primary hyperaldosteronism (Conn's syndrome)

Etiology

• aldosterone-producing adenoma (50-90% of cases)
  • generally unilateral
  • rarely malignant
• bilateral adrenal hyperplasia (idiopathic form)
  • glucocorticoid-remediable hyperaldosteronism
    • 11-beta hydroxysteroid dehydrogenase deficiency
  • idiopathic form

Epidemiology

• female:male ratio 2:1
• occurs most commonly ages 30-50
• incidence as high as 1% of hypertensive patients
• underdiagnosed in patients with resistant hypertension & chronic kidney disease

Pathology

• aldosterone secreting adrenal adenoma vs adrenal hyperplasia
• hyposecretion of renin
• hypersecretion of aldosterone

Genetics

• family history

Clinical manifestations

• treatment-resistant hypertension*
• unprovoked hypokalemia
• muscle cramping
• nocturia
• thirst

* diastolic hypertension without edema

Laboratory

• indications for testing
  • untreated hypertension with sustained blood pressure (BP) > 150/100 mm Hg
  • resistant hypertension (> 140/90 mm Hg) with 3-drug therapy including a diuretic
  • hypertension & an adrenal incidentaloma
  • hypertension & hypokalemia (spontaneous or diuretic-induced)
  • hypertension & 1st degree relative with primary hyperaldosteronism
  • hypertension & family history of hypertension < 40 years of age
• initial screening consists of midmorning ambulatory (seated) plasma renin + plasma aldosterone in a normovolemic, normokalemic patient
  • discontinue spironolactone or eplerenone 6 weeks prior to testing
  • screening positive (strongly suggestive) if plasma aldosterone > 15 ng/dL* & plasma aldosterone/renin activity ratio > 20
    • or plasma aldosterone/renin activity ratio

  > 23 ng/dL / ng/mL/hr (positive)
  > 23 ng/dL / ng/mL/hr sensitivity of 97%, specificity of 94%
  > 67 ng/dL / ng/mL/hr sensitivity of 100%
         ^        ^
         |        |
   aldosterone  renin -> angiotensin-1

• plasma renin in a patient taking ACE inhibitor or ARB
  • a low plasma renin is a positive screening test
  • a high plasma renin rules out hyperaldosteronism
• serum K+, unprovoked hypokalemia (> 50%); almost 50% without hypokalemia
• suppressed plasma renin* that fails to increase during volume depletion (upright posture, sodium depletion)
• elevated plasma aldosterone* that does not suppress appropriately with volume expansion (salt loading)
• 24-hour urine aldosterone cutoff of 12 ug (gold standard for diagnosis)

* plasma levels of aldosterone variable

* 38% of patients with at least 1 level < 15 ng/dL, 14% with at least 1 level < 10 ng/dL

Diagnostic procedures

• adrenal vein sampling prior to surgery to confirm source of aldosterone secretion & lateralization when imaging shows adrenal adenoma
  • even when imaging fails to show adrenal adenoma, some patient have unilateral adrenal hyperplasa, thus adrenal vein sampling still indicated

Radiology

• CT or MRI of adrenals*

* after laboratory confirmation of autonomous hyperaldosteronism

Complications

• disease interaction(s) of primary hyperaldosteronism, chronic renal failure & resistant hypertension

Management

• adrenalectomy for aldosterone-secreting adenoma
  • medical management (aldosterone antagonist) may be non-inferior to adrenalectomy
• aldosterone antagonists for adrenal hyperplasia
  • spironolactone 25-100 mg every 8 hours (drug of choice)
  • eplerenone (off label use, less gynecomastia)
• potassium-sparing diuretics second line
  • triamterene
  • amiloride
• not sensitive to dexamethasone
• referral to a specialty center for patients with elevated plasma aldosterone/renin activity ratio & plasma aldosterone or for patients who do not respond to empirical trials of aldosterone antagonists
• see hyperaldosteronism

More general terms

• hyperaldosteronism
• chronic endocrine disease

Patient information

primary hyperaldosteronism (Conn's syndrome) patient information