Primary Aldosteronism

Paul S. Kellerman, M.D., FACPAssociate Professor

Division of Nephrology

EPIDEMIOLOGY OF HYPERTENSION

U.S. PREVALENCE

50,000,000, 27% of adults (1988-94)

WORLDWIDE PREVALENCE 1,000,000,000

65,000,000, 31% of adults (1999-2000) (Fields et al, Hypertension, October 2004)

FREQUENCY OF VARIOUS DIAGNOSES IN HYPERTENSIVE PATIENTS – 1980s

PRIMARY CARE REFERRAL

Essential 92-95% 89%

Chronic kidney dis 3-6% 5%

Renovascular dis 0.2-1.0% 4%

Pheochromocytoma 0.1-0.2% 0.2%

Aldosteronism 0.1-0.3% 0.5%

Cushing’s syndrome 0.1-0.2% 0.2%

Coarctation 0.1-0.2% 1%

Oral contraceptives 0.2-1.0%

DIFFERENTIATION OF SECONDARY FROM ESSENTIAL HYPERTENSION

• Know presentation and course of essential hypertension

• Know signs and symptoms of secondary etiologies

Essential Hypertension• Onset in 30s and 40s• Gradual onset• Gradual progression of HTN/slow addition of

medications• Lack of severe end-organ damage• Family history• Often associated with obesity• Lack of signs and symptoms of secondary

causes• Lack of laboratory evidence of secondary causes

Secondary Hypertension• Hypertension onset at age extremes <30 >50• Rapid onset of severe hypertension• More severe chronic end-organ damage

– Grade III/IV retinopathy, LVH/CHF, CKD

• Lack of family history• Sign and symptoms of secondary etiologies• Laboratory evidence of secondary etiologies• Emergent hypertension• Resistant hypertension

Primary AldosteronismSecondary cause of hypertension due to excessive secretion of aldosterone from the adrenal gland, due either to tumor or hyperplasia.

FREQUENCY OF VARIOUS DIAGNOSES IN HYPERTENSIVE PATIENTS - 2007

PRIMARY CARE REFERRAL

Essential 92-95% 89%

Chronic kidney dis 3-6% 5%

Renovascular dis 0.2-1.0% 4%

Pheochromocytoma 0.1-0.2% 0.2%

Aldosteronism 5-13%

Cushing’s syndrome 0.1-0.2% 0.2%

Coarctation 0.1-0.2% 1%

Oral contraceptives 0.2-1.0%

DDx of Aldosteronism from Essential Hypertension

Aldo-Producing

Adenoma

Adrenal Hyperplasia

Low-renin essential HTN

Age Middle-aged Older Older

Hypokalemia Frequent Less common Uncommon

Plasma renin levels

Very low Low Low

Plasma aldo levels

Very high High-normal Normal

Plasma aldo suppressibility to volume

Minimal Partial Complete

Young WF, Endocrinology 144:2208-13, 2003.

When to Screen for Aldosteronism

• Hypertension and Spontaneous Hypokalemia

• Hypertension and Adrenal Tumor

• Resistant Hypertension (20% incidence)

Incidence of Aldosteronism Increases with Hypertension

Severity

Mosso L et al. Hypertension 42:161, 2003

Laboratory Screening

• Plasma aldosterone concentration (PAC) and plasma renin activity (PRA)

• Drawn from ambulant seated patient

• Morning blood draw

• Potassium must be normalized (not hypokalemic) to avoid false suppression of aldosterone

Positive Screening Meriting Further Investigation for PA

Aldosterone-Renin Ratio (ARR)>30 (20-60?) – PRA is normalized to 0.5 if <0.5

AND

Aldosterone level>15 ng/dL

Potential Alterations in ARR with Medications

• Beta-blockers– False +ARR (lower renin, but also therefore lower aldosterone)

• Angiotensin receptor blockers (>ACE Inh)– False –ARR (lower aldosterone, raises renin)

• Diuretics– With thiazides and loop diuretics, may not be much effect,

since raise both aldo and renin, so ratio doesn’t change much– Spironolactone should be stopped (increased aldosterone)

• Calcium channel blockers– Minimal effects

May not matter for ARR (Gallay BJ, et al. Am J Kidney Dis 37:699-705, 2001)

Do we need to stop medications for ARR?

Aldosterone Suppression Tests

• IV Saline suppression – 500 mL 0.9% NaCl/hr for four hours OR 500 mL 0.9% NaCl over 30

minutes, then 500 mL/hr for 2 hours (1.5 liters over 2.5 hours)• Draw PAC at time 0, 120, 150 minutes for short test

– Suppression if PAC <8.5 ng/dL (<6 normal >10 PA)

• Oral sodium chloride suppression test– 10 gms NaCl daily for 4 days– On day 4, collect 24 hour urine aldosterone, sodium

– Suppression if aldosterone<14 mcg and sodium > 200 mEq/24 hours

• Fludrocortisone suppression test – high salt diet and large doses of Florinef over a 4 day hospitalization

%ARR with lack of suppression – mean 60% , range 26-95% (Kaplan NM, J Hypertension 22:863-69, 2004)

Imaging for Aldosteronism• CT – thin cuts of adrenal glands• MRI• 131-I-iodocholesterol

Imaging for Aldosteronism

• Problems with CT/MRI– Lots of False Positives

• Only can image adenoma if > 1cm• Of these, 1/3 are incidentaloma (no

lateralization on adrenal vein sampling)

– Lots of False Negatives• Up to 1/3 of adenomas are missed

because of small size (lateralize on adrenal vein sampling)

Role for Adrenal Vein Sampling

When to use:

Unilateral adenoma > 40 years old

“High risk APA” with normal adrenals on CT scan or mild asymmetry

Role for Adrenal Vein Sampling

“High Probability” APA

Severe HTN

Hypokalemia (<3)

Higher Aldo levels

plasma >25 ng/dL

urine > 30 mcg/24 hrs

Age < 50

BUT: AVS is only good in very experienced hands – technically very difficult

Therapy

• If tumor with lateralization, laparascopic adrenalectomy

• If tumor without lateralization (incidentaloma), or hyperplasia, then aldosterone blockade– Spironolactone– Eplerinone

Primary Aldosteronism in 2007• The incidence of primary aldosteronism due to adrenal

hyperplasia as defined by saline suppression is much higher than previously thought.

• Hypokalemia is often not present with hyperplasia and is not a sine qua non for diagnosis.

• Resistant hypertensives have a high incidence of primary aldosteronism.

• Controversy exists as to definitive ARR thresholds, medication use during suppression testing, and adrenal imaging.

• AVS is the “gold standard” but not often available due to technical limitations

Case

• Does she have hyperaldosteronism?– Likely, but not confirmed

• If so, is this hyperplasia or adenomatous (did the CT miss it)?– Unlikely adenoma, given age, very

mild hypokalemia (almost normokalemia), HTN severity

• Is the treatment appropriate?

UW HYPERTENSION CLINIC

• Multidisciplinary HTN clinic– Nephrology (Kellerman)– Cardiology (Moncher)– Endocrinology (Shenker)

• At the UW Kidney Clinic on Fish Hatchery Road

• 270-5656