You are in: eMedicine Specialties > Radiology > GENITOURINARY HyperaldosteronismArticle Last Updated: Apr 8, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 13
  Author: Ali Nawaz Khan, MBBS, FRCS, FRCP, FRCR, LRCP, Chairman of Medical Imaging, Professor of Radiology, NGHA, King Fahad National Guard Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia Ali Nawaz Khan is a member of the following medical societies: American Institute of Ultrasound in Medicine, Radiological Society of North America, Royal College of Physicians, Royal College of Physicians and Surgeons of the United States, Royal College of Radiologists, and Royal College of Surgeons of England Coauthor(s): Sumaira MacDonald, MBChB, PhD, MRCP, FRCR, Lecturer, Sheffield University Medical School; Endovascular Fellow, Sheffield Vascular Institute; Durre Sabih, MBBS, MSc, Visiting Faculty, Department of Nuclear Medicine, Pakistan Institute of Applied Sciences and Nishtar Medical College, Director, Multan Institute of Nuclear Medicine and Radiotherapy; Muhammad Sohaib, MBBS, MSc, Senior Medical Officer, Assistant Professor, Department of Medical Sciences, Pakistan Institute of Engineering and Applied Sciences Editors: John L Haddad, MD, Clinical Associate Professor, Department of Radiology, Weill Medical College of Cornell University; Director of Body MRI, Department of Radiology, Methodist Hospital in Houston; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Joshua A Becker, MD, Professor, Department of Radiology, New York University School of Medicine; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; Eugene C Lin, MD, Clinical Assistant Professor of Radiology, University of Washington Medical School Author and Editor Disclosure Synonyms and related keywords: primary hyperaldosteronism, primary aldosteronism, Conn syndrome, aldosterone hypersecretion, adrenal adenoma, adrenal gland tumor, adrenal gland hyperplasia, aldosterone-producing tumor, adrenal gland carcinoma, aldosterone excess, aldosterone-producing adenoma, APA, aldosterone-producing adrenal adenoma, aldosteronoma, secondary aldosteronism, idiopathic hyperaldosteronism INTRODUCTIONSection 2 of 13
  BackgroundPrimary aldosteronism, also termed Conn syndrome, is clinically characterized by hypertension and hypokalemia. Primary aldosteronism was first described in 1955 as a syndrome related to the hypersecretion of aldosterone by an adrenal adenoma. Although primary aldosteronism accounts for 0.05-2% of cases of hypertension in the general population, recognition of the disease is important because patients readily respond to the removal of the adrenal gland tumor. The most common cause of primary aldosteronism is an adrenal adenoma; most of the remaining cases result from adrenal gland hyperplasia. Adrenal carcinoma is an extremely rare cause of primary aldosteronism. In 75-90% of patients with a solitary aldosterone-producing tumor, surgical adrenalectomy corrects the hypertension and hypokalemia. PathophysiologyClinical manifestations of primary hyperaldosteronism are caused by aldosterone excess in the renal tubules. Aldosterone promotes the excessive preservation of sodium at the expense of potassium loss. Sodium retention promotes water retention, an expansion in the extracellular volume, hypertension, and a suppression of renin production. Excessive potassium loss causes hypokalemic alkalosis, which may be associated with various complications, including muscular weakness, tetany, and abnormal electrocardiographic findings. In 65-89% of patients, primary aldosteronism occurs as a result of 1 or more aldosterone-producing adenomas (APAs). In 65-70% of patients, the aldosteronoma is solitary, while in 13% of patients, multiple adenomas are present, and in 6% of patients, microadenomatosis exists.1, 2, 3, 4 Adrenal carcinoma rarely causes primary aldosteronism and occurs in less than 1% of patients. Malignant adrenal tumors often secrete aldosterone in addition to glucocorticoids. These patients may present with hypertension or the manifestations of Cushing syndrome. Small aldosteronomas have an average size of 1.7 cm (range, 0.5-3.5 cm), the left adrenal gland is affected more often, and the tumors are bilateral in 6% of patients. The diagnosis of primary aldosteronism is based on the typical biochemical findings of hypokalemia, hypernatremia, depletion of magnesium, elevated bicarbonate levels, low plasma pH, and elevated aldosterone levels in the serum and urine. However, this biochemical pattern is not unique to primary aldosteronism; it may be seen in secondary aldosteronism as well. The demonstration of suppressed renin levels is vital to the diagnosis.2 A sodium chloride suppression test can be used to demonstrate the inability to suppress aldosterone secretion. This suppression testing involves the administration of large amounts of sodium chloride over 3-5 days, which causes hypokalemia in 80-90% of patients with primary aldosteronism. This response is associated with muscle weakness, cardiac arrhythmia, carbohydrate intolerance, and nephrogenic diabetes insipidus. Hypertension associated with primary aldosteronism is usually benign, but in rare cases, malignant hypertension may develop.4 FrequencyUnited StatesIn 0.05-2% of patients with hypertension, the condition is caused by primary aldosteronism. Mortality/Morbidity
SexThe male-to-female ratio is 1:2. AgePrimary aldosteronism occurs in patients aged 30-50 years. AnatomySince computed tomography (CT) scanning has become the standard technique in diagnostic adrenal imaging, differentiating normal from abnormal adrenal glands is essential. Normal adrenal glands are identified in almost all patients with the help of CT scans, whereas a normal left-sided gland is identified in 45% of patients and a normal right-sided gland is identified in 80% of patients with the help of ultrasonograms.6, 7 Cross-sectional images obtained by using CT scanning and MRI show the adrenal glands as thin, folded structures with an anteromedial ridge and 2 posterior or posterolateral limbs. These limbs, which appear winglike, are joined together at the superior aspect of the gland, placed at the upper pole of the kidney. Inferiorly, the limbs open, straddling the upper poles of the kidney. MRI scans can show the adrenal glands elegantly and in many planes. With standard CT scanning, only cross-sectional images may need to be interpreted. On the most cephalic CT scan section, the gland usually has a linear appearance with an anteroposterior orientation or a slanted, anterior-to-posterolateral orientation.7, 8, 9, 10, 11 The midsections of the gland present a Y-shaped configuration. Occasionally, the anteromedial ridge is small or not well developed, resulting in an inverted, V-shaped gland. The normal adrenal limbs measure 3-6 mm in thickness, 4-6 cm in length, and 2-3 cm in width. The variation in size explains why some hyperfunctioning glands are seen to be normal in size on images and at surgery. Clinical DetailsPrimary aldosteronism is characterized by moderate-to-severe hypertension without edema. Biochemically, the condition is associated with hypokalemia, metabolic alkalosis, and hyperaldosteronism not appropriately suppressed during volume expansion and depression of plasma renin activity. With hypokalemic alkalosis, various symptoms, including muscular weakness, polydipsia, polyuria, nocturia, paresthesia, tetany, headaches, and abnormal electrocardiographic features, may develop.1, 2, 3, 4, 5 Other abnormalities that are associated with primary aldosteronism are subarachnoid hemorrhage, postural hypotension, and bradycardia. A neonatal, idiopathic form of hyperaldosteronism has been described that presents with functional gastrointestinal tract symptoms associated with hypokalemia and hypertension. Preferred ExaminationThe workup in patients in whom primary aldosteronism is suspected usually starts with appropriate biochemical analysis, after which, thin-collimation CT scanning is performed.1, 6 If CT scan findings are equivocal, radionuclide studies and MRI should be performed.8 If doubt concerning the diagnosis remains and if CT scans do not show a mass in the adrenal glands, adrenal venous sampling is recommended. Plain radiographs have no significant role. Ultrasonography has little to contribute unless the adrenal tumor is large, which is seldom the case. However, ultrasonography is an excellent modality for the investigation of hypertension. Limitations of TechniquesHypersecreting adrenal glands may appear to be normal in size on images, because the size of the adrenal gland may be compared to a normal measurement and because the healthy adrenal gland varies considerably in size. The adrenal glands also vary in size and weight as a result of illness or stress. This size discrepancy is a particular problem with APAs, because they are often small and difficult to detect. In one series, the average diameter of an APA was 18 mm, and 20% of tumors were smaller than 1 cm. In earlier generations of CT scanners, the sensitivity for detecting APAs was 50-70%. In current CT scanners, the sensitivity has been improved to 82-88%. Diagnosis by using CT scans is hampered by the detection of ipsilateral or contralateral, nonfunctioning adenomas, which leads to a false-positive diagnosis of adrenal hyperplasia. CT scanning is not reliable in distinguishing between hyperplasia and adenoma in patients with multiple, bilateral nodules.6, 7, 12, 13 DIFFERENTIALSSection 3 of 13
Other Problems to Be ConsideredNonfunctioning adrenal adenoma associated with incidental hypertension RADIOGRAPHSection 4 of 13
FindingsConventional radiography has no role in the diagnosis of APA. CT SCANSection 5 of 13
FindingsAfter a diagnosis of hyperaldosteronism has been established clinically and biochemically, dedicated CT scanning of the adrenal glands is performed using thin (3-mm) collimation. Nonenhanced and enhanced CT scans are obtained.6, 7, 9, 12, 13 The mean attenuation level in adrenal adenomas is -2.2 HU. Among hyperfunctioning adenomas, aldosteronomas have the lowest attenuation levels. In patients with primary hyperaldosteronism, CT scan findings may be normal, or scans may show nodular or multinodular glands. Degree of ConfidenceCT scanning has a sensitivity of 60-80% in detecting APAs. CT appears more reliable at revealing tumors larger than 1 cm. Conversely, 20% of tumors may be missed. In one series, the average diameter of an APA was 18 mm, and 20% tumors were smaller than 1 cm. With earlier-generation CT scanners, the sensitivity for detecting APAs was 50-70%. The sensitivity of current scanners has been improved to 82-88%. The specificity of CT scanning in the detection of APAs is 77%.6, 7, 12, 13 False Positives/NegativesCT scan findings of ipsilateral or contralateral, nonfunctioning adenomas lead to a false-positive diagnosis of adrenal hyperplasia. CT scanning is not reliable in distinguishing hyperplasia from adenoma in patients with multiple, bilateral nodules. MRISection 6 of 13
FindingsEarly experience with MRI in the diagnosis of APA has been encouraging. APAs are iso-intense or hypo-intense relative to the liver on T1-weighted images; they are slightly hyperintense on T2-weighted images. Chemical-shift imaging is a useful method for the characterization of adrenal masses. It is based on the principle that fat protons precess faster than do water protons. Chemical-shift MRI is highly sensitive and specific for the differentiation of benign from malignant adrenal tumors, because benign adrenal tumors contain fat, while malignant adrenal tumors rarely do. With chemical-shift imaging, the signal intensity has been found to decrease on out-of-phase images in 86% of patients with APAs and in 89% of patients with bilateral adrenal hyperplasia.8, 9, 10, 11 Degree of ConfidenceA sensitivity of 70-100% and a specificity of 64-100% have been reported in the detection of APAs with MRI.8, 9, 10, 11 False Positives/NegativesFalse-positive diagnoses have occurred in cases of idiopathic hyperaldosteronism, bilateral nodular hyperplasia, primary hypertension, and primary hypertension associated with nonfunctioning adrenal adenoma. ULTRASONOGRAPHYSection 7 of 13
FindingsUltrasonograms may reveal a significantly sized APA, but because APAs tend to be small, the overall sensitivity of ultrasonography is poor. Compared with the adrenal tumors in Cushing disease, larger APAs are easier to identify, because neither retroperitoneal nor subcutaneous fat is obtrusive, as it is with Cushing disease. Degree of ConfidenceUltrasonographic findings contribute little to the diagnosis unless the adrenal tumor is large, which is seldom the case. However, ultrasonography is an excellent modality for the investigation of hypertension. False Positives/NegativesThe exact sensitivity of ultrasonography in the diagnosis of APA is not known, but it appears to be low. Similar to other types of cross-sectional imaging, ultrasonography may incidentally demonstrate nonfunctioning masses in the adrenal glands. NUCLEAR MEDICINESection 8 of 13
FindingsIodine-131-6β-iodomethylnorcholesterol (NP-59) is a cholesterol analog that binds to low-density lipoprotein receptors of the adrenal cortex and is the primary radionuclide used to image the adrenal cortex.12 Imaging is usually performed after dexamethasone suppression to reduce high background tracer uptake by the zona fasciculata. The normal glands (which show uptake of the radionuclide) are identified on day 5 or thereafter. Early, bilateral depiction of the glands (that is, before day 5) implies adrenal hyperplasia, whereas early, unilateral early depiction implies an APA. Detection rate of APA can be improved by using single-photon emission CT (SPECT) scanning.13 Degree of ConfidenceCT scanning is an excellent modality for the detection of APAs; bilateral hyperplasia is usually inferred by the absence of an adrenal tumor. In contrast, NP-59 scanning provides a specific diagnosis of adrenal hyperplasia. Accuracy and sensitivity of 80-95% can be obtained. Smaller adenomas, which are not clearly depicted on CT scans, can be detected on NP-59 scans.13 False Positives/NegativesPrimary aldosteronism must be clinically and biochemically diagnosed before the radionuclide study is performed, because secondary hyperaldosteronism produces bilateral tracer uptake that is indistinguishable from that of primary, autonomous, bilateral hyperplasia. In addition, all drugs that disturb the renin-angiotensin-aldosterone axis must be withdrawn before imaging. The extremely rare mineralocorticoid-secreting carcinoma also demonstrates NP-59 uptake.13 Scintigraphy must be performed in the appropriate clinical setting, because NP-59 uptake has been described in benign, nonsecretory adenoma, as well as in metastatic lung cancer, metastatic colon cancer, lymphoma, myelolipoma, ganglioneuroma, adrenal cysts, and adrenocortical carcinoma. Tracer uptake at extra-adrenal sites also has been reported.13 ANGIOGRAPHYSection 9 of 13
FindingsBecause APAs are small and are not usually vascular, selective adrenal angiography is seldom helpful. However, adrenal phlebography has a useful role in the investigation of APA, because the splaying of veins around APAs can help in identifying even small tumors. If contrast medium is refluxed into the veins of the APA, a wheel-spoke pattern is seen in the intratumoral veins. Because APAs are small, a vigorous retrograde venous injection is usually required to detect the tumors; this vigorous injection is not without risk, because extravasation may occur. Extravasation is a particular problem if the catheter is wedged into the vein. Extravasation can be painful and has been associated with adrenal infarction. Adrenal vein thrombosis is also a known complication of adrenal phlebography, which has been linked to adrenal infarction. Adrenal insufficiency has been described as a result of bilateral adrenal infarction. Adrenal vein thrombosis is more likely to occur if the catheter is wedged in the adrenal vein and left there for several minutes during the procedure. The most useful technique in the investigation of primary aldosteronism is adrenal venous sampling.7, 9, 14 Blood samples are obtained from both adrenal veins for aldosterone level analysis; hormone level ratios are compared with each other and with levels in the inferior vena cava below the adrenal veins. In experienced hands, this technique can achieve a high sensitivity; however, it is a time-consuming procedure that necessitates prolonged cannulation of adrenal veins and increases the risk of adrenal vein thrombosis. In addition, the adrenal veins are small, and collecting 7 mL of blood for sampling is not easy. This is particularly a problem when blood is collected from the right adrenal vein, in which a short vein enters the inferior vena cava directly. Some venous samples thus acquired may be diluted by blood from the inferior vena cava on the right and from the phrenic or renal vein on the left. To overcome the problem of dilution, cortisol levels can be measured from the same samples. A low cortisol level suggests dilution by nonadrenal blood, whereas a high cortisol level indicates a relatively pure sample. When aldosterone and cortisol are measured in blood samples from the same site, an aldosterone-cortisol ratio that corrects the concentration of aldosterone for dilution can be calculated. Degree of ConfidenceAn accuracy of 95% and a sensitivity of 75% have been reported with adrenal venous sampling. Adrenal venous sampling is required for the definitive diagnosis of primary aldosteronism and for the detection of laterality of the adrenal lesion.14 False Positives/NegativesThe dilution of blood from the inferior vena cava on the right and from the renal or phrenic vein on the left can lead to erroneous results in adrenal venous sampling. INTERVENTIONSection 10 of 13
Although primary aldosteronism accounts for 0.05-2% of cases of hypertension in the general population, recognition of the disease is important because patients readily respond to the removal of the adrenal gland tumor. In 75-90% of patients with a solitary APA, surgical adrenalectomy corrects hypertension and hypokalemia. ACKNOWLEDGMENTSSection 11 of 13
Basil Issa, MBBCh, MRCP, Consulting Staff, North Manchester Heath Care NHS Trust, contributed to this article. MULTIMEDIASection 12 of 13
REFERENCESSection 13 of 13
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