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Pathophysiology > Lectures 3 and 4 > Flashcards

Lectures 3 and 4 Flashcards

1
Q

True or False: Familial Hyperaldosteronism (Type 1) is caused by overexpression of Cyp11B2 and, therefore, leads to overproduction of hormones

A

True

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2
Q

Polyclonal and Monoclonal Expansions arise due to proliferation (increase in number of hormone producing cells) - lead to ___ production of hormones

A

over

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3
Q

Graves Disease is proliferation due to: abnormal stimulus and it is associated with:
A. Polyclonal Expansion
B. Monoclonal Expansion

A

A. Polyclonal Expansion

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4
Q

Monoclonal expansions are due to proliferation of somatic mutation. What are two types of tumors that may result as a consequence?

A

1) Pituitary tumor
2) Parathyroid tumor

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5
Q

True or False: Deletion of GH gene can result in abnormal hormone synthesis while mutations in calcium receptor can result in hypoparathyroidism

A

True

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6
Q

In ____ Syndrome, there is abnormal development of hormone producing cells, which leads to: hypogonadism

A

Kallman Syndrome

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7
Q

True or False: Auto-immunity (T1DM), genetics, and surgery can result in hormone underproduction

A

True

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8
Q

True or False: Endocrine gland tumors usually lead to excess of hormone production

A

True

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9
Q

True or False: Lack of endocrine hormones due to endocrine tumor can result in: thyroid cancer, non-functioning pituitary tumor, or metastasis

A

True

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10
Q

Iodothyronine Deiodinase Type 3 (D3) expressing tumor deactivates T3 and T4 leading to a condition known as _____ ____

A

Consumptive Hypothyroidism

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11
Q

What are the three major portions of the adrenal gland cortex? What molecule are they associated with?

A

Zona Glomerulosa
- Aldosterone

Zona Fasiculata
- Cortisol

Zona Reticularis
- Androgens

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12
Q

True or False: All coricosteroids have cholesterol backbone

A

True

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13
Q

___ are made on demand and have a slow response to stimulus

A

Steroid hormones

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14
Q

The zona glomerulosa is the only region that expresses CYP_____.

However, it does not express CYP____

A
  • expresses: CYP11B2
  • does not express: CYP17A1 (17a-hydroxylase)
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15
Q

High levels of cytochrome b5 confers 17,20-lyase activity on CYP17A1 located in the ___
A. Zona Glomerulosa
B. Zona Reticularis
C. Zona Fasiculata

A

B. Zona Reticularis

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16
Q

There is no 17-hydroxylase co-factor in the Zona ____

A

Zona Fasciculata

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17
Q

ACTH regulates the synthesis of cortisol and testosterone (via their respective zones) – but does NOT regulate it in the Zona ___

A

glomerulosa

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18
Q

ACTH is not involves in the synthesis of:
A. Aldosterone
B. Testosterone
C. Cortisol

A

A. Aldosterone

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19
Q

Mineralcorticoids regulate extracellular volume and control homeostasis of __
A. Na
B. Cl
C. K
D. Ca

A

C. K

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20
Q

Which of the following actions does not belong to the mineralcorticoids?
A. Upregulate and activate basolateral Na/K pumps and ENaC/s
B. Secrete Na/H20 into the blood
C. Reabsorb Na/H2O into blood
D. Secrete K ions into urine

A

B. Secrete Na/H20 into the blood

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21
Q

How does Aldostersone affect:
- Na reabsorption
- Blood volume
- Renal perfusion pressure
- Renin release

A

Aldosterone increases all except renin release (decrease)

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22
Q

What effect does Ang II have on blood pressure and renin release?

A

Ang II causes vasoconstriction, thereby increasing blood pressure and decreasing renin release

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23
Q

____ is a condition associated with excess mineralcorticoids

___ is a syndrome or disease associated with excess cortisol

A

Hyperaldosteronism
Cushing Syndrome or Disease

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24
Q

What is the main symptom see in primary hyperaldosteronism?
A. Chest pain
B. Bruising
C. Striae
D. Hypertension

A

D. Hypertension

  • Na retention
  • Most common cause of secondary HTN
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25
Q

Is hypokalemia a good predictor of primary aldosteronism?

A

No

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26
Q

To diagnose primary aldosteronism, plasma ___ concentration must be ELEVATED while plasma ___ activity or concentration must be LOW

A

elevated = plasma aldosterone concentration

low = PRA (plasma renin activity) or PRC (plasma renin concentration)

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27
Q

True or False: Familial hyperaldosteronism type 1 (inappropriate ACTH-dependent activity of CYP11B2) can lead to primary aldosteronism

A

True

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28
Q

What is the cause of a majority (60%) of primary aldosteronism?
A. Familial Hyperaldosteronism Type 1
B. Conn Syndrome (Adrenocortical Neoplasm)
C. Bilateral Idiopathic Hyperaldosteronism

A

C. Bilateral Idiopathic Hyperaldosteronism

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29
Q

What is the most common cause of Conn Syndrome (Adrenocortical Neoplasm)?

A

APA (aldosterone producing adenoma)
- rare: adrenocortical carcinoma

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30
Q

A sodium restricted diet and which two MC receptor antagonists can be used to treat Bilateral Idiopathic Hyperaldosteronism (form of primary hyperaldosteronism)?

A

Eplerenone
Spironolactone

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31
Q

True or False: A unilateral adrenalectomy can treat ____ ___and ____ ___

A

adrenal adenomas and unilateral hyperplasias

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32
Q

____ is secreted in a pulsatile fashion with a circadian rhythm

A

ACTH

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33
Q

When is one’s ACTH at its highest?

A

Upon waking
(lowest in evening)

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34
Q

How does cortisol affect the skeletal muscle?

A

1) decreases glucose uptake - [also case in adipocytes]
2) net protein catabolism
3) suppress synthesis of amino acid transporters

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35
Q

True or False: Cortisol decreases epinephrine synthesis in adrenal medulla and decreases glucose release in the liver

A

False - cortisol increase epi and glucose release

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36
Q

Cortisol is permissive for the actions of which five molecules?

A

NE
Epi
ADH (vasopressin)
GH
Glucagon

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37
Q

Striae, obesity/weight gain, round face, dorsal fat pad, and ecchymoses is most suggestive of ______
A. excess aldosterone
B. excess androgens
C. excess cortisol

A

C. excess cortisol (hypercortisolemia)

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38
Q

A patient with hypercortisolemia has an adrenocortical tumor and has been taking prednisone for a long-term infection. Is her excess cortisol level likely ACTH independent or ACTH dependent?

A

ACTH-independent

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39
Q

Pituitary hypersecretion of ACTH can lead to ___ Disease (ACTH dependent). The majority of ACTH-secreting masses are ___ or ___

A

Cushing’s Disease; adenomas/microadenomas

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40
Q

Four common causes of Cushing’s Syndrome?

A

1) Taking ‘roids
2) Adrenocortical tumor
3) Ectopic secretin of CRH
4) Ectopic secretion of ACTH by non-pit tumor

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41
Q

B/l adrenocortical hyperplasia with widening of ZF and ZR is associated with:
A. Adrenocortical Tumors
B. Cushing’s Disease
C. Cushing’s Syndrome

A

B. Cushing’s Disease

42
Q

True or False: Both ACTH and Cortisol follow a circadian rhythm, meaning levels are highest in AM and low in the PM

A

True

43
Q

True or False: There is resistance to normal GC feedback inhibition in Cushing’s Syndrome

A

False - this is the case in Cushing’s Disease

44
Q

How are ACTH pulse frequency, pulse amplitude, and circadian rhythmic secretion affected by Cushing’s Disease?

A

Frequency and pulse amplitude is increased
Circadian rhythmic secretion is lost

45
Q

Transphenoidal hypophysectomy is used to treat ___ _____

A

Cushing’s Disease

46
Q

What is the most common cause of pathogenesis in Cushing’s Syndrome?

A

Iatrogenic Cushing’s Syndrome

47
Q

What is the most common endogenous cause of Cushing’s Syndrome?

A

1) Primary adrenal neoplasm (carcinoma or adenoma)
2) Secretion of ectopic ACTH (non-pit) tumor
- small cell carcinoma of lung

48
Q

In Cushing’s Syndrome, non-pituitary tumors that secrete ACTH are frequently small cell _____ of the lung

A

carcinoma

note: rapid decline in pt health is to be expected

49
Q

In Cushing’s Syndrome, a patient with a primary adrenal neoplasm (e.g adenoma or carcinoma) have ACTH-___ secretion of cortisol (elevated cortisol and low ACTH)

A

ACTH-independent

50
Q

How are adrenal adenomas treated?

A

Unilateral adrenalectomy

51
Q

What are the effects of abruptly decreasing serum free cortisol?

A

Suppress endogenous ACTH secretion
Lower plasma ACTH
Atrophy of adrenal cortex
Limited endogenous cortisol synthesis

**hard time maintaining blood pressure and elevating glucose during stress

52
Q

What two medications can be used to inhibit steroidogenic enzymes to treat Cushing’s Syndrome?

A

Metyrapone and Ketoconazole

53
Q

True or False: Ketoconazole is more selective for cortisol and does not affect the synthesis of other steroid hormones

A

False - Metyrapone more closely targets cortisol and is more selective for cortisol

Ketoconazole does affect synthesis of other steroid hormones - less specific for cortisol

54
Q

Which of the following is a glucocorticoid receptor antagonists used for treating patients with Cushing’s Syndrome and accompany hyperglycermia?
A. Mitotane
B. Mifepristone
C. Metyrapone
D. Octreotide

A

B. Mifepristone

55
Q

Which of the following drugs treats Cushing’s Syndrome by suppressing ACTH secretion?
A. Mitotane
B. Mifepristone
C. Metyrapone
D. Octreotide

A

D. Octreotide

56
Q

Which of the following is a chemotherapeutic drug that is primarily used to treat adrenal carcinomas (Cushing’s Syndrome)?
A. Mitotane
B. Mifepristone
C. Metyrapone
D. Octreotide

A

A. Mitotane

57
Q

A patient has decreasing height percentile and increasing weight, as well as osteoporosis and HTN. What should be ruled out in their case?

A

Cushing’s Syndrome

58
Q

Unexplained osteoporosis, striae, muscle weakness, and easy bruising are the most discriminating signs of ____ ____

A

Cushing’s Syndrome

59
Q

Which of the following methods for measuring cortisol is an integrated measure of serum free cortisol that can be normal in 8-15% of Cushing’s Syndrome patients?
A. Longer Low Dose Dex (2mg) Suppression
B. Low Dose Dex (1 mg) Suppression
C. Late Night Salivary Cortisol
D. Urinary Free Cortisol Excretion (24 hrs)

A

D. Urinary Free Cortisol Excretion (24 hrs)

60
Q

True or False: In Urinary Free Cortisol Excretion, as cortisol secretion increases, binding capacity of cortisol-binding globulin is exceeded and results in a disproportionate rise in urinary free cortisol

A

True

61
Q

Where is cortisol oxidized, reduced (conjugated) or hydroxylated?
A. Liver
B. Kidney
C. Urine

A

A. Liver

62
Q

Where is cortisol reduced, thereby preventing cortisol activation of aldosterone-R?
A. Liver
B. Kidney
C. Urine

A

B. Kidney

63
Q

______ is measured to identify the cortisol level in urine

A

17-hydroxycorticosteroids

64
Q

Which of the following molecules is elevated in hypercortisolemia?
A. Tetrohydrocortisols
B. Cortols
C. 6 beta-hydroxycortisol

A

C. 6 beta-hydroxycortisol

65
Q

Hypercortisolemia results in elevated urinary ____ and its metabolites

A

free cortisol

66
Q

Which of the following more closely reflects serum free cortisol and is 96% specific for dx of Cushing’s Syndrome?
A. Longer Low Dose Dex (2mg) Suppression
B. Low Dose Dex (1 mg) Suppression
C. Late Night Salivary Cortisol
D. Urinary Free Cortisol Excretion (24 hrs)

A

C. Late Night Salivary Cortisol

  • two measurements between 23-2400
67
Q

How does a supraphysiologic dose of dexamethasone affect ACTH and cortisol secretion in normal person vs. Cushing’s Syndrome patient?

A

Normal: suppression of ACTH and cortisol secretion
Cushing’s Syndrome: failure to suppress

68
Q

What could cause false positive in the longer, low-dose dexamethasone suppression test (2 mg/day for 48 hrs)?

A

Certain drugs may increased clearance of dexamethasone

69
Q

A patient has Cushing’s Syndrome. Which is most likely the dx?
A. ACTH dependent Cushing’s Syndrome
B. ACTH independent Cushing’s Syndrome

A

A. ACTH dependent Cushing’s Syndrome

70
Q

If morning plasma ACTH (8-10 AM) is below normal, what does that suggest?
A. Ectopic ACTH
B. Adrenal tumor
C. Cushing’s Disease

A

B. Adrenal tumor
- ACTH independent hypercortisolemia

71
Q

Measuring ______ can aid in differentiating between ACTH -dependent and ACTH-independent causes of Cushing’s Syndrome

A

morning plasma ACTH

72
Q

Normal ACTH levels at 9 AM, with MODESTLY elevated in the remainder suggests:
A. Ectopic ACTH
B. Adrenal tumor
C. Cushing’s Disease

A

C. Cushing’s Disease

73
Q

Extremely high ACTH levels indicate:
A. Ectopic ACTH
B. Adrenal tumor
C. Cushing’s Disease

A

A. Ectopic ACTH

74
Q

True or False: In Cushing’s Disease, the negative feedback control of ACTH is reset to a higher level than normal

A

True

75
Q

True or False: In Cushing’s Disease, cortisol levels may not suppressed with low level dexa, but do with high doses

A

True

76
Q

In the high dose dexa test, ___ mg of dex is given Q6hrs for 48hrs (16 mg total) and plasma/urinary free cortisol is measured at 0 and 48 hrs.

It is a positive test in 90% of patients with _____

A

2 mg; Cushing’s Disease

77
Q

A CRH test is done on a patient and there is no response. What is the dx?
A. Normal
B. Cushing’s disease
C. Ectopic ACTH syndrome

A

C. Ectopic ACTH syndrome

78
Q

A CRH test is done on a patient and there is a more than 50% increased in ACTH and more than 20% increase in cortisol. What is the dx?
A. Normal
B. Cushing’s disease
C. Ectopic ACTH syndrome

A

B. Cushing’s disease

79
Q

A CRH test is done on a patient and there is a 15-20% increased in ACTH and cortisol. What is the dx?
A. Normal
B. Cushing’s disease
C. Ectopic ACTH syndrome

A

A. Normal

80
Q

What is the method of choice for examining the pituitary?

A

MRI

81
Q

If a patient has hypokalemic alkalosis, they most likely have:
A. Cushing’s Disease
B. Ectopic ACTH syndrome

A

B. Ectopic ACTH syndrome

82
Q

What is the mechanism by which hypokalemic alkalosis develops in patient’s with ectopic ACTH syndrome?

A
  • Cortisol saturates HSD11B2, result in: cortisol-induced MC HTN
  • Also have high levels of DOC (deoxycorticosterone) – which is an ACTH dependent MC
83
Q

High definition CT/MRI scan of thorax, abdomen, and pelvis can be used to detect ______

A

ectopic ACTH syndrome

84
Q

Adrenal disease is an example of ___ adrenocortical insufficiency

ACTH deficiency is an example of ___ adrenocortical insufficiency

A

Primary
Secondary

85
Q

True or False: Low glucocorticoids and low androgens is found in both ACTH deficiency (secondary adrenocortical insufficiency) and adrenal disease (primary AD insufficiency)

A

True

86
Q

Although GC are low in adrenal disease, how is ACTH affected?

A

ACTH is elevated

87
Q

Hyperpigementation of skin, progressive weakness and fatigue, as well as GI disturbances suggests which primary adrenocortical insufficiency?

A

Addison’s Disease

88
Q

In anterior pituitary corticotrophs, pre-opiomelanocortin (POMC) can be cleaved into which four molecules?

A

N-terminal protein
Joining protein
ACTH
and B-lipotropin

89
Q

In melanocytes and hypothalamus, __ is produced, allow for appetite regulation and melanin production

A

a-MSH

90
Q

True or False: a-MSH regulates weightloss via acting in the hypothalamus

A

True

91
Q

What does it mean if a patient with Addison’s Disease has low cortisol secretion and low ACTH?
A. Secondary adrenocortical insufficiency
B. Primary adrenocortical insufficiency

A

A. Secondary adrenocortical insufficiency

92
Q

If a patient has low cortisol secretion and high ACTH. Upon measuring Aldosterone levels, they are low. What is the dx?
A. Secondary adrenocortical insufficiency
B. Primary adrenocortical insufficiency

A

B. Primary adrenocortical insufficiency

93
Q

What is responsible for 70% of all cases of Addison’s Disease in the West?

What is responsible for Addison’s disease worldwide?

A

Autoimmune adrenalitis
Infectious disease

94
Q

In autoimmune adrenalitis, there are autoimmune antibodies to which two key steroidogenic enzymes?

A

21-hydroxylase (CYP21A2)
17-hydroxylase (CYP17)

95
Q

In autoimmune adrenalitis, there are autoantibodies to CYP21A2 , which is found in the Zona __ and Zona ___

In autoimmune adrenalitis, there are autoantibodies to CYP17, which is found in the Zona ___ and Zona ___

A
  • CYP21A2: Zone glomerulosa and Zona fasciculata
  • CYP17: Zona fasciculata and Zona reticularis
96
Q

How can long-term replacement therapy be used to treat Addison’s Disease?

A

Hydrocortisone/Pred to mimic normal cortisol secretion
- Large dose upon waking
- Small dose at night

97
Q

___ is a mineralcorticoid replacement and liberal salt intake can be used to treat Addison’s Disease long-term

A

Fludrocortisone

98
Q

___ is an androgen replacement in women that can treat Addison’s Disease

A

DHEA

99
Q

Three causes of secondary adrenocorticoid insufficiency (pituitary hypofunction)?

A

1) Pituitary surgery
2) Hypothalamic impaired CRH secretion
3) Pituitary adenoma that comprises normal function - low or absent ACTH

100
Q

A patient has severe Cushing’s Disease. Surgery cannot be scheduled for several months, so the physician plans to treat patient in interim with a drug she describes as a “potent inhibitor of corticosteroid synthesis.” Which drug best fits that description?
A. Dexamethasone
B. Hydrocortisone
C. Ketoconazole
D. Prednisone
E. Spironolactone

A

C. Ketoconazole

Pathophysiology (26 decks)

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