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PHAR 255 - Therapeutics (3) > Thyroid > Flashcards

Thyroid Flashcards

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1
Q

Colloid Cell role?

A

-Store building blocks (Tyrosine, Iodide, Thyroglobulin).

-Hormonal assembly & storage.

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2
Q

Follicular Cell role?

A

-Transport cells… Pump building blocks into the Colloid & aid in T3 / T4 secretion into circulation.

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3
Q

Parafollicular Cell role?

A

-Calcitonin release (blood / bone Ca2+ balance).

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4
Q

What are the three building blocks required for MIT / DIT synthesis?

A

1) Iodide
2) Thyroglobulin
3) Tyrosine

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5
Q

Physiologic ratio of T4 : T3?

A

13 : 1

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6
Q

How much more potent is T3 (versus T4)?

A

4x

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7
Q

What do T3 & T4 do to the Heart? Adipose Tissue? Muscle?

A

Heart: Increase HR & force of contraction.

Adipose Tissue: Catabolic (fat breakdown).

Muscle: Catabolic (muscle breakdown).

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8
Q

What do T3 & T4 do to Bone? Nervous System? Gut?

A

Bone: Developmental.

Nervous System: Developmental.

Gut: Metabolic.

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9
Q

What percentage of T3 in circulation is derived from peripheral T4 to T3 conversion?

A

80% (20% comes directly from the Thyroid Gland).

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10
Q

What triggers TSH release?

A

Low circulating T3 / T4 levels.

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11
Q

Chronically low serum Iodide levels cause an ______ (increase or decrease) in Thyroid Hormone production?

A

Decrease; Initially, it increases (compensatory mechanism causing upregulation of receptors & transporters at level of the Thyroid), but chronically depleted Iodide levels cause reduced T3 / T4 production.

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12
Q

An initial excess of Iodide causes an ______ (increase or decrease) in Thyroid Hormone production.

A

Decrease; Chronic elevations (beyond 7d in length) cause increased T3 / T4 production & secretion as we’re escaping the negative feedback loop.

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13
Q

What percentage of total T3 / T4 is protein bound (& therefore physiologically inactive)? What percentage is free & able to invoke physiological effects?

A

Protein Bound: 99.66%
Free: 0.33%

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14
Q

Out of every ten patients with Thyroid Disease, _____ are women.

A

eight

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15
Q

At what age do we see hypothyroidism rates at and above 25%?

A

65yrs+

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16
Q

Most common form of Hyperthyroidism?

A

Toxic Diffuse Goiter (aka Graves Disease)

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17
Q

What are the four types of Hyperthyroidism?

A

1) Toxic Diffuse Goiter

2) Toxic Multi-Nodular Goiter

3) Acute Phase of Thyroiditis

4) Toxic Adenoma

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18
Q

Other name for Toxic Multi-Nodular Goiter?

A

Plummers Disease

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19
Q

Goiter is defined as what?

A

Generalized Thyroid Enlargement.

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20
Q

Describe Graves Disease.

A

-Young females (20-50yrs).

-Autoimmune in nature… ABs against TSH Receptor.

-Most common hyperthyroidism form!

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21
Q

Why does Graves Disease induce Hyperthyroidism?

A

AB binding to TSH Receptors means that negative feedback loop can’t work… Leads to loss of TSH production!

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22
Q

Describe Plummers Disease.

A

-Old females (> 50yrs).

-2nd most common form of hyperthyroidism.

-Iodine deficiency most common trigger for nodular growth.

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23
Q

How does Iodine deficiency in Plummers Disease invoke hyperthyroidism?

A

-Less T4, Thyroid Cells enlarge & mutate, become constitutively active!

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24
Q

T or F: Toxic Multi-Nodular Goiter develops rapidly (over course of a few months).

A

False… Several years to develop (slow process).

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25
How is hyperthyroidism invoked in those with Acute Thyroiditis?
Inflammation leads to increased permeability of Colloid Cells... Become leakier, leads to T3 / T4 seepage into circulation via Passive Diffusion mechanisms!
26
T or F: Acute Thyroiditis will eventually lead to hypothyroidism.
True... T3 / T4 stores eventually will become depleted with increased leakage into circulation!
27
How do benign tumors on the Thyroid invoke hyperthyroidism?
Tumors become active & secrete T3 / T4, but DO NOT respond to the Negative Feedback Loop (constitutively active similar to Plummers Disease).
28
Clinical presentation of hyperthyroidism?
-Hand Tremors -Diarrhea -Heat Intolerance -Weight Loss -Weakness -Tachycardia -Amenorrhea -Sweaty -HTN -Insomnia
29
Unique symptoms to Graves Disease?
-Exophthalmos ("Bug Eyes") -Periorbital Edema -Diplopia (Double Vision) -Pre-Tibial Myxedema (Purpley / Orangeish rash on shins)
30
Jane has the following clinical values: Serum TSH = 0.09mIU / L Free T3 = 5.8pmol / L Free T4 = 13pmol / L What type of Hyperthyroidism does she potentially have?
Toxic Diffuse (Graves)... -Very depleted Serum TSH -Elevated Free T3 -Normal Free T4
31
Gladys has the following clinical values: Serum TSH = 0.09mIU / L Free T3 = 5.8pmol / L Free T4 = 100pmol / L What type of hyperthyroidism might she have?
Toxic Diffuse (Graves)... -Very depleted Serum TSH -Elevated Free T3 -Extremely elevated Free T4
32
Cassandra has the following lab values: Serum TSH = 0.09mIU / L Free T3 = 5.8pmol / L Free T4 = 25pmol / L What type of hyperthyroidism might she have?
Toxic Multi-Nodular (Plummers)... -Very depleted Serum TSH -Elevated Free T3 -Slightly elevated Free T4 ***Toxic Diffuse possible though (Free T4 ranges from normal to greatly elevated)! ***
33
Why is Amiodarone a clinically significant interaction as it pertains to T3 / T4 synthesis and release?
Can invoke both Hyper and Hypothyroidism (typically increases synthesis / release of T3 & T4).
34
What are our three options for treating hyperthyroidism?
1) Drugs (Thioamides & Beta Blockers) 2) Radioactive Iodine 3) Thyroidectomy
35
What are the Thioamide drugs used for treating hyperthyroidism?
Methimazole Propylthiouracil
36
Why is pre-treatment with Thioamides necessary before Radioactive Iodine therapy?
RAI can initially exacerbate hyperthyroidism!
37
Of the three hyperthyroid treatment options (Thioamides / RAI / Thyroidectomy), which ones are more typically curative?
RAI & Thyroidectomy... Thioamides are most often a temporary fix, but curative options should be considered if disease state isn't controlled on just Thioamides.
38
Why is PTU considered to be a more potent drug than MMI?
-PTU inhibits Thyroid Peroxidase-mediated T3 & T4 production, as well as peripheral tissue conversion of T4 to T3. -MMI only acts within the Thyroid... No effects on peripheral tissue conversions!
39
How do Beta Blockers work in hyperthyroidism?
-Block peripheral tissue conversion of T4 to T3 (similar to PTU). -To be used for symptomatic relief (Palpitations, Tachycardia, Anxiety, Tremors, Heat Intolerance).
40
In terms of dose titration trends, how do we see PTU & MMI dosed?
ID: High MD: Low -Trends is in reverse of usually seen dosing... Thyroid should start to shrink when one receives high initial doses (necessitating dose reduction).
41
How long does it take the Thyroid & its negative feedback loop to establish new homeostatic setpoints (upon PTU / MMI dose administration)?
4 to 6 wks
42
Common therapeutic duration of PTU / MMI use?
12 - 18mths
43
Is it true that experienced side effects of Propylthiouracil are dose-related?
False... Dose-related for MMI (but NOT for PTU).
44
What are the commonly experienced side effects of the Thioamide drugs?
-GI Upset -Rash -Abnormal Taste & Smell -Joint Pain ***RATES TYPICALLY HIGHER WITH PTU***
45
Important counseling point to stress to patients initiating Thioamides?
-"Push through side effects as best as you can!" -Tolerance develops over course of 4wks, & pharmacological alternatives for hyperthyroidism are sparce!
46
Transient decreases in neutrophil count are generally okay in those initiating Thioamides. However, a reduction >/= ___ - ___ % is troublesome.
20 - 30% (can progress into Agranulocytosis)
47
Important counseling point upon Thioamide initiation (as it pertains to illness)?
-"If you ever feel something beyond minor illness lasting past a couple days, go get bloodwork done!" -Want to establish that patients aren't neutropenic, or else minor illness can progress into something potentially fatal (body is less able to fight infection off)!
48
What other important counseling point should you mention to someone starting PTU specifically?
"Here's what to look out for in terms of Liver issues... Tired, Darkened or intensively yellowed urine, Jaundice, Upper Right Quadrant Pains".
49
When do Liver panels become concerning to someone initiating PTU or MMI?
-AST / ALTs > 3x upper limit of normal! -Assess those who are Alcoholics closely as well.
50
In 1st Trimester, which Thioamide is safest? 2nd & 3rd Trimester?
1st: PTU 2nd / 3rd: MMI
51
Which Thioamide demonstrates quicker euthyroid onset: PTU or MMI?
MMI (8wks versus 12wks for PTU)
52
What is the preferred Beta Blocker in hyperthyroidism (due to its short DOA & ability to withdraw or titrate quickly)?
Propranolol
53
What are the compelling indications for Radioactive Iodine usage?
-Mild Hyperthyroidism -Normal / Slightly Enlarged Gland -No Exophthalmos
54
When is Radioactive Iodine outright a contraindication?
-Pregnancy / Lactation -Severe Hyper / Exophthalmos
55
What patient groups are the only ones we won't pre-treat with Thioamides?
-Allergy -Severe Hepatotoxicity or Agranulocytosis incident
56
If one is to pre-treat with Thioamides prior to RAI administration, how should we do it?
1) Initiate 4-6wks prior to RAI. 2) Stop 3d prior to RAI. 3) Restart 3d after RAI. 4) Taper & d/c once thyroid levels decline.
57
Important counseling point for those on RAI?
First five days: No exchanging eating utensils or sharing food, avoidance of close contact with pregnant women or young children.
58
What are some preceding events that can trigger Thyroid Storm / Thyrotoxicosis?
-RAI / Thyroidectomy -Direct Trauma -Infection -Birthing
59
What drug measures must be initiated for someone experiencing Thyroid Storm?
-Beta Blockers (Sx Relief) -High Dose Anti-Thyroid Meds (PTU preferred due to increased potency) -Iodine 1hr post Anti-Thyroid -Steroids (block T4 --- T3 conversion)
60
Most common form of hypothyroidism?
Hashimoto's (aka Chronic Autoimmune Thyroiditis)
61
How does Hashimoto's work?
ABs bind to TSH Receptors, directly destroys Thyroid Cells.
62
Two most common drug-induced causes of hypothyroidism?
Lithium, Amiodarone
63
How does Lithium induce hypothyroidism?
Blocks iodine transport into the Thyroid (thus building block necessary for Thyroid synthesis can't get in & couple).
64
How does Amiodarone induce hypothyroidism?
Increased release of Thyroid Hormone leads to eventual depletion!
65
What are the clinical presentations of hypothyroidism?
-Weight Gain -Fatigue -Cold Intolerance -Bradycardia -Constipation -Heavy Menstruation
66
How do lab test values differ between Subclinical & Chronic Autoimmune Thyroiditis (ie. Hashimoto's)?
Sub: Slightly elevated TSH (between 4.5 - 10mIU / L), normal Free T3 & T4. Hash: Greatly elevated TSH (> 10mIU / L), reduced Free T3, greatly reduced Free T4.
67
What drugs reduce TSH levels?
Amiodarone, GCs, Metformin
68
What drugs decrease T4 to T3 conversion?
Amiodarone, GCs, BBs
69
What drugs increase T3 / T4 metabolism?
All the seizure drugs!!!
70
When is Liothyronine add-on appropriate?
Patients inadequately controlled on Levothyroxine!
71
Does Liothyronine have effects on just T3?
YES! NO T4 EFFECTS!
72
Relative to Levothyroxine, would you expect reduced or heightened rates of adverse cardiac effects for those on Liothyronine?
Heightened (due to T3 effects).
73
If I had a Serum TSH level between 4.5 and 10mIU / L (ie. Slightly Elevated), what would be an appropriate empirical Levothyroxine dose?
25 - 50mcg ***This is the empirical dose for Subclinical Hypothyroidism based upon baseline TSH levels!***
74
What is the average replacement dose of Levothyroxine (on a / kg / day basis)?
1.6mcg / kg / day
75
Because of its poor bioavailability, when is the best time to take Levothyroxine?
1st thing in AM (promotes better adherence), 30mins before breakfast (empty stomach very important).
76
What is the titration plan for Levothyroxine users?
12.5 - 25mcg to start, increase by same interval q4-6wks!
77
Side effects of Levothyroxine?
Basically anything seen in clinical presentation of hyperthyroidism! -CV Risk -BMD Reductions -All other signs of hyper
78
What drugs reduce absorption of Levothyroxine?
-H2 Blockers (Ranitidine) -Antacids (Tums) -PPIs (Omeprazole / Pantoprazole / Esomeprazole) -Ca2+ / Multivitamins -Bile Acid Sequestrants (Cholestyramine)
79
By how many hours should we space Levothyroxine dosing to avoid DDIs with therapies that reduce absorption?
2-4hrs... If Raloxifene specifically, then 12hrs!
80
What types of drugs increase Levothyroxine metabolism?
-Ciprofloxacin -Phenytoin -Carbamazepine -Rifampin ***Pregnancy does as well!***
81
Symptomatic improvements should be seen in how many weeks on Levothyroxine? Max effects?
Sx Relief: 2-3wks Max Effect: 4-6wks
82
Most patients with Subclinical Hypothyroidism don't require treatment. However, when might we want to consider treatment?
-Develop Hypothyroidism symptoms / clinical presentations -Planning to become pregnant -Developed heart failure -Extremely young patient
83
A patient comes in after 6wks complaining of a lack of hypothyroidic relief. What questions should you ask?
-Taking at same time of day? -Other comorbidities (ie. Celiac)? -Taking with food? Other drugs? Dairy? -Recently become pregnant?

PHAR 255 - Therapeutics (3) (7 decks)

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