Материал: Advanced Imaging of the Abdomen - Jovitas Skucas

Cushing’s disease. These glands are most often smooth in outline, with only a minority containing nodules. The less common nodular appearance mimics an adrenal adenoma, especially if hyperplasia is unilateral.

Primary Adrenal Causes

Primary adrenal causes of Cushing’s syndrome, or ACTH-independent causes, are less common and include adenoma, carcinoma, and primary adrenal hyperplasia. A rare variant encountered in pediatrics and young adults is primary pigmented nodular adrenocortical disease,which is due to hypersecretion of cortisol by multiple intraadrenal pigmented or “black” cortical adenomas.

About two-thirds of patients with primary Cushing’s syndrome have adenomas and onethird carcinomas. Rarely, adenomas develop bilaterally. Even an adrenocortical carcinoma in one gland and a contralateral adenoma have been described (25); CT simply showed bilateral adrenal tumors.

Primary adrenal hyperplasia is uncommon. It tends to be bilateral, with the adrenal glands having a somewhat nodular appearance. One patient developed unilateral nodular hyperplasia and an atrophic contralateral gland (26).

The 5-year survival rate for those with these carcinomas is about 30%.

Imaging

In a patient with hypercortisolism, a CT or MR finding of an enlarged unilateral adrenal gland is suggestive of an adenoma. A symptomatic adenoma generally is round or oval and several centimeters in diameter. Calcifications are uncommon. An adenoma is homogeneous and of soft-tissue–to-water density. Some of the less dense adenomas mimic a cyst, but their functioning status cannot be predicted from their attenuation values. The contralateral gland tends to be atrophic secondary to ACTH suppression by the hyperfunctioning adenoma. They exhibit little contrast enhancement.

Functioning adenomas have a similar MR appearance to that of nonfunctioning adenomas (discussed previously), although some functioning adenomas contain little lipid and thus

ADVANCED IMAGING OF THE ABDOMEN

do not lose signal intensity on opposed-phase chemical shift images (an exception is with aldosterone-producing tissue, discussed below; see Aldosteronism).

Computed tomography in 11 patients with primary adrenal Cushing’s syndrome and later proven primary adrenal hyperplasia revealed massively enlarged, multinodular adrenal glands (27); these glands were hypointense to liver on T1and hyperintense on T2-weighted MR images.

Magnetic resonance imaging is at least equal to CT and superior to US in detecting hyperfunctioning adrenocortical tumors in patients with Cushing’s syndrome; these tumors are hyperintense relative to liver on T2-weighted sequences, thus differing from most nonfunctioning adrenal adenomas, which tend to be hypoto isointense.

Selenium-75-methylnorcholesterol and I- 131–NP-59 scintigraphy detect endocrine functioning adrenal tumors. A rough relationship exists between radiotracer uptake and the degree of functional autonomy and I-131– NP-59 scintigraphy is both a functional and a localization test in Cushing’s syndrome. It is an adjunct to CT and MRI. This test has almost 100% specificity and sensitivity in detecting these tumors. Cortical adenomas have increased-to-normal uptake and malignant tumors a decreased-to-absent radiotracer uptake. Symmetric visualization or mild asymmetry of the adrenals in a setting of hypercortisolism almost always represents adrenal hyperplasia. More marked asymmetry suggests an adenoma. Unilateral adrenal gland visualization is typical for an adenoma; the adenomaproduced cortisol decreases pituitary ACTH production, which in turn shuts off function in a normally functioning contralateral adrenal gland. Cysts likewise have no uptake. Prior surgery also results in asymmetric uptake. Scintigraphy allows the localization of any residual postoperative adrenal tissue.

Aldosteronism

Clinical

Primary aldosteronism (Conn’s syndrome) is secondary to either an aldosterone-secreting neoplasm or adrenal hyperplasia. Over half of

ADRENALS

primary aldosteronism is due to a functioning adrenocorticoid adenoma (aldosteronoma). Hyperplasia, usually bilateral, accounts for most of the rest, with a carcinoma being rare. Bilateral adenomas have been reported. Some patients with Conn’s syndrome have grossly normal-appearing glands. A pheochromocytoma and primary hyperaldosteronism have occurred simultaneously; whether this is a coincidence or an unknown interreaction is conjecture.

The mineralocorticoid aldosterone is involved in blood volume and serum potassium homeostasis, which in turn regulate aldosterone secretion by the zona glomerulosa in the adrenal cortex. Excessive secretion leads to hypertension, hypokalemia, and suppression of plasma renin activity, a condition also known as mineralocorticoid hypertension (28). This is not a simple condition; although in most patients the two stimuli for aldosterone production (potassium and angiotensin II) tend to be low, some patients have normal serum potassium levels. Familial hyperaldosteronism is described. A curious sideshow is pseudohypermineralocorticism, caused by an excess of mineralotropics other than aldosterone.

Although mineralocorticoid hypertension is not common, its significance lies in its being a potentially correctable cause of high blood pressure. One should keep in mind that aldosteronism also develops in primary renovascular hypertension but the latter entity is associated with high serum renin levels while in primary aldosteronism the renin levels are low.

Hypoaldosteronism is rare. It appears to be due to inadequate stimulation of aldosterone secretion or a defect in the adrenal synthesis of aldosterone. An unusual cause of secondary hypoaldosteronism (called pseudohypoaldosteronism by some) is seen in some infants with urinary tract infection, with or without urinary tract obstruction. Clinically, hypoaldosteronism results in hypotension and hyperkalemia. Imaging has no role in its diagnosis.

Imaging

importance. The adrenal glands are significantly larger in patients with bilateral adrenal hyperplasia than in those with an aldosteronoma. One study achieved 100% sensitivity when a CT mean limb width of >3mm was used to diagnose bilateral adrenal hyperplasia, and 100% specificity when limb width was 5mm or greater (29). Unless imaging identifies a tumor, such differentiation is generally sought by bilateral adrenal venous sampling.

Aldosteronomas tend to be small; discrete nodules are difficult to visualize. Thus among 18 aldosterone-producing adrenal adenomas, 89% were detected with CT but only 28% with US (30). Adrenal hyperplasia in Conn’s syndrome ranges from diffuse and bilateral to nodular (Fig. 16.2). Thus one or more nodule may represent either an adenoma or nodular hyperplasia. Complicating this picture is the presence of the occasional unrelated incidental adrenal tumor.

Similar to Cushing adenomas, aldosteronomas contain varying amounts of lipid. As a result, some have CT attenuation values close to that of water and their CT appearance can mimic a cyst.

Calcifications develop only in an occasional benign aldosteronoma.

A distinction between unilateral aldosteronomas, which are treated surgically, and bilateral hyperplasia, treated medically, is of obvious

Figure 16.2. Conn’s syndrome. Computed tomography (CT) reveals bilateral adrenal hyperplasia. (Courtesy of Algidas Basevicius, M.D., Kaunas Medical University, Kaunas, Lithuania.)

In 20 patients with primary hyperaldosteronism, 50% had aldosterone-producing adenomas and 50% bilateral adrenal hyperplasia (31); MRI detected adenomas with a sensitivity of 70% and specificity of 100%, with adenomas being isoto hypointense relative to liver on T1and slightly hyperintense on T2-weighted images. Of interest is that signal intensity decreased on out-of-phase chemical shift images in 86% of adenomas and 89% of adrenal hyperplasia, indicating the presence of lipid.

Iodine-131–NP-59 scintigraphy appears to be complementary to CT and MR in differentiating between adenomas and adrenal hyperplasia, being especially useful with a unilateral hyperplastic nodule. Scintigraphy visualizes these tumors as hot nodules, with an occasional warm nodule.

Bilateral adrenal venous sampling distinguishes most but not all adenomas from hyperplasia. Blood samples are obtained after stimulation with ACTH. With bilateral hyperplasia, after stimulation aldosterone levels increase in blood samples from both adrenals; on the other hand, a more marked unilateral increase is detected with an aldosteronoma.

Therapy

Patients with bilateral glomerulosa hyperplasia and those amenable to glucocorticoid therapy are treated medically. Adenomas are resected, but keep in mind that hypertension persists in 30% to 50% of patients after resection even if they are biochemically cured. Such persistent postoperative hypertension suggests coexisting essential hypertension.

Several patients with Conn syndrome and Cushing’s syndrome have been treated by CTguided acetic acid injected into their adrenal nodules (32); follow-up revealed cystic degeneration. A few aldosteronomas have also been treated by transcatheter arterial embolization with absolute ethanol.

Medullary Tumors

With some adrenal medullary tumors even a combination of histology, immunochemistry, and cytophotometric techniques achieves only a differentiation between benign and malignant states, and even then at times with difficulty.

ADVANCED IMAGING OF THE ABDOMEN

Pheochromocytoma (Paraganglioma)

Clinical

A pheochromocytoma is a paraganglioma located in the adrenal medulla. An inconsistent terminology is in use when describing corresponding extraadrenal neoplasms; some authors refer to them as extraadrenal pheochromocytomas if they are functioning and paragangliomas if nonfunctioning, while others call all extraadrenal tumors paragangliomas and simply specify the site and functioning status.

A paraganglioma originates from chromaffin neural crest tissue that has migrated to form the paraganglionic system. Most are located between the diaphragm and the inferior renal pole, with the most common extraadrenal site being in the organ of Zuckerkandl near the inferior mesenteric artery origin. An occasional one involves the inferior vena cava, urinary bladder, or even the broad ligament. About 10% occur in children, where a familial prevalence is evident and is more likely to be extraadrenal and multicentric. A number of pheochromocytomas have been detected during pregnancy and postpartum.

A pheochromocytoma produces an excess of catecholamines, and most of these patients have elevated catecholamine levels. An occasional one is part of a complex tumor; thus it can contain mesenchymal elements. Or, a cortical carcinoma or adenoma exhibits neuroendocrine differentiation. About 10% of pheochromocytomas are malignant. In general, extraadrenal paragangliomas are more malignant and metastasize more readily than their adrenal counterparts. The malignant potential of some is difficult to establish even by histology, the one definite finding of malignancy being the presence of metastases at sites normally devoid of chromaffin cells.

Although many patients with a pheochromocytoma are hypertensive, overall this condition is a rare cause of hypertension. Pheochromocy- toma-induced hypertension tends to be paroxysmal, but differentiation from other causes of hypertension is difficult. A rare paraganglioma (pheochromocytoma) undergoes spontaneous rupture and extraperitoneal hemorrhage, at times resulting in an acute abdomen (Fig. 16.3).

The prevalence of pheochromocytomas is increased in several disorders—neurofibro- matosis, von Hippel-Lindau disease, Sturge-

Weber syndrome, tuberous sclerosis, and multiple endocrine neoplasia (MEN) syndrome. Anatomically, some pheochromocytomacontaining glands are normal in size. Bilateral tumors are more prevalent in both MEN II patients and those with von Hippel-Lindau disease; some of these patients also develop extraadrenal pheochromocytomas. Thus detection of bilateral or familial pheochromocytomas warrants a search for other unsuspected tumors. Of note is that a large minority of these patients with a pheochromocytoma are asymptomatic and have normal blood pressure and normal catecholamine testing. Nevertheless, in patients with von Hippel-Lindau disease and MEN II syndrome, the measurement of plasma normetanephrine and metanephrine achieves a sensitivity and specificity of over 95% in detecting pheochromocytomas (33).

Intravenous ionic contrast may precipitate a hypertensive crisis in a patient with a pheochromocytoma. Premedication with an a-adrener- gic blocking agent appears prudent prior to intravenous (IV) contrast agent administration to prevent an adrenergic crisis, although the need for such blockage is not well established for nonionic contrast agents.

Imaging

A review of 282 patients who underwent pheochromocytoma resection in France between 1980 and 1991, found unilateral tumors

in 67%, bilateral ones in 19%, and extraadrenal in 14% (34); the sensitivities of imaging in detecting these tumors were 89% for CT,98% for MRI, and 81% for I-131-MIBG scintigraphy.

If imaging reveals no adrenal tumor in a patient suspected of a pheochromocytoma, imaging of other extraadrenal sites, including bladder, is necessary. Scintigraphy with I-131- MIBG is useful to detect extraadrenal and bilateral tumors.

Most pheochromocytomas are readily imaged by CT, US, and MRI (Fig. 16.4), yet the clinical and imaging findings are not always straightforward, even in a setting of elevated catecholamines. Intrinsically solid tumors, necrosis, and hemorrhage result in a cystic appearance and, as a result, they have a variable imaging appearances. It is with cystic tumors that the differential diagnosis between cystic pheochromocytomas, necrotic carcinomas, and metastases becomes problematic. An aid to diagnosis is that aside from necrotic regions, these are very hypervascular tumors and postcontrast CT shows marked contrast enhancement.

Another source for confusion is that a minority of adrenal pheochromocytomas contain sufficient microscopic fat to result in a CT attenuation of <10HU and thus mimic an adenoma (35); after contrast enhancement some of these hypodense tumors also reveal >60% contrast washout on 10-min images, similar to adenomas.

Some contain linear or laminated calcifications (Fig. 16.5). Aside from several anecdotal reports, pheochromocytomas do not contain sufficient lipid to influence their imaging appearance.

Nonnecrotic pheochromocytomas tend to be hypointense-to-isointense to liver on T1and hyperintense on T2-weighted images. Their lack of fat reflects their hyperintense T2weighted fat-suppressed appearance. They tend to exhibit progressive enhancement postcontrast MR. Nevertheless, a sufficient number of pheochromocytomas have an atypical low signal intensity on T2-weighted images and not all hyperintense adrenal tumors represent pheochromocytomas, so that reliance on a hyperintense T2-weighted appearance results in a low sensitivity in diagnosing a pheochromocytoma (Fig. 16.6).

Scintigraphy with I-123-MIBG achieves an 80% to 90% detection rate for these tumors; MIBG SPECT sensitivity approaches 100%. This tracer accumulates in adrenergic tissue throughout the body, including metastases. Optimal scan timing is variable, with scans often obtained 24 to 48 hours postinjection. An occasional metastasis is detected only on earlier scans. Indium-111 pentetreotide scintigraphy appears to have similar detection ability as I-123-MIBG, but it has not been studied as extensively.

2-[18F]-fluoro-deoxy-D-glucose PET detected tumors in 76% of patients with pheochromocytomas, with most benign, malignant, and metastatic foci avidly concentrating FDG (36); in fact, several pheochromocytomas not accumulating MIBG showed intense FDG uptake, although MIBG images tended to be as good or better for tumors concentrating both agents. A majority of pheochromocytomas also reveal uptake during (11C)-hydroxyephedrine- PET scanning (37).

Therapy

The treatment of choice for most pheochromocytomas is surgical resection, although an occasional one is treated by catecholamine pharmacotherapy. Resection consists of either adrenalectomy or adrenal-sparing surgery, with a laparoscopic approach commonly employed. A pheochromocytoma has been treated with percutaneous radiofrequency ablation (23).

Neuroblastoma/Ganglioneuroma

Clinical

The most common abdominal neoplasm of early childhood, a neuroblastoma originates from neuroblasts in sympathetic ganglia. The adrenal glands are the most common site, with