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LMP301 Lecture 9: Adrenal Disease Flashcards

Adrenal Diseases

1
Q

Where are the adrenal glands?

A

On top of the kidneys

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2
Q

What happens to the adrenal gland during stressful situations?

A

enlarge

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3
Q

Adrenal gland is divided into…

A
  • cortex

- medulla

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4
Q

The cortex of the adrenal gland is divided into…

A
  • zona glomerulosa
  • zona fasciculata
  • zona reticularis
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5
Q

The adrenal medulla is a part of the…

A

SNS

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6
Q

Zona glomerulosa secretes….

A

aldosterone

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7
Q

zona fasciculata secretes…

A
  • cortisol

- adrenal androgens & estrogens

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8
Q

zona reticularis secretes…

A
  • cortisol

- adrenal androgens & estrogens

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9
Q

The adrenal medulla secretes…

A
  • E
  • NE
  • Dopamine
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10
Q

What is the first enzyme to act on cholesterol during the biosynthesis of steroid hormones?

A

Cholesterol side chain cleavage hormone

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11
Q

What are the steroid hormones?

A
  • aldosterone
  • cortisol
  • testosterone
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12
Q

ACTH

A

Signal needed for biosynthesis of steroid hormones

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13
Q

Enzyme cascade for aldosterone synthesis

A
  1. Cholesterol side chain cleavage hormone
  2. 3B-hydroxysteroid dehydrogenase
  3. 21 OH’ase
  4. 11 OH’ase
  5. 18 OH’ase
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14
Q

Enzyme cascade for cortisol synthesis

A
  1. Cholesterol side chain cleavage hormone
  2. 17 OH’ase
  3. 3B-hydroxysteroid dehydrogenase
  4. 21 OH’ase
  5. 11 OH’ase
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15
Q

Enzyme cascade for testosterone synthesis

A
  1. Cholesterol side chain cleavage hormone
  2. 17 OH’ase
  3. 17,20 OH’ase
  4. 3B-hydroxysteroid dehydrogenase
  5. 21 OH’ase
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16
Q

Which enzyme is unique to aldosterone synthesis?

A

18 OH’ase

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17
Q

Pathway of aldosterone synthesis

A
  1. Cholesterol
  2. Pregnenolone
  3. Progesterone
  4. Deoxycorticosterone
  5. Corticosterone
  6. Aldosterone
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18
Q

Pathway of cortisol synthesis

A
  1. Cholesterol
  2. Pregnenolone
  3. 17-OH pregnenolone
  4. 17-OH progesterone
  5. 11-deoxycortisol
  6. Cortisol
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19
Q

Pathway of testosterone synthesis

A
  1. Cholesterol
  2. Pregnenolone
  3. 17-OH pregnenolone
  4. DHEA
  5. Androstenedione
  6. Testosterone
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20
Q

Cortisol can affect…

A

metabolism of carbs, proteins, and fat

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21
Q

Effect of cortisol on carb metabolism

A

Raise blood glucose

  • gluconeogenesis in liver
  • reduce glucose used and stored
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22
Q

Effect of cortisol on protein metabolism

A

Break down muscle

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23
Q

Effect of cortisol on fat metabolism

A

Break down fat

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24
Q

What happens when glucocorticoids are present in excess?

A

cause central distribution of fat -> goes to face, neck, trunk

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25
How do cortisol travel in the body?
90 - 98% is bound to proteins - albumin - cortisol binding globulin (CBG)
26
When can an increase of CBG be found?
- Pregnancy | - Estrogen treatment
27
How is cortisol metabolized in the body?
1. Liver | 2. Excreted in urine
28
Axis that controls cortisol secretion
Hypothalamic-pituitary-adrenaocortical axis 1. Hypothalamus -> CRH 2. a. pituitary -> ACTH 3. adrenal cortex -> cortisol
29
Feedback of cortisol
Cortisol inhibits ACTH and CRH
30
What stimulates production of CRH?
Stress | Sleep/wake
31
What is too much cortisol called?
Cushing's syndrome
32
Possible causes of Cushing's syndrome
- tumour at pituitary (ACTH overproduction) - ectopic ACTH - adrenal gland tumour (excess cortisol) - exogenous glucocorticoids
33
Ectopic ACTH
ACTH produced by cells other than the pituitary
34
What cells may produce ACTH, other than pituitary?
small cell carcinoma in the lung
35
some sources of exogenous glucocorticoids
- oral - inhaled - topical creams
36
Clinical features of Cushing's Syndrome
- Acne - Moon face - Osteoporosis - abdominal fat - stripes on abdomen - high BP - buffalo hump
37
At what time during the day is cortisol levels the highest?
Morning
38
What is used to screen for Cushing's?
24h urine test: - High cortisol in the urine - Can also be caused by stress & obesity
39
What tests are used to diagnose Cushing's?
- plasma cortisol - low dose dexamethasone test - high dose dexamethasone test - plasma ACTH
40
dexamethasone is...
a cortisol analogue
41
When is plasma cortisol measured?
8AM | 10 PM
42
What is looked for in a plasma cortisol test?
Cortisol will not vary with time of day in patients with Cushing's
43
What is looked for in a low dose dexamethasone test?
- normal: slow cortisol production by 50% | - Cushing's: can't slow cortisol production
44
What is looked for in a high dose dexamethasone test?
- Cushing's disease: slow cortisol productivity by 50% | - Other causes: will not slow cortisol productivity
45
Why is high dose dexamethasone test used?
Which of the Cushing's syndrome causes it was
46
Difference between Cushing's disease and syndrome
Disease: cause is specifically a pituitary tumour producing too much ACTH Syndrome: tissues being exposed to too much cholesterol for too long
47
What is looked for in plasma ACTH?
- high ACTH = ectopic ACTH tumors | - low ACTH = adrenal tumours
48
What order are tests used to diagnose Cushing's?
1. Screening: plasma cortisol 2. Confirmation: low dose dexamethasone 3. Differential diagnosis of cause: high dose dexamethasone; plasma ACTH
49
Cortisol is the counter hormone of...
insulin
50
Aldosterone is only produced in the zona glomerulosa because...
- doesn't have 17 OH'ase - have 18 OH'ase - have 18 hydroxysteroid dehydrogenase
51
What regulates aldosterone production and secretion?
- Renin-ANG II system (major) - ACTH - Potassium
52
Biological effect of aldosterone
Raise BP: - Na and H2O retention - K and H secretion
53
Why is hypertension seen in patients with Cushing's?
all cortisol precursors and cortisol have some kind of mineralocorticoid effects (SAME EFFECT AS ALDOSTERONE)
54
Renin is released in response to...
- Low tubular Na+ - Low BP at renal arteries - SNS stimulation
55
Increased K+ has what effect on aldosterone?
Stimulates secretion/production
56
ACTH has what effect on aldosterone?
Very little effect, especially in normal situations
57
Function of renin
angiotensinogen -> ANG I
58
Function of ACE
ANG I -> ANG II
59
Clinical features of excess aldosterone
- high BP - neuromuscular weakness due to lack of K+ - polydipsia & polyuria
60
Why is a symptom of excess aldosterone polydipsia & polyuria?
- hypokalemia causes ADH resistance = more water secreted
61
nephrotic diabetes insipidus is caused by...
ADH resistance
62
High aldosterone is...
Conn's syndrome | Low-renin hyperaldosteronism
63
High aldosterone is usually due to...
adrenal tumours
64
Conn's syndrome is ___ hyperaldosteronism
primary
65
Secondary hyperaldosteronism = high ___
renin
66
Secondary hyperaldosteronism is usually associated with...
renal, heart, liver disease
67
Secondary hyperaldosteronism is also known as...
renal artery stenosis
68
Which type of hyperaldosteronism is more common?
secondary
69
Primary hyperaldosteronism: sequence of events
1. adrenal gland secretes a lot of aldosterone 2. aldosterone causes increased Na+ retention & increase K+ loss 4. High Na+ causes decreased renin 5. causes decreased ANG II
70
Secondary hyperaldosteronism: sequence of events
1. Decreased blood flow at renal artery 2. Increased renin 3. Increased ANG II 4. Increased aldosterone 5. Increased Na+ retention 6. Increased K+ loss (also caused by high aldosterone)
71
Diagnosis of hyperaldosteronism
- low K+ (a lot excreted) - High aldosterone - renin low (primary) - renin high (secondary)
72
Acid-base status in patients with hyperaldosteronism?
Metabolic alkalosis (H+ secreted because Na+ is retained)
73
Low aldosterone is ___ disease
Addison's
74
Addison's disease (and what is it due to?)
Low aldosterone | - Due to autoimmune destruction of the cortex
75
Causes of hypoadrenalism
- Autoimmune destruction of cortex - Gland destruction caused by tuberculosis, infections, cancer - Secondary / tertiary hypoadrenalism caused by ACTH deficiency (pituitary / hypothalamus problem) - Long-term corticosteroid therapy: breaks the HPA axis
76
Difference between primary and secondary and tertiary hypoadrenalism
- primary: problem at adrenal gland (ACTH high) - secondary: problem at a. pituitary (ACTH low) - tertiary: problem at hypothalamus (CRH low)
77
Clinical features of hypoadrenalism
- lethargy - anorexia - weight loss - increased pigment in hand and mouth (Addison's) - abdominal pain
78
Why is there increased pigment for Addison's?
melanocyte-stimulating hormone is secreted along with ACTH (which is secreted in high amounts)
79
Acute crisis for hypoadrenalism
- dehydration - hypotension - nausea - vomiting
80
Biochemical features of hypoadrenalism
- low NA+ - high K+ - mild metabolic acidosis - hyperuremia - hypoglycemia - high ACTH (primary)
81
Diagnosis of hypoadrenalism
Short Synacthen test
82
Problem with testing serum aldosterone
Have to have normal to compare to (the normal must be from the same person)
83
Synacthen is a ____ analogue
1-24 ACTH
84
Short Synacthen test is also called...
ACTH stimulation test
85
Short Synacthen test
1. measure serum cortisol 2. give synacthen 3. measure cortisol 30 min later
86
Interpreting short Synacthen test
Normal: cortisol rise rapidly Addison's: no change Adrenal atropy: slight rise
87
Anti-hypertensive agents used (RAAS)
- ACE inhibitor - ANG II receptor blocker - Block aldosterone receptor - Block renin receptor

LMP301 (18 decks)

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