Conference Coverage

Expert simplifies diagnosis of endocrine hypertension




ORLANDO – The diagnosis of hypertension with its origin in the endocrine system may appear complex, but it does not have to be. Primary aldosteronism may be underappreciated and underdiagnosed. On the other hand, catecholamine-secreting tumors are rare, but they often come to mind in making a diagnosis of endocrine hypertension. Dr. William Young Jr., professor of medicine at the Mayo Clinic, Rochester, Minn., presented cases in a lively session of audience participation at the annual meeting of the America Association of Clinical Endocrinologists. Later, Dr. Young summarized some of the key points in an interview, which has been edited for brevity.

Frontline Medical News: What is the endocrinologist’s role in working up the patient who has hypertension of suspected endocrine origin?

Dr. William Young Jr.: The first is knowing when to suspect endocrine hypertension. The most common form of endocrine hypertension is primary aldosteronism. So this is the adrenal-dependent autonomous production of aldosterone, which leads to high blood pressure, volume expansion, and sometimes hypokalemia. One of the concepts that many clinicians forget is that only about 30% of patients with primary aldosteronism present with hypokalemia. So 70% of patients with this disorder don’t have hypokalemia. They look like any other person with high blood pressure.

Dr. William Young Jr.

Dr. William Young Jr.

So when should we look for primary aldosteronism? Onset of high blood pressure at a young age, for example, less than age 30, drug resistant hypertension – so three drugs [with] poor control. Twenty percent of those patients will prove to have primary aldosteronism. Simply poorly controlled hypertension is another group; [or] family history of primary aldosteronism, so all first degree relatives should be tested. Or a patient who has hypertension and has had an incidental discovery of an adrenal mass should also be tested for primary aldosteronism.

Unfortunately, most primary care providers ... think that this is a complicated and dense endocrine disorder, and they frequently will not look for it, but it’s actually very simple. Some of the complexities are historical in nature in that when this disorder was first described, several rules were made for what medications a patient could be on, for example. And it’s difficult to comply with those rules. For example, if you have a patient who’s on five drugs and has poor control, you’re not going to switch him to the two drugs that are recommended because they are weak antihypertensives. It wouldn’t be ethical to do so. [The two drug classes are the calcium channel blocker verapamil and the alpha-1 antagonists doxazosin (Cardura) and terazosin (Hytrin).]

So the best thing to do regardless of what drugs the patient is on – it doesn’t matter if they’re on ACE inhibitors or angiotensin-receptor blockers or diuretics – just get a morning blood sample as your aldosterone and plasma renin activity. If aldosterone is high or generous, greater than 15 ng/dL, if the plasma renin activity is less than 1 ng/mL per hour, that’s a positive case detection test.

That doesn’t prove the patient has primary aldosteronism. The sensitivity/specificity of aldosterone and renin case detection testing is about 75%. So most patients need confirmatory testing, which would either be the saline infusion test or the 24-hour urine for aldosterone on a high-sodium diet. And once primary aldosteronism is confirmed, then we would do an adrenal-directed CT scan.

The problem with the findings in the adrenal glands on CT is that the prevalence of adrenal nodularity increases with age. So people in their 60s and 70s can have adrenal nodules that have nothing to do with aldosterone production. So whereas if the patient is less than age 35 and CT shows a unilateral macroadenoma, the contralateral adrenal is perfectly normal appearing, and the patient has a marked primary aldosteronism – so spontaneous hypokalemia, plasma aldosterone over 30 ng/dL – that subset of patients could go straight to surgery and skip adrenal vein sampling. However, everyone else over age 35 if they want to pursue the surgical option, adrenal vein sampling is a key test.

FMN: Is there anything that rules out primary aldosteronism?

Dr. Young: If the plasma aldosterone level is less than 10 ng/dL it makes primary aldosteronism very unlikely, and if the renin level is higher than 1 ng/mL per hour, that makes primary aldosteronism very unlikely.

FMN: What about working up pheochromocytoma?

Dr. Young: Clinicians, unlike with primary aldosteronism, where they don’t look for it enough, for pheochromocytoma they look for it a lot, and it’s really rare. Between 0.1 and 0.01% of the hypertensive population will prove to have pheochromocytoma.


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