Full Guideline: The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment
JCEM | May 2016
John W. Funder (Chair), Robert M. Carey, Franco Mantero, M. Hassan Murad, Martin Reincke, Hirotaka Shibata, Michael Stowasser, and William F. Young, Jr
The 2016 guideline on Primary Aldosteronism is an update of the previous version from 2008. This guideline addresses:
- Deciding when to screen a patient with hypertension for primary aldosteronism
- Using diagnostic tests for screening and diagnosing patients
- Determining when it is appropriate to surgically remove an overactive adrenal gland
- Deciding when to treat with mineralocorticoid antagonists
Essential Points
The Endocrine Society recommends primary aldosterone screening for people who meet one of the following criteria:
- Those who have sustained blood pressure above 150/100 in three separate measurements taken on different days;
- People who have hypertension resistant to three conventional antihypertensive drugs;
- People whose hypertension is controlled with four or more medications;
- People with hypertension and low levels of potassium in the blood;
- Those who have hypertension and a mass on the adrenal gland called an adrenal incidentaloma;
- People with both hypertension and sleep apnea;
- People with hypertension and a family history of early-onset hypertension or stroke before age 40; and
- All hypertensive first-degree relatives of patients with primary aldosteronism.
Summary of Recommendations
+ 1.0 Case Detection
- 1.1 We recommend case detection of primary aldosteronism (PA) in patients with sustained blood pressure (BP) above 150/100 mm Hg on each of three measurements obtained on different days, with hypertension (BP >140/90 mm Hg) resistant to three conventional antihypertensive drugs (including a diuretic), or controlled BP (<140/90 mm Hg) on four or more antihypertensive drugs; hypertension and spontaneous or diuretic-induced hypokalemia; hypertension and adrenal incidentaloma; hypertension and sleep apnea; hypertension and a family history of early onset hypertension or cerebrovascular accident at a young age (<40 years); and all hypertensive first-degree relatives of patients with PA. (1∣⊕⊕⚪⚪)
- 1.2 We recommend using the plasma aldosterone/renin ratio (ARR) to detect possible cases of PA in these patient groups. (1∣⊕⊕⊕⚪)
+ 2.0 Case Confirmation
- 2.1 Instead of proceeding directly to subtype classification, we recommend that patients with a positive ARR undergo one or more confirmatory tests to definitively confirm or exclude the diagnosis (1∣⊕⊕⚪⚪). However, in the setting of spontaneous hypokalemia, plasma renin below detection levels plus plasma aldosterone concentration (PAC) >20 ng/dL (550 pmol/L), we suggest that there may is no need for further confirmatory testing. (2∣⊕⚪⚪⚪)
+ 3.0 Subtype Classification
- 3.1 We recommend that all patients with PA undergo adrenal computed tomography (CT) as in the initial study in subtype testing to exclude large masses that may represent adrenocortical carcinoma and to assist the interventional radiologist and surgeon where anatomically appropriate. (1∣⊕⊕⊕⚪)
- 3.2 We recommend that when surgical treatment is feasible and desired by the patient, an experienced radiologist should use adrenal venous sampling (AVS) to make the distinction between unilateral and bilateral adrenal disease (1∣⊕⊕⊕⚪). Younger patients (<age 35 years) with spontaneous hypokalemia, marked aldosterone excess, and unilateral adrenal lesions with radiological features consistent with a cortical adenoma on adrenal CT scan may not need AVS before proceeding to unilateral adrenalectomy. (2∣⊕⚪⚪⚪)
- 3.3 In patients with an onset of confirmed PA earlier than 20 years of age and in those who have a family history of PA or stroke at a young age (<40 years), we suggest genetic testing for familial hyperaldosteronism type 1 (FH-I) (glucocorticoid remediable aldosteronism [GRA]) (2∣⊕⊕⚪⚪). In very young patients with PA, we suggest testing for germline mutations in KCNJ5 causing familial hyperaldosteronism type 3 (FH-III). (2∣⊕⚪⚪⚪)
+ 4.0 Treatment
- 4.1 We recommend unilateral laparoscopic adrenalectomy for patients with documented unilateral PA (ie, aldosterone-producing adenoma [APA] or unilateral adrenal hyperplasia [UAH]) (1∣⊕⊕⊕⚪). If a patient is unable or unwilling to undergo surgery, we recommend medical treatment including a mineralocorticoid receptor (MR) antagonist (1∣⊕⊕⊕⚪). If an ARR-positive patient is unwilling or unable to undergo further investigations, we similarly recommend medical treatment including an MR antagonist. (1∣⊕⊕⚪⚪)
- 4.2 In patients with PA due to bilateral adrenal disease, we recommend medical treatment with an MR antagonist (1∣⊕⊕⚪⚪); we suggest spironolactone as the primary agent, with eplerenone as an alternative. (2∣⊕⚪⚪⚪)
- 4.3 In patients with GRA, we recommend administering the lowest dose of glucocorticoid to lower ACTH and thus normalize BP and potassium levels as the first-line treatment (1∣⊕⚪⚪⚪). In addition, if BP fails to normalize with glucocorticoid alone, an MR antagonist may be added. For children, the glucocorticoid dosage should be adjusted for age and body weight, and BP targets should be determined from age- and gender-specific published normative data.
