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PBL PY2 Fall > Thyroid Therapeutics > Flashcards

Thyroid Therapeutics Flashcards

1
Q

what are the functional units of the thyroid?

A

follicles

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2
Q

follicles contain colloid that are made up mostly of ____

A

thyroglobulin

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3
Q

iodine is oxidized by ____ and is bound to ____ to form MIT

A

thyroid peroxidase; tyrosine residues

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4
Q

when MIT binds to another iodine, it forms ____

A

DIT

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5
Q

DIT + DIT = ___

A

T4

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6
Q

MIT + DIT = ___

A

T3

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7
Q

the thyroid makes and secretes what 2 main hormones?

A
  1. tetraiodothyronine (T4)

2. Triiodothyronine (T3)

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8
Q

T4 is the prohormone for ___

A

T3

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9
Q

T4 is biologically inactive in target tissues until it is converted to T3

A

t

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10
Q

which thyroid hormone is biologically active and is responsible for majority of thyroid hormone effects?

A

T3

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11
Q

thyroid hormones are required for the ____ of all cells

A

homeostasis

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12
Q

thyroid hormones influence what 3 cell functions?

A
  1. differentiation
  2. growth
  3. metabolism
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13
Q

why are thyroid hormones considered the major metabolic hormones?

A

bc they target virtually every tissue in the body

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14
Q

what is the Wolff-Chaikoff Effect?

A

a protective autoregulatory mechanism during times of excess iodine supplemention

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15
Q

the Wolff-Chaikoff effect inhibits what 3 things?

A
  1. organification of iodine in thyroid gland
  2. formation of thyroid hormones in the follicle
  3. release of hormones in the bloodstream
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16
Q

how long does the Wolff-Chaikoff effect last?

A

several days to weeks

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17
Q

the loss of the Wolff-Chaikoff effect leads to ____

A

thyrotoxicosis

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18
Q

being unable to escape the Wolff-Chaikoff effect leads to ____

A

hypothyroidism

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19
Q

prevalence of hypothyroidism in females: ___%

A

2

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20
Q

prevalence of hypothyroidism in males: ___%

A

0.1

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21
Q

the risk for hypothyroidism ____ (increases vs decreases) with age

A

increases

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22
Q

what is the origin of primary hypothyroidism?

A

thyroid

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23
Q

what are some of the causes of primary hypothyroidism?

A
  1. Hashimotos (most common)
  2. Congenital
  3. idiopathic
  4. iodine deficiency (rare in Canada)
  5. radioactive iodine treatment for hyper
  6. surgery
  7. drugs
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24
Q

where is the origin of secondary hypothyroidism?

A

pituitary

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25
Q

what are the causes of secondary hypothyroidism?

A

TSH deficiency, pituitary dx\tumor

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26
Q

where is the origin of tertiary hypothyroidism?

A

hypothalamus

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27
Q

what are the causes of tertiary hypothyroidism?

A

TRH deficiency, hypothalamic tumor

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28
Q

how can amiodarone lead to hypothyroidism?

A

can alter enzyme activity to decrease the conversion of T4 to T3

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29
Q

what is the management of overt amiodarone-induced hypothyroidism?

A
  1. keep amiodarone and add levothyroxine
    (may require higher doses of synthroid)
  2. stop amiodarone (may resolve hypo, unless there is an underlying condition)
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30
Q

what are 2 predisposing factors for amiodarone induced hypothyroidism?

A
  1. dietary iodine

2. underlying thyroid dysfunction

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31
Q

what is the most common cause of primary hypothyroidism?

A

Hashimoto’s thyroiditis

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32
Q

describe the autoimmune component of Hashimoto’s thyroiditis

A

excessive production of thyroid antibodies and destruction of thyroid cells

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33
Q

t/f there is genetic predisposition for Hashimoto’s thyroiditis

A

t

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34
Q

what is the typical presentation of Hashimoto’s thyroiditis?

A

hypothyroidism and goiter

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35
Q

less than ___% of Hashimotos patients have hyperthyroidism, what is this called??

A

5%; hashitoxicosis

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36
Q

what are some psychological signs of hypothyroidism?

A

poor memory or concentration

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37
Q

what is an auditory symptom of hypothyroidism?

A

poor hearing

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38
Q

what is a pharynx symptom of hypothyroidism?

A

hoarseness

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39
Q

what are cardio symptoms of hypothyroidism?

A

slow heart rate, pericardial effusion

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40
Q

what are some hypothyroid symptoms that can be seen in the extremities?

A
  1. coldness

2. carpal tunnel syndrome

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41
Q

what are some general symptoms of hypothyroidism?

A

fatigue, feeling cold, weight gain with poor appetite, hairloss

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42
Q

what are some respiratory symptoms of hypothyroidism?

A

SOB, pleural effusion

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43
Q

what are some skin symptoms of hypothyroidism?

A

paresthesia and myxedema

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44
Q

what are some symptoms of hypothyroidism in the GI tract?

A

constipation, ascites

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45
Q

what are some symptoms of hypothyroidism in the reproductive system?

A

menorrhagia

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46
Q

what is the normal range for TSH?

A

0.35-4.3 mIU/L

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47
Q

what will the lab value for TSH look like if the patient has overt hypothyroidism?

A

increased (usually greater than 10)

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48
Q

what will the TSH look like if a patient has subclinical hypothyroidism?

A

increased slightly (4-10)

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49
Q

what is the normal range for FT4?

A

9.5-19 pmol/L

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50
Q

what will the lab value for FT4 look like if the patient has overt hypothyroidism?

A

decreased

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51
Q

what will the lab value for FT4 look like if the patient has subclinical hypothyroidism?

A

normal

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52
Q

what is the normal range for FT3?

A

2.6-5.7 pmol/L

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53
Q

what will the FT3 look like in a patient with overt hypothyroidism?

A

decreased, but it is not helpful for diagnosing

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54
Q

what will teh value for FT3 look like in a patient with subclinical hypothyroidism?

A

normal

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55
Q

what drug is used to treat hypothyroidism?

A

synthroid (levothyroxine)

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56
Q

t/f there is no indication for L-triidothyronine, desiccated thyroid hormones, or combos of T4/T3

A

t

57
Q

how soon should you recheck the TSH after starting a patient on or adjusting the dose of synthroid?

A

6-8 weeks

58
Q

the dosage adjustments of synthroid are made by looking at what lab value?

A

TSH

59
Q

why is synthroid the drug of choice for hypothyroidism?

A

chemically stable, predictable, uniform potency, well absorbed, UID dosing, relatively low cost

60
Q

what is the T1/2 of synthroid?

A

7 days

61
Q

the effects of synthroid are first seen within___ and max effect within ___

A

2-3; 4-6

62
Q

the reversal of skin and hair changes caused by hypothyroidism can take how long to reverse?

A

several months

63
Q

t/f patients need to take synthroid at a consistent time each day

A

t

64
Q

what are the ADRs of synthroid?

A
  1. hyperthyroidism
  2. CV complications (esp if high dose, long-standing hypothyroidism or pre-existing CV conditions)
  3. loss of bone mass and fractures at excessive doses
65
Q

starting dose of synthroid in uncomplicated adults

A

1.6-1.7 mcg/kg/day; 100-125 mcg/day is the avg replacement dose

66
Q

how is the synthroid dose adjusted in uncomplicated adults?

A

25mcg every 6-8 weeks

67
Q

what is the starting dose of synthroid in older adults?

A

<1.6mcg/kg/day (50-100 mcg/day –> start cautiously)

68
Q

how is the synthroid dose adjusted in older adults?

A

12.5-25mcg every 6-8 weeks (or slower)

69
Q

what is the starting dose of synthroid for patients with CVD?

A

12.5-25mcg/day

70
Q

how are synthroid doses adjusted in patients with CVD?

A

increase by 12.5-25mcg every 2-6 weeks as tolerated (very sensitive)

71
Q

what is the starting dose of synthroid for patients with long-standing (> 1 year) hypothyroidism?

A

25 mcg/day

72
Q

how is the synthroid dose adjusted in patients with long-standing hypothyroidism?

A

increase by 25mcg every 4-6 weeks as tolerated

73
Q

how is the syntroid dose adjusted if a patient becomes pregnant?

A

most will require at 45% increase in dose; increase by 2 tabs/week and monitor

74
Q

in pregnancy, where do we want to see the values for TSH and FT4?

A

TSH: normal
FT4: upper normal range

75
Q

what are the risks of hypothyroidism in pregnancy?

A

Many, including: cretinism or congenital hypothyroidism in utero or in neonate (developmental impairment)

76
Q

what causes Myxedema coma?

A

longstanding uncorrected hypothyroidism

77
Q

the signs and symptoms of hypothyroidism are more pronounced in myxedema coma and they include ___

A

hypothermia, delayed deep tendon reflexes, altered level of consciousness, psychosis, hypoxia/CO2 retention, hypoglycemia, hyponatremia, coma

78
Q

what are some precipitating causes of Myxedema Coma?

A 
cold weather
hyponatremia
stress (surgery, infection, trauma) 
comorbidities (MI, diabetes, fluid/electrolyte abnormalities) 
Drugs (anesthetics, opioids)
79
Q

what is given to manage myxedema coma?

A
  1. IV synthroid and then PO
  2. corticosteroids is cortisol is low (some recommend in all until adrenal function confirmed)
  3. supportive therapies (fluids, ventilation etc.)
  4. treating comorbidities
80
Q

what is the most common cause of hyperthyroidism?

A

Grave’s Dx

81
Q

what causes Grave’s Dx?

A

it is an autoimmune condition where thyroid receptor antibody (TRAb) has the ability to stimulate TH synthesis bc it is similar to TSH

82
Q

aside from Grave’s Dx, what are 4 causes of hyperthyroidism?

A
  1. toxic uninodular or multinodular goiters (iodine may exacerbate)
  2. exogenous thyroid hormone excess (self administration)
  3. tumours
  4. drug-induced (iodides, amiodarone etc.)
83
Q

what is Jod-Basedow Phenomenon?

A

iodine-induced thyrotoxicosis

84
Q

what causes Jod-Basedow phenomenon?

A

occurs in predisposed individuals due to an underlying thyroid disorder (like multinodular goiters or Grave’s Dx)

85
Q

Jod-Basedow phenomenon may be seen more when patient is using what drug? What is this called?

A

Amiodarone; Type 1 amiodarone-induced thyrotoxicosis

86
Q

Jod-Basedow is a loss of ___ effect

A

Wolff-Chaikoff

87
Q

How is Type 1 amiodarone-induced thyrotoxicosis managed?

A

may continue amiodarone and start thioamides (and potassium perchlorate for 2-6 weeks); if refractory then you remove the thyroid

88
Q

Type 1 amiodarone-induced thyrotoxicosis is caused by ___ induced effects

A

iodine

89
Q

type 2 amiodarone-induced thyrotoxicosis is caused by ____ effects

A

intrinsic

90
Q

Type 2 amiodarone induced thyrotoxicosis is ____ thyroiditis

A

destructive inflammatory

91
Q

what is the management of type 2 amiodarone-induced thyrotoxicosis?

A
  1. usually d/c amiodarone
  2. treat with corticosteroids
  3. thioamines are usually not helpful
92
Q

what are predisposing factors for type 2 amiodarone-induced thyrotoxicosis?

A

dietary iodine, underlying thyroid dysfunction

93
Q

Mixed forms of amiodarone induced thyrotoxicosis are also possible, how are these treated?

A

combination of methimazole and corticosteroids

94
Q

what are the psychological symptoms of hyperthyroidism?

A

nervousness and irritability

95
Q

what are the general symptoms of hyperthyroidism?

A

difficulty sleeping, heat intolerance, weight loss or gain with increased appetite

96
Q

what are the occular symptoms of hyperthyroidism?

A

bulging eyes, unblinking stare, vision changes

97
Q

what are the cardio symptoms of hyperthyroidism?

A

palpitations, fast heart rate

98
Q

how may someone’s menstrual sycle be affected by hyperthyroidism?

A

may have a lighter period

99
Q

how can hyperthyroidism affect pregnancy?

A

first trimester miscarriage, excessive vomiting, impaired fertility

100
Q

what would you expect the lab value of TSH to look like in a overt hyperthyroid patient?

A

decreased (<0.1)

101
Q

what would you expect the lab value for TSH in subclinical hyperthyroidism?

A

decreased (<0.3)

102
Q

what would you expect the lab value for FT4 to look like in an overt hyperthyroid patient?

A

increased

103
Q

what would you expect the lab value of FT4 to look like in a patient with subclinical hyperthyroidism?

A

normal

104
Q

what would you expect the value of FT3 to look like in a patient with overt hyperthyroidism?

A

increased (T3 toxicosis common)

105
Q

what would you expect the value of FT3 to look like in a patient with subclinical hyperthyroidism?

A

normal

106
Q

what are the 4 treatment strategies for hyperthyroidism?

A
  1. thioamides (methimazole & PTU)
  2. radioactive iodine
  3. surgery
  4. adjuvants (iodides, BB, CCB, corticosteroids)
107
Q

when is RAI contraindicated?

A

pregnancy and confirmed or suspected thyroid malignancy

108
Q

when is ATD treatment c/i?

A

if the patient has major ADR

109
Q

when is surgery c/i?

A

comorbidities with increased surgery risk and or limited life expectancy

110
Q

ATD should be used with caution in patients with ___dx

A

liver

111
Q

surgery should be used with caution if the patient has what comorbidities?

A

pulmonary HTN, congestive HF

112
Q

what is the MOA of methimazole?

A

blocks organification of thyroid hormone synthesis

113
Q

what are the indications for methimazole?

A

drug of choice for hyperthyroidism in adults and children, except during the first trimester or during thyroid storm

114
Q

what is the starting dose of methimazole?

A

30-40mg PO UID or divided BID

115
Q

what is the maintenace dose of methimazole?

A

5-10mg PO daily

116
Q

how long should patients be on the starting dose of methimazole?

A

6-8 weeks or until euthyroid

117
Q

how long should patients by on maintenace doses of hyperthyroid medication?

A

12-18 months

118
Q

what are the ADRs of methimazole?

A

skin rashes, GI, joint pain, cholestatic jaundice, agranulocytosis, aplasia cutis, embryopathy syndrome in pregnancy

119
Q

what is the MOA of PTU?

A

blocks organification of thyroid hormone synthesis AND blocks the conversion of T4 to T3

120
Q

when is PTU the drug of choice?

A

thyroid storm and 1st trimester of pregnancy

121
Q

what is the starting dose of PTU?

A

100-200mg PO Q6-8 hours

122
Q

what is the maintenance dose of PTU?

A

50-150mg PO daily

123
Q

what are the ADRs of PTU?

A

skin rashes, GI symptoms, joint pain, agranulocytosis, increased transaminases, hepatitis/hepatotoxicity (sometimes fatal)

124
Q

what needs to be monitored for both methimazole & PTU?

A

liver enzymes, and CBC with differential baseline and if signs/symptoms and annually

125
Q

what is the MOA of radioactive iodine?

A

destruction of the thyroid gland

126
Q

RAI shows some benefit within ___months, euthyroid in ____ months and hypothyroid within ___ months

A

1, 3-6, 3-12

127
Q

when is RAI indicated?

A

adults who are poor surgical candidates or have C/i to thioamides

128
Q

what is the dosing of RAI?

A

given as a single dose which is determined based on the weight of the thyroid

129
Q

thioamides need to be stopped ___before RAI treatment

A

> 1 week

130
Q

how soon before RAI should iodides be stopped?

A

2 months

131
Q

what are some adjunct therapies to RAI?

A

corticosteroids if orbitopathy, BB, or CCB

132
Q

what are some of the ADRs of RAI?

A

hypothyroidism, worsening orbitopathy, possible risk for malignancy

133
Q

what are the risks of hyperthyroidism in pregnancy?

A

many; miscarriage, perinatal death, prematurity

134
Q

how is hyperthyroidism treated in pregnancy?

A

PTU 1st trimester, then switch to methimazole for rest of pregnancy and lactation; some with Grave’s Dx require no treatment or lower doses in the second or third trimester (monitor closely post-delivery)

135
Q

what is thyroid storm?

A

exaggerated manifestations of thyrotoxicosis (hyperthyroidism); a life-threatening medical emergency

136
Q

what are the symptoms of thyroid storm?

A

high fever, tachycardia, tachypnea, dehydration, NVD, delirium, coma

137
Q

what are the precipitating causes of thyroid storm?

A

stress (burn, surgery, infection, childbirth); metabolic disturbances; drugs (withdrawal of antithyroid medications, ASA overdose)

138
Q

how is thyroid storm managed?

A
  1. antithyroid medication (PTU) and or iodide (SSKI)
  2. corticosteroids, propranolol
  3. supportive therapy (fluids, ventillation)
  4. treat the unerlying cause

PBL PY2 Fall (21 decks)

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