Approach to Secondary Hypertension

Case Presentation: A Curious Case of Hypertension

Last week in #AMReport at @WCHospital (#WCHMorningReport) we reviewed an approach to secondary hypertension. We discussed a case of a young man who with new onset of severe hypertension, refractory to multiple antihypertensive agents. After work up for secondary causes of hypertension, he was found to have primary hyperaldosteronism.

Learning Points

  1. When to Consider Secondary Hypertension
  2. Causes of Secondary Hypertension
  3. Screening for Primary Hyperaldosteronism
  4. Confirmatory Testing for Primary Hyperaldosteronism
  5. Treatment for Primary Hyperaldosteronism

When to Consider Secondary Hypertension

  • 5-15% of all adults with hypertension will have a secondary cause of hypertension
  • Consider evaluation in patients with:
    • Resistant hypertension
      • I.e., Persistent hypertension despite adequate doses of 3 or more medications
      • Always assess for issues with compliance
    • Severe or accelerated course of hypertension
    • Abrupt onset of hypertension
    • Exacerbation of previously controlled hypertension
      • But remember to assess for issues with medication compliance
    • Early or late onset hypertension
      • As per American Guidelines, onset at age < 30 years or onset of diastolic hypertension at age >65 years
    • Anti-hypertensive medication intolerance
      • For example, in renal artery stenosis, increase in Cr level more than 30% with use of ACEI or ARB
    • Suggestive features on history, exams or labs (e.g., unprovoked or excessive hypokalemia)

Causes of Secondary Hypertension

Causes secondary hypertension

Check out pages 7-10 of the ACC Guidelines for more information!

Screening for Primary Hyperaldosteronism

Who to Screen?

As per the Hypertension Canada Guidelines, screening for primary hyperaldosteronism should be considered in hypertensive patients with any of:

  • Unexplained spontaneous hypokalemia (K+< 3.5 mmol/L) or marked diuretic- induced hypokalemia (K+< 3.0 mmol/L)
  • Resistance to treatment with ≥ 3 drugs
  • An incidental adrenal adenoma

How to Screen?

Screening should include assessment of plasma aldosterone and plasma renin activity or plasma renin to determine an aldosterone to renin ratio.  The exact cut off for a positive screening test depends on the units of measurements used. There are specific requirements for collection including:

  • Hypokalemia should be corrected and sodium intake should be liberalized
  • Agents that markedly affect the results of testing (aldosterone antagonists, potassium sparing and wasting diuretics) should be withdrawn  4-6 weeks prior.
  • If results are not diagnostic,  you many need to repeat testing 2 weeks after withdrawing other medications that can interfere with test accuracy such as beta-blockers, centrally acting alpha-2 agonists, ACEI, ARB, DHB CCBs and direct acting renin inhibitors.
  • If possible, oral contraception should be discontinued for 1 month prior to testing.

Confirmatory Testing for Primary Hyperaldosteronism

Confirmatory testing to demonstrate inappropriate autonomous hypersecretion of aldosterone may include any one of the following:

  • Oral sodium loading test
  • IV sodium loading
  • Captopril suppression test
  • Fludrocortisone suppression testing (though not listed in Canadian guidelines)

Failure to suppress aldosterone is abnormal!


Localization (unilateral vs bilateral secretion) 

  • Once primary hyperaldosteronism is confirmed, CT (or MRI) can help localize the presence of an adrenal lesion/adenoma (vs. bilateral adrenal hyperplasia).
  • However, an adrenal lesion that is identified may be non-functional!
  • Therefore, if surgery is considered to remove a suspected unilateral source of primary hyperaldosteronism, selective adrenal venous sampling should be considered. AVS can help verify that the abnormal adrenal gland is, in fact, the source of the hypersecretion

Treatment Options

  • Unilateral laparoscopic adrenalectomy for unilateral PA or unilateral adrenal hyperplasia
    • A proportion of  patients will remain hypertensive and warrant close follow-up
  • Medical treatment with an MR antagonist recommended if bilateral adrenal disease or not a surgical candidate or decline surgery
  • Consider glucocorticoid remediable aldosteronism in young patients and/or those with a family history of PA or stroke at a young age

Additional Reading

  1. Hypertension Canada Guidelines
  2. Endocrine Society Guidelines

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