Adrenal neoplasia

Lance Wilson ANZCVS surgery resident forum 2015

Australian College of Veterinary Scientists

Fellowship Examination

June/July 2009

Small Animal Surgery

Paper 1

Principles

4 Adrenal tumours are commonly functional tumours. A five-year-old cattle dog is

presented with hypertension and a 5 x 3 x 3 cm unilateral left-sided adrenal mass

found on abdominal ultrasound. Answer all of the following:

a) Describe the causes of unilateral adrenal enlargement.

b) Discuss what further investigation would be ideal before considering surgical

removal of the adrenal mass.

c) Discuss preferred preoperative stabilisation in a clinically well dog.

d) Discuss complications associated with adrenalectomy. Describe appropriate

anaesthetic and peri-operative management options to reduce and manage these.

SMALL ANIMAL SURGERY 2005 – FELLOWSHIP – PAPER 2

Answer only FOUR (4) of the six questions.

Subsections of questions are of equal value unless stated otherwise.

1. Surgery is sometimes indicated in the management of canine hyperadrenocorticism. Discuss the surgical approaches for management of this condition (33%). Include in your answer a discussion of the main intra-operative and post-operative risks/complications (33%) and strategies to minimise these risks (34%).

Outline

• Anatomy/physiology

• Classification

• Clinical findings/diagnosis

• Imaging

• Therapeutic options

• Surgical techniques

• Complications

• Outcomes/prognosis

Adrenal anatomy – regional• Paired• Retroperitoneal• Closely associated with kidneys and

great vessels• Right

• More cranial• Near hilus of R kidney• Adherent to vena cava• Covered cranio-ventrally by R lateral

and caudate process of caudate liver lobes

• Left• Larger• Medial to cranial pole L kidney• Adjacent to aorta

Adrenal anatomy – vascular

• Arterial• 20-30 arterioles arising

from phrenicoabdominal, aorta, renal and lumbar a

• Forms sub-capsular plexus

• Venous• Sinusoids

• Adrenal veins

• Left empties into L renal

• Right empties into CVC

Adrenal anatomy - microscopic

• Capsule

• Cortex• Z. glomerulosa (Z. arcuata

and Z. intermedia)

• Z. fasciculata

• Z. reticularis

• Medulla• Sympathetic ganglion

Adrenal function• Z. glomerulosa

• Mineralocorticoids – aldosterone• Electrolytes and blood pressure• RAAS mediated

• Z. fasciculata• Glucocorticoids - cortisone• Metabolism• Hypothalamic-pituitary-adrenal axis

• Z. reticularis• Sex steroids - androgens and oestrogens

• Medulla• Catecholamine's• Adrenalin (80%) and noradrenalin (20%)• Stress response and metabolism• Sympathetic nervous system

Types of adrenal masses

1. Benign vs. malignant

2. Functional vs. non-functional

3. Primary vs. metastatic

Types of adrenal masses1. Benign

• Hyperplasia• Adrenocortical adenoma

• 58-67% adrenocortical tumours

2. Malignant• Adrenocortical

adenocarcinoma• 33-42% adrenocortical

tumours

• Adrenomedullary phaeochromocytoma

• Metastatic • Other - sarcoma

Types of adrenal masses1. Functional

• Adrenocortical – 75-78%• Glucocorticoids

• Hyperadrenocorticism (Cushings disease)

• Mineralocorticoids • Primary aldosteronism (Conn’s

syndrome)

• Sex hormones – very rare• Hormone precursors – very rare

• 17-OH progesterone• Deoxycorticosterone

• Phaeochromocytoma 16-22%• Adrenalin

2. Non-functional• Adrenocortical• “Incidentaloma”• Metastatic tumour• Other primary - sarcoma

Cortisol secreting tumour

• Signalment/CSx/PEx• Median age 11 years

• No sex/breed predilection

• PU/PD/PP

• Panting

• Abdominal enlargement

• Alopecia

• Lethargy

• Muscle weakness

Cortisol secreting tumour• Diagnostic approach• CBC/MBA/UA

• Stress leukogram, increased ALKP and chol, low USG, proteinuria

• LDDST• No suppression (> 41.1 nmol/l) at 4 or 8 hours

• Endogenous ACTH• <10 pg/ml

• ACTHST• 60% sensitivity

• Inhibin (de-sexed dogs)• Median inhibin 0.82 ng/ml with cortisol

secreting tumours vs. undetectable for phaeo• Bromel JVIM 2013

• Abdominal imaging• Adrenal mass with atrophied contralateral

adrenal

Aldosterone secreting tumour • Signalment/CSx/PEx

• Most common adrenal tumour in cats• Very rare in dogs• Median age 13 years • No sex or breed predilection• Polymyopathy

• Weakness, plantigrade stance, limb stiffness, muscle atrophy, cervical ventro-flexion, collapse

• PU/PD/PP• Abdominal mass• Systolic murmur, arrhythmia• Hypertension

• SBP > 180mmHg

• Ophthalmologic abnormalities• Retinal haemorrhage, blindness

Aldosterone secreting tumour• Diagnostic approach• CBC/MBA/UA

• Hypo K+, increased CK, increased BUN, increased crea

• Plasma aldosterone• >388 ng/dL

• Plasma aldosterone:renin (PARR)• Javadi JVIM 2004

• Urine aldosterone:creatinine (UACR)• Djajadiningrat-Laanen JVIM 2008

• Fludrocortisone acetate suppression test• <50% suppression UACR suggestive of

primary hypoaldosteronism• Djajadiningrat-Laanen JVIM 2013

• Abdominal imaging• Adrenal mass with atrophied

contralateral adrenal

Phaeochromocytoma• Signalment/CSx/PEx

• Median age 11 years• No sex/breed predilection• Episodic collapse• Generalised weakness• Muscle wasting• Panting• Tachypnoea• Tachycardia• Hypertension• Blindness

• Retinal haemorrhage and detachment

CSx OFTEN SPORADIC

Phaeochromocytoma• Diagnostic approach• CBC/MBA/UA

• Generally WNLs

• LDDST• WNLs

• Plasma free Normetadrenaline• > 5.52 nmol/L • Gostelow JVIM 2013

• Urine Normetadrenaline:creatine• >4 times normal highly suggestive• Quante JVIM 2010

• Serum inhibin (de-sexed dogs)• Undetectable inhibin highly supportive of

phaeo over adrenocortical tumour• Bromel JVIM 2013

• Abdominal imaging• Adrenal mass with normal-sized contralateral

adrenal

“Incidentaloma”

• Cook JAVMA 2014

• IAGL 4% abdominal U/S

• 13% underwent Sx or PM

• 30% found to be malignant

• All malignant > 20mm, all benign < 20mm

• Recommendations• PEx, BP, CBC/MBA/UA, LDDST,

ACTHST, aldosterone

• Abdominal imaging 1, 2, 4, 6 months then Q 6 months

Imaging• Adrenal

• Ultrasound• CT• MRI

• Staging • < 10% met rate malignant

adrenal masses• Abdominal U/S• Thoracic radiographs• Thoracic/abdominal CT• Abdominal MRI

Ultrasound• Adrenal enlargement readily noted and

measured• Non-invasive, readily available, scan for

concurrent and metastatic disease• No GA required• Cook JAVMA 2014

• 100% benign adrenal masses < 20mm

• Pey JAVMA 2014• Contrast U/S• Heterogeneity of contrast

enhancement and less regional blood volume in malignant tumours

• Davis VRU 2014• U/S for vascular invasion• 100% sens, 96% spec CVC invasion

Computed Tomography• Contrast CT imaging modality of choice• Rapid, minimally invasive, good soft tissue

resolution• Thoracic CT• Requires GA• Schultz JVRU 2009

• 92% sens 100% spec for vascular invasion

• Gregori VRU 2014 • Excellent agreement between CT signs of

invasion and surgical findings

• Rodriguez Pineiro JVIM 2011• Maximal adrenal diameter ratio on

reformatted CT images > 2.08 highly suggestive of adrenocortical tumour over pituitary dependant hyperplasia

Treatment options• Surgery

• Functional• > 20 mm• Vascular invasion• No metastatic disease

• Not surgery• Non-functional• < 20 mm• No malignant

characteristics• Severe co-morbidities

Non-surgical management • Cortisol-secreting

• Trilostane• Mitotane• Median survival time 16.5 mth

• Aldosterone-secreting• Amlodipine• Spironolactone• K+ supplementation

• Phaeochromocytoma• 131I metaiodobenzylguanidine

• Bommarito JAAHA 2011

• Amlodipine• Alpha-adrenergic antagonists• Median survival 17.8 mth

• Arenas Vet Rec 2013• BWT, tumour size and metastatic disease -

ve prognosis

• Non-functional• Regular abdominal imaging

Pre-surgical considerations – general

• Anticipate haemorrhage• Blood type, cross match, blood

products available

• Wide surgical clip

• Perioperative antibiosis• Cephazolin 22 mg/kg IV Q 120

min

• Anaesthesia • Direct arterial BP, central line,

ECG, ETCO2, SPO2

• Ionotropes, pressors, colloids

Peri-operative considerations – Cortisol secreting tumour• Trilostane

• 1-2mg/kg BID 3-4 weeks pre-op• ACTHST and electrolytes 1-14 day after starting• Aim for reduction CSx and post ACTH 2-5 ug/dL

• Anticoagulant therapy• Heparinised plasma intra-op• Heparin SQ 2-3 days• Frequent walks

• Glucocorticoids• Dexamethasone 0.05-0.1mg/kg in fluids over 6

hour peri-op• Dex BID until transition to oral pred• Taper pred over 3-4 months

• Mineralocorticoids• If Na+ < 135mRq/L or K+ > 6.5mEq/L• DOCP Q 25d as required

• Non-absorbable sutures linear alba?• Leave skin sutures >14d

Peri-operative considerations –aldosterone secreting tumour

• K+ supplementation intra and post-op

• Anti-hypertensive drugs• Amlodipine

• High salt diet early post-op

Pre-surgical considerations –phaeochromocytoma• Chronic catecholamine

exposure• Phenoxybenzamine 0.5-

2.5mg/kg BID 2-3 weeks• Herrera JVIM 2008 peri-op

mortality 48>13%

• Tachyarrhythmia's• Beta antagonists,

Lignocaine

• Anti-hypertensive drugs• Amlodipine, nitroprusside

Surgery

• Open surgery• Ventral midline +/-

paracostal extension

• Paracostal

• Intercostal

• Laparoscopy• Tumours <50mm without

CVC invasion

• Lateral

• Sternal

Surgery – general considerations• Bipolar vessel sealing devices,

haemoclips and sterile cotton-tipped applicators

• Begin dissection by incising peritoneum lateral to tumour

• Ligate/clip/seal phrenicoabdominal vein laterally

• Retract tumour medially• Dissect cranially, caudally and

dorsally • Ligate/clip/seal

phrenicoabdominal vein medially

Ventral midline• Dorsal recumbency• Xiphoid to caudal abdomen• Left adrenal

• Caudal retraction left kidney• Retract descending colon medially and caudally

• Right adrenal• Transect hepatorenal ligament• Cranial retraction right lateral and caudate lobe

and caudal retraction right kidney• Retract duodenum medially and caudally

• Can be combined with paracostal incision• Advantages

• Allows full exploratory coeliotomy + biopsies • More familiar approach• Less pain?• Improved exposure of vascular structures?

• Disadvantages• Difficult access

• Right adrenal• Deep-chested dogs

Paracostal• Lateral recumbency• Paracostal incision caudal to 13th rib

from epaxial muscles to rectus abdominis

• Grid approach• Ventral retraction of kidney• Advantages

• Improved access to dorsal abdomen

• Decreased risk of dehiscence?

• Disadvantages• Unable to perform exploratory

coeliotomy

Intercostal approach – Andrade et al. Vet Surg 2014

• Right adrenal masses

• Left lateral recumbency

• Vertical incision 12th ICS

• Advantages• Improved access to right

adrenal

• Decreased need for retraction

• Disadvantages• Incision through IC muscles

• Requires thoracostomy tube

Vascular invasion• 9.5-55% adrenal masses• Right > left?

• Kyles JAVMA 2003

• Phaeochromocytoma 10-55%• Adrenocortical carcinoma 2-

21%• Typically via

phrenicoabdominal vein to CVC

• Can extend to right atrium

Surgery – vascular invasion• Rumel tourniquets

• Left adrenal• CVC pre-renal and pre-hepatic• Possibly left and right renal

• Right adrenal• CVC post-renal and pre-hepatic

• Longitudinal venotomy• Partial caval wall resection• Vascular clamp• Simple continuous/continuous

cruciate closure 5-0 synthetic monofilament

• Caval temporary ligation < 20 min

Laparoscopy – lateral• Mayhew JAVMA 2014 and Jimenez

Pelaez Vet Surg 2008• Lateral recumbency• 3-4 port• Camera port 3-5cm lat to umbilicus via

modified Hassan or Veress• Instrument port cranio-dorsal and

caudo-dorsal• Optional 4th port for retraction• Mayhew JAVMA 2014

• Lap compared with open• Median surgery 90 min cf. 120 min

open• 1/23 conversions, no perioperative

deaths, shorter hospital stay

Laparoscopy – sternal

• Naan Vet Surg 2013

• Sternal recumbency

• Sternum and pelvis raised

• Allowed ventral displacement of viscera

• 3 port technique

• Median surgery time 73 min

• 1/9 peri-op mortality

Complications• Intra-operative

• Haemorrhage• Ventricular fibrillation• Hypertension• Hypotension

• Post-operative• Haemorrhage• Infection• Wound dehiscence• Thromboembolism • Pancreatitis• DIC• ARF• Ventricular tachycardia

Prognostic factors• Tumour size

• >5cm mass – ve prognostic • Massari JAVMA 2011

• 1mm increase in size 7.9% increase mortality• Lang JAAHA 2011

• Tumour type• Adenoma > carcinoma =/> phaeo

• Phaeo –ve prognostic• Barrera JAVMA 2013

• Tumour invasiveness• Presence of CVC thrombus –ve prognostic

• Massari JAVMA 2011, Barrera JAVMA 2013• Barrera peri-op mortality 71% CVC thrombus

• Kyles JAVMA 2003, Lang JAHHA 2011 - NSD

• Thrombus size• Local thrombus > extensive thrombus

• Barrera JAVMA 2013• Peri-op mortality 100% extensive thrombus

• Nephrectomy• Concurrent nephrectomy –ve prognostic

• Schwartz JAVMA 2008

• Metastatic disease• Presence of metastatic disease –ve prognostic

• Massari JAVMA 2011

• Planned vs. emergency surgery• Emergent adrenalectomy due to haemorrhage –ve prognostic

• Lang JAAHA 2011• Peri-op mortality 50% vs. 5%

• Perioperative factors• Anaesthesia time, complications, haemorrhage, intra-op transfusion, DIC,

pancreatitis, hypotension, ARF• Lo JVIM 2014, Barrera JAVMA 2013, Lang JAAHA 2011, Schwartz JAVMA

2008

Outcome and prognosis• Lose big/win big• Peri-operative mortality dogs 12-60%

• More recent studies 12-33%• Barrera JAVMA 2013 peri-op mortality 33%; 21% adrenocortical

carcinoma and 52% phaeochromocytoma• Massari JAVMA 15%• Lang JAAHA 2011 12% - 5% planned• Schwartz JAVMA 2008 22%

• Peri-operative mortality cats 20%• Lo JVIM 2014

• BUT if survive peri-op period have a good prognosis• Median survival times dogs 1.3-4 years recent studies

• Andrade Vet Surg 2014, Barrera JAVMA 2013, Massari JAVMA 2011, Lang JAAHA 2011, Schwartz JAVMA 2008

• Median survival time cats aldosterone secreting tumour 3.5 years• Lo JVIM 2014

• Improved peri-operative survival with laparoscopic techniques• 1/31 (3%) peri-op death in last 2 publications• BUT skewed towards smaller tumours with no vascular invasion

Important/recent papers

• Outcomes/prognosis• Lo JVIM 2014

• Barrera JAVMA 2013

• Massari JAVMA 2011

• Lang JAAHA 2011

• Schwartz JAVMA 2008

• Kyles JAVMA 2003

• Laparoscopy• Mayhew JAVMA 2014

• Naan Vet Surg 2013

1.Pey P, Rossi F, Vignoli M, Duchateau L, Marescaux L, Saunders JH. Use of contrast-enhanced ultrasonography to characterize adrenal gland tumors in dogs. American Journal of Veterinary Research. 2014;75(10):886-92.

2.Mayhew PD, Culp WTN, Hunt GB, Steffey MA, Mayhew KN, Fuller M, et al. Comparison of perioperative morbidity and mortality rates in dogs with noninvasive adrenocortical masses undergoing laparoscopic versus open adrenalectomy. Journal of the American Veterinary Medical Association. 2014;245(9):1028-35.

3.Lo AJ, Holt DE, Brown DC, Schlicksup MD, Orsher RJ, Agnello KA. Treatment of aldosterone-secreting adrenocortical tumors in cats by unilateral adrenalectomy: 10 cases (2002-2012). J Vet Intern Med. 2014;28(1):137-43.

4.Gregori T, Mantis P, Benigni L, Priestnall SL, Lamb CR. COMPARISON OF COMPUTED TOMOGRAPHIC AND PATHOLOGIC FINDINGS IN 17 DOGS WITH PRIMARY ADRENAL NEOPLASIA. Vet Radiol Ultrasound. 2014.

5.Cook AK, Spaulding KA, Edwards JF. Clinical findings in dogs with incidental adrenal gland lesions determined by ultrasonography: 151 cases (2007-2010). J Am Vet Med Assoc. 2014;244(10):1181-5.

6.Bertazzolo W, Didier M, Gelain ME, Rossi S, Crippa L, Avallone G, et al. Accuracy of cytology in distinguishing adrenocortical tumors from pheochromocytoma in companion animals. Veterinary clinical pathology / American Society for Veterinary Clinical Pathology. 2014;43(3):453-9.

7.Andrade N, Rivas LR, Milovancev M, Radlinsky MA, Cornell K, Schmiedt C. Intercostal approach for right adrenalectomy in dogs. Vet Surg. 2014;43(2):99-104.

8.Withrow SJ, Vail DM, Page RL. Withrow & MacEwen's small animal clinical oncology. St. Louis, Missouri: Elsevier; 2013.

9.Naan EC, Kirpensteijn J, Dupre GP, Galac S, Radlinsky MG. Innovative approach to laparoscopic adrenalectomy for treatment of unilateral adrenal gland tumors in dogs. Vet Surg. 2013;42(6):710-5.

10.Larson RN, Schmiedt CW, Wang A, Lawrence J, Howerth EW, Holmes SP, et al. Adrenal gland function in a dog following unilateral completeadrenalectomy and contralateral partial adrenalectomy. J Am Vet Med Assoc. 2013;242(10):1398-404.

11.Kool MM, Galac S, Spandauw CG, Kooistra HS, Mol JA. Activating mutations of GNAS in canine cortisol-secreting adrenocortical tumors. J Vet Intern Med. 2013;27(6):1486-92.

12.Gostelow R, Bridger N, Syme HM. Plasma-free metanephrine and free normetanephrine measurement for the diagnosis of pheochromocytoma in dogs. J Vet Intern Med. 2013;27(1):83-90.

13.Djajadiningrat-Laanen SC, Galac, Boeve MH, Boroffka SA, Naan EC, J IJ, et al. Evaluation of the oral fludrocortisone suppression test for diagnosing primary hyperaldosteronism in cats. J Vet Intern Med. 2013;27(6):1493-9.

14.Bromel C, Nelson RW, Feldman EC, Munro CJ, Kass PH, Vico AE, et al. Serum inhibin concentration in dogs with adrenal gland disease and in healthy dogs. J Vet Intern Med. 2013;27(1):76-82.

15.Barrera JS, Bernard F, Ehrhart EJ, Withrow SJ, Monnet E. Evaluation of risk factors for outcome associated with adrenal land tumors with or without invasion of the caudal vena cava and treated via adrenalectomy in dogs: 86 cases (1993-2009). J Am Vet Med Assoc. 2013;242(12):1715-21.

16.Arenas C, Perez-Alenza D, Melian C. Clinical features, outcome and prognostic factors in dogs diagnosed with non-cortisol-secreting adrenal tumours without adrenalectomy: 20 cases (1994-2009). Vet Rec. 2013;173(20):501.

17.Tobias KM, Johnston SA. Veterinary surgery: small animal. St. Louis, Mo: Elsevier/Saunders; 2012.

18.Smith RR, Mayhew PD, Berent AC. Laparoscopic adrenalectomy for management of a functional adrenal tumor in a cat. J Am Vet Med Assoc. 2012;241(3):368-72.

19.Kudnig ST, Seguin B. Veterinary surgical oncology. Chichester, West Sussex: Wiley-Blackwell; 2012.

20.Guillaumot PJ, Heripret D, Bouvy BM, Christiaens G, Poujade A, Delverdier M, et al. 49-month survival following caval venectomy without nephrectomy in a dog with a pheochromocytoma. J Am Anim Hosp Assoc. 2012;48(5):352-8.

21.Gojska-Zygner O, Lechowski R, Zygner W. Functioning unilateral adrenocortical carcinoma in a dog. Can Vet J 2012;53(6):623-5.

22.Davis MK, Schochet RA, Wrigley R. Ultrasonographic identification of vascular invasion by adrenal tumors in dogs. Vet Radiol Ultrasound. 2012;53(4):442-5.

23.Rodriguez Pineiro MI, de Fornel-Thibaud P, Benchekroun G, Garnier F, Maurey-Guenec C, Delisle F, et al. Use of computed tomography adrenalgland measurement for differentiating ACTH dependence from ACTH independence in 64 dogs with hyperadenocorticism. J Vet Intern Med. 2011;25(5):1066-74.

24.Massari F, Nicoli S, Romanelli G, Buracco P, Zini E. Adrenalectomy in dogs with adrenal gland tumors: 52 cases (2002-2008). J Am Vet Med Assoc. 2011;239(2):216-21.

25.Lang JM, Schertel E, Kennedy S, Wilson D, Barnhart M, Danielson B. Elective and emergency surgical management of adrenal gland tumors: 60 cases (1999-2006). J Am Anim Hosp Assoc. 2011;47(6):428-35.

26.Djajadiningrat-Laanen S, Galac S, Kooistra H. Primary hyperaldosteronism: expanding the diagnostic net. J Feline Med Surg. 2011;13(9):641-50.

27.Bommarito DA, Lattimer JC, Selting KA, Henry CJ, Cohen M, Johnson GC. Treatment of a malignant pheochromocytoma in a dog using 131I metaiodobenzylguanidine. J Am Anim Hosp Assoc. 2011;47(6):e188-94.

28.Wimpole JA, Adagra CF, Billson MF, Pillai DN, Foster DJ. Plasma free metanephrines in healthy cats, cats with non-adrenal disease and a cat with suspected phaeochromocytoma. J Feline Med Surg. 2010;12(6):435-40.

29.Quante S, Boretti FS, Kook PH, Mueller C, Schellenberg S, Zini E, et al. Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or pheochromocytoma, and in healthy dogs. J Vet Intern Med. 2010;24(5):1093-7.

30.Gostelow R, Syme H. Plasma metadrenalines in canine phaeochromocytoma. Vet Rec. 2010;166(17):538.

31.Galac S, Kars VJ, Klarenbeek S, Teerds KJ, Mol JA, Kooistra HS. Expression of receptors for luteinizing hormone, gastric-inhibitory polypeptide, and vasopressin in normal adrenal glands and cortisol-secreting adrenocortical tumors in dogs. Domestic animal endocrinology. 2010;39(1):63-75.

32.Schultz RM, Wisner ER, Johnson EG, MacLeod JS. Contrast-enhanced computed tomography as a preoperative indicator of vascular invasion from adrenal masses in dogs. Vet Radiol Ultrasound. 2009;50(6):625-9.

33.Schultz RM, Wisner ER, Johnson EG, MacLeod JS. Contrast-enhanced computed tomography as a preoperative indicator of vascular invasion from adrenal masses in dogs. Vet Radiol Ultrasound. 2009;50(6):625-9.

34.Fransson BA, Keegan RD, Ragle CA, Haldorson GJ, Greene SA. Hemodynamic changes during laparoscopic radiofrequency ablation of normal adrenal tissue in dogs. Vet Surg. 2009;38(4):490-7.

35.Schwartz P, Kovak JR, Koprowski A, Ludwig LL, Monette S, Bergman PJ. 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(1):77-84.

36.Kook PH, Boretti FS, Hersberger M, Glaus TM, Reusch CE. 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. 2007;21(3):388-93.

37.Louvet A, Lazard P, Denis B. Phaeochromocytoma treated by en bloc resection including the suprarenal caudal vena cava in a dog. J Small Anim Pract. 2005;46(12):591-6.

38.Ash RA, Harvey AM, Tasker S. Primary hyperaldosteronism in the cat: a series of 13 cases. J Feline Med Surg. 2005;7(3):173-82.

39.Labelle P, Kyles AE, Farver TB, De Cock HE. Indicators of malignancy of canine adrenocortical tumors: histopathology and proliferation index. Vet Pathol. 2004;41(5):490-7.

40.Kyles AE, Feldman EC, De Cock HE, Kass PH, Mathews KG, Hardie EM, 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(5):654-62.

41.Syme HM, Scott-Moncrieff JC, Treadwell NG, Thompson MF, Snyder PW, White MR, et al. Hyperadrenocorticism associated with excessive sex hormone production by an adrenocortical tumor in two dogs. J Am Vet Med Assoc. 2001;219(12):1725-8, 07-8.

42.Anderson CR, Birchard SJ, Powers BE, Belandria GA, Kuntz CA, Withrow SJ. Surgical treatment of adrenocortical tumors: 21 cases (1990-1996). J Am Anim Hosp Assoc. 2001;37(1):93-7.

43.Reine NJ, Hohenhaus AE, Peterson ME, Patnaik AK. Deoxycorticosterone-secreting adrenocortical carcinoma in a dog. J Vet Intern Med. 1999;13(4):386-90.

44.Hoerauf A, Reusch C. Ultrasonographic characteristics of both adrenal glands in 15 dogs with functional adrenocortical tumors. J Am Anim Hosp Assoc. 1999;35(3):193-9.

45.Barthez PY, Marks SL, Woo J, Feldman EC, Matteucci M. Pheochromocytoma in dogs: 61 cases (1984-1995). J Vet Intern Med. 1997;11(5):272-8.