EPIDEMIOLOGY OF HYPERTENSION

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Primary Aldosteronism
Paul S. Kellerman, M.D., FACP
Associate Professor
Division of Nephrology
EPIDEMIOLOGY OF
HYPERTENSION
U.S. PREVALENCE
50,000,000, 27% of adults (1988-94)
65,000,000, 31% of adults (1999-2000)
(Fields et al, Hypertension, October 2004)
WORLDWIDE PREVALENCE
1,000,000,000
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 Aldosteronism
Secondary 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
Age
Hypokalemia
Plasma renin
levels
Plasma aldo
levels
AldoProducing
Adenoma
Middle-aged
Frequent
Adrenal
Hyperplasia
Low-renin
essential HTN
Older
Less common
Older
Uncommon
Very low
Low
Low
Very high
High-normal
Normal
Partial
Complete
Plasma aldo
Minimal
suppressibility
to volume
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
Do we need to stop medications for ARR?
• 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)
Aldosterone Suppression Tests
%ARR with lack of suppression – mean 60% , range 26-95%
(Kaplan NM, J Hypertension 22:863-69, 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 <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
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
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