Hyperaldosteronism is caused by the hypersecretion of the hormone aldosterone by the adrenal cortex, leading to the clinical syndrome of hypertension and hypokalemia. This syndrome was originally described by Conn in 1955 and thus is often referred to as Conn’s syndrome.1 In approximately 50% to 60% of cases, hyperaldosteronism is caused by a solitary adrenal nodule or “aldosteronoma.” The remainder of cases (~30% to 40%) are caused by bilateral adrenal hyperplasia.2 Unilateral adrenal hyperplasia and aldosterone-producing ovarian tumor may also cause hyperaldosteronism.

Approximately 5% of the time, patients present with an angiotensin-2–responsive adenoma, although this type of presentation is rare. In 1% of cases, familial hyperaldosteronism type I (FH1), also known as glucocorticoid-remediable hyperaldosteronism (GRA) and familial hyperaldosteronism type II, causes hyperaldosteronism. GRA is an autosomal dominant disease that is characterized by high aldosterone levels and low renin levels. With GRA, symptoms are reversed by glucocorticoid administration because aldosterone levels are controlled by adrenocorticotropic hormone (ACTH) rather than by normal angiotensin II (Figure 13-1). Adrenocortical carcinoma and metastatic disease may also cause high aldosterone levels. A quick and simplified schematic of the physiology of aldosterone is shown in Figure 13-1.

Most cases of hyperaldosteronism affect younger adults between the ages of 30 and 50 years, with a female preponderance three times higher than that of males. Many studies have demonstrated evolving etiologies of hyperaldosteronism depending on how the disease is defined. Hypertensive patients who are at risk for increased aldosterone levels include very young patients with refractory hypertension and those with a strong family history of an aldosteronoma. According to the Joint National Committee, the prevalence of primary hyperaldosteronism is 1.99% in subjects with stage 1 hypertension, 8.02% in stage 2 hypertension, and 13.2% in stage 3 hypertension. In patients with resistant hypertension, the prevalence of primary aldosteronism has been reported to be 17% to 20%, but African-American and black South African subjects have lower renin levels than white subjects.3 Ethnicity, age, and gender differences have not had a profound effect on the prevalence of hyperaldosteronism.

In most cases of hyperaldosteronism, mild to moderate hypertension occurs, making the diagnosis more elusive until essential hypertension is ruled out. Hypokalemia, as often seen in patients with hyperaldosteronism, may cause muscle weakness, cramping, paralysis, fatigue, and headaches.4 It also has accompanying hypernatremia without pedal edema and may present with polyuria, polydipsia, and increased liability to urinary tract infections secondary to impairment of urinary concentration and acidification.5 A thorough physical examination should be performed to look for signs of adrenal pathology, including obesity, short stature, striae, hirsutism, peripheral weakness, abdominal bruits (renal artery stenosis), and peripheral edema.

Accurate diagnosis of aldosteronoma includes a combination of clinical suspicion, symptoms, biochemical testing, and imaging results. In patients with primary or secondary hyperaldosteronism, hypernatremia, hypokalemia (serum K+ <3.4 mEq/L), aldosteroneuria (12 ug/d), hypomagnesemia, hypophosphatemia, and increased urinary 17-hydroxysteroid may be seen.

Plasma renin activity is useful in differentiating primary from secondary hyperaldosteronism. A PAC:PRA (Plasma Aldosterone Concentration:Plasma Renin Activity) ratio above 25 ng/dL is sensitive and specific in the screening and diagnosis of primary hyperaldosteronism.2 Classification of this ratio is as follows: low ratios (0.21 to 0.98) indicate adrenal insufficiency, normal ratios (2.8 to 23.2) indicate secondary hyperaldosteronism, and ratios above 105 indicate primary hyperaldosteronism.6

It is also important to remember that many antihypertensive drugs, such as spironolactone, angiotensin-converting enzyme inhibitors, and diuretics, affect renin aldosterone regulation and should be discontinued 4 to 6 weeks before diagnostic studies are performed.4

Historically, a postural stimulation, or “salt-loading,” test (Table 13-1) was used to confirm the diagnosis; however, the sensitivities were low, and these studies have largely fallen into disuse. An iodocholesterol scan (NP-59) is also seldom used because of limited availability, low accuracy in detecting small lesions, and the requirement for dexamethasone suppression.4 In the era of computed tomography (CT) scanning, NP-59 and postural stimulation testing (salt loading) are rarely necessary.