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Basics ⬇

Basics

Definition

APUDomas are tumors of the cells known as amine precursor uptake and decarboxylation (APUD) cells. APUDomas are peptide-secreting cells that synthesize and metabolize biogenic amines; they are located throughout the body (thyroid, adrenal medulla) and the gastrointestinal tract. Pheochromocytomas consist of chromaffin cells that originate from neural crest cells within the adrenal medulla or sympathetic ganglia (paragangliomas).

Pathophysiology

Clinical signs develop as a result of the space-occupying nature of the tumor and its metastases or from excessive secretion of catecholamines (e.g., hypertension, tachycardia). Signs of hypertension and tachycardia may be constant or paroxysmal.

Systems Affected

  • Cardiovascular
  • Neurologic
  • Renal
  • Respiratory

Incidence/Prevalence

Uncommon disease in dogs; rare in cats

Signalment

Species

Dog and rarely cat

Breed Predilections

Boxer, miniature poodle, and German shepherd dog

Mean Age and Range

  • Median age in dogs is 11 years; range is 1–16 years
  • Older cats

Signs

General Comments

  • The predominant signs result from alpha-mediated vasoconstriction and beta-mediated cardiac effects that cause systemic hypertension or tachyarrhythmias.
  • Signs of hypertension may be constant or paroxysmal. Signs may be present for more than a year or develop suddenly resulting in death.
  • Thirty percent of cases are asymptomatic and only identified at necropsy.

Historical Findings

  • Clinical signs are often episodic or acute
  • Generalized weakness and lethargy are common
  • Anorexia
  • Vomiting
  • Weight loss
  • Panting, dyspnea
  • Diarrhea
  • Whining, pacing
  • Ascites, edema
  • PU/PD
  • Shakes/shivers
  • Epistaxis
  • Adypsia

Physical Examination Findings

  • May be normal
  • Lethargy, depression
  • Tachypnea, dyspnea
  • Thin, emaciated
  • Weakness
  • Peripheral edema
  • Ascites
  • Cardiac arrhythmias
  • Systolic murmur
  • Rales
  • Pale or hyperemic mucous membranes
  • Abdominal mass
  • Dehydration
  • Blindness
  • Abdominal pain

Causes

Chromaffin cell tumor

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Hyperadrenocorticism
  • Hyperaldosteronism
  • Essential hypertension (cats)
  • Renal disease with secondary hypertension

CBC/Biochemistry/Urinalysis

  • Nonregenerative anemia
  • Hemoconcentration
  • Leukocytosis
  • Mild hyperglycemia
  • Mild uremia
  • Increased liver enzymes
  • Hypoalbuminemia
  • Hypocalcemia
  • Proteinuria

Other Laboratory Tests

Arterial Blood Pressure

Systolic >180 or diastolic >95 mmHg is diagnostic for hypertension. Only 50% of animals with pheochromocytoma are hypertensive when blood pressure is measured because of the episodic nature of secretion of some tumors.

Electrocardiography

Sinus tachycardia is the most common arrhythmia; ventricular premature contractions less common.

Imaging

Abdominal Radiography

  • Abdominal mass (30%)
  • Calcification of the adrenal mass (10%)
  • Hepatomegaly
  • Renal displacement
  • Abnormal renal contour
  • Ascites
  • Enlargement of the caudal venal cava

Thoracic Radiography

  • Generalized cardiomegaly
  • Pulmonary congestion or edema

Abdominal Ultrasonography

  • Unilateral adrenal mass
  • Tumor invasion of the caudal vena cava and other adjacent structures
  • Intra-abdominal and liver metastasis

Other Imaging Modalities

  • CT scan and MRI
  • Scintigraphy using 123I-metaiodobenzylguanidine scan

Diagnostic Procedures

  • Plasma catecholamines:
    • >2,000 pg/mL supports diagnosis or pheochromocytoma.
  • Urinary catecholamine and catecholamine metabolites:
    • Total excretion over 24 hours is required or cathecholamine/metanephrine to creatinine ratio.
    • No vanilla ingestion, drugs, or radiographic contrast agents prior to obtaining the urine sample.
    • 10–15% false positives.
    • Urine must be acidified (pH <3).
    • Low sensitivity (0.42) compared with plasma catecholamines (0.97).

    • Metanephrine/normetenephrine-normal <1.3 µg/day.

      Catecholamine/metanephrine to creatinine ratio: normal = 53–323.

    • Total urinary catecholamines-normal <250 µg/day.
  • Phentolamine test:
    • Used in hypertensive patients to evaluate the dependence of catecholamines on maintaining hypertension.
    • After a stable arterial blood pressure is obtained, an IV bolus of phentolamine (0.5–1.5 mg) is given.
    • Blood pressure is recorded every 30 seconds for the first 3 minutes and every minute thereafter for an additional 7 minutes.
    • Test is positive if the fall in blood pressure is >35 mmHg systolic or 25 mmHg diastolic and the decline lasts at least 5 minutes.
    • High incidence of false-positives and hypotension.
  • Provocative tests:
    • Histamine, tyramine, glucagon may cause hypertensive crisis.

Pathologic Findings

Immunohistochemical staining of tumor tissues with chromogranin A or synaptophysin allows differentiation of pheochromocytomas from other tumor types.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

  • Surgical removal of the tumor is the treatment of choice.
  • Medical therapy is most commonly used to stabilize patients prior to surgery.

Client Education

Survival times may be as long as 3 years following successful resection of tumor. In cats, removal of tumor is often curative; these are often benign as opposed to the malignant tumors seen in dogs.

Surgical Considerations

Preoperative Care

  • Phenoxybenzamine (0.2–1.5 mg/kg PO q12h) 1–2 weeks prior to surgery.
  • Atenolol, a -1 selective antagonist (0.2–1 mg/kg PO q12–24h), can be used to control clinically significant supraventricular tachycardia.

Complications and Patient Monitoring

Common complications-hypertension, severe tachycardia, other cardiac arrhythmias, and hypovolemia/hypotension.

Anesthesia

  • Induce anesthesia with a narcotic agent or propofol.
  • Maintain anesthesia with isoflurane.

Surgery

Unilateral adrenalectomy and often thrombectomy. Manipulation of the tumor may cause severe hypertension if patient is not properly premedicated.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

  • Pre- and intraoperative hypertension can be treated with phentolamine (0.02–0.1 mg/kg IV to effect).
  • Cardiac arrhythmias and severe tachycardia-common problems; usually respond to -blocking agents such as esmolol (0.5 mg/kg slow IV bolus followed by 0.05–0.2 mg/kg/minute IV infusion).

Contraindications

  • Anesthetic agents-morphine, meperidine, xylazine, and ketamine.
  • Severe hypertension can develop if a nonselective -blocker (e.g., propranolol) is used without prior alpha-adrenergic blockade (e.g., phentolamine, phenoxybenzamine).

Precautions

Nonselective beta blockade can lead to fatal hypertension.

Alternative Drug(s)

N/A

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

Blood pressure, central venous pressure, and ECG are closely monitored in the immediate postoperative period (24–72 hours).

Possible Complications

Postoperative-intra-abdominal hemorrhage, hypotension, peritonitis, sepsis.

Expected Course and Prognosis

Prognosis is guarded to fair.

Miscellaneous ⬆

Miscellaneous

Associated Conditions

Multiple endocrine neoplasia types II and III

Pregnancy/Fertility/Breeding

N/A

Abbreviations

  • APUD = amine precursor uptake and decarboxylation
  • CT = computed tomography
  • ECG = electrocardiogram
  • MRI = magnetic resonance imaging
  • PU/PD = polyuria/polydipsia
  • VMA = vanillylmandelic acid

Suggested Reading

Bathez PY, Marks SL, Woo J, Feldman ED, Matteucci M. Pheochromocytoma in dogs: 61 cases (1984–1995). J Vet Intern Med 1997, 11(5):272–278.

Greco DS. APUDomas and other emerging feline endocrinopathies. In: August JR, ed., Consultations in Feline Internal Medicine IV. Philadelphia: Saunders, 2001, pp. 181–185.

Kook PH, Grest P, Quante S, et al. Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a phaeochromocytoma. Vet Rec 2010, 166(6):169–174.

Kyles AE, Feldman EC, De Cock HEV, 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.

Author Deborah S. Greco

Consulting Editor Deborah S. Greco