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Primary Hyperaldosteronism

posted Apr 23, 2014, 8:41 AM by Eliany Mejia   [ updated Apr 23, 2014, 8:57 AM ]

Did you ever wonder why so many of your patients have persistent HTN in the setting of multiple antihypertensive medications? Yes, aside from the fact that they may not be taking their medications one should always think about secondary causes of hypertension. I follow a 45 year old man with a PMHx of “poorly controlled” HTN. He is on HCTZ 25 mg daily, Lisinopril 40 mg daily, Metoprolol 100mg daily, and Nifedipine 90 mg daily. His blood pressure on our last visit was 162/90. He “swears” that he takes his medications as prescribed. Physical exam is wnl. His labs are pertinent for K 3.3, BUN/Cr 15/0.9, and CO2 31.

Secondary causes of HTN are more common then you may think. Here’s the list in order of incidence. I will focus on primary hyperaldosteronism as it was the diagnosis in my patient.

1.      OSA

2.      EtOH

3.      Primary renal disease (acute and chronic renal disease – particularly those with glomerular or vascular disorders) and renovascular disease such as renal artery stenosis.

4.      OCPs in women

5.      Iatrogenic or drug induced – most commonly NSAIDs and Antidepressants

6.      Primary hyperaldosteronism

7.      Other endocrinopathies such as cushings syndrome, hypothyroidism, hyperthyroidism, hyperparathyroidism

8.      Pheocromocytoma

9.      Coarctation of the aorta – predominantly seen in younger patient population and children.

Adrenal Gland - Histology
Primary hyperaldosteronism is characterized by excessive autonomous aldosterone production by the adrenal gland (zona glomerulosa – remember salt, sugar, sex?), independent of the renin-angiotensin system. It is caused by - solitary aldosterone-producing adrenal adeoma (40-50%), or bilateral adrenal hyperplasia 50-60% (also known as - idiopathic primary hyperaldosteronism), rarely unilateral hyperplasion or adrenal carcinoma.

Manifestations: Refractory hypertension, hypokalemia (50% can be eukalemic), and metabolic alkalosis. The prevalence of hyperaldosteronism in patients with HTN is variable between 1-5%. Therefore consider this diagnosis in all patients with refractory hypertension, and particularly hypokalemia in the setting of HCTZ use.

Diagnosis: is made by biochemical testing: simultaneously measuring the midmorning plasma aldosterone level (which will typically be elevated > 15 pmol/L) and plasma renin activity (which will typically be suppressed or undetectable). A ratio of plasma aldosterone (ng/dL) to plasma renin activity (ng/mL/H) of greater than 30 has a 90% sensitivity and specificity for the diagnosis of primary hyperaldosteronism. Of note, in patients on ACE inhibitors, ARBs, or direct renin inhibitors – one would expect a high serum renin level (remember the mechanism of these medications?); therefore if the renin activity is low this is suggestive of primary hyperaldosteronism. Patients on spironolactone or eplerenone, both aldosterone antagonists, should hold medications one week prior to biochemical testing as these medications can lead to abnormal results. Once biochemical diagnosis is made (aldosterone:renin ratio >30) one should confirm the diagnosis with a salt loading test – where you would expect to see persistent elevation of the plasma aldosterone level in response to high salt load. Once diagnosis is confirmed patients should have a CT of the adrenal glands to define the pathologic cause. The CT will help differentiation between a solitary adrenal adenoma, often <2cm, vs bilateral adrenal hyperplasia – characterized by diffuse or focal enlargement of both adrenal glands.

Treatment goals: Normalize blood pressure, resolve hypokalemia, and attain normal aldosterone level. Treatment is dependent on primary etiology. If hyperaldosteronsim is secondary to a solitary adrenal adenoma, the treatment of choice is laproscopic adrenalectomy – particularly in young patients <40 years old. After removal of the adrenal adenoma potassium levels normalize in >90% and blood pressure normalizes in 66% of pts – allowing for better control with antihypertensives in the rest. On the other hand, the treatment of choice for patients with bilateral adrenal hyperplasia (leading to hyperaldosteronism) is medical therapy with aldosterone antagonists such as spironolactone and eplerenone. Spironolactone is a non-specific aldosterone antagonist – can cause gynecomastia, by blocking the androgen receptor, and is therefore teratogenic in pregnancy (developing male fetus). Eplerenone is a more selective aldosterone antagonist and has fewer side effects.

My patient had bilateral adrenal hyperplasia. His blood pressure, hypokalemia, and metabolic alkalosis improved on Eplerenone 50mg daily – obtaining the prior authorization was a pain in the ass. Thanks for reading, hope this was somewhat useful.

Eliany Mejia,
Apr 23, 2014, 8:50 AM