PBL PY2 Fall > Thyroid Therapeutics > Flashcards

Thyroid Therapeutics Flashcards

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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
what are the causes of secondary hypothyroidism?
TSH deficiency, pituitary dx\tumor
26
where is the origin of tertiary hypothyroidism?
hypothalamus
27
what are the causes of tertiary hypothyroidism?
TRH deficiency, hypothalamic tumor
28
how can amiodarone lead to hypothyroidism?
can alter enzyme activity to decrease the conversion of T4 to T3
29
what is the management of overt amiodarone-induced hypothyroidism?
1. keep amiodarone and add levothyroxine (may require higher doses of synthroid) 2. stop amiodarone (may resolve hypo, unless there is an underlying condition)
30
what are 2 predisposing factors for amiodarone induced hypothyroidism?
1. dietary iodine | 2. underlying thyroid dysfunction
31
what is the most common cause of primary hypothyroidism?
Hashimoto's thyroiditis
32
describe the autoimmune component of Hashimoto's thyroiditis
excessive production of thyroid antibodies and destruction of thyroid cells
33
t/f there is genetic predisposition for Hashimoto's thyroiditis
t
34
what is the typical presentation of Hashimoto's thyroiditis?
hypothyroidism and goiter
35
less than ___% of Hashimotos patients have hyperthyroidism, what is this called??
5%; hashitoxicosis
36
what are some psychological signs of hypothyroidism?
poor memory or concentration
37
what is an auditory symptom of hypothyroidism?
poor hearing
38
what is a pharynx symptom of hypothyroidism?
hoarseness
39
what are cardio symptoms of hypothyroidism?
slow heart rate, pericardial effusion
40
what are some hypothyroid symptoms that can be seen in the extremities?
1. coldness | 2. carpal tunnel syndrome
41
what are some general symptoms of hypothyroidism?
fatigue, feeling cold, weight gain with poor appetite, hairloss
42
what are some respiratory symptoms of hypothyroidism?
SOB, pleural effusion
43
what are some skin symptoms of hypothyroidism?
paresthesia and myxedema
44
what are some symptoms of hypothyroidism in the GI tract?
constipation, ascites
45
what are some symptoms of hypothyroidism in the reproductive system?
menorrhagia
46
what is the normal range for TSH?
0.35-4.3 mIU/L
47
what will the lab value for TSH look like if the patient has overt hypothyroidism?
increased (usually greater than 10)
48
what will the TSH look like if a patient has subclinical hypothyroidism?
increased slightly (4-10)
49
what is the normal range for FT4?
9.5-19 pmol/L
50
what will the lab value for FT4 look like if the patient has overt hypothyroidism?
decreased
51
what will the lab value for FT4 look like if the patient has subclinical hypothyroidism?
normal
52
what is the normal range for FT3?
2.6-5.7 pmol/L
53
what will the FT3 look like in a patient with overt hypothyroidism?
decreased, but it is not helpful for diagnosing
54
what will teh value for FT3 look like in a patient with subclinical hypothyroidism?
normal
55
what drug is used to treat hypothyroidism?
synthroid (levothyroxine)
56
t/f there is no indication for L-triidothyronine, desiccated thyroid hormones, or combos of T4/T3
t
57
how soon should you recheck the TSH after starting a patient on or adjusting the dose of synthroid?
6-8 weeks
58
the dosage adjustments of synthroid are made by looking at what lab value?
TSH
59
why is synthroid the drug of choice for hypothyroidism?
chemically stable, predictable, uniform potency, well absorbed, UID dosing, relatively low cost
60
what is the T1/2 of synthroid?
7 days
61
the effects of synthroid are first seen within___ and max effect within ___
2-3; 4-6
62
the reversal of skin and hair changes caused by hypothyroidism can take how long to reverse?
several months
63
t/f patients need to take synthroid at a consistent time each day
t
64
what are the ADRs of synthroid?
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
starting dose of synthroid in uncomplicated adults
1.6-1.7 mcg/kg/day; 100-125 mcg/day is the avg replacement dose
66
how is the synthroid dose adjusted in uncomplicated adults?
25mcg every 6-8 weeks
67
what is the starting dose of synthroid in older adults?
<1.6mcg/kg/day (50-100 mcg/day --> start cautiously)
68
how is the synthroid dose adjusted in older adults?
12.5-25mcg every 6-8 weeks (or slower)
69
what is the starting dose of synthroid for patients with CVD?
12.5-25mcg/day
70
how are synthroid doses adjusted in patients with CVD?
increase by 12.5-25mcg every 2-6 weeks as tolerated (very sensitive)
71
what is the starting dose of synthroid for patients with long-standing (> 1 year) hypothyroidism?
25 mcg/day
72
how is the synthroid dose adjusted in patients with long-standing hypothyroidism?
increase by 25mcg every 4-6 weeks as tolerated
73
how is the syntroid dose adjusted if a patient becomes pregnant?
most will require at 45% increase in dose; increase by 2 tabs/week and monitor
74
in pregnancy, where do we want to see the values for TSH and FT4?
TSH: normal FT4: upper normal range
75
what are the risks of hypothyroidism in pregnancy?
Many, including: cretinism or congenital hypothyroidism in utero or in neonate (developmental impairment)
76
what causes Myxedema coma?
longstanding uncorrected hypothyroidism
77
the signs and symptoms of hypothyroidism are more pronounced in myxedema coma and they include ___
hypothermia, delayed deep tendon reflexes, altered level of consciousness, psychosis, hypoxia/CO2 retention, hypoglycemia, hyponatremia, coma
78
what are some precipitating causes of Myxedema Coma?
``` cold weather hyponatremia stress (surgery, infection, trauma) comorbidities (MI, diabetes, fluid/electrolyte abnormalities) Drugs (anesthetics, opioids) ```
79
what is given to manage myxedema coma?
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
what is the most common cause of hyperthyroidism?
Grave's Dx
81
what causes Grave's Dx?
it is an autoimmune condition where thyroid receptor antibody (TRAb) has the ability to stimulate TH synthesis bc it is similar to TSH
82
aside from Grave's Dx, what are 4 causes of hyperthyroidism?
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
what is Jod-Basedow Phenomenon?
iodine-induced thyrotoxicosis
84
what causes Jod-Basedow phenomenon?
occurs in predisposed individuals due to an underlying thyroid disorder (like multinodular goiters or Grave's Dx)
85
Jod-Basedow phenomenon may be seen more when patient is using what drug? What is this called?
Amiodarone; Type 1 amiodarone-induced thyrotoxicosis
86
Jod-Basedow is a loss of ___ effect
Wolff-Chaikoff
87
How is Type 1 amiodarone-induced thyrotoxicosis managed?
may continue amiodarone and start thioamides (and potassium perchlorate for 2-6 weeks); if refractory then you remove the thyroid
88
Type 1 amiodarone-induced thyrotoxicosis is caused by ___ induced effects
iodine
89
type 2 amiodarone-induced thyrotoxicosis is caused by ____ effects
intrinsic
90
Type 2 amiodarone induced thyrotoxicosis is ____ thyroiditis
destructive inflammatory
91
what is the management of type 2 amiodarone-induced thyrotoxicosis?
1. usually d/c amiodarone 2. treat with corticosteroids 3. thioamines are usually not helpful
92
what are predisposing factors for type 2 amiodarone-induced thyrotoxicosis?
dietary iodine, underlying thyroid dysfunction
93
Mixed forms of amiodarone induced thyrotoxicosis are also possible, how are these treated?
combination of methimazole and corticosteroids
94
what are the psychological symptoms of hyperthyroidism?
nervousness and irritability
95
what are the general symptoms of hyperthyroidism?
difficulty sleeping, heat intolerance, weight loss or gain with increased appetite
96
what are the occular symptoms of hyperthyroidism?
bulging eyes, unblinking stare, vision changes
97
what are the cardio symptoms of hyperthyroidism?
palpitations, fast heart rate
98
how may someone's menstrual sycle be affected by hyperthyroidism?
may have a lighter period
99
how can hyperthyroidism affect pregnancy?
first trimester miscarriage, excessive vomiting, impaired fertility
100
what would you expect the lab value of TSH to look like in a overt hyperthyroid patient?
decreased (<0.1)
101
what would you expect the lab value for TSH in subclinical hyperthyroidism?
decreased (<0.3)
102
what would you expect the lab value for FT4 to look like in an overt hyperthyroid patient?
increased
103
what would you expect the lab value of FT4 to look like in a patient with subclinical hyperthyroidism?
normal
104
what would you expect the value of FT3 to look like in a patient with overt hyperthyroidism?
increased (T3 toxicosis common)
105
what would you expect the value of FT3 to look like in a patient with subclinical hyperthyroidism?
normal
106
what are the 4 treatment strategies for hyperthyroidism?
1. thioamides (methimazole & PTU) 2. radioactive iodine 3. surgery 4. adjuvants (iodides, BB, CCB, corticosteroids)
107
when is RAI contraindicated?
pregnancy and confirmed or suspected thyroid malignancy
108
when is ATD treatment c/i?
if the patient has major ADR
109
when is surgery c/i?
comorbidities with increased surgery risk and or limited life expectancy
110
ATD should be used with caution in patients with ___dx
liver
111
surgery should be used with caution if the patient has what comorbidities?
pulmonary HTN, congestive HF
112
what is the MOA of methimazole?
blocks organification of thyroid hormone synthesis
113
what are the indications for methimazole?
drug of choice for hyperthyroidism in adults and children, except during the first trimester or during thyroid storm
114
what is the starting dose of methimazole?
30-40mg PO UID or divided BID
115
what is the maintenace dose of methimazole?
5-10mg PO daily
116
how long should patients be on the starting dose of methimazole?
6-8 weeks or until euthyroid
117
how long should patients by on maintenace doses of hyperthyroid medication?
12-18 months
118
what are the ADRs of methimazole?
skin rashes, GI, joint pain, cholestatic jaundice, agranulocytosis, aplasia cutis, embryopathy syndrome in pregnancy
119
what is the MOA of PTU?
blocks organification of thyroid hormone synthesis AND blocks the conversion of T4 to T3
120
when is PTU the drug of choice?
thyroid storm and 1st trimester of pregnancy
121
what is the starting dose of PTU?
100-200mg PO Q6-8 hours
122
what is the maintenance dose of PTU?
50-150mg PO daily
123
what are the ADRs of PTU?
skin rashes, GI symptoms, joint pain, agranulocytosis, increased transaminases, hepatitis/hepatotoxicity (sometimes fatal)
124
what needs to be monitored for both methimazole & PTU?
liver enzymes, and CBC with differential baseline and if signs/symptoms and annually
125
what is the MOA of radioactive iodine?
destruction of the thyroid gland
126
RAI shows some benefit within ___months, euthyroid in ____ months and hypothyroid within ___ months
1, 3-6, 3-12
127
when is RAI indicated?
adults who are poor surgical candidates or have C/i to thioamides
128
what is the dosing of RAI?
given as a single dose which is determined based on the weight of the thyroid
129
thioamides need to be stopped ___before RAI treatment
> 1 week
130
how soon before RAI should iodides be stopped?
2 months
131
what are some adjunct therapies to RAI?
corticosteroids if orbitopathy, BB, or CCB
132
what are some of the ADRs of RAI?
hypothyroidism, worsening orbitopathy, possible risk for malignancy
133
what are the risks of hyperthyroidism in pregnancy?
many; miscarriage, perinatal death, prematurity
134
how is hyperthyroidism treated in pregnancy?
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
what is thyroid storm?
exaggerated manifestations of thyrotoxicosis (hyperthyroidism); a life-threatening medical emergency
136
what are the symptoms of thyroid storm?
high fever, tachycardia, tachypnea, dehydration, NVD, delirium, coma
137
what are the precipitating causes of thyroid storm?
stress (burn, surgery, infection, childbirth); metabolic disturbances; drugs (withdrawal of antithyroid medications, ASA overdose)
138
how is thyroid storm managed?
1. antithyroid medication (PTU) and or iodide (SSKI) 2. corticosteroids, propranolol 3. supportive therapy (fluids, ventillation) 4. treat the unerlying cause
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