Download Aldosteronism

Aldosteronism
Armed Forces Academy of Medical
Sciences
Outline
• Review normal physiology of RAAS system
• Review normal physiology of Aldosterone
• Primary hyperaldosteronism
– Types
– Symptoms
– Diagnosis
– Treatment
Normal Structure of Nephron
Renin-Angiotensin-Aldosterone System
(RAAS)
• Controls water reabsorption through the manipulation of
sodium reabsorption
• Renin release by kidney in response to
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Fluid loss
Hypotension
Low Sodium intake
Systemic Vasoconstriction
• These factors are sensed by
– Baroreceptors (stretch receptors)
• Afferent arteriole
– Cardiac and arterial baroreceptors
– Macula Densa
• Early Distal Convoluted Tubule
RAAS Physiology
Stimulus
Angiotensinogen
Arterial Constriction
Renin
Angiotensin II
Angiotensin I
Sodium Retention
Angiotensin Converting
Enzyme (ACE)
RAAS Physiology
• Effects of Angiotensin II
– Increases Na Retention
• Through direct stimulation of the Proximal Convoluted
Tubule (PCT)
• Increases Aldosterone secretion
– Aldosterone increases sodium retention in corticol collecting
tubule
• Increased Na retention leads to increased water
reabsorption
– Direct systemic arterial vasoconstriction
• Increased blood pressure
RAAS Physiology
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Aldosterone Synthesis
• Synthesized in adrenal cortex
– Zona glomerulosa
Normal Mechanism of Aldosterone
Action
• Increase number of open sodium channels in
the luminal membrane of the principal cells in
the cortical collecting tubule
– Increased sodium reabsorption
• Removal of Na makes lumen electronegative
– Potassium is secreted from the cells into the
electronegative urine to even out charge
Primary Aldosteronism
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Conn’s syndrome
Aldosterone-producing adenoma (30-60%)
Bilateral idiopathic Hyperaldosteronism
Unilateral adrenal hyperplasia
Bilateral macronodular adrenal hyperplasia
Familial hyperaldosteronism
– Type 1
– Type 2
• Pure aldosterone-producing adrenocortical carcinomas
– Ectopic aldosterone-secreting tumors
Clinical Features of Primary
Aldosteronism
• Hypertension
• Hypokalemia
• Metabolic Alkalosis
• Other electrolyte abnormalities
• Lack of edema
Clinical Features of Primary
Aldosteronism: Hypertension
• Frequently substantially elevated (> 160 / 100)
• Generally resistant to multiple antihypertensive
medications
• Hypervolemia
– Markedly reduces renin secretion
• Persistent hypervolemia leads to increased
systemic vascular resistance (SVR)
• Aldosterone is potent hypertensive agent
– Even high normal levels of aldosterone associated with
hypertension
Clinical Features of Primary
Aldosteronism: Hypokalemia
• Increased urinary potassium wasting
• Serum potassium remains stable for the short
term
– Aldosterone induced potassium wasting
counterbalanced by potassium retaining effect of
hypokalemia
• Progressive hypokalemia only occurs if another
factor is added
– Increased aldosterone production
– Initiation of diuretic medication
Clinical Features of Primary
Aldosteronism: Hypokalemia
• Patients with primary aldosteronism due to
adrenal hyperplasia often do NOT have
hypokalemia
– Phenomenon not understood
• Symptoms of hypokalemia
– Mild cases are asymptomatic
– Mild elevation of blood pressure
– Muscle weakness, cramps, myalgias
– ECG changes
Clinical Features of Primary
Aldosteronism: Other Effects
• Metabolic Alkalosis
– Due to increased urinary hydrogen ion excretion
as a result of aldosterone stimulating Na-H
transporter
• Mild Hypernatremia
– Often between 143 – 147 mEq/L
• Hypomagnesemia
– Urinary magnesium wasting
– Not well understood
Hyperaldosteronism and Cardiac Risk
• Patients with primary hyperaldosteronism have
higher risk of cardiovascular complications then
patients with hypertension
• Retrospective study of 124 patients with primary
aldosteronism to 465 patients with essential
hypertension
– Two groups matched for age, gender, degree of BP
elevation
– Higher rates of stroke, myocardial infarction, atrial
fibrillation in hyperaldosteronism group
Journal American College
Cardiology 2005; 45 (8): 1243
Diagnosis of Primary
Hyperaldosteronism
• First step is to measure Plasma Renin Activity
(PRA) and Plasma Renin Concentration (PRC)
• PRA and PRC levels affected by diuretic use
• PRA and PRC should be LOW in primary
aldosteronism
• Measure the Plasma Aldosterone
Concentration
– Calculate PAC/PRA ratio
Calculating the PAC/PRA ratio
• Measure levels at 0800
• Test can be done while patient takes most of
his antihypertensive medications
– Must hold spironolactone or eplerenone
• Will falsely elevated PRA
– ACE inhibitor and ARBs will also affect PRA
• Normal value of PAC/PRA 4-10
– Primary aldosteronism average 30-50
Interpreting the PAC/PRA ratio
• Primary Aldosteronism: PRA suppressed, PAC
increased (usually > 15 ng/dL)
– PAC > 20 and PAC/PRA > 30 is 90% specific for primary
aldosteronism
• Secondary Aldosteronism (renovascular disease):
PRA and PAC increased, PAC/PRA < 10
• Other (hypercoritsolism, licorice root ingestion):
both PRA and PAC suppressed
Establishing Subtype
• Adrenal CT
– Differentiates adenoma from hyperplasia
– Normal adrenal glands does not exclude hyperplasia
• Adrenal carcinoma suspected with > 4 cm
adrenal mass
Confirming Diagnosis
• Adrenal vein sampling
– Interventional radiologist
obtains aldosterone levels
from each adrenal vein
– Differentiates bilateral
from unilateral disease
• Indications for adrenal
vein sampling
– Confirm unilateral disease
in anyone considering
surgery
– When PAC/PRA is
abnormal but CT scan
normal
Treatment of Primary
Hyperaldosteronism
• Treatment or primary aldosteronism is based
on whether aldosterone hypersecretion is
– Unilateral
– Bilateral
• Goal of therapy is to prevent morbidity and
mortality associated with
– Hypertension
– Hypokalemia
– Increased cardiovascular risk
Treatment of Unilateral Adenoma or
Hyperplasia
• Surgery: Unilateral adrenalectomy
– Unilateral adenoma
– Unilateral hyperplasia
• Partial adrenalectomy inadequate
• Laparoscopic better than open
– Shorter hospital stay
– Less complications
2008 Endocrine Society Guidelines
Post-Op Management of Unilateral
Adrenalectomy
• Hypertension and hypokalemia controlled
medically
– Spironolactone or Eplerenone
• Plasma aldosterone should be measured the day
after surgery to asses for cure
• Patients monitored for hyperkalemia as
spironolactone, potassium supplements and antihypertensives are discontinued
Medical Therapy for Unilateral Adrenal
Hyperplasia or Adenoma
• Surgical treatment is preferred method
• Medical therapy with aldosterone antagonists
is effective
– 50 point reduction in systolic BP
– 30 point reduction in diastolic BP
– Increase in serum potassium of > 1.0 mEq/L
• Also include low salt diet, regular exercise
• No efficacy difference between spironolactone
and eplerenone
Precautions with Spironolactone
• Monitor serum potassium and creatinine
frequently during first 6 weeks of therapy
• Spironolactone will increase half life of digoxin
• Concurrent NSAID use will blunt antihypertensive effects of aldactone
• Patients may develop breast tenderness,
decreased libido, gynecomastia
Treatment of Bilateral Adrenal
Hyperplasia
• Generally milder disease than adrenal adenoma
– Less aldosterone secretion
– Less severe hypertension and hypokalemia
• Patients should be treated with long term
aldosterone antagonist
– Aldosterone or Eplerenone
– May need thiazide diuretic or ACE inhibitor
• Partial Adrenalectomy has been tried and failed
Conclusions
• Primary hyperaldosteronism is one of the
more common causes of hypertension
• It often presents as hypertension and
hypokalemia
• It causes increased cardiovascular morbidity
and mortality beyond it’s hypertension
• There are many subtypes
– Must diagnosis each subtype as treatment varies