evaluation and management of the patient with hypertension and hypokalemia stephen l. aronoff, md

Evaluation and Management Evaluation and Management of the Patient with of the Patient with Hypertension and Hypertension and

HypokalemiaHypokalemiaStephen L. Aronoff, MDStephen L. Aronoff, MD

When to Expect When to Expect Mineralocorticoid ExcessMineralocorticoid Excess

HypertensionHypertension Hypokalemia Hypokalemia Metabolic alkalosisMetabolic alkalosis

Less than 50% with Primary Less than 50% with Primary Aldosteronism are hypokalemiaAldosteronism are hypokalemia

Differential Diagnosis of Differential Diagnosis of Hypokalemia and normal BPHypokalemia and normal BP

Surreptitious vomitingSurreptitious vomiting Bartter’s SyndromeBartter’s Syndrome Rare primary aldosteronismRare primary aldosteronism

Other Causes of Hypertension Other Causes of Hypertension and Hypokalemiaand Hypokalemia

Renovascular DiseaseRenovascular Disease Diuretic therapyDiuretic therapy Cushing’s SyndromeCushing’s Syndrome Licorice ingestionLicorice ingestion CAH CAH Rare renin-secreting tumorsRare renin-secreting tumors

When to Screen Patient for When to Screen Patient for Primary AldosteronismPrimary Aldosteronism

HypokalemiaHypokalemia Severe, resistant or relatively acute Severe, resistant or relatively acute

HTHT Adrenal incidentalomaAdrenal incidentaloma Primary aldosteronism occurs in 1-Primary aldosteronism occurs in 1-

2% up to 5-10% of all hypertensives 2% up to 5-10% of all hypertensives – probably an over-estimate– probably an over-estimate

Consider screening Consider screening Hypertensive patients under Hypertensive patients under

30 for secondary causes30 for secondary causes With mild to severe hypertensionWith mild to severe hypertension No FH of hypertensionNo FH of hypertension Non-obeseNon-obese

Initial Approach to Patient with Initial Approach to Patient with HT and HypokalemiaHT and Hypokalemia

Plasma renin activityPlasma renin activity Plasma aldosterone concentrationPlasma aldosterone concentration

Plasma Renin Activity in Plasma Renin Activity in Hypokalemia and HTHypokalemia and HT

LowLow

Primary mineralocorticoid excessPrimary mineralocorticoid excess

HighHigh

Diuretic therapyDiuretic therapy

Reno-vascular HTReno-vascular HT

Malignant HTMalignant HT

Rare – renin-secreting tumorRare – renin-secreting tumor

Plasma Aldosteronism/Plasma Plasma Aldosteronism/Plasma Renin ActivityRenin Activity

Test in AMTest in AM Un-interpretable with spironolactone Un-interpretable with spironolactone

or eplerenone RX – stop for 6 weeksor eplerenone RX – stop for 6 weeks Other K+ diuretics OKOther K+ diuretics OK ACEI and ARB’s may falsely elevate ACEI and ARB’s may falsely elevate

PRAPRA

(undetectable PRA strongly (undetectable PRA strongly suggestive)suggestive)

Plasma Aldosteronism/Plasma Plasma Aldosteronism/Plasma Renin ActivityRenin Activity

Normal ratio 4 – 10Normal ratio 4 – 10 Primary aldosteronism 30 – 50Primary aldosteronism 30 – 50 PRA low in many with essential HT PRA low in many with essential HT

but high PAC (>15 ng/dl) and but high PAC (>15 ng/dl) and abnormal ratio are uncommonabnormal ratio are uncommon

Cut-off for high PAC/PRA is lab Cut-off for high PAC/PRA is lab dependent. Thus increased PAC is dependent. Thus increased PAC is part of dx requirementpart of dx requirement

Other Lab TestingOther Lab Testing

24 hour urine Potassium – usually not 24 hour urine Potassium – usually not necessary to demonstrate K+ wastingnecessary to demonstrate K+ wasting

Unless PRA not suppressedUnless PRA not suppressed PAC not elevatedPAC not elevated Clinical suspicion of surreptitious vomiting Clinical suspicion of surreptitious vomiting

or laxative abuseor laxative abuse Inappropriate K+ wasting is > 30mg daily Inappropriate K+ wasting is > 30mg daily

in hypokalemic patientin hypokalemic patient Urine Na+ > 50meq dailyUrine Na+ > 50meq daily

Confirmation of Primary Confirmation of Primary AldosteronismAldosteronism

Elevated PAC/PRAElevated PAC/PRA Salt load (after control of HT and Salt load (after control of HT and

correction of K+)correction of K+) Dietary for 3 daysDietary for 3 days 5000mg Na+ diet or 1gm NaCl 5000mg Na+ diet or 1gm NaCl

tablets – 2 tidtablets – 2 tid Watch out for worsening HT and Watch out for worsening HT and

hypokalemia hypokalemia

Confirmation of Primary Confirmation of Primary Aldosteronism – Cont’dAldosteronism – Cont’d

33rdrd day of high salt diet – collect 24 hr day of high salt diet – collect 24 hr urine for aldosterone, sodium and urine for aldosterone, sodium and creatininecreatinine

24 hr urine Na+ should be > 200meq 24 hr urine Na+ should be > 200meq to show adequate Na+ loadingto show adequate Na+ loading

Urine aldosterone > 14 mcg/24 hrs Urine aldosterone > 14 mcg/24 hrs consistent with primary consistent with primary hyperaldosteronismhyperaldosteronism

Confirmation of Primary Confirmation of Primary Aldosteronism – Cont’dAldosteronism – Cont’d

IV sodium chlorideIV sodium chloride Baseline plasma aldosterone levelBaseline plasma aldosterone level 2 liters NS IV over 4 hours2 liters NS IV over 4 hours Repeat plasma aldosterone levelRepeat plasma aldosterone level Primary hyperaldosteronism – Primary hyperaldosteronism –

plasma aldosterone level does not plasma aldosterone level does not suppresssuppress

Nonaldosterone Nonaldosterone Mineralocorticoid ExcessMineralocorticoid Excess

Suppressed PRA and low plasma or Suppressed PRA and low plasma or urine aldosterone valueurine aldosterone value

CausesCauses Some types of CAH or familial cortisol Some types of CAH or familial cortisol

resistanceresistance Chronic licorice ingestionChronic licorice ingestion Severe cases of Cushing’s syndromeSevere cases of Cushing’s syndrome Deoxycorticosterone producing tumorDeoxycorticosterone producing tumor

Familial HyperaldosteronismFamilial Hyperaldosteronism

Type 1 – glucocorticoid-remediable Type 1 – glucocorticoid-remediable aldosteronismaldosteronism

Secondary to ACTH stimulation of Secondary to ACTH stimulation of aldosterone secretionaldosterone secretion

Type 2 – not ACTH dependent and Type 2 – not ACTH dependent and not suppressible with dexamethasonenot suppressible with dexamethasone

Genetic defect unknownGenetic defect unknown They can have APA or IPA or bothThey can have APA or IPA or both

Differentiating Adrenal Differentiating Adrenal Adenoma from HyperplasiaAdenoma from Hyperplasia

30 – 60 % Adrenal adenomas30 – 60 % Adrenal adenomas APA have higher aldosterone APA have higher aldosterone

secretion ratessecretion rates Adrenal hyperplasia less severe with Adrenal hyperplasia less severe with

less hypokalemialess hypokalemia PAC/PRA > 32 had 100% sensitivity PAC/PRA > 32 had 100% sensitivity

and 61% specificity for APA in one and 61% specificity for APA in one studystudy


Patients with APAPatients with APA

More severe HTMore severe HT

More profound hypokalemia - < 3.0More profound hypokalemia - < 3.0

Higher plasma (>25 ng/dl) and Higher plasma (>25 ng/dl) and urinary (>30 mcg/24 hrs) levels of urinary (>30 mcg/24 hrs) levels of aldosteronealdosterone

Younger - < 50Younger - < 50


Radiographic TestsRadiographic Tests Hypo-dense unilateral Hypo-dense unilateral

macroadenoma (>1 cm) likely APAmacroadenoma (>1 cm) likely APA Abnormality in both glands likely Abnormality in both glands likely

hyperplasia although both glands my hyperplasia although both glands my appear normal on CT or MRIappear normal on CT or MRI


Radiographic TestsRadiographic Tests Some investigators suggest low K+, Some investigators suggest low K+,

nonsuppressible hyperaldosteronism, nonsuppressible hyperaldosteronism, PAC/PRA ratio > 50 and a unilateral mass PAC/PRA ratio > 50 and a unilateral mass can go directly to surgerycan go directly to surgery

But – in 3 studies of 32 pts. – 11 patients But – in 3 studies of 32 pts. – 11 patients (1/3) had bilateral hyperplasia(1/3) had bilateral hyperplasia

Absence of mass does not exclude APAAbsence of mass does not exclude APA Bilateral lesions do not exclude APABilateral lesions do not exclude APA CT may be accurate only 50% of timeCT may be accurate only 50% of time


Adrenal Vein SamplingAdrenal Vein Sampling Gold standardGold standard APA - >4 fold step-up of PACAPA - >4 fold step-up of PAC Best performed with continuous Best performed with continuous

infusion of ACTH (50 mcg per hour)infusion of ACTH (50 mcg per hour) Measure cortisol in same sample to be Measure cortisol in same sample to be

sure samples from adrenal veinssure samples from adrenal veins Cortisol from right adrenal 25% higher Cortisol from right adrenal 25% higher

and 10 times higher than peripheral and 10 times higher than peripheral veinvein


Adrenal Vein SamplingAdrenal Vein Sampling Most useful when no adrenal abnormalityMost useful when no adrenal abnormality Both adrenal glands abnormal but asymmetricBoth adrenal glands abnormal but asymmetric One study – 41% with normal CT and 49% with One study – 41% with normal CT and 49% with

bilateral micronodules on CT had unilateral bilateral micronodules on CT had unilateral APAAPA

In 203 pts. with primary aldosteronism – 51% In 203 pts. with primary aldosteronism – 51% with unilateral micro-nodule and 66% with with unilateral micro-nodule and 66% with unilateral macro-nodule had ipsilateral aldo unilateral macro-nodule had ipsilateral aldo hypersecretionhypersecretion

evaluation and management of the patient with hypertension and hypokalemia stephen l. aronoff, md

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