressure, ophthalmic examination, and ECG. Because changes occur intermittently (when catecholamines are secreted), repeated evaluations may be necessary. Abdominal ultrasound is more sensitive than radiographs for detection of pheochromocytoma, and CT is ideal for detecting local invasion. 14,19 Because of the episodic nature of catecholamine release and lack of commercial assays, blood or urine catecholamine evaluation is rarely performed. Provocative endocrine testing is not recommended due to the risk of hypertensive crisis, and suppression testing has not been validated in dogs.
Biological Behavior/Metastasis
Pheochromocytomas may be benign, malignant, unilateral, or bilateral. Metastatic disease or local invasion is reported in approximately 13% to 24% or 39% to 52% of dogs with pheochromocytoma, respectively. 14,15 The most common sites for metastases include regional lymph nodes, liver, lung, spleen, kidney, and bone. 14
Therapy and Prognosis
Because of the potentially aggressive biologic behavior and life-threatening sequelae, surgical removal should be recommended for any dog with a pheochromocytoma. Median survival is 15 months for dogs undergoing adrenalectomy for pheochromocytoma. 20 The patient should be stabilized before surgical therapy with medications such as phenoxybenzamine, an α-adrenergic blocker. 21-23 For patients with tachycardia or cardiac arrhythmias, β-blocking agents such as propranolol are indicated. 21,23,24 It is imperative that β-adrenergic blockade is not attempted without prior α-adrenergic blockade to avoid life-threatening hypertension. 21,25 Ideally, anesthesia and surgery should only be performed by individuals with great familiarity and experience with the management of pheochromocytoma.
ADRENAL TUMORS IN CATS
Incidence/Etiology/Risk Factors
Adrenal tumors are infrequent, with cortisol and aldosterone being the most commonly produced hormones. 26 Pheochromocytomas are extremely rare. 27,28
Signalment and Clinical Features
Middle-aged to older, female cats are most commonly affected. Clinical signs vary based on hormone production (see Table 26-1 ). 29
Diagnosis and Staging
Diagnosis of an adrenal tumor is based on histopathology and imaging. 30 A thorough endocrinologic evaluation is indicated (see Table 26-2 ) in any cat with an adrenal mass. Low-dose dexamethasone (LDDS) test is the diagnostic test of choice to detect cortisol excess in cats.
Biological Behavior/Metastasis
Approximately 50% of adrenal cortical tumors in cats are carcinomas. 26,29 Reports of metastasis are infrequent. 31
Therapy and Prognosis
Adrenalectomy is the recommended treatment for adrenal tumors in cats. 32 There are reports of successful alleviation of clinical signs using trilostane in cats with cortisol-secreting adrenal tumors. 33-35 Prognosis is guarded to grave for cats with functional adrenal tumors producing cortisol or androgens. 29,32
For cats with aldosterone-secreting adrenal tumors, hypertension and/or hypokalemia should be corrected prior to invasive therapy. Spironolactone, (an aldosterone antagonist), and potassium supplementation can be used to stabilize the patient pre-operatively or as long-term medical management, with reported survical times of a 1- to 3 year. 26,36 Adrenalectomy is definitive therapy, and for cats surviving the immediate post-operative period, survival times of 1 to 8 years have been reported. 26,37
PITUITARY TUMORS IN DOGS
Pituitary tumors include growth hormone–producing somatotroph adenomas and adrenocorticotropic hormone (ACTH)–producing corticotroph adenomas. Carcinomas are rare. Pituitary adenomas are classified based on diameter as microadenomas (< 1 cm) or macroadenomas (> 1 cm).
Incidence/Etiology and Risk Factors
Corticotroph adenomas are by far the most common type of pituitary tumor in dogs. Corticotroph carcinomas and somatotroph adenomas are rare. 38-40
Signalment and Clinical Features
Pituitary tumors are more common in middle-aged to older dogs, with females being slightly overrepresented. Clinical findings related to pituitary dependent HAC are similar to those seen with cortisol-secreting adrenal cortical tumors (see Table 26-1 ). Dogs with pituitary macroadenomas may present with neurologic signs including disorientation, ataxia, inappetence, circling, pacing, seizures, facial nerve deficits, stupor, head pressing, and adipsia. 41,42
Diagnosis and Staging
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