Adrenal Adenoma

From: e-medicine

Workup
Laboratory Studies
Because AAs may be hormonally silent, biochemical screening is warranted.
Most frequently, cortisol produces subclinical Cushing syndrome.
This occurs when the AA autonomously secretes cortisol at levels high enough to suppress corticotropin but too low to produce Cushing stigmata.
Patients do not have increased rates of hypertension or diabetes mellitus, but they may have features of metabolic syndrome, including hypertension, dyslipidemia, and impaired glucose tolerance.
Patients may have reduced bone density and osteoporosis.
Patients are prone to adrenal insufficiency once the cortisol-secreting tumor is removed. This postoperative adrenal insufficiency is caused by corticotropin suppression and adrenal cortical atrophy of the contralateral adrenal gland (see image below and Image 3).
Because urinary free cortisol levels may be within the reference range, a 1-mg overnight dexamethasone suppression test is needed to diagnose subclinical Cushing syndrome.

The most important hormonally silent AA is pheochromocytoma.
They are present in approximately 1 in 1000 autopsies.
If the prevalence of AAs is 10-100 in 1000, then 1-10% of AIs are pheochromocytomas (see image below and Image 4).
Pheochromocytomas should be considered in all AA cases because they are more common than previously thought, the diagnosis is often overlooked, and a failure to recognize them may lead to patient death.
A 24-hour urine catecholamines and metabolites evaluation remains a good test for the diagnosis of pheochromocytoma, but it is not as sensitive as free metanephrine testing, which is available in laboratories around the United States.
A 1981 series by Sutton et al reported that less than one quarter of pheochromocytomas found postmortem were diagnosed antemortem.9 Retrospective analysis found that more than 90% of these patients had characteristic symptoms suggesting the unrecognized tumors were not silent. Many of the patients died of causes possibly related to the pheochromocytoma. Approximately 29% died unexpectedly during surgery, 27% died from cardiovascular causes, and 17% died from cerebrovascular causes.
Assume all AAs have a pheochromocytoma until proven otherwise, especially when paroxysmal hyperadrenergic symptoms are present.
Exclude the presence of pheochromocytoma prior to performing a fine-needle aspiration (FNA) biopsy on the AM.
Primary hyperaldosteronism is a less compelling, but nevertheless important, diagnosis.
Surgical intervention can cure the hypertension and hypokalemia.
The test of choice is an upright plasma aldosterone–to–renin ratio. A plasma aldosterone concentration–to–plasma renin activity ratio greater than 30 and a plasma aldosterone concentration of greater than 0.5 nmol/L (18 ng/dL) are suggestive of primary aldosteronism.
Hyperaldosteronism is usually identified by suppressed upright plasma renin levels and concomitant elevated plasma aldosterone levels.
Other secreted hormones can include estrogens, androgens, and 17-hydroxyprogesterone.
They are associated with AAs, carcinomas, and hyperplasia.
They often manifest clinically and therefore do not require presumptive screening.
Imaging Studies
CT scanning is preferred because it is more cost-effective than MRI to delineate size, shape, and appearance. A smooth homogeneous lesion smaller than 4 cm with a low attenuation value (Hounsfield units) is usually benign. A larger inhomogeneous lesion with irregular borders and a higher attenuation score should be considered for malignancy.
MRI is as effective as CT scanning for distinguishing benign from malignant lesions and is superior for detecting pheochromocytomas. A benign adenoma has a T2-weighted intensity similar to liver tissue.
Plain radiography, tomography, and ultrasonography are less sensitive and are used less frequently since the advent of CT scanning and MRI.
Other scanning techniques include iodine I 131 metaiodobenzyl guanidine, for pheochromocytoma; iodine I 131-6-b-iodomethylnorcholesterol (NP-59 cholesterol), for adrenocortical lesions; and positron emission tomography; however, these test are not widely available and data on their clinical usefulness is insufficient.

The following are features of pheochromocytomas:
They vary in size, consistency, and margins.
They can be bilateral.
They are strongly enhanced with contrast.
They show high signal intensity on T2-weighted images, owing to their vascularity.

The following are features of adrenal carcinomas:
Adrenal carcinomas are often larger than 6 cm in diameter, with an irregular margin.
Adrenal carcinomas demonstrate a soft tissue inhomogeneous density on CT scans, which enhances with contrast.
Adrenal carcinomas are unilateral, sometimes with local invasion and lymphadenopathy and metastases.
Adrenal cortical carcinomas have an intermediate increased intensity on T2-weighted MRIs.
Myelolipomas show characteristic images of fat.
Hemorrhage shows characteristic images of blood.

The following are features of Bilateral AMs:
Bilateral AMs should always raise the possibility of hemorrhage, especially in patients with coagulopathies or those on anticoagulant therapy.
Clinical symptoms include flank pain, nausea and vomiting, fever, and hypotension.
Diagnosis can be made with a rapid corticotropin stimulation test demonstrating decreased cortisol reserve.
Bilateral AMs usually suggest certain systemic diseases that can produce adrenal insufficiency. They should be recognized early.
Fungal or tuberculosis infection may be present.
Granulomatous diseases (eg, histoplasmosis, tuberculosis) are characteristically homogeneous and may show calcifications.
Most metastatic disease to the adrenal gland is unilateral, but lymphoma may be bilateral and can cause adrenal insufficiency.
A 21-hydroxylase deficiency can produce unilateral AMs, but bilateral AMs are more common. To recognize this, measure the level of corticotropin-stimulated plasma 17-hydroxyprogesterone.
In a patient with primary hyperaldosteronism, bilateral AIs suggest bilateral adrenal hyperaldosteronism (idiopathic hyperaldosteronism). Confirm this by adrenal venous sampling to demonstrate bilateral plasma aldosterone secretion.
Long-standing, corticotropin-dependent Cushing syndrome may result in large AMs.
Another very rare cause of Cushing syndrome is adrenal-dependent macronodular hyperplasia associated with extremely large adrenal glands.
Procedures
Adrenal FNA helps identify metastatic, systemic, and hemorrhagic disease of the adrenal glands. It cannot distinguish between benign and malignant primary adrenal tumors.
It should be used only when AMs cannot be diagnosed clinically or hormonally.
Use CT scanning to guide a 23- or 25-gauge needle into the left or right adrenal gland.
If a metastatic lesion is found, initiate a search for the primary cancer.
If adrenal tissue is found, consider surgical removal.
Pheochromocytoma should always be excluded before performing FNA biopsy to avoid the potential for a hypertensive crisis.
In a study on the sensitivity of percutaneous adrenal biopsy in the detection of malignant adrenal neoplasms, Mazzaglia and Monchik concluded that such biopsies are not diagnostically useful in patients with isolated AIs.10 Reporting on 163 adrenal biopsies, including 30 performed on isolated AIs, the investigators found the negative predictive value of percutaneous biopsy to be too low for use in ruling out malignancy in isolated AIs. The results also indicated that biopsy is valuable for diagnosing metastatic carcinoma in cases of nonadrenal primary malignancy.
Histologic Findings
Findings are based on the AM cell type.

Treatment
Medical Care
Adrenal insufficiency
Adrenal insufficiency should be the first consideration, especially with bilateral AMs.
A corticotropin test with 60-minute cortisol levels helps rule out the diagnosis.
If found, suspect granulomatous disease, hemorrhage, or lymphoma.
A 21-hydroxylase deficiency can also be diagnosed with a 60-minute post-corticotropin plasma 17-hydroxyprogesterone level.
Hormonal excess
Use the 1-mg overnight dexamethasone suppression test, urinary free cortisol test, a urinary metanephrine–to–creatinine ratio, and a renin-to-aldosterone ratio.
If found, surgical removal is usually indicated.
Exceptions that do not warrant surgery include bilateral adrenal diseases such as corticotropin-dependent Cushing disease or bilateral hyperaldosteronism.
If no hormonal excess is found and the corticotropin test results were unremarkable, FNA helps distinguish between adrenal and metastatic disease.
Metastatic disease is managed according to the type of primary cancer.
Adrenal disease should be removed if the diameter is greater than 6 cm. Otherwise, follow up with repeat CT scans at periodic intervals.
Surgical Care
No randomized trials have compared laparotomy versus laparoscopic adrenalectomy; however, abdominal laparotomy is preferred for bilateral disease and pheochromocytoma.
Fiberoptic laparoscopy is used for visualization, biopsy, and removal.
A transthoracic approach is faster than fiberoptic laparoscopy but has a longer postoperative recovery period.
Other experimental approaches, including a laparoscopic robot and augmented-reality visualization of the surgical field, have been described.
Consultations
An endocrinologist should be consulted to review the results of endocrine testing.
Diet
No specific diet recommendations are necessary.
Activity
No activity restrictions are necessary.
Medication