Primary Aldosteronism

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Primary Aldosteronism

• Paul S. Kellerman, M.D., FACP
• Associate Professor
• Division of Nephrology

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EPIDEMIOLOGY OF HYPERTENSION
U.S. PREVALENCE 50,000,000, 27 of adults
(1988-94) WORLDWIDE PREVALENCE 1,000,000,000
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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 Cushings syndrome
0.1-0.2 0.2 Coarctation
0.1-0.2 1 Oral contraceptives
0.2-1.0
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DIFFERENTIATION OF SECONDARY FROM ESSENTIAL
HYPERTENSION

• Know presentation and course of essential
  hypertension
• Know signs and symptoms of secondary etiologies

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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

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Secondary Hypertension

• Hypertension onset at age extremes lt30 gt50
• 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

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Primary Aldosteronism
Secondary cause of hypertension due to excessive
secretion of aldosterone from the adrenal gland,
due either to tumor or hyperplasia.
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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 Cushings syndrome 0.1-0.2
0.2 Coarctation 0.1-0.2 1
Oral contraceptives 0.2-1.0

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DDx of Aldosteronism from Essential Hypertension
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Young WF, Endocrinology 1442208-13, 2003.
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When to Screen for Aldosteronism

• Hypertension and Spontaneous Hypokalemia
• Hypertension and Adrenal Tumor
• Resistant Hypertension (20 incidence)

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Incidence of Aldosteronism Increases with
Hypertension Severity
Mosso L et al. Hypertension 42161, 2003
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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

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Positive Screening Meriting Further Investigation
for PA

• Aldosterone-Renin Ratio (ARR)gt30 (20-60?) PRA
  is normalized to 0.5 if lt0.5
• AND
• Aldosterone levelgt15 ng/dL

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Potential Alterations in ARR with Medications
Do we need to stop medications for ARR?

• Beta-blockers
• False ARR (lower renin, but also therefore lower
  aldosterone)
• Angiotensin receptor blockers (gtACE 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 doesnt 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 37699-705, 2001)
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Aldosterone Suppression Tests
ARR with lack of suppression mean 60 , range
26-95 (Kaplan NM, J Hypertension
22863-69, 2004)

• 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 lt8.5 ng/dL (lt6 normal gt10 PA)
• Oral sodium chloride suppression test
• 10 gms NaCl daily for 4 days
• On day 4, collect 24 hour urine aldosterone,
  sodium
• Suppression if aldosteronelt14 mcg and sodium gt
  200 mEq/24 hours
• Fludrocortisone suppression test
• high salt diet and large doses of Florinef over a
  4 day hospitalization

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Imaging for Aldosteronism

• CT thin cuts of adrenal glands
• MRI
• 131-I-iodocholesterol

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Imaging for Aldosteronism

• Problems with CT/MRI
• Lots of False Positives
• Only can image adenoma if gt 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)

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Role for Adrenal Vein Sampling
When to use Unilateral adenoma gt 40 years
old High risk APA with normal adrenals on CT
scan or mild asymmetry
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Role for Adrenal Vein Sampling
High Probability APA Severe HTN Hypokalemia
(lt3) Higher Aldo levels plasma gt25 ng/dL
urine gt 30 mcg/24 hrs Age lt 50
BUT AVS is only good in very experienced hands
technically very difficult
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Therapy

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

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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

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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?

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UW HYPERTENSION CLINIC

• Multidisciplinary HTN clinic
• Nephrology (Kellerman)
• Cardiology (Moncher)
• Endocrinology (Shenker)
• At the UW Kidney Clinic on Fish Hatchery Road
• 270-5656