With the widespread use of CT and MRI scanning, incidental findings in non-target organs are common. Incidental adrenal masses (so-called adrenal incidentalomas) are defined as masses in the adrenal gland that are >10 mm in size. They are amongst the most common incidental findings with the incidence ranging from 4%-10% of all abdominal/pelvic scans depending on the age and sex of the patient. The challenge to the clinician is to determine which of these findings are of clinical significance and warrant further work-up.
II. Diagnostic Approach
A. What is the differential diagnosis for this problem?
Once found, the differential diagnosis for an adrenal mass is surprisingly broad. The principal considerations are as follows:
Non-secretory adrenal adenoma: benign growth of the adrenal gland that is not hypersecretory. This is the most common type and constitutes up to 80% of all incidentalomas in some studies.
Functional tumors of the adrenal gland that come in principally four varieties:
Cortisol-secreting adenoma causing subclinical or overt Cushing’s syndrome. These tumors arise from the zona fasciculata of the adrenal cortex.
Aldosteronoma causing mineralocorticoid excess and Conn’s syndrome. These tumors arise from the zona glomerulosa of the adrenal cortex.
Pheochromocytoma: functional tumor of the chromaffin cells of the adrenal medulla that causes a characteristic syndrome of headache, palpitations and paroxysmal hypertension.
Rarely tumors of the zona reticulata may arise that cause hypersecretion of sex hormones.
Adrenocortical carcinoma: Approximately 5% of incidentalomas. These may arise from any subtype and may be hypersecretory.
Congenital adrenal hyperplasia: is often bilateral.
Metastatic disease: This compromises 2.5% of incidentalomas. The may be bilateral in some instances.
Other less common non-functional tumors such as: cysts, pseudocysts with hemorrhage, myelolipoma, neuroblastoma, ganglioneuroma, infiltrative disease such as amyloid, and granulomas.
B. Describe a diagnostic approach/method to the patient with this problem
The evaluation of an adrenal incidentaloma focuses on two principal questions:
Is it functional? This is determined on the basis of careful history, examination and laboratory analysis looking for signs of adrenal hormone excess. Most functional tumors will need to be surgically removed to avoid sequelae of long-term adrenal hormone excess.
Is it malignant? This is most often determined on the basis of tumor size and imaging characteristics. For primary adrenal tumors that are malignant, surgical excision is appropriate. For metastatic disease found in the adrenal gland, treatment needs to be considered in the context of the patient’s overall care.
The answers to the above questions guide management as will be described below.
1. Historical information important in the diagnosis of this problem.
In attempting to answer the question of whether the tumor is functional, history should focus on the following:
Signs of cortisol excess: Does the patient have a history of hypertension? Weight gain? Diabetes? Infertility? Patients with cortisol excess may also present with easy bruising, poor wound healing, weakness, new acne or excessive facial hair growth. Note, often cortisol-secreting adenomas are subclinical.
Signs of aldosterone excess: Does the patient have hypertension? Hypokalemia? Hypernatremia? Metabolic Alkalosis? Note, these laboratory findings are not sensitive and the majority of patients with primary hyperaldosteronism will have normal potassium.
Signs of pheochromocytoma: Patients should be asked about headache, palpitations, panic attacks, orthostasis, tremulousness, flushing or pallor, and constipation.
All patients should have a careful family history inquiring about a history of adrenal tumors, or other cancer syndromes.
Those with malignant tumors or metastatic disease may experience night sweats, anorexia, weight loss, and pain.
2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.
First question: Are there stigmata of glucocorticoid excess? This would include the characteristic moon facies, buffalo hump, abdominal obesity, paper-thin skin, and abdominal striae. Patients may also have evidence of hypertension.
Second question: Are there stigmata of pheochromocytoma? Evidence of hypertension by displaced point of maximal impulse, pallor, orthostatic hypotension.
Third question: Is there evidence of widespread malignancy? Enlarged lymph nodes, palpable masses.
3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.
Initial laboratory testing should focus on establishing whether there is cortisol excess, hyperaldosteronism, or abundant catecholamine production. The decision about whether to pursue this testing in the inpatient setting should be undertaken based upon the specific clinical circumstances and the specific test. In some instances, these tests may be accomplished more easily in the hospitalized patient, but in others the required preparation and typical lack of clinical urgency allows that they be obtained in the outpatient setting after discharge.
Patients should have an overnight dexamethasone suppression test (1mg) to assess for inadequate suppression.
In patients with hypertension and/or hypokalemia, morning measurement of plasma aldosterone and renin should be completed. This is often done as an outpatient as many blood pressure medications must be held for 4-6 weeks prior to testing as to not interfere with test results.
Patients should have urinary 24-hour metanephrines and catecholamines measured to assess for excess levels.
With regards to radiographic studies:
CT and MRI are equally effective in distinguishing between malignant and benign masses. There are many characteristics of the mass that can help with this determination (see below).
Ultrasound is insensitive for detecting masses < 3 cm. It is unable to differentiate between malignant and benign lesions. In patients with known cancer and evidence of an adrenal mass, positron emission tomography (PET) imaging can be considered to evaluate for metastasis as the possible cause.
In patients with concern for pheochromocytoma, occasionally a metaiodobenzylguanidine (MIBG) nuclear medicine scan is utilized to localize any extra-adrenal tumor, but this is not part of the routine work-up for an adrenal adenoma.
C. Criteria for Diagnosing Each Diagnosis in the Method Above.
A morning serum cortisol of greater than 5mcg/dL suggests cortisol excess and the patient should undergo confirmatory testing as outlined in the chapter on adrenal adenoma.
Evidence of abnormal metanephrines or catecholamines suggests pheochromocytoma and the patient should undergo work-up as outlined in the chapter on pheochromocytoma.
A plasma renin activity ratio of greater than or equal to 20 and a plasma aldosterone concentration of greater than or equal to 15 ng/dL suggest hyperaldosteronism and the patient should undergo confirmatory testing as outlined in the chapter on adrenal adenoma and Conn’s syndrome.
Clues on imaging
Adrenocortical adenomas tend to be small (usually less than 4 cm), with smooth edges and are homogeneous on CT. They are isotense on MRI and grow slowly. There is a fast washout of CT dye on delayed imaging.
Pheochromocytomas are usually large, with smooth edges, and are heterogeneous on CT. They are usually vascular appearing (hyperintense on MRI), may have cysts or necrosis, and grow slowly. Currently investigations are underway to determine if imaging features alone, without biochemical testing, might be sufficient to exclude the presence of a pheochromocytoma.
Adrenocortical carcinomas are heterogeneous appearing, large (greater than 4 cm), with irregular borders. They often have a density of >10 Hounsfield units on un-enhanced CT and a delayed washout of CT dye. They are typically vascular appearing (hyperintense on MRI), and may have necrosis. They are usually fast growing (greater than 2 cm per year).
Metastases are quite variable in appearance but are typically bilateral. They are often irregular appearing, heterogeneous and vascular appearing (hyperintense on MRI).
D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.
III. Management while the Diagnostic Process is Proceeding
A. Management of adrenal mass.
Management of hypertension if urgent is appropriate. If there is concern the mass may be a pheochromocytoma, it is prudent to use alpha-blockers before initiation of any beta blockers. Beta blockers should not be given prior to alpha blockade because blocking peripheral beta adrenergic recprots with unopposed stimulation of alpha receptors will lead increased blood pressure.
If a patient has uncontrolled blood sugars as a result of untreated or undiagnosed glucocorticoid excess, then initiation of oral hypoglycemic agents or insulin is appropriate.
The diagnostic work-up of an asymptomatic mass doesn’t necessarily warrant an inpatient stay and can be deferred to outpatient primary care physician and endocrinology follow-up with the appropriate communication and documentation. For symptomatic patients, the appropriate timing of work-up can be determined on a case-by-case basis.
B. Common Pitfalls and Side-Effects of Management of this Clinical Problem
Major pitfalls can occur in the failure to hand off and follow-up a documented mass seen incidentally on inpatient imaging. Frontline providers should determine if a patient needs immediate diagnosis if suggestive of cancer, and/or management of complications from hormonal excess. If not, appropriate communication with the patient regarding the need to follow-up as an outpatient should occur and be documented routinely. In addition, the inpatient providers should communicate with the outpatient primary care physician to ensure appropriate steps are taken for diagnosis.
IV. What's the evidence?
Kuzu, I, Zuhur, SS, Ozel, A, Ozturk, FY, Altuntas, Y. “Is Biochemical Assessment of Pheochromocytooma Necessary in Adrenal Incidentalomas with Magnetic Resonance Imaging Features Non-Suggestive of Pheochromocytoma”. Endocr Pract. 2015.
Nieman, KL. “Approach to the patient with an adrenal incidentaloma”. J Clin Endocrinol Metab. vol. 95. 2010. pp. 4106-4113.
Ng, VWS, Ma, RCW, So, WY, Choi, KC, Kong, A, Cockram, CS, Chow, CC. “Evaluation of Functional and Malignant Adrenal Incidentalomas”. . vol. 170. 2010. pp. 2017-2020.
Terzolo, M, Stigliano, A, Chiodini, I. “AME position statement on adrenal incidentaloma”. Eur J Endocrinol. vol. 164. 2011. pp. 851
Young, WF. “The Incidentally Discovered Adrenal Mass”. . vol. 356. 2007. pp. 601-610.
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- I. Problem/Condition
- II. Diagnostic Approach
- A. What is the differential diagnosis for this problem?
- B. Describe a diagnostic approach/method to the patient with this problem
- 1. Historical information important in the diagnosis of this problem.
- 2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.
- 3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.
- C. Criteria for Diagnosing Each Diagnosis in the Method Above.
- D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.
- III. Management while the Diagnostic Process is Proceeding
- A. Management of adrenal mass.
- B. Common Pitfalls and Side-Effects of Management of this Clinical Problem