Mineralocorticoid Excess
Hyperaldostronism
Epidemiology
• first description of a patient with an
aldosterone-producing adrenal adenoma
(Conn's syndrome)
• mineralocorticoid excess was thought to
represent a rare cause of hypertension
• a much higher prevalence is now recognized,
ranging from 5 to 12%
• The prevalence is higher when patients are
preselected for hypokalemic hypertension
• The most common cause of mineralocorticoid
excess is primary hyperaldosteronism,
reflecting excess production of aldosterone by
the adrenal zona glomerulosa.
Causes of Mineralocorticoid Excess
Etiology
• Bilateral micronodular hyperplasia is more
common than unilateral adrenal adenomas
• Bilateral adrenal hyperplasia is usually
micronodular but can also contain larger
nodules that might be mistaken for a
unilateral adenoma.
• rare instances, caused by an adrenocortical
carcinoma.
Causes of Mineralocorticoid Excess
Clinical Manifestations
• Excess activation of the mineralocorticoid
receptor leads to potassium depletion and
increased sodium retention, with the latter
causing an expansion of extracellular and
plasma volume.
• Increased ENaC activity also results in
hydrogen depletion that can cause metabolic
alkalosis.
• Aldosterone also has direct effects on the
vascular system, where it increases cardiac
remodeling and decreases compliance.
• Aldosterone excess may cause direct damage
to the myocardium and the kidney glomeruli,
in addition to secondary damage due to
systemic hypertension.
• The clinical hallmark of mineralocorticoid
excess is hypokalemic hypertension
• serum sodium tends to be normal due to the
concurrent fluid retention, which in some
cases can lead to peripheral edema.
• Hypokalemia can be exacerbated by thiazide
drug treatment, which leads to increased
delivery of sodium to the distal renal tubule,
thereby driving potassium excretion.
• Severe hypokalemia can be associated with
1. muscle weakness
2. overt proximal myopathy
3. even hypokalemic paralysis
• Severe alkalosis contributes to muscle cramps
and, in severe cases, can cause tetany
Diagnosis
• should be restricted to those who exhibit
1. hypertension associated with drug resistance
2. Hypokalemia
3. an adrenal mass
4. hypertension before the age of 40 years
• The accepted screening test is concurrent
1. measurement of plasma renin and
aldosterone
2. calculation of the aldosterone-renin ratio
(ARR)
• serum potassium needs to be normalized
prior to testing.
Screening
Confirmatory Tests
Intravenous Saline Infusion Test
• Two liters of 0.9% sodium chloride solution is infused
intravenously with an infusion pump over 4 hours with
the patient recumbent.
• Blood pressure and heart rate are monitored during
the infusion.
• At the completion of the infusion, blood is drawn for
measurement of PAC.
1. normal subjects :PAC levels decrease to less than 5
ng/dL,
2. primary aldosteronism : more than 10 ng/dL.
3. Indeterminate : PAC values between 5 and 10 ng/dL
Oral Sodium Loading Test
• hypertension and hypokalemia controlled
• high-sodium diet (supplemented with sodium chloride
tablets if needed) for 3 days, with a goal sodium intake
of 5000 mg (equivalent to 218 mEq of sodium or 12.8 g
sodium chloride
• On the third day of the highsodium diet, a 24-hour
urine specimen is collected for measurement of
aldosterone, sodium, and creatinine.
• Urinary aldosterone excretion of more than 12 μg/24
hours is consistent with autonomous aldosterone
secretion
Fludrocortisone Suppression Test
• fludrocortisone acetate is administered for 4
days (0.1 mg every 6 hours) in combination
with sodium chloride tablets (2 g three times
daily with food).
• Blood pressure and serum potassium levels
must be monitored daily.
• In the setting of low PRA, failure to suppress
the upright 10 a.m. PAC to less than 6 ng/dL on
day 4 is diagnostic of primary aldosteronism
Localization
Adrenal Venous Sampling
• cortisol-corrected aldosterone lateralization
ratios greater than 4.0: unilateral source of
aldosterone like APA 95% sensitivity and
100% specificity
• zone of overlap :ratios greater than 3.0 but
less than 4.0 represent
• bilateral aldosterone secretion : Ratios less
than 3.0
Treatment
• Patients younger than 40 years with
confirmed mineralocorticoid excess and a
unilateral lesion can go straight to surgery
• Laparoscopic adrenalectomy is the preferred
approach.
• Patients who are not surgical candidates, or
with evidence of bilateral hyperplasia based
on CT or AVS, should be treated medically
Medical treatment
mineralocorticoid receptor antagonist
• Spironolactone: started at 12.5–50 mg bid and
titrated up to a maximum of 400 mg/d to control
blood pressure and normalize potassium.
• Side effects include
1. menstrual irregularity
2. decreased libido
3. gynecomastia
• eplerenone : more selective MR antagonist .
Doses start at 25 mg bid and it can be titrated up
to 200 mg/d.
• Another useful drug is the sodium channel
blocker amiloride (5–10 mg/bid).