(M) Lec 4: Adrenal Glands (Aldosterone to Medulla) Flashcards

1
Q
  • The major electro-regulating hormone
  • Most abundant/potent mineralocorticoid
  • The main determinant of renal extraction of potassium
A

Aldosterone

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2
Q
  1. Aldosterone controls the ____ levels in the body
  2. It also facilitates the excretion of ____
  3. It promotes a ____ ratio exchange between sodium for potassium or hydrogen
A
  1. Sodium-Chloride
  2. Potassium and Hydrogen
  3. 1:1
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3
Q

What androgens are needed for the production of aldosterone?

A

18-Hydroxysteroid Androgens

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4
Q

What are the three stimulators of aldosterone?

A
  1. Angiotensin II
  2. ACTH
  3. Elevated plasma/serum potassium
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5
Q

What are the four suppressors of aldosterone?

A
  1. Progesterone and Dopamine
  2. ANP
  3. Intracellular Calcium
  4. Drugs (ketoconazole, ACE inhibitors, NSAIDs, and heparin)
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6
Q

Clinical Disorders of Aldosterone

  • Caused by an aldosterone-secreting adrenal adenoma
  • Is associated with elevated plasma aldosterone and low plasma renin
  • Presents with hypertension, hypokalemia, mild hypernatremia, and metabolic alkalosis
A

Primary Hyperaldosteronism (Conn’s Disease)

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7
Q

Clinical Disorders of Aldosterone

What is the screening test for Primary Hyperaldosteronism (Conn’s Disease)?

A

Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA)

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8
Q

Clinical Disorders of Aldosterone

In the Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA) for Primary Hyperaldosteronism, a PAC level and PAC/PRA ratio of what would be suggestive for the disease?

A
  1. PAC level > 15ng/dL
  2. PAC/PRA ratio of > 30
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9
Q

Clinical Disorders of Aldosterone

In the Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA) for Primary Hyperaldosteronism, a PAC/PRA ratio of what would be diagnostic for the disease?

A

PAC/PRA ratio of > 50

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10
Q

Clinical Disorders of Aldosterone

What are the 2 confirmatory tests for Primary Hyperaldosteronism (Conn’s Disease)?

A
  1. Saline Suppression Test
  2. Captopril Suppression Test
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11
Q

Clinical Disorders of Aldosterone

This test:
- Involves infusing 2L of 0.9% saline over 4 hours or administering 10-12 mg NaCl tablets daily for 3 days
- Negative result: aldosterone is suppressed
- Positive result: aldosterone level > 10ng/dL

A

Saline Suppression Test

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12
Q

Clinical Disorders of Aldosterone

A PAC level of 5 to 9 ng/dL is indicative of what disorder?

A

Idiopathic Hyperaldosteronism

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13
Q

Clinical Disorders of Aldosterone

This test:
- Is a substitute for the Oral Salt Tolerance Test
- Is a non-invasive procedure of measuring aldosterone levels

A

Captopril Suppression Test

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14
Q

Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA)

This suggests a primary defect in aldosterone secretion (Addison’s disease, heparin therapy, and an aldosterone biosynthetic defect)

A. High PRA and high PAC
B. High PRA and low PAC
C. Low PRA and high PAC
D. Low PRA and low PAC

A

B. High PRA and low PAC

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15
Q

Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA)

Suggests primary hyperaldosteronism (Conn’s disease due to an adrenal adenoma or bilateral hyperplasia)

A. High PRA and high PAC
B. High PRA and low PAC
C. Low PRA and high PAC
D. Low PRA and low PAC

A

C. Low PRA and high PAC

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16
Q

Plasma Aldosterone Concentration/Plasma Renin Activity Ratio (PAC/PRA)

Presents with Liddle’s syndrome, hyporeninemic hypoaldosteronism, 11-hydroxylase deficiency, and drug-induced mineralocorticoid excess

A. High PRA and high PAC
B. High PRA and low PAC
C. Low PRA and high PAC
D. Low PRA and low PAC

A

D. Low PRA and low PAC

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17
Q

Clinical Disorders of Aldosterone

  • Occurs as a result of excessive renin production
  • Presents with elevated plasma levels of aldosterone and renin
A

Secondary Hyperaldosteronism

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18
Q

Clinical Disorders of Aldosterone

Renal artery stenosis, diuretic therapy, malignant hypertension, and congenital defects in renal salt transport such as Bartter’s syndrome and Gitelman’s syndrome are all diseases of secondary hyperaldosteronism that cause what symptom?

A

Hypokalemia

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19
Q

Clinical Disorders of Aldosterone

  • A congenital disorder characteried by increased ENAC activity in the collecting ducts due to the absence of aldosterone
  • It resembles primary aldosteronism clinically, but aldosterone level is low and with the absence of hypertension
A

Liddle’s Syndrome (Pseudohyperaldosteronism)

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20
Q

Clinical Disorders of Aldosterone

  • A bumetanide-sensitive chloride channel mutation
  • A rare potassium-losing autosomal recessive disorder caused by defective NaCl reabsorption in the thick ascending loop of Henle
  • Presents with elevated aldosterone and renin
A

Bartter’s Syndrome

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21
Q

Clinical Disorders of Aldosterone

  • A thiazide-sensitive transporter mutation
  • Associated with a defect in NaCl reabsorption that occurs in the DCT
  • Accompanied by elevated aldosterone
A

Gitelman’s Syndrome

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22
Q

Clinical Disorders of Aldosterone

  • This is due to the destruction of the adrenal glands and deficiency of glucocorticoids
  • Associated with a 21-Hydroxylase deficiency
  • Presents with hyperkalemia and metabolic acidosis
A

Hypoaldosteronism

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23
Q

Clinical Disorders of Aldosterone

What 2 tests can be used for diagnosing hypoaldosteronism?

A
  1. Furosemide Stimulation/Upright Posture Test
  2. Saline Suppression Test
24
Q

Clinical Disorders of Aldosterone

In the Furosemide Stimulation/Upright Posture Test for Hypoaldosteronism, what is the positive result?

A

Low plasma aldosterone level

25
Q

Clinical Disorders of Aldosterone

In the Saline Suppression Test for Hypoaldosteronism, what is the positive result?

A

High aldosterone level

26
Q
  • These serve as precursors for the production of androgens and estrogens in tissue
  • Are produced as byproducts of cortisol synthesis that are regulated by ACTH
A

Weak Androgens

27
Q

What are the 2 precursors of androgens?

A
  1. Pregnenolone
  2. 17-Hydroxypregnenolone
28
Q

What are 2 examples of androgens?

A
  1. Dehydroepiandrostenedione (DHEA)
  2. Androstenedione
29
Q
  1. Excessive production of androgens results in ____ (3)
  2. Excessive production can be confirmed by measuring ____ and ____
A
  1. Virilization, Infertility, and Amenorrhea
  2. Total and Free Testosterone
30
Q

This is composed primarily of chromaffin cells that secrete catecholamines

A

Adrenal Medulla

31
Q

Adrenal Medulla

What is the precursor for catecholamines (e.g. dopamine and norepinephrine)?

A

L-Tyrosine

32
Q

Adrenal Medulla

Norepinephrine and epinephrine are metabolized by what 2 enzymes to form metanephrines and VMA?

A
  1. Monoamine oxidase
  2. Cathecol-O-methyl transferase (COMT)
33
Q

Adrenal Medulla

This enzyme catalyzes the conversion of norepinephrine to epinephrine especially in times of stress

A

Phenylethanolamine N-methyltransferase (PNMT)

34
Q

Adrenal Medulla

What is the ratio of norepinephrine to epinephrine in serum?

35
Q

Adrenal Medulla

The medullary hormones are ____% protein-bound

36
Q

Adrenal Medulla

What three hormones are produced by the adrenal medulla?

A
  1. Norepinephrine
  2. Epinephrine
  3. Dopamine
37
Q

Hormones of the Medulla

  • A primary amine
  • Produced by the sympathetic ganglia or the adrenal medulla itself
  • Highest concentrations are found in the brain
  • Acts as neurotransmitters in both the CNS and sympathetic nervous system
A

Norepinephrine

38
Q

Hormones of the Medulla

What is the major norepinephrine metabolite in the CSF and is also found in urine?

A

3-methoxy-4-hydroxyphenylglycol (MHPG)

39
Q

Hormones of the Medulla

What is the major norepinephrine metabolite in the blood?

A

Vanillylmandelic acid (VMA)

40
Q

Hormones of the Medulla

  • Aka Adrenaline (Fight or Flight Hormone)
  • The most abundant medullary hormone
  • Produced from norepinephrine and comes only from the adrenal
A

Epinephrine

41
Q

Hormones of the Medulla

  • This increases glucose concentrations
  • Best collected from an indwelling catheter
  • Its major metabolites are VMA, metanephrines, normetanephrines, and HMA
A

Epinephrine

42
Q

Hormones of the Medulla

  • A primary amine which is the major intact hormone in urine
  • A catecholamine produced in the body by the decarboxylation of 3,4-dihydroxyphenylalanine
  • Highest concentrations are found in the brain
43
Q

Hormones of the Medulla

What is the major metabolite of dopamine?

A

Homovanillic acid (HVA)

44
Q

Clinical Disorders of the Medulla

  1. A medullary tumor abundant in adults
  2. A medullary tumor abundant in children
A
  1. Pheochromocytoma
  2. Neuroblastoma
45
Q

Clinical Disorders of the Medulla

What 2 methods can diagnose pheochromocytomas and neuroblastomas?

A
  1. Chromatography
  2. Radioimmunoassays
46
Q

Clinical Disorders of the Medulla

  • Tumors of the adrenal medulla or sympathetic ganglia
  • Commonly seen in the 3rd to 5th decade of life
  • Due to the overproduction of catecholamines
  • Presents with tachycardia, headaches, tightness of chest, sweating, and hypertension
A

Pheochromocytoma

47
Q

Clinical Disorders of the Medulla

What is the screening test for Pheochromocytomas?

A

High Plasma Metanephrines and Normetanephrines by HPLC

Note: Stop intake of caffeine, nicotine, and anti-depressants for 5 days

48
Q

Clinical Disorders of the Medulla

What is the confirmatory test for Pheochromocytomas?

A

High 24-hour Urinary Excretion of Metanephrines and Normetanephrines

49
Q

Clinical Disorders of the Medulla

Pharmacological Tests for Pheochromocytomas:
- Differentiates pheochromocytomas (not suppressed) from neurogenic hypertension (50% decreased cathecolamines)
- Used only if the plasma catecholamines are greater than 1000pg/mL

A

Clonidine Suppression Test

50
Q

Clinical Disorders of the Medulla

Pharmacological Tests for Pheochromocytomas:
- Used if it is highly suggestive of pheochromocytoma
- Only if the patient’s blood pressure is normal and cathecolamines are modestly elevated (3-fold increase)

A

Glucagon Stimulation Test

51
Q

Clinical Disorders of the Medulla

  • A fatal malignant condition in children resulting to excessive production of norepinephrine
  • Positive result: high urinary excretion of HVA or VMA or both and dopamine
  • Specimens for testing are 24H urine and plasma
A

Neuroblastoma

52
Q

Patient Preparation for Medullary Tests

  1. The patient should undergo overnight ____
  2. Avoid smoking or caffeinated beverages at least ____ hours prior to collection
  3. The patient is placed in a ____ position in a quiet environment and a ____ lock is inserted intravenously
A
  1. Fasting
  2. 24 hours
  3. Reclining; heparin
53
Q

Specimen Considerations for Medullary Tests

  1. The preferred method of blood collection to eliminate anxiety of venipuncture
  2. In urine preservation, what preservative is used?
A
  1. Catheterization
  2. 10mL of 6N HCl
54
Q

Patient Preparation for Medullary Tests

  1. After 20 to 30 minutes, blood is collected in a ____ EDTA tube
  2. Plasma concentrations of cathecolamines are affected by body positioning and samples must be collected after ____ minutes in a stable position
A
  1. Pre-chilled EDTA
  2. 30 minutes
55
Q

Specimen Considerations for Medullary Tests

  1. This is a test to assess the quality of urine collection (0.8 g/day of urine creatinine is needed to validate its completeness)
  2. Blood samples must be transported on ____
A
  1. 24H urine creatinine test
  2. Ice