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DECEMBER 2011
ADRENAL MASSES
INCIDENTAL AND NON-INCIDENTAL – 6 PAGES
An adrenal mass is suspect when the maximum width of the adrenal gland exceeds 1.5
cm, there is loss of normal architecture/shape or there is asymmetry in shape/ size between the
affected adrenal gland and the other adrenal gland. This is initial criteria however and many
benign exceptions exist. Bulbous enlargement of the cranial or caudal pole of the adrenal gland is
common in dogs with normal adrenal glands and can be misinterpreted as an adrenal mass. If the
mass does not have obvious signs of aggressive behavior then an abdominal ultrasound should
always be repeated to confirm that the mass is a repeatable finding before pursuing further
diagnostics or surgery.
Incidental adrenal lesions should be investigated clinically if they are diagnosed. Nonneoplastic adrenal lesions such as cysts or granulomas are very rare in dogs or cats and the high
incidence of metastatic lesions justifies a thorough endocrinologic screening and evaluation for
non-adrenal neoplasms. Incidental adrenal masses may appear to be nonfunctional at the time of
diagnosis although it seems likely that they are actually subclinically functional. The diagnosis of
functional adrenal tumors is discussed below but identification of a nonfunctional, incidental
adrenal mass creates a management dilemma.
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Adrenal tumors are rare in cats and represent 0.2% of all feline tumors. In a retrospective
study from UC Davis that included all cats that underwent complete necropsy over a 20-year
period, 30% had adrenocortical tumors, 10% were pheochromacytomas, and 60% were
metastatic tumors. Fewer than half of the metastatic tumors were seen grossly on necropsy.
Primary adrenal tumors represent 1-2% of all canine tumors. In the same retrospective study,
41% had adrenocortical tumors, 32% were pheochromatcytomas, and 27% were metastatic
lesions. Lymphoma was the most common cancer to spread to the adrenal glands in both
species. In dogs, other metastatic tumours commonly identified included hemangiosarcoma,
mammary carcinoma, histiocytic sarcoma, pulmonary carcinoma, and melanoma. The left and
the right gland were affected equally, as were the cortex and medulla. The notable exception was
that all metastatic melanomas remained confined to the medulla (pp588-589, Withrow and
MacEwen’s Small Animal Clinical Oncology, 4th Ed, 2007, Saunders/Elsevier).
Malignant/Benign/Functional/Non-Functional: How to decide?
It may be difficult to determine if the mass is malignant/benign/functional/nonfunctional prior to
surgical removal and histopathology in some cases. A thorough review of the clinical signs,
physical examination findings, routine blood, urine tests and performance of appropriate
hormonal tests should be done to determine the functional status of an incidental adrenal mass.
Blood pressure must be measured. Malignancy is more often associated with larger masses, such
as those that measure greater than 2 cm. Invasion of the mass into surrounding organs or blood
vessels also supports malignancy as does the detection of additional mass lesions with abdominal
ultrasound and thoracic radiographs. Use of imaging modalities such as CT and MR will likely
provide additional data on the characteristics of specific adrenal lesions for use in diagnosis and
treatment planning, particularly as pertains to vascular or other invasion. However, CT scanning
may not predict surgical resection potential, as this decision may be made in surgery, with gross
inspection of the lesion. Calcification also suggests malignancy but may also be found as an
age-related dystrophic change in both dogs and cats. Three-view thoracic radiographs must be
performed in these patients to screen for metastatic disease.
Ultrasonography is the primary instrument (mainly for diagnostic value, minimal cost, and
general availability) for assessment of tumor size, aggressive non-capsulated vs. capsulated
appearance, vascular invasion, and hepatic or other metastasis. NPO +/- low enema preparation
of the patient is ideal to enhance visibility around the ascending and descending colon. US
guided biopsy or FNA may be possible on the larger masses especially on the left side. However,
adjacent vascular structures can often prevent the feasibility of this procedure. Blood pressure
must be measured and hypertension corrected prior to any FNA or biopsy of the mass.
Controversy exists regarding the safety of US-guided FNA and particularly biopsy, as some
consider this a relatively contraindicated procedure. Complications include hemorrhage,
arrythmias, seeding of the needle tract, damage to adjacent organs and death.
Diagnosis of the Functional Adrenal Mass:
Cortisol-Secreting: Cortical adrenal tumors (adenoma, adenocarcinoma) are
responsible for 15-20% of patients with hyperadrenocorticism. Cortisol-secreting
tumours are usually unilateral (bilateral in 10-20%), may invade the aorta on the left or
the vena cava on the right, and metastasize to the liver and lungs most frequently.
History and clinical signs are typical for the suspected HAC patient. Work-up should
consist of a CBC, chemistry panel, and urinalysis. Urine culture is recommended as
many patients with HAC have occult urinary tract infections. UPC may be indicated.
Further specific testing for the presence of HAC may include a LDDST or an ACTH
stimulation test in addition to the abdominal ultrasound. Thoracic radiographs are
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recommended. A coagulation panel (PT and PTT) should be done to check for
hypocoagulability and a D-dimer can help suggest hypercoagulability. TEG is helpful if
available. Ultrasound usually reveals a small or atrophied contra lateral adrenal gland.
The atrophy is a result of suppression of pituitary ACTH secretion. 10-20% of cases have
bilateral disease and patients with concurrent pituitary-dependent hyperadrenocorticism
and an adrenal tumour have been reported.. Adenomas of the adrenal gland were
generally < 2 cm in diameter and carcinomas were of any size, often > 2 cm.
Calcification does not appear to be predictive for either adenoma or carcinoma.
Catecholamine-Producing: Pheochromocytoma is a tumor derived from the chromaffin
cells of the adrenal medulla that is relatively common in dogs but rare in cats. These
should be considered malignant until proven otherwise. Invasion/entrapment/compression
of the CVC is common. Mural invasion/luminal narrowing of the aorta, renal vessels,
adrenal vessels, and hepatic veins may also occur. Clinical signs associated with this
type of tumor are usually related to invasion of local structures, metastases, or secretion
of catecholamines. The most common clinical signs of excess catecholamines include
generalized weakness, episodic collapse, tachypnea, panting, tachycardia, cardiac
arrhythmias, and possibly neurological signs secondary to systemic hypertension.
Catecholamine release and hypertension tends to be episodic so failure to document
systemic hypertension does not rule out pheochromocytoma. Ultrasound: The contra
lateral adrenal gland is usually normal in size and shape with a catecholamine-producing
adrenal tumor. Pheochromocytomas uncommonly calcify. Specific hormonal tests
(urinary catecholamine concentrations or their metabolites) are not routinely done. Since
hypertension, tachycardia, and arrhythmias commonly occur during anesthesia induction
and during surgical manipulation of the tumor, dogs must receive phenoxybenzamine (a
non-competitive alpha-adrenergic antagonist) for 1-2 weeks prior to surgery. If
tachycardia persists, it may also be necessary to employ a beta-blocker such as atenolol
or propranolol. However, the beta-blockers can only be started AFTER alpha-adrenergic
blockade has already been initiated, to prevent unopposed alpha-adrenergic stimulation
and worsening hypertension.
Aldosterone-Secreting: (rare in dog and cat). Clinical signs (Conn’s Syndrome) are
related to excessive secretion of aldosterone which causes sodium retention and
potassium depletion. The resulting symptoms include lethargy, weakness, mild
hypernatremia, severe hypokalemia (usually < 3.0 mEq/L), and systemic hypertension.
Ultrasound usually reveals a normal contra lateral adrenal gland, but may show normal
adrenals (bilateral hyperplasia). Documenting increased plasma aldosterone
concentrations prior to and after ACTH administration is used to confirm the diagnosis. If
weakness and severe hypokalemia are present, plasma aldosterone concentrations can be
measured in addition to plasma cortisol concentrations during the ACTH stimulation test.
Surgery is usually the treatment of choice but medical management may consist of
potassium supplementation, anti-hypertensive therapy, and spironolactone (aldosterone
antagonist).
Progesterone-Secreting: Although a functional tumor arising from the zona reticularis of
the adrenal cortex could secrete excessive amounts of estrogen, progesterone or
testosterone, to date, only progesterone-secreting adrenocortical tumors in cats have been
documented. Clinical signs can include: diabetes mellitus and feline fragile skin
syndrome, which is characterized by progressively worsening dermal and epidermal
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atrophy, patchy endocrine alopecia, and easily torn skin. Ultrasound usually notes a
normal contra lateral adrenal gland. Diagnosis requires documenting an increased
plasma progesterone concentration with the adrenal panel from the University of
Tennessee panel.. The clinical features mimicked feline hyperadrenocorticism, which is
the primary differential diagnosis. Results of tests of the pituitary-adrenocortical axis are
normal to suppressed in cats with progesterone-secreting adrenal tumors.
Deoxycorticosterone (precursor of aldosterone)-Secreting: (rare) Clinical signs are
related to the mineralocorticoid activity and include weakness, marked hypokalemia, and
systemic hypertension. Tests: Increased plasma deoxycorticosterone and non detectable
plasma aldosterone concentrations were documented in the dog.
17-OH-progesterone (precursor of cortisol)-Secreting: (rare) Clinical signs are similar
to hyperadrenocorticism. Tests: Pre- and post-ACTH stimulation plasma 17-OHprogesterone concentrations will be increased.
To Cut or Not to Cut?
If endocrine testing has ruled out the presence of a functional cortical tumor, and
pheochromocytoma is confirmed by eliminating the other possibilities and aggressive
sonographic characteristics are present, the phenoxybenzamine should be initiated prior to
adrenalectomy. If a cortisol producing adrenal tumor has been documented then surgical
resection or medical therapy with trilostane or mitotane should be considered.Mitotane has direct
cytotoxic effects and has been shown both to decrease tumor size and to decrease metastatic
burden. However, it may be necessary to use high dosages. Trilostane may also be efficacious.
Earlier studies comparing trilostane vs mitotane yielded conflicting results. However, a recent
paper (JR Helm et al, 2011) compared survival times and factors that influence survival in dogs
with adrenal-dependent HAC treated with mitotane or trilostane. The overall median survival
time was 277 days. The MST for dogs without evidence of metastatic disease was 402 days; it
was 61 days for dogs with evidence of metastatic disease (statistically significant). The median
survival time for dogs treated with trilostane was 353 days and 102 days for mitotane. This
difference was not considered statistically significant in this study. The MST for mitotane in this
study differed from other studies that reported 320 days MST for mitotane. Either mitotane or
trilostane appear to be reasonable choices in medical management for cortisol-producing adrenal
tumours.
Indications for medical therapy include gross pulmonary metastatic disease evident
before surgery, an unresectable or incompletely respectable tumour, residual disease after
adrenalectomy, unacceptable anesthetic and surgical risk to the patient, and refusal of surgery by
the owner.
The biggest dilemma is whether to perform an adrenalectomy if hormonal tests for
hyperadrenocorticism and serum electrolyte concentrations are normal and clinical signs and
systemic hypertension suggestive of pheochromocytoma are not present.
Further non-invasive work-up for a potential pheochromocytoma may be possible in the
future. An abstract at ACVIM 2011 (EN-9) suggests that measurement of plasma free
metanephrines (catecholamine breakdown products) may show promise as a diagnostic test for
pheochromocytomas. A study from JVIM 2010 reported that urinary epinephrine,
norepinephine and metanephrine to creatinine ratios did not differ between dogs with
hyperadrenocorticism and pheochromacytomas. The urinary normetanephrine to creatinine ratio
was significantly higher in dogs with pheochromacytoma than with HAC, especially if the cutoff level used was 4 times the level for normal dogs.
An aggressive approach (i.e., adrenalectomy) is based on the assumption that the mass
is malignant until proven otherwise and should be removed before metastasis has occurred. In
theory, this approach would offer the best chance for long-term survival. However, the age of the
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patient, the size of the mass, the presence of concurrent diseases, the level of invasion into other
organs, and the probability that metastases already exist should weigh into the decision. Poor
surgical candidates generally include: dogs compromised from effects of hypercortisolemia,
older animals, those with concurrent disease, those in which invasion is aggressive and surgical
or post surgical complications are likely, those with very large masses which have likely already
metastasized, and those with documented potential metastatic disease. In addition,
adrenalectomy may not be indicated when the mass is small (< 3 cm diameter) and
nonfunctional, and the patient is healthy. Anderson et al. recently reported an approximate 45%
success rate of surgical resection in 102 cases of adrenal masses with positive prognosis
inversely proportionate to tumor size.
In cases of concurrent hepatic nodular changes identified by ultrasound, hepatic biopsy
assessment can be performed prior to surgery to rule out metastatic disease in cases of suspicious
lesions visualized by ultrasound. Often Cushings disease causes benign nodular hyperplasia of
the liver which should NOT be automatically interpreted as a sign of hepatic metastasis during
an ultrasound exam. Alternatively, suspicious lesions should be confirmed and biopsied at
surgery. Post operative complications include delayed wound healing due to excessive corticoid
circulation and wasting, hemorrhage, sepsis, and thromboembolism.
A recent paper examined pre-operative prognostic factors in the surgical treatment of
adrenal gland tumors in 41 dogs (J Am Vet Med Assoc 2008; 232; 77-84). Similar to other
studies (up to 51%), this study reported high perioperative complication rate (35%).
Intraoperative mortality rate was 4.8% and perioperative mortality rate was 22%. Like the
patients in other studies, if the patient survived to discharge from the hospital, however, he/she
had a long survival time. Other studies have found that removal of caval thrombi is not
associated with higher morbidity and mortality rates. In this study, pre-operative factors that
were associated with a shorter survival time included weakness or lethargy, thrombocytopenia,
increased BUN, increased PTT, increased AST and hypokalemia. Intra-operative hemorrhage
and/or the need for a concurrent nephrectomy were associated with shorter survival times. From
this perspective, pre-operative imaging with CT may help determine if nephrectomy is indicated.
Post-operative complications included adrenal gland insufficiency, acute renal failure,
pancreatitis, septic peritonitis, and suspected pulmonary thromboembolism. Post-operative
complications associated with a shorter survival included pancreatitis and acute renal failure.
Tumour type, completeness of surgical excision, and microscopic vascular invasion were NOT
significantly associated with survival time. Detection of gross lesions at surgery and histological
evidence of metastatic disease were not significantly associated with survival time. Many dogs
had gross lesions in other organs, but most did not prove metastatic on histopathology. Tumor
size and volume were not significantly associated with survival time.
References:
Diagnostic Approach to the Incidental Adrenal Mass, WSAVA 2002 Congress,
Richard W. Nelson, DVM, Diplomate ACVIM,School of Veterinary Medicine, University of California,Davis, CA,
USA\Management of Endocrine Neoplasia,
World Small Animal Veterinary Association World Congress Proceedings, 2001, Steven Withrow, United States.
ACVIM 2002-2010.
Ettinger’s Textbook of Veterinary Internal Medicine 2010.
Proceedings of the 2011 ACVIM Forum (Abstract EN-9)
JR Helm et al. A Comparison of Factors that Influence Survival in Dogs with Adrenal-Dependent
Hyperadrenocorticism Treated with Mitotane or Trilostane JVIM 2011; 25: 251-260.
S. Quante et al. Urinary catecholamine and metanephrine to creatinine ratios in dogs with hyperadrenocorticism or
pheochromocytoma, and in normal dogs. JVIM 2011; 24 (5): 1093-97.
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Johanna Frank DVM DVSc Diplomate ACVIM (Internal Medicine)
New Jersey Mobile
Eric Lindquist DMV (Italy), DABVP K9 & Feline Practice
Cert. IVUSS
Director NJ Mobile Associates, Founder SonoPath.com
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