Evaluation and Management of the Patient with Hypertension and Hypokalemia

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Evaluation and Management of the Patient with
Hypertension and Hypokalemia

• Stephen L. Aronoff, MD

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When to Expect Mineralocorticoid Excess

• Hypertension
• Hypokalemia
• Metabolic alkalosis
• Less than 50 with Primary Aldosteronism are
  hypokalemia

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Differential Diagnosis of Hypokalemia and normal
BP

• Surreptitious vomiting
• Bartters Syndrome
• Rare primary aldosteronism

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Other Causes of Hypertension and Hypokalemia

• Renovascular Disease
• Diuretic therapy
• Cushings Syndrome
• Licorice ingestion
• CAH
• Rare renin-secreting tumors

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When to Screen Patient for Primary Aldosteronism

• Hypokalemia
• Severe, resistant or relatively acute HT
• Adrenal incidentaloma
• Primary aldosteronism occurs in 1-2 up to 5-10
  of all hypertensives probably an over-estimate

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Consider screening Hypertensive patients under 30
for secondary causes

• With mild to severe hypertension
• No FH of hypertension
• Non-obese

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Initial Approach to Patient with HT and
Hypokalemia

• Plasma renin activity
• Plasma aldosterone concentration

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Plasma Renin Activity in Hypokalemia and HT

• Low
• Primary mineralocorticoid excess
• High
• Diuretic therapy
• Reno-vascular HT
• Malignant HT
• Rare renin-secreting tumor

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Plasma Aldosteronism/Plasma Renin Activity

• Test in AM
• Un-interpretable with spironolactone or
  eplerenone RX stop for 6 weeks
• Other K diuretics OK
• ACEI and ARBs may falsely elevate PRA
• (undetectable PRA strongly suggestive)

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Plasma Aldosteronism/Plasma Renin Activity

• Normal ratio 4 10
• Primary aldosteronism 30 50
• PRA low in many with essential HT but high PAC
  (gt15 ng/dl) and abnormal ratio are uncommon
• Cut-off for high PAC/PRA is lab dependent. Thus
  increased PAC is part of dx requirement

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Other Lab Testing

• 24 hour urine Potassium usually not necessary
  to demonstrate K wasting
• Unless PRA not suppressed
• PAC not elevated
• Clinical suspicion of surreptitious vomiting or
  laxative abuse
• Inappropriate K wasting is gt 30mg daily in
  hypokalemic patient
• Urine Na gt 50meq daily

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Confirmation of Primary Aldosteronism

• Elevated PAC/PRA
• Salt load (after control of HT and correction of
  K)
• Dietary for 3 days
• 5000mg Na diet or 1gm NaCl tablets 2 tid
• Watch out for worsening HT and hypokalemia

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Confirmation of Primary Aldosteronism Contd

• 3rd day of high salt diet collect 24 hr urine
  for aldosterone, sodium and creatinine
• 24 hr urine Na should be gt 200meq to show
  adequate Na loading
• Urine aldosterone gt 14 mcg/24 hrs consistent with
  primary hyperaldosteronism

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Confirmation of Primary Aldosteronism Contd

• IV sodium chloride
• Baseline plasma aldosterone level
• 2 liters NS IV over 4 hours
• Repeat plasma aldosterone level
• Primary hyperaldosteronism plasma aldosterone
  level does not suppress

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Nonaldosterone Mineralocorticoid Excess

• Suppressed PRA and low plasma or urine
  aldosterone value
• Causes
• Some types of CAH or familial cortisol
  resistance
• Chronic licorice ingestion
• Severe cases of Cushings syndrome
• Deoxycorticosterone producing tumor

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Familial Hyperaldosteronism

• Type 1 glucocorticoid-remediable aldosteronism
• Secondary to ACTH stimulation of aldosterone
  secretion
• Type 2 not ACTH dependent and not suppressible
  with dexamethasone
• Genetic defect unknown
• They can have APA or IPA or both

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Differentiating Adrenal Adenoma from Hyperplasia

• 30 60 Adrenal adenomas
• APA have higher aldosterone secretion rates
• Adrenal hyperplasia less severe with less
  hypokalemia
• PAC/PRA gt 32 had 100 sensitivity and 61
  specificity for APA in one study

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Differentiating Adrenal Adenoma from Hyperplasia

• Patients with APA
• More severe HT
• More profound hypokalemia - lt 3.0
• Higher plasma (gt25 ng/dl) and urinary (gt30
  mcg/24 hrs) levels of aldosterone
• Younger - lt 50

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Differentiating Adrenal Adenoma from
HyperplasiaRadiographic Tests

• Hypo-dense unilateral macroadenoma (gt1 cm) likely
  APA
• Abnormality in both glands likely hyperplasia
  although both glands my appear normal on CT or MRI

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Differentiating Adrenal Adenoma from
HyperplasiaRadiographic Tests

• Some investigators suggest low K,
  nonsuppressible hyperaldosteronism, PAC/PRA ratio
  gt 50 and a unilateral mass can go directly to
  surgery
• But in 3 studies of 32 pts. 11 patients (1/3)
  had bilateral hyperplasia
• Absence of mass does not exclude APA
• Bilateral lesions do not exclude APA
• CT may be accurate only 50 of time

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Differentiating Adrenal Adenoma from
HyperplasiaAdrenal Vein Sampling

• Gold standard
• APA - gt4 fold step-up of PAC
• Best performed with continuous infusion of ACTH
  (50 mcg per hour)
• Measure cortisol in same sample to be sure
  samples from adrenal veins
• Cortisol from right adrenal 25 higher and 10
  times higher than peripheral vein

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Differentiating Adrenal Adenoma from
HyperplasiaAdrenal Vein Sampling

• Most useful when no adrenal abnormality
• Both adrenal glands abnormal but asymmetric
• One study 41 with normal CT and 49 with
  bilateral micronodules on CT had unilateral APA
• In 203 pts. with primary aldosteronism 51 with
  unilateral micro-nodule and 66 with unilateral
  macro-nodule had ipsilateral aldo hypersecretion