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Endo > Hyperaldosteronism/Pheochromocytoma > Flashcards

Hyperaldosteronism/Pheochromocytoma Flashcards

1
Q

Describe the mechanism of the Renin-Angiotensin-Aldosterone-System:

A
  1. Begins as the liver releases angiotensinogen
  2. Decreases in blood pressure is sensed in the glomerulus and trigger release of renin from the juxtaglomerular cells
  3. Renin is an enzyme that catalyzes the cleavage of the decapeptide angiotensin I from angiotensinogen (a.k.a. renin substrate)
  4. Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme (ACE)
    • ACE is primarily found in most vascular endothelia
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2
Q

How does angiotensin II increase blood pressure?

A
  1. Vasoconstriction
  2. Increases aldosterone release from the zona glomerulosa of the adrenal cortex
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3
Q
  1. What are the increases aldosterone secretion?
  2. What are the effects of aldosterone?
A
  1. Increased by other stimuli:
    • potassium (hyperkalemia) and acutely by ACTH.
  2. Causes increased sodium (and hence water) reabsorption in the renal tubules.
    • increases vascular volume
    • increases blood pressure
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4
Q

Negative Feedback of RAAS:

  1. Direct
  2. Indirect
A
  1. Direct
    • Ang II directly inhibits renin release
  2. Indirect
    • ↑ Ang II and aldosterone ⇒ ↑ blood volume and pressure ⇒ ↓ stimulation of renin release
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5
Q

Where does aldosterone act?

A

Aldosterone works in the distal convoluted tubule and affects sodium/potassium channels

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6
Q
  1. What does aldosterone cause reabsorption of?
  2. How is the ion balance maintained?
  3. What is the overall effect?
A
  1. Aldosterone causes increased reabsorption of sodium from the tubules, thereby causing increased sodium retention in the body
  2. In order to maintain ionic balance, potassium and hydrogen are secreted into the tubule in place of sodium
  3. This process leads to overall fluid retention and increased blood volume
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7
Q

What is the consequence of excess aldosterone?

A
  • net loss of potassium ⇒ hypokalemia
  • metabolic alkalosis
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8
Q

What drug classes affect the RAAS?

A
  1. Direct renin inhibitors
  2. ACE inhibitors
  3. Angiotensin receptor blockers (ARB)
  4. Mineralocorticoid receptor antagonist
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9
Q

Give examples of RAAS drugs:

A
  1. Direct renin inhibitors
    • Aliskiren
  2. ACE inhibitors
    • Lisinopril, enalapril, and captopril
  3. Angiotensin receptor blockers (ARB)
    • Losartan, candesartan, and irbesartan
  4. Mineralocorticoid receptor antagonist
    • Spironolactone and eplerenone
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10
Q

Primary Hyperaldosteronism:

  1. Where is the problem?
  2. What is different about aldosterone secretion compared to normal?
  3. What happens as aldosterone levels increase?
A
  1. In primary hyperaldosteronism, the adrenal gland(s) secrete excessive amounts of aldosterone
    • either an adenoma on one adrenal or both adrenals that have undergone hyperplasia
  2. Secretion is autonomous and is not under the normal regulation from renin and angiotensin II
  3. As aldosterone levels increase,
    • indirect negative feedback causes decreases in renin production
    • downstream decreases in angiotensin
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11
Q

When should testing for primary aldosteronism be considered?

A
  • HTN and hyperkalemia
  • Resistant HTN (3 drugs and poor BP control)
  • Adrenal incidentaloma and HTN
  • Onset of HTN at a young age (< 30 y)
  • Severe HTN (≥ 160 mmHG systolic or ≥ 100 mmHg diastolic)
  • Whenever considering secondary HTN
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12
Q

What should be obtained in patients suspected of having primary hyperaldosteronism?

A

plasma aldosterone:renin activity ratio

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13
Q

Plasma aldosterone:renin activity ratio

  • Normal
  • In patients with primary hyperaldosteronism
A
  • Normal
    • ratio should be < 20
      • aldosterone < 20 ng/dL
      • renin activity 1-4 ng/mL/hour (depending on sodium intake)
  • In subjects with primary hyperaldosteronism
    • ratio > 20 or 30
      • ↑ aldosterone level (> 12 ng/dL)
      • ↓ plasma renin activity (< 1 ng/mL/hour)
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14
Q
  • What is the best scan to determine PHA?
    • When should this scan be done?
  • Once a diagnosis of PHA is confirmed, what else must be determined?
A
  • CT scan is the best when trying to determine PHA (may be hard to see anatomic structures)
    • only should be done after a confirmed biochemical diagnosis
  • Once the diagnosis of primary hyperaldosteronism has been secured, it is necessary to determine if this is from a unilateral or bilateral adrenal source
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15
Q

What is expected from an AVS if the PHA is from a unilateral source?

A
  • Aldosterone levels from the affected adrenal gland will be quite elevated
  • Importantly, the contralateral adrenal venous blood should have an aldosterone level that is quite low
    • even lower than the inferior vena cava
  • High aldosterone levels ⇒ suppression of renin
    • Causes the adrenal gland without autonomous production to produce low levels of aldosterone
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16
Q

What is expected from an AVS if the PHA is from a **bilateral **source?

A

aldosterone levels in adrenal venous blood are elevated bilaterally and there is no gradient between the right or left adrenal

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17
Q

Causes of Primary Hyperaldosteronism:

A
  1. Aldosterone-secreting adrenocortical adenoma
  2. Bilateral hyperplasia of zona glomerulosa
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18
Q

Causes of Secondary Hyperaldosteronism:

A
  • Renal ischemia
  • Decreased intravascular volume
    • Congestive heart failure
    • Chronic diuretic or laxative use
    • Hypoproteinemic states (cirrhosis, nephrotic syndrome)
  • Sodium-wasting disorders
    • Chronic renal failure
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19
Q
  • Secondary hyperaldosteronism is the result of ….
    • What patient population is particularly vunerable?
A
  • …. excess aldosterone production in response to increased RAAS activity
    • It occurs in patients with renal artery stenosis, where renal perfusion pressure is decreased
20
Q

What is the **important differential **between primary and secondary hyperaldosteronism?

A
  • Primary hyperaldosteronism ⇒ ↓ renin levels
  • Secondary hyperaldosteronism ⇒ ↑ renin levels
    • appropriate physiologic stimualtion
21
Q
  • A definitive unilateral tumor by CT or MRI in a young person can be treated with _________ ___________
  • In most cases (no unilateral adrenal nodule, bilateral adrenal nodules, or patients >40 years of age), ___ is necessary
A
  • A definitive unilateral tumor by CT or MRI in a young person can be treated with laparoscopic adrenalectomy
  • In most cases (no unilateral adrenal nodule, bilateral adrenal nodules, or patients >40 years of age), AVS is necessary
22
Q

If aldosterone production is unilateral, _________ ____________ is the preferred approach

A

If aldosterone production is unilateral, laparoscopic adrenalectomy is the preferred approach

  • medical management is also appropriate in many patients
23
Q

If aldosterone production is bilateral, _______ ___________ is used

A

If aldosterone production is bilateral, medical management is used

24
Q

What medical management is used for PHA?

A

Mineralocorticoid receptor antagonists

  • spironolactone and eplerenone
  • competitive receptor antagonists
  • By blocking aldosterone actions
    • decrease sodium and water retention
    • increase serum potassium levels
25
Q

What else can affect the mineralocorticoid receptor (2)?

A
  • Type 1 apparent mineralocorticoid excess (AME)
  • Liddle Syndrome
26
Q

How is cortisol normally handled?

A
  • Cortisol is a potent mineralocorticoid and bind to the mineralocorticoid receptor with an affinity similar to aldosterone
  • In the normal state, cortisol is in much greater plasma concentrations
  • If cortisol is not “deactivated” in the kidney, its high relative concentration would negate aldosterone regulation of the mineralocorticoid receptor
  • The mineralocorticoid receptor in the kidney is protected by 11-HSD2 which rapidly converts cortisol to cortisone
    • ​which lacks potent mineralocorticoid activity
27
Q

What is the pathophysiology of AME?

A
  • result of impaired activity of the microsomal enzyme 11-beta hydroxysteroid dehydrogenase type 2 (11- HSD2)
  • High levels of cortisol accumulate in the kidney
    • activate the mineralocorticoid receptor and create a physiological picture similar to aldosterone excess
28
Q

What can be consumed and causes a deficiency in 11-HSD2?

A

glycyrrhizic acid (licorice root and chewing tobacco)

29
Q

The clinical phenotype of patients with AME includes:

A
  • **low aldosterone **
  • normal plasma cortisol levels
  • hypertension
  • hypokalemia
  • metabolic alkalosis
  • low renin activity
30
Q

Liddle’s syndrome is caused by mutations in the ….

A

amiloride-sensitive epithelial sodium channel (ENaC)

31
Q

What is the clinical picture of Liddle Syndrome?

A
  • low renin and aldosterone levels
  • increased sodium reabsorption
  • potassium wasting
  • hypertension
  • hypokalemia
32
Q

How is Liddle Syndrome treated?

A

amiloride and triamterene (K+ sparing diuretics)

33
Q

Describe the pathway for catecholamine synthesis:

A
34
Q

Drugs with adrenergic effects:

  • Phenylephrine
  • Albuterol
A
  • Phenylephrine
    • α agonist
    • causes vasoconstriction and raises blood pressure
  • **Albuterol **
    • **β2 agonist **
    • causes bronchodilation and the ability to increase ventilation
    • used for asthma and bronchoconstriction
35
Q
  • Where is norepinephrine mainly secreted from?
  • Where is epinephrine mainly secreted from?
    • What is the reason behind this?
A
  • Sympathetic postganglionic nerve fibers ⇒ mainly norepinephrine
  • Adrenal medullary (chromaffin) cells ⇒ mainly epinephrine
    • ​adrenal medulla is bathed in high cortisol
      concentration produced by the adrenal cortex
    • cortisol induces the expression of PNMT
36
Q

Catecholamine Effects:

  1. **Heart **
  2. **Blood vessels **
  3. Pancreas (β cells)
A
  1. **Heart **
    • ​​Increased heart rate
      • Tachycardia ⇒ Palpitations
      • Tachyarrhythmia ⇒ Angina pectoris
    • Increased contractility
      • Increased myocardial O2 consumption ⇒ Angina pectoris
      • Myocarditis ⇒ Congestive heart failure
      • Cardiomyopathy
  2. **Blood vessels **
    • ​​Arteriolar constriction
      • Hypertension ⇒ Headache, Congestive heart failure, Angina pectoris
    • Venoconstriction
      • Decreased plasma volume ⇒ Dizziness,
        Orthostatic hypotension, Circulatory collapse
  3. Pancreas (β cells)
    • Suppression of insulin release
      • Carbohydrate intolerance ⇒ Hyperglycemia, Glucosuria
37
Q

What are the classic symptoms of pheochromocytomas?

A
  • hypertension (90%)
  • headaches (80%)
  • diaphoresis (70%)
  • palpitations (60%)
38
Q

Pheochromocytomas vs. Paragangliomas

  • Definition?
  • Main catecholamine secreted?
A
  • Pheochromocytomas
    • tumors of the chromaffin cells of the adrenal medulla
    • secrete excessive amounts of both **epinephrine and norepinephrine **
  • Paragangliomas
    • tumors that arise from extra-adrenal ganglia of the sympathetic nervous system.
    • paragangliomas and metastases of pheochromocytomas generally secrete primarily norepinephrine
39
Q

Testing for pheochromocytoma:

  • What is the main test in a 24hr urine sample?
  • What is the main test for the plasma?
  • What are the main imaging studies used?
A
  • 24hr urine sample
    • catecholamines
  • ​Plasma
    • metanephrines
  • ​Imaging studies
    • CT
    • MRI
40
Q

When should imaging be done when there is a suspected pheochromocytoma?

A

After confirmatory biochemical diagnosis!

41
Q

Diagnosis of pheochromocytoma is made through the demonstration of catecholamine excess via 2 tests, ….

A

plasma free metanephrines & urinary catecholamines

42
Q

Secretion of large amounts of catecholamines from secretory vesicles causes a ________ _____ and can lead to __________ _____

A

Secretion of large amounts of catecholamines from these secretory vesicles causes a paroxysmal event and can lead to hypertensive crisis

  • due to excessive metanephrines in the plasma
43
Q

What is the best imaging test for a pheochromocytoma?

A

CT scan of the abdomen/adrenal glands

44
Q
  • What is the only curative therapy for pheochromocytoma?
  • Why can this be potentially dangerous?
A

only curative therapy is surgical removal of the tumor

  • Unilateral adrenalectomy
  • During surgical removal of a pheochromocytoma the manipulation of the tumor can cause __release of excessive amounts of catecholamines
  • This surge in catecholamines can cause profound vasoconstriction and resultant hypertensive emergency
45
Q

What should be done for patients prior to surgery for a pheochromocytoma?

A

patients should be treated with alpha-adrenergic blockers

  • catecholamine induced vasoconstriction is prevented
46
Q
  1. What is the α blocker of choice?
  2. What else can potentially be given along with it?
    • When should this second drug be given?
A
  1. Phenoxybenzamine
    • nonselective α blocker
      • ​long half-life of about 24hours
    • does not block the synthesis of catecholamines
    • synthesis of catecholamines and metanephrines tends to increase during α blockade
  2. A β1 blocker might also be needed
    • Therapy with alpha blockers tends to increase the heart rate
    • **Given after appropriate alpha blockade is achieved **
      • Otherwise, it can cause a paradoxical worsening of hypertension
47
Q

Besides anti-adrenergics, what else should be done prior to surgery for pheochromocytoma?

A

make sure the patient is well-hydrated

Endo (18 decks)

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