Primary aldosteronism is caused by several difference specific entities. 60 to 70% is due to bilateral idiopathic hyperaldosteronism (idiopathic hyperplasia). Unilateral aldosterone producing adenomas are the cause for 30 to 40%. Less common causes include unilateral hyperplasia, familial hyperaldosteronism, and pure aldosterone producing adrenocortical carcinoma and ectopic aldosterone secreting tumors. The approach to diagnosing primary aldosteronism, with an emphasis on aldosterone-producing adenomas and bilateral idiopathic hyperaldosteronism. The following is my summary of the “The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline” which was published in 2016 (Funder 2016).
To Begin
Is recommended to test for primary aldosteronism in patients with:
Resistant hypertension on 3 drugs
Controlled hypertension on 4 or more drugs
Sustained blood pressure >150/100
Hypertension and an adrenal incidentaloma
Hypertension and sleep apnea
Hypertension and first degree family members with primary aldosteronism
Hypertension and spontaneous or low dose diuretic-induced hypokalemia
Family history: of hypertension and CVA that occurred before 40 years of age
How to Interpret the Aldosterone-Renin Ratio (Case Detection)
Firstly, it is important to know that aldosterone-renin ratio (ARR) is most sensitive when samples are collected in the morning after the patient has been out of bed for at least 2 hours, and usually after they have been seeded for 5 to 15 minutes. Ideally, the patient should have undershirt intake before testing and they should be potassium replete. Mineralocorticoid antagonists should be withdrawn for at least four weeks before testing. If possible, medications with minimal effects on the plasma aldosterone levels can be used. These medications include slow-release verapamil, hydralazine, prazosin, doxazosin, and terazosin. If all potentially problematic agents cannot be safely withdrawn, the ARR should be performed and the results considered in the light of the potential compounding factors. For example, in some patients with severe primary aldosteronism, treatment with mineralocorticoid antagonists cannot be safely continued. In this setting, primary aldosteronism related testing can be pursued as long as renin is suppressed.
The ARR is variable and there is no single cutoff value for ARR that lets you know that someone has primary aldosteronism. For case detection, the guidelines place a high value on avoiding the risks associated with missing primary aldosteronism and does for going the opportunity of surgical cure and the reduction for excess cardiovascular morbidity with specific medical treatment. It places a lower value on avoiding the risk of classifying a hypertensive patient as having primary aldosteronism and exposing then to additional diagnostic testing. The recommendations also place a high value avoiding the risk associated with missing a diagnosis of a unilateral forms of primary aldosteronism and us the opportunity of possibly curative intervention on by unilateral adrenalectomy. It places a lower value on avoiding the risks associated of expose the patient's with bilateral primary aldosteronism to additional diagnostic testing
Despite the lack of a definite ratio, primary aldosteronism should be suspected when the PRA is suppressed to <1ng/mL/hr and the PAC is greater than 10ng/dL. The greater the ratio, though, the higher the sensitivity.
For example, the combination of a PAC above 20ng/dL and a PAC/PRA ratio >30 had a sensitivity and specificity of 90% for a diagnosis of primary aldosteronism. It is possible, in the context of low renin activity, to have a ratio of >30, but have a low PAC. In one study, four out of 74 patients with PAC <15 ng/dL had unilateral, surgically correctable primary aldosteronism. Around 26 patients out of this 74 patient population had aldosterone which failed to suppress during fludrocortisone suppression testing. There are two conclusions from this study. Firstly, it is possible to have primary aldosteronism with a low PAC. Secondly, it can be inferred that a patient with a relatively low PAC of <15ng/dL is more common in bilateral adrenal hyperplasia than in patients with aldosterone-producing adenomas (Stowasser 2004).
In addition, the following factors have an impact on renin and aldosterone levels:
Case Confirmation
Confirmatory testing places a high value on sparing patients with false-positive ARR tests from undergoing costly and intrusive lateralization procedures.
Confirmatory testing does not need to be performed in patients with spontaneous hypokalemia or undetectable plasma renin activity and plasma aldosterone concentration greater than 20 ng/dL. These patients can progress directly to subtype classification.
The current literature does not identify a gold standard confirmatory test for primary aldosteronism. Four testing protocols; oral sodium loading, saline infusion, fludrocortisone suppression, and Captopril challenge are in common use. There is no definitive evidence that one single test is optimal. The choice of confirmatory test is commonly determined by considering cost, patient appliance, laboratory routine, and local expertise.
The UpToDate author for this particular topic, uses oral sodium loading as the confirmatory test. For oral sodium loading, after hypertension and hypokalemia are controlled, a high-sodium diet is given for 3 Days. Patients should be given instructions on the sodium content of foods they need in order to consume 5000mg of sodium per day. If a patient is unable to tolerate these high sodium foods, they can be given sodium chloride tablets, 2g three times daily. Since sodium loading typically increases kaliuresis and hypokalemia, serum potassium should be measured daily and aggressive replacement of potassium chloride should be prescribed and monitored almost daily. On the third day of the high-sodium diet, serum electrolytes are measured and a 24-hour urine specimen is collected for measurement of aldosterone, sodium, and creatinine. The 24-hour urine sodium excretion should exceed 200 mEq (4600 mg) to document adequate sodium loading. Urine aldosterone excretion >12 mcg/24 hours in this setting is consistent with hyperaldosteronism.
Subtype Classification
Adrenal CT is recommended. MRI has no advantage over CT as it is more expensive and has less spatial resolution.
Imaging though, cannot reliably visualized microadenomas or distinguish nonfunctioning incidentalomas from aldosterone producing adenomas with confidence. This means that adrenal vein sampling is the most accurate means of differentiating unilateral from bilateral forms of primary aldosteronism. Because ARR is often associated with false positives, patient's should only undergo adrenal vein sampling if they have positive confirmatory testing as adrenal vein sampling is extensive and invasive the sensitivity and specificity of adrenal vein sampling is 95 and 100%, respectively for detecting unilateral aldosterone excess. Adrenal vein sampling is the gold standard test to distinguish unilateral from bilateral primary aldosteronism.
Treatment
Adrenalectomy is preferred for unilateral primary aldosteronism . Blood pressure should be well controlled preoperatively. Potassium supplementation and spironolactone should be discontinued on postoperative day one. Postoperatively, the patient should be allowed to have a liberal salt diet to prevent hyperkalemia due to contralateral adrenal gland suppression. Patient should be allowed to have a liberal salt diet to prevent hyperkalemia due to contralateral adrenal gland suppression from primary hyperaldosteronism. If the patient does not want surgery or if surgery is not appropriate, then spironolactone should be started at 12.5mg daily and increased gradually to a maximum dose of 100mg daily. Gynecomastia occurs in 6.9% of patients with a spironolactone dose <50mg daily and in more than 50% in those with doses >50mg daily. Epleronone has half the mineralocorticoid effect as spironolactone, but is reasonable if the patient cannot tolerate spironolactone.
References
Stowasser, M., & Gordon, R. D. (2004). Primary aldosteronism—careful investigation is essential and rewarding. Molecular and cellular endocrinology, 217(1-2), 33-39.
Funder, J. W., Carey, R. M., Mantero, F., Murad, M. H., Reincke, M., Shibata, H., ... & Young Jr, W. F. (2016). The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. The Journal of Clinical Endocrinology & Metabolism, 101(5), 1889-1916.