Pheochromocytoma

From Dog
Gross appearance of an adrenal pheochromocytoma[1]

Pheochromocytoma is a rare neuroendocrine malignant neoplasia of the adrenal medullary chromaffin cells, characterized by excessive catecholamine production[2].

Rare non-adrenal pheochromocytomas have also been reported involving heart tissue in the dog (paraganglioma[3], intracardiac chromaffin chemodectoma[4]).

Both noradrenaline (norepinephrine) and adrenaline (epinephrine) can be produced by these tumors. These tumors are often locally invasive and may infiltrated the renal capsule, retroperitoneum or suprarenal vena cava[5]. Vascular invasion usually occurs by way of the lumen of the phrenicoabdominal vein with subsequent intraluminal extension into other veins, rather than by erosion through vessel walls[6].

Distant metastasis occurs primarily to bone[7], but have also been reported in the kidneys, spleen, lungs, heart and liver[8].

Concurrent hyperadrenocorticism has also been reported[9].

These tumors are usually diagnosed in older dogs, which present with acute lethargy, vomiting, hypertension (>160 mmHg), polyuria and polydipsia due to excessive catecholamine stimulation of renal tubular cells[10]. Ascites may be present in dogs where metastatic thrombus of the vena cava has resulted in caval hypertension and secondary serous effusion[11].

Spontaneous rupture of these tumors in previously asymptomatic dogs may result in patients suddenly presenting with lethargy, pale mucous membranes, hemoglobinuria and periumbilical discoloration attributable to intra-abdominal hemorrhage[12][13].

Imaging studies with ultrasonography, computed tomography[14] or positron emission tomography[15] usually reveals an adrenal mass which can vary in size from 1 - 20 cm.

Using immunoassays[16], urinalysis shows significantly higher urinary epinephrine, norepinephrine and normetanephrine to creatinine ratios[17][18]. This must be differentiated from stress-induced urinary cathecholaminuria[19].

A definitive diagnosis is made on histological examination of biopsied adrenal tissue.

A differential diagnosis would include diabetes insipidus, chronic renal disease, dilated cardiomyopathy, hypoadrenocorticism and hyperadrenocorticism.

Treatment usually requires unilateral or bilateral adrenalectomy. Intraoperative and postoperative complications developed in up to 50% of dogs, with a post-operative mortality rate around 20%[20].

Preoperative institution of long-term phenoxybenzamine therapy for 3 - 4 weeks[21]. Resection of the suprarenal caudal vena cava if metastases are involved[22].

Radioactive iodine (I131) has been used, but with poor response[23].

Major complications of pheochromocytoma are tumor-induced retroperitoneal hemorrhage and aortic and vena caval thromboembolism, effecting a poorer survival rate in these cases[24][25][26].

Prognosis is guarded with metastasis, with median survival times of 1 - 2 years post-diagnosis[27].

The unpredictable nature of pheochromocytomas warrants follow-up ultrasound or CT examinations in dogs with non-resectable tumors or monitoring remaining adrenal gland[28].

References

  1. GFMer
  2. Tischler AS et al (2004) Animal models of pheochromocytoma. Histol Histopathol 19(3):883-995
  3. Shaw TE et al (2010) Aortic body tumor in full-sibling English bulldogs. J Am Anim Hosp Assoc 46(5):366-370
  4. Wey AC & Moore FM (2012) Right atrial chromaffin paraganglioma in a dog. J Vet Cardiol 14(3):459-464
  5. Guillaumot PJ et al (2012) 49-month survival following caval venectomy without nephrectomy in a dog with a pheochromocytoma. J Am Anim Hosp Assoc 48(5):352-358
  6. Schultz RM et al (2009) Contrast-enhanced computed tomography as a preoperative indicator of vascular invasion from adrenal masses in dogs. Vet Radiol Ultrasound 50(6):625-629
  7. Boes K et al (2009) What is your diagnosis? Shoulder mass in a dog with lameness. Vet Clin Pathol 38(4):511-515
  8. Sako T et al (2001) Immunohistochemical evaluation of a malignant phecochromocytoma in a wolfdog. Vet Pathol 38(4):447-450
  9. Hylands R (2005) Veterinary diagnostic imaging. Malignant pheochromocytoma of the left adrenal gland invading the caudal vena cava, accompanied by a cortisol secreting adrenocortical carcinoma of the right adrenal gland. Can Vet J 46(12):1156-1158
  10. van Aalst PM et al (2007) A phaeochromocytoma in a Lhasa Apso dog. Tijdschr Diergeneeskd 132(10):393-395
  11. Schoeman JP & Stidworthy MF (2001) Budd-Chiari-like syndrome associated with an adrenal phaeochromocytoma in a dog. J Small Anim Pract 42(4):191-194
  12. Whittemore JC et al (2001) Nontraumatic rupture of an adrenal gland tumor causing intra-abdominal or retroperitoneal hemorrhage in four dogs. J Am Vet Med Assoc 219(3):329-333
  13. Schermerhorn T et al (1998) Cullen's sign and haemoglobinuria as presenting signs of retroperitoneal haemorrhage in a dog. J Small Anim Pract 39(10):490-494
  14. Spall B et al (2011) Imaging diagnosis-metastatic adrenal pheochromocytoma in a dog. Vet Radiol Ultrasound 52(5):534-537
  15. Berry CR et al (2002) Imaging of pheochromocytoma in 2 dogs using p-[18F] fluorobenzylguanidine. Vet Radiol Ultrasound 43(2):183-186
  16. Francis RC et al (2010) Detection of catecholamines and metanephrines by radio-immunoassay in canine plasma. Vet J 183(2):228-231
  17. Quante S et al (2010) Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs. J Vet Intern Med 24(5):1093-1097
  18. Kook PH et al (2010) Urinary catecholamine and metadrenaline to creatinine ratios in dogs with a phaeochromocytoma. Vet Rec 166(6):169-174
  19. Kook PH et al (2007) Urinary catecholamine and metanephrine to creatinine ratios in healthy dogs at home and in a hospital environment and in 2 dogs with pheochromocytoma. J Vet Intern Med 21(3):388-393
  20. Kyles AE et al (2003) Surgical management of adrenal gland tumors with and without associated tumor thrombi in dogs: 40 cases (1994-2001). J Am Vet Med Assoc 223(5):654-662
  21. Herrera MA et al (2008) Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing adrenalectomy for pheochromocytoma. J Vet Intern Med 22(6):1333-1339
  22. Louvet A et al (2005) Phaeochromocytoma treated by en bloc resection including the suprarenal caudal vena cava in a dog. J Small Anim Pract 46(12):591-596
  23. Bommarito DA et al (2011) Treatment of a malignant pheochromocytoma in a dog using 131I metaiodobenzylguanidine. J Am Anim Hosp Assoc 47(6):188-194
  24. Massari F et al (2011) Adrenalectomy in dogs with adrenal gland tumors: 52 cases (2002-2008). J Am Vet Med Assoc 239(2):216-221
  25. Santamarina G et al (2003) Aortic thromboembolism and retroperitoneal hemorrhage associated with a pheochromocytoma in a dog. J Vet Intern Med 17(6):917-922
  26. Pradelli D et al (2003) Tumour thrombus: direct endoluminal 'caudal caval vein-right atrium' extension in a dog affected by adrenal neoplasia. Vet Res Commun 27(1):787-789
  27. Lang JM et al (2011) Elective and emergency surgical management of adrenal gland tumors: 60 cases (1999-2006). J Am Anim Hosp Assoc 47(6):428-435
  28. Rosenstein DS (2000) Diagnostic imaging in canine pheochromocytoma. Vet Radiol Ultrasound 41(6):499-506