Introduction
Background
Primary 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.
Axial enhanced CT scan in a 32-year-old woman who presented with hypertension shows a low-attenuating 2.8-cm suprarenal mass (A) (same patient as in Image 1 in Multimedia). Histologic results obtained after surgery confirmed a tumor due to Conn syndrome.
Longitudinal sonogram through the left kidney in a 32-year-old woman who presented with hypertension shows a 3-cm hypoechoic but solid mass superior to the upper pole of the kidney. Initially, the mass was regarded as a nonfunctioning adenoma unrelated to the patient's hypertension. Subsequently, mild hypokalemia developed. Surgical resection confirmed a tumor due to Conn syndrome.
Scintigram obtained by using iodine-131-6β-iodomethylnorcholesterol (NP-59) in a 59-year-old man with hypertension shows fairly intense radionuclide uptake in the right adrenal tumor (same patient as in Image 7 in Multimedia). At surgery, a Conn tumor was confirmed.
Pathophysiology
Clinical 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
An adrenal myelolipoma is a benign, fatty tumor that is not hormonally active, but in very rare cases, it is associated with functional adrenal disorders. Jung and colleagues reported a case of bilateral adrenal myelolipomas associated with primary hyperaldosteronism.5
Frequency
United States
In 0.05-2% of patients with hypertension, the condition is caused by primary aldosteronism.
Mortality/Morbidity
- In 75-90% of patients with a solitary APA, surgical adrenalectomy corrects hypertension and hypokalemia.
- Most other patients have idiopathic hyperaldosteronism associated with bilateral adrenal hyperplasia; in these patients, surgery rarely cures hypertension.
Sex
The male-to-female ratio is 1:2.
Age
Primary aldosteronism occurs in patients aged 30-50 years.
Anatomy
Since 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.
Presentation
Primary 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 Examination
The 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 Techniques
Hypersecreting 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
Differential Diagnoses
Other Problems to Be Considered
Nonfunctioning adrenal adenoma associated with incidental hypertension
Secondary hyperaldosteronism associated with an incidental, nonfunctioning adenoma
Idiopathic hyperaldosteronism
Liddle syndrome (pseudohyperaldosteronism)
Gordon syndrome (pseudohyperaldosteronism type II, familial hypertensive hyperkalemia)
Secondary hyperaldosteronism due to an extra-adrenal stimulus from hyperreninemia (adrenal embryologic rest neoplasms in a kidney or ovary)
More on Hyperaldosteronism |
 Overview: Hyperaldosteronism |
| Imaging: Hyperaldosteronism |
| Follow-up: Hyperaldosteronism |
| Multimedia: Hyperaldosteronism |
| References |
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References
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Pimenta E, Calhoun DA. Resistant hypertension and aldosteronism. Curr Hypertens Rep. Nov 2007;9(5):353-9. [Medline].
Jung SI, Kim SO, Kang TW, et al. Bilateral adrenal myelolipoma associated with hyperaldosteronism: report of a case and review of the literature. Urology. Dec 2007;70(6):1223.e11-3. [Medline].
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Nocaudie-Calzada M, Huglo D, Lambert M, et al. Efficacy of iodine-131 6beta-methyl-iodo-19-norcholesterol scintigraphy and computed tomography in patients with primary aldosteronism. Eur J Nucl Med. Oct 1999;26(10):1326-32. [Medline].
Hwang I, Balingit AG, Georgitis WJ, et al. Adrenocortical SPECT using iodine-131 NP-59. J Nucl Med. Aug 1998;39(8):1460-3. [Medline]. [Full Text].
Nishikawa T, Saito J, Omura M. Adrenal venous sampling is absolutely requisite for definitively diagnosing primary aldosteronism as well as for detecting laterality of the adrenal lesion. Hypertens Res. Nov 2007;30(11):1009-10. [Medline]. [Full Text].
Zarnegar R, Bloom AI, Lee J, et al. Is adrenal venous sampling necessary in all patients with hyperaldosteronism before adrenalectomy?. J Vasc Interv Radiol. Jan 2008;19(1):66-71. [Medline].
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Haenel LC 4th, Hermayer KL. A case of unilateral adrenal hyperplasia: the diagnostic dilemma of hyperaldosteronism. Endocr Pract. Mar-Apr 2000;6(2):153-8. [Medline].
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Further Reading
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
