CHAPTER 17 Adrenal Glands
Histologically, each adrenal gland is composed of two different types of tissue with different functions: the peripheral cortex and the central medulla. The adrenal cortex is derived embryologically from coelomic mesoderm that develops into three stratified zones of cortical tissue (zona glomerulosa, zona fasciculata, and zona reticularis) that are vital to fluid-electrolyte homeostasis. The adrenal medulla is derived from neural crest ectoderm and produces a variety of catecholamines that regulate hemodynamics and respond to stress. Table 17-1 provides a summary of the regional production of hormones.
The normal adrenal glands reside in a superior and anteromedial recess of the perirenal space, and adhere to the innermost layer of the perirenal fascia at this location. The right adrenal gland can usually be identified in a location superior to the right kidney with some tissue protruding between the posterior margin of the inferior vena cava and the medial portion of the right diaphragmatic crus. Often, the entire right adrenal gland is superior to the kidney, although a small portion may extend inferiorly anterior to the kidney. The short, right adrenal vein can be identified in most cases (Fig. 17-1). The adrenal vein is occasionally a useful landmark for identifying the adrenal gland when a mass distorts structures in the suprarenal region.
Figure 17-1 Axial image from contrast-enhanced computed tomographic examination demonstrates the right adrenal vein as it bridges the body of the adrenal gland and posterior wall of the inferior vena cava.
Pearl: Identification of the right adrenal vein can be useful in attempting to determine whether a large mass in the right upper quadrant arises from the adrenal gland or the adjacent kidney or liver.
The left adrenal gland usually can be identified anterior and medial to the superior pole of the left kidney, and just lateral to the medial aspect of the left diaphragmatic crus. Vascular structures neighboring the left adrenal gland can sometimes cause confusion. For example, tortuous segments of the splenic artery and vein can course vertically adjacent to the left adrenal gland, simulating a nodule. For this reason, it is important to trace each adjacent structure before diagnosing an adrenal mass.
The cross-sectional appearance of the left adrenal gland often simulates an inverted “Y” shape, whereas the right more often simulates an inverted “V” shape. Because laparoscopic partial adrenalectomy can now be performed for functioning adenomas, it is sometimes helpful to provide a precise description for the location of small adrenal nodules. The anterior limb is usually described as the body of the gland. The posterior limbs are usually described as medial or lateral.
Note that the normal adrenal medulla has sufficient volume to result in fullness in the central part of the gland. A mildly rounded appearance of the adrenal gland at its center where the three limbs join is normal and should not be mistaken for a nodule.
For some of us, the complexities of endocrinology exemplify the part of medicine we deliberately left behind when we chose to pursue radiology. Fear not! Only a rudimentary understanding of several laboratory values will be discussed to facilitate the radiologist as an intelligent investigator in imaging adrenal disease. We will divide the laboratory tests into those that assess cortical function and those that assess medullary function.
As mentioned previously, the adrenal cortex produces three main categories of substances: (1) aldosterone that regulates sodium absorption in the kidney and other organs, thus affecting electrolyte balance; (2) cortisol that regulates carbohydrate, protein, lipid, and nucleic acid metabolism; and (3) androgens (dehydroepiandrosterone [DHEA], dehydroepiandrosterone sulfate [DHEAS], and androstenedione) that play a role in the development of secondary sex characteristics in male individuals and virilization in female individuals (if excessive).
In addition to regulating fluid–electrolyte balance by promoting sodium retention, aldosterone also promotes renal potassium excretion. Therefore, hyperaldosteronism is suspected in the presence of hypertension, hypernatremia, and hypokalemia.
Cortisol production in the adrenal cortex is regulated through a feedback mechanism to prevent overproduction. A dexamethasone suppression test introduces exogenous steroid that should suppress the normal adrenal cortex. Failure of suppression indicates unregulated cortisol production (Cushing syndrome).
17-Ketosteroids are found in the urine mainly as a breakdown product of androgens with a minor component coming from the breakdown of glucocorticoids. Increased levels of 17-ketosteroids in the urine usually indicate an adrenal causative agent for virilization in female individuals (carcinoma, hyperplasia) rather than an ovarian causative factor (arrhenoblastoma, polycystic ovarian syndrome).
A tumor of the chromaffin cells in the sympathetic nervous system is called pheochromocytoma if it arises within the adrenal medulla and paraganglioma when it arises in an extraadrenal location. Even when benign, these tumors can be lethal through the episodic release of catecholamines in the settings of stress, induction of anesthesia, voiding, pregnancy, biopsy, or manipulation. The rapid release of large amounts of catecholamines can result in headaches, palpitations, nausea, chest or abdominal pain, or hypertensive crisis.
The episodic nature of catecholamine release made the laboratory diagnosis of pheochromocytoma problematic in the past. Measurable levels of epinephrine and norepinephrine remain in the bloodstream for only a limited time; therefore, serum analysis is often unfruitful unless the sample is obtained immediately after or during a crisis. Because epinephrine and norepinephrine and their breakdown product vanillylmandelic acid (VMA) and metanephrine persist for a longer time in urine, urine assays have become the preferred method of diagnosis and are reported to have an accuracy rate as high as 95%. If immediate blood samples are available, assays may be able to determine whether epinephrine or norepinephrine is the predominant catecholamine. This can be useful in localizing tumors because the dominant catecholamine produced by the adrenal medulla is epinephrine, whereas extraadrenal paragangliomas produce mainly norepinephrine. Both epinephrine and norepinephrine are metabolized into VMA.
18F-FDG is taken up in greater quantity by cells with more rapid metabolism (including cancer cells)
CT, Computed tomography; 18F-FDG, F-18 fluorodeoxyglucose; MIBG, metaiodobenzylguanidine I123; MRI, magnetic resonance imaging; NCCT, noncontrast-enhanced computed tomography; PET, positron emission tomography.
Figure 17-3 Using positron emission tomography (PET) to characterize a small adrenal mass. A, Axial image from unenhanced computed tomography in a woman with known metastatic breast cancer demonstrates a small, soft-tissue attenuation mass in the left adrenal gland. B, The same image fused with fluoro-2-deoxy-D-glucose (FDG) PET image demonstrates increased uptake within the lesion (SUV = 3.6) compared with the background activity in the liver (SUV = 2.5, not shown). SUV, Standardized uptake value.
(Courtesy Kevin Banks, M.D.)
A number of normal and abnormal structures can mimic an adrenal mass. Adrenal mimics are much more common on the left side because of potential collateral venous pathways around the spleen and proximity of the left adrenal gland to the stomach and pancreas. Having a high index of suspicion is helpful in identifying subtle signs, such as traces of air in a gastric diverticulum, enhancement similar to nearby splenic tissue, or contiguity with adjacent vascular structures. Table 17-3 lists the most common mimics of adrenal masses.
|Plane-dependent pseudolesion on computed tomography (Fig. 17-5)|
|Splenic varices (Fig. 17-6)|
|Tortuous splenic artery|
|Accessory spleen (Fig. 17-7)|
• Uptake on technetium-99m-labeled, heat-damaged, red blood cell study or liver-spleen scan with single-photon emission computed tomography
|Tumors of the celiac ganglion (ganglioneuroma)|
|Tumor of adjacent organ (e.g., kidney, stomach) or perirenal space (e.g., liposarcoma)|
Figure 17-5 Plane-dependent pseudomass of the left adrenal gland. A, Axial image from a contrast-enhanced computed tomographic scan demonstrates a vague masslike appearance of the lateral limb caused by volume averaging (outlined by arrows). B, A coronal reformation demonstrates a horizontal configuration of the lateral limb with no mass.
Figure 17-6 Splenorenal varix as adrenal pseudomass. A, Axial unenhanced computed tomographic image demonstrates an apparent mass in the body of the left adrenal gland. B, On an axial image in the portal phase of enhancement, the lesion enhances uniformly compared with other portal structures and was found to be continuous with the splenic vein.
Figure 17-7 Axial image from a contrast-enhanced computed tomographic examination demonstrates bilateral adrenal pseudomass lesions. A patient with portal hypertension was referred for biopsy of left adrenal lesion. Notice the thin fat plane between the accessory spleen and left adrenal gland. Large varices cause an unusual pseudomass on the right side.
Associated imaging, physical examination, and laboratory findings are often essential to definitive characterization of an adrenal lesion. An adrenal mass in a patient with hypertension is likely to be an adenoma when associated with hypernatremia (Conn syndrome) or hirsutism and obesity (Cushing syndrome), but is more likely to be a pheochromocytoma if there is a history of episodic flushing. Each of these clinical syndromes is described in the section “Hyperfunctioning Lesions of the Adrenal Gland.”
A known history of cancer increases the likelihood that a given adrenal mass is metastatic disease. More specific patterns of multiorgan involvement suggest syndrome-associated adrenal neoplasms, such as pheochromocytoma associated with neurofibromatosis, multiple endocrine neoplasia or von Hippel–Lindau syndrome (Fig. 17-8). A retroperitoneal mass in a young girl with hypertension and associated masses in the lung (pulmonary chondroma) or stomach (gastrointestinal stromal tumor) is suspicious for an extraadrenal paraganglioma in Carney’s triad.
Figure 17-8 Axial image from a contrast-enhanced computed tomographic examination demonstrates bilateral adrenal masses, as well as multiple masses in the pancreas and liver. The adrenal masses proved to be pheochromocytomas (metastatic to the liver), and the pancreatic masses islet cell tumors. This constellation of findings contributed to the ultimate diagnosis of von Hippel–Lindau disease.
The size of an adrenal mass is a relatively strong discriminator between benign and malignant lesions. Most adrenal adenomas are small, averaging just larger than 2 cm in diameter in most series. At autopsy, only 2% of adrenal adenomas are larger than 4 cm and 0.03% are larger than 6 cm. Metastases, adrenal cortical carcinomas, and pheochromocytomas are often large at time of presentation (Fig. 17-9 and 17-10). Ninety-two percent of adrenal cortical carcinomas are larger than 6 cm at time of diagnosis. Thus, a small adrenal mass (<3 cm) with no suspicious imaging features in a patient without known risk for metastases can be followed with serial imaging unless an additional study (noncontrast computed tomography (CT), washout CT, or magnetic resonance imaging [MRI]) can characterize the mass definitively. A mass larger than 5 cm is suspicious for malignancy until proved otherwise.
Figure 17-9 Axial image from a contrast-enhanced computed tomographic examination demonstrates a large right adrenal mass, partially displacing the inferior vena cava (IVC) anteriorly. This was surgically proved to be adrenal carcinoma.
Figure 17-10 Axial computed tomographic image of abdomen demonstrates a large right adrenal mass invading the inferior vena cava (IVC) in a patient with metastatic lung cancer. Caval extension is more common on the right side because of the short length of the right adrenal vein.
As a rule of thumb, an adrenal limb thicker than 10 mm is considered to be enlarged. Unfortunately, adrenal shape is only occasionally helpful in characterizing adrenal gland enlargement. Diffuse bilateral enlargement of the adrenal glands usually indicates adrenal hyperplasia and can be either smooth or have a nodular contour (Fig. 17-11). Adrenal hyperplasia is associated with clinical findings of Conn or Cushing syndrome in adults and children, as well as virilization in infants. Uncommonly, adrenal metastases can cause diffuse enlargement of the gland (Fig. 17-12), although metastatic enlargement is usually less symmetric than that seen with hyperplasia.
The number of adrenal masses is a weak discriminator between benign and malignant lesions. Adrenal adenomas, carcinomas, metastases, lymphoma, and pheochromocytomas can all present as solitary or multiple adrenal masses. Nodular hyperplasia is easily mistaken for multiple metastatic nodules in a patient at risk for metastatic disease.