An adrenal incidentaloma is an adrenal mass that is generally 1 cm or more in diameter that is found incidentally during abdominal imaging done for reasons other than suspicion for an adrenal mass3, 4. In a review of 25 studies looking at a total of 87,065 autopsies, adrenal adenomas were found at a rate of 6%, with a range of 1-25% among the studies3. In a study of 520 subjects undergoing CT of the chest for lung cancer screening, 4.4% were found to have adrenal masses5. The possibility of finding an adrenal mass with imaging increases with age. Reviews have shown that the probability of finding an adrenal lesion in a patient between the ages of 20-29 is approximately 0.2%, while it is almost 7% in patients above 70 years old3. In a review of 2,005 incidentally discovered adrenal masses, 82.5% were nonfunctioning benign lesions, 11.4% were functioning adenomas, and 7.2% were malignant lesions. Of the malignant lesions, 65.3% were adrenocortical carcinoma and 34.7% were metastasis6, 7. Of functional masses, 46.5% caused Cushing’s syndrome, 44.7% were pheochromocytoma, and 8.8% were aldosteronoma. Of nonfunctioning benign lesions, 61% were adenoma, 10% myelolipoma, 6% adrenal cyst, and 5.6% ganglioneuroma7.
The work up of an adrenal incidentaloma includes, first, biochemical evaluation to determine if the mass is functional and, second, imaging to assess whether the mass appears malignant or benign. Resection of functional adrenal lesions is usually recommended in medically fit patients who can tolerate surgery. Resection of suspicious or malignant appearing lesions, or indeterminate lesions larger than 4cm, is also recommended in medically fit patients. Resection of lesions metastatic to the adrenal gland(s) is occasionally recommended only for select patients in whom the adrenal lesion is the only site of disease.
A careful history and physical examination may reveal specific signs and symptoms suggestive of a functional tumor. However, an asymptomatic patient should still be considered for laboratory testing, as 5% of tumors will demonstrate subclinical function. Of note, pheochromocytomas must be assessed prior to invasive procedure or surgery, since untreated pheochromocytoma can lead to potentially lethal intraoperative hemodynamic instability. Biochemical evaluation of sex hormones is only rarely required, as discussed below.
Symptoms of Cushing’s syndrome can include weight gain, central obesity, rounded facies, dorsocervical fat pad, easy bruising, thin skin, poor wound healing, purple abdominal striae, acne, hirsutism, infertility, depression, irritability, and opportunistic infections. Signs may include hypertension, diabetes, impaired glucose tolerance, osteoporosis, osteopenia, hypokalemia, and leukocytosis with relative lymphopenia. Screening tests include a twenty-four hour urine cortisol test with values greater than three to four times normal limits being highly suggestive of autonomous cortisol secretion. Abnormal values less than three to four times normal are inconclusive. An overnight 1 mg dexamethasone suppression test is 95% sensitive for Cushing’s syndrome7. Serum cortisol levels greater than 5 mcg/dL are highly suggestive of autonomous cortisol secretion and serum cortisol levels <1.8 mcg/dl excludes Cushing’s syndrome. If cortisol levels are elevated, ACTH levels must then be obtained.
The possibility of pheochromocytoma must also be investigated. Symptoms usually occur in paroxysms and include tachycardia, palpitations, pallor, tremor, headache, and diaphoresis. Signs include hypertension, orthostatic hypotension, pallor, retinopathy, fever, and tremor. Screening should start with 24-hour urine fractionated catecholamines and urine total metanephrines or plasma fractionated metanephrines. If positive, plasma-free metanephrine and normetanephrine levels should be obtained because of their high sensitivity (97-100%) and high specificity (69-98%) when obtained together7. Patients should stop taking tricyclic antidepressants, amphetamines, and decongestants prior to testing because they can cause false positive results7.
Symptoms of primary hyperaldosteronism may include nocturia, polyuria, muscle cramps, and palpitations. Signs may include hypertension, hypernatremia, and hypokalemia. Tests should include supine and erect plasma renin activity (PRA) and plasma aldosterone concentration (PAC) that should be measured in the morning. Patients cannot be on spironolactone, eplerenone, or amiloride for this test as these medications may skew the results. A PAC:PRA ratio greater than or equal to 20 is a positive result. A PAC greater than 20 ng/dl and a ratio of greater than 30 is highly sensitive (90%) and specific (91%) for aldosteronoma8.
Other less common types of functional adrenal tumors include sex hormone secreting adrenocortical tumors and non-classic congenital adrenal hyperplasia.3 Routine screening for these diseases is not recommended and should be based on clinical manifestations. Symptoms of sex-hormone secreting tumors include hirsutism and virilization and these patients should be screened for excess androgens or estrogens if symptoms are present. Symptoms of hyperandrogenism may be seen in non-classic congenital adrenal hyperplasia, and a cosyntropin-stimulation test with measurement of cortisol precursors should be done in these cases3.
In addition to testing the mass for function, the mass must be evaluated for the possibility of malignancy including metastatic disease or adrenocortical carcinoma. Metastatic disease is frequently bilateral to the adrenal glands and usually the primary tumor has previously been identified3. The prevalence of adrenocortical carcinomas amongst adrenal incidentalomas ranges from 1.2 to 12% among different studies4. Patients with adrenocortical carcinoma are usually 40-50 years old and have a poor prognosis. The two most important predictive factors of adrenocortical carcinoma are the size of the lesion and appearance on imaging3. Adrenocortical carcinomas are usually large (greater than 4 cm in diameter), irregular with unclear margins, heterogeneous with mixed densities, usually solitary and unilateral, vascular on contrast enhanced CT, and have delayed washout with contrast. Necrosis, hemorrhage, and calcifications are commonly seen in these lesions and are often observed to grow rapidly (greater than 2 cm per year) 3. MRI may be useful in patients with a contrast allergy. For a detailed discussion on adrenal imaging, one is referred to a recent review11 and the American College of Radiology appropriateness criteria12.
The mass in our patient had many of the imaging characteristics of adrenocortical carcinoma including size more than 4 cm, heterogeneous appearance, the enhancement pattern, and presence of calcifications. Almost half of adrenocortical carcinomas are functional with hypercortisolism most commonly seen7. The mass in our patient was non-functional.
Of benign adrenal masses, adrenal hemangiomas are relatively uncommon. While there are limited data, adrenal hemangiomas has been found in a 2:1 female to male ratio, are usually unilateral, and have been found most often in the 6th and 7th decade of life2. These lesions typically are larger than 10 cm1, ranging from 2 to 25 cm in diameter. One case report published in 2015 reported a 42 cm adrenal hemangioma1. While typically asymptomatic, patients with adrenal hemangiomas may present with abdominal pain due to mass effect or hypovolemic shock due to hemorrhage from the mass.
On histopathological evaluation, most adrenal hemangiomas are cavernous with enlarged masses of blood-filled sinusoidal channels that have eroded and displaced normal tissues2. They are found in the adrenal cortex and have multiple dilated vascular channels lined by a single layer of vascular endothelium surrounded by a wall of collagen9. They are thought to be congenital masses that enlarge over time because of vascular ectasia9. Less commonly, adrenal hemangiomas are capillary and include a small tuft of sub-mucosal capillaries arranged in radiating loops or lobules. In both subtypes, there is variable hemorrhage, necrosis, degeneration, calcification, and fibrosis throughout the mass2, 9.
The main findings of adrenal cavernous hemangioma on CT are a hypodense, heterogeneous lesion with calcifications. Calcifications that appear speckled throughout the mass have also been seen and are phleboliths in the dilated vascular spaces of the lesion10. CT with contrast shows a characteristic peripheral irregular enhancement pattern with progression from the periphery towards the center1, as seen in our patient. While this centripetal enhancement pattern is felt by some to be specific for adrenal hemangiomas1, this radiographic characteristic can also be seen in adrenocortical carcinoma and other adrenal lesions such as hemorrhage, tuberculosis, and neuroblastoma9. As such, adrenal hemangiomas can be difficult to distinguish from adrenocortical carcinomas on imaging, as noted in our patient.
Adrenalectomy is recommended if a mass is functional or has malignant potential. If functional studies are all normal, and the mass is small (less than 4cm) and does not appear malignant on imaging, , the mass can be observed with repeat imaging for the first 6-12 months and then annual screening for 4 years. The typically recommended size criteria suggestive of malignant potential is a mass that is 4 cm or greater in diameter or that enlarges by 1 cm or more during observation3. In our case, the size and atypical characteristics on imaging lead to resection of the mass.
The surgical approach depends on the characteristics of the lesion. Most incidentalomas can be resected laparoscopically, however an open surgical approach should be used if there is malignant potential, or if the mass is large (greater than 6 to 10cm) and likely difficult to remove7.