Aldosteronism (Hyperaldosteronism, Primary)

Maria Andrievskaya, M.D.
Kausik Umanath, M.D., M.S.

Basic Information

Definition

Primary hyperaldosteronism is a clinical syndrome characterized by hypertension, hypokalemia, and excessive aldosterone secretion despite a low plasma renin activity (PRA) or low direct renin concentration (DRC).

Synonyms

Hyperaldosteronism
Primary aldosteronism
Conn’s syndrome

ICD-10CM CODES
E26.0	Primary hyperaldosteronism
E26.1	Secondary hyperaldosteronism
E26.8	Other hyperaldosteronism
E26.9	Hyperaldosteronism, unspecified

Epidemiology & Demographics

Incidence

5% to 10% of patients with hypertension

Prevalence

More common in females

Physical Findings & Clinical Presentation

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Generally asymptomatic
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If significant hypokalemia is present, possible muscle cramping, weakness, paresthesias
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Hypertension
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Polyuria, polydipsia

Etiology

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Aldosterone-producing adenoma (40%-60%)
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Idiopathic hyperaldosteronism (>30%)
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Glucocorticoid-suppressible hyperaldosteronism (<1%)
•

Aldosterone-producing carcinoma (<1%)

Diagnosis

Differential Diagnosis

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Diuretic use
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Hypokalemia from vomiting, diarrhea
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Renovascular hypertension
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Other endocrine neoplasm (pheochromocytoma, deoxycorticosterone-producing tumor, renin-secreting tumor)

Workup

Fig. 1 provides guidance on when to consider testing for primary aldosteronism. Fig. 2 describes a diagnostic approach to patients with suspected primary aldosteronism. CT, MRI, and adrenal vein sampling (AVS) are used to distinguish unilateral from bilateral increased aldosterone secretion. This distinction will dictate treatment options since unilateral primary aldosteronism is treated surgically, by resection, rather than medically.

FIG.1

Algorithm provides guidance on when to consider testing for primary aldosteronism and use of the ratio of plasma aldosterone concentration (PAC) to plasma renin activity (PRA) as a case-detection tool.

*PRC*, Plasma renin concentration.

Melmed S, Polonsky KS, Larsen PR, Kronenberg HM: *Williams textbook of endocrinology,* ed 12, Philadelphia, 2011, Saunders.

FIG.2

Diagnostic approach to patients with suspected primary aldosteronism.

Cortisol concentration ratio in an adrenal vein four times greater than that in the other adrenal vein and/or an aldosterone/cortisol concentration ratio from the vein of the unaffected adrenal that is less than the ratio in the vena cava. Urinary loss of potassium can be documented by measuring potassium excretion in a 24-hour collection of urine; excretion of more than 30 mEq per day in the presence of hypokalemia indicates potassium wasting. An alternative and simpler approach is to obtain a random sample of urine to calculate fractional excretion of potassium. A fractional excretion greater than 10% when hypokalemia is present indicates potassium wasting. *AME,* Syndrome of apparent mineralocorticoid excess; *APA,* aldosterone-producing adenoma; *CAH,* congenital adrenal hyperplasia; *CT,* computed tomography; *DOC,* deoxycorticosterone; *ectopic ACTH,* production of corticotrophin by a tumor outside the pituitary gland; *serum 18-(OH)-B,* serum concentration of 18-hydroxycorticosterone.

From Runge MS, Greganti MA: *Netter’s internal medicine,* Philadelphia, 2008, Saunders.

Laboratory Tests

Routine laboratory tests can be suggestive but are not diagnostic of primary aldosteronism. Common abnormalities are:

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Spontaneous hypokalemia or severe hypokalemia while receiving conventional doses of diuretics
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Possible alkalosis and hypernatremia

Imaging Studies

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Adrenal CT scans (Fig. E3) or MRI may be used to localize neoplasm.

FIG.E3

Aldosterone-secreting adenoma.

A tiny left adrenal nodule (arrow) was identified as a benign aldosterone-secreting adenoma by adrenal vein sampling and surgical resection.

From Webb WR, Brant WE, Major NM: Fundamentals of body CT, ed 4, Philadelphia, 2015, Saunders.
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Adrenal scanning with iodocholesterol (NP-59) or 6-beta-iodomethyl-19-norcholesterol after dexamethasone suppression. The uptake of tracer is increased in those with aldosteronoma and absent in those with bilateral idiopathic adrenal hyperplasia and adrenal carcinoma.

Treatment

Nonpharmacologic Therapy

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Regular blood pressure monitoring and controlled low-sodium diet, tobacco avoidance, maintenance of ideal body weight, and regular exercise

Acute General Rx

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Control of blood pressure and hypokalemia with eplerenone, spironolactone, or amiloride
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Surgery (unilateral adrenalectomy) for aldosterone-producing adenoma (APA)

Chronic Rx

Chronic medical therapy with spironolactone, eplerenone, or amiloride to control blood pressure and hypokalemia is necessary in all patients with bilateral idiopathic adrenal hyperplasia. Eplerenone causes less gynecomastia in men and menstrual irregularities in women because of greater mineralocorticoid receptor selectivity, but is generally more expensive than spironolactone or amiloride.

Disposition

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Unilateral adrenalectomy normalizes hypertension and hypokalemia in 70% of patients with APA after 1 year. After 5 years, 50% of patients remain normotensive.

Referral

Surgical referral for unilateral adrenalectomy after confirmation of unilateral APA or carcinoma

Pearls & Considerations

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Frequent monitoring of blood pressure and electrolytes postoperatively is necessary because normotension after unilateral adrenalectomy may take up to 4 months.
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With increased use of the DRC, care must be taken in interpreting results, as the aldosterone to DRC ratio is yet to be as widely validated as the aldosterone-to-PRA ratio.
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A recent cohort study revealed that suppression of renin and higher aldosterone concentrations in the context of renin suppression are associated with an increased risk for hypertension and possibly also with increased mineralocorticoid receptor activity. These readings suggest a clinically relevant spectrum of subclinical primary aldosteronism (renin-independent aldosteronism) in normotension.¹

Ferri – Aldosteronism (Hyperaldosteronism, Primary)