Next steps when BP won’t come down
A poor response to therapy should trigger a search for a secondary cause of hypertension. Use this review as your guide.
Kidney disease may be a consequence or a cause
The overall prevalence of hypertension in patients with renal disease is 60%,22 but varies according to the type of nephropathy. Eighty-seven percent of patients with diabetic nephropathy also have hypertension, and hypertension and diabetes are the 2 most common causes of end-stage renal disease.23,24
A combination of 2 or more drugs is usually needed to achieve the target BP of <130/80 mm Hg in patients with diabetes.21 ACE inhibitors and angiotensin receptor blockers have been found to slow the progression of diabetic nephropathy.25-27
Is renal artery stenosis to blame?
Renal artery stenosis is the most common form of secondary hypertension that’s reversible, affecting about 0.2% to 3.1% of hypertensive patients.5,6,28 The condition leads to renal ischemia, thereby stimulating the renin-angiotensin-aldosterone axis and causing secondary hyperaldosteronism.
In younger patients, especially women between 15 and 50 years of age, fibromuscular disease is the most common cause of renovascular hypertension.29,30 In older patients, atherosclerosis (which accounts for 90% of renovascular hypertension) is more likely.29,30
The choice of initial imaging tests includes duplex renal ultrasonography, magnetic resonance angiography (MRA), and spiral computed tomographic angiography. Contrast angiography is the gold standard, but it carries a risk of contrast-induced nephropathy. Duplex ultrasonography and MRA do not use iodinated contrast media, and are safe for patients with chronic kidney disease.8
Treatment. Percutaneous transluminal renal artery angioplasty is a treatment option for patients with renal artery stenosis. Angioplasty achieves higher cure rates for patients with fibromuscular dysplasia than for those with atherosclerotic renal artery stenosis.31 Most patients referred for renal artery revascularization have atherosclerosis. Because they’re generally older individuals with comorbidities, the benefits of stent revascularization for this group is controversial. Such patients require antihypertensive therapy with drugs that block the renin-angiotensin system.32
Endocrine disorders must be ruled out
Primary hyperaldosteronism is thought to be present in 0.3% to 1.4% of patients with hypertension.5,6 The prevalence varies widely from one source to another, however, and may be as high as 5% to 20% among patients with resistant hypertension.33,34
Hyperaldosteronism is related to either an aldosterone-secreting adrenal adenoma (in about 40% of cases) or bilateral adrenal hyperplasia (in the remaining 60%), and leads to increased sodium reabsorption and, typically, to a loss of potassium.35
Renin-secreting tumor, which usually arises from the juxtaglomerular cells of the kidney, is a rare cause of hyperaldosteronism. Extrarenal renin-secreting tumors have also been reported.36
What should raise your suspicion. Suspect hyperaldosteronism in patients who have both hypertension and hypokalemia, but keep in mind that not all patients with hyperaldosteronism have low serum potassium.37 Further laboratory evaluation should include a simultaneous measurement of plasma aldosterone (PA) and plasma renin activity (PRA). Patients with hyperaldosteronism will have elevated PA and suppressed PRA.
Testing considerations. It is important to ensure that the PA/PRA test is performed in the morning, with the patient in an upright position.36 He or she should be on a high sodium diet in preparation for the test, consuming 2 to 3 grams of sodium per meal for ≥2 days.37
In patients with a positive PA/PRA ratio (≥20), a 24-hour urinary aldosterone excretion test should be performed. A finding >12 to 14 mcg, along with a PRA <1.0 ng/mL per hour, confirms the diagnosis of primary hyperaldosteronism.18,37 Computed tomography or magnetic resonance imaging of the adrenal glands will distinguish between aldosterone-producing adenoma and bilateral adrenal hyperplasia.
Treatment. Laparoscopic adrenalectomy is the accepted surgical treatment of primary hyperaldosteronism.37 Patients with bilateral disease due to idiopathic hyperaldosteronism are not candidates for surgery and should be treated medically, with potassium-sparing diuretics such as spironolactone.
Cushing’s syndrome is marked by rapid weight gain
High BP may be a manifestation of Cushing’s syndrome, which affects 0.1% to 0.5% of patients with hypertension.5-7 Other signs and symptoms of Cushing’s syndrome include fatigue, weakness, hirsutism, amenorrhea, moon facies, dorsal hump, purple striae, truncal obesity, and hypokalemia. Rapid weight gain is the most common manifestation, and typically the one for which patients seek medical attention.38
The most widely used screening test for Cushing’s syndrome is a 24-hour urine collection measuring urinary-free cortisol.9 Normal urinary cortisol excretion is 20 to 100 mcg/dL in 24 hours; most patients with Cushing’s syndrome produce >250 mcg/dL in that time frame.9
Once hypercortisolism is established, determination of the cause is the next step. A serum adrenocorticotropic hormone (ACTH) level is needed to localize it. Normal (9-52 pg/mL) or elevated ACTH indicates a pituitary or ectopic source, while low levels of ACTH are an indication of an adrenal source.9,39
