Ex 4. L4 Thyroid Hormones 2 (38) Flashcards

1
Q

TSH test

A

Measures: Pituitary TSH level
Reference range: 0.5-5.0 mlU/L
Comments: Gold Standard. Most sensitive index for hyperthyroidism, and replacement therapy
Looking to shift to higher TSH level for elderly patients

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2
Q

Free T4 test

A

Direct measurement of free thyroxine
Reference range: 0.7-1.9ng/dL
Comments: Most accurate. May be normal in mild thyroid disease

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3
Q

Test of Autoimmunity: ATgA

A

Measures: Antibodies to thyroglobulin
Reference range: Variable
Comments: + in autoimmune thyroid disease: Undetectable during remission

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4
Q

Test of autoimmunity: TPO-Ab

A

Measures: Thyroperoxidase antibodies
Reference range: variable
Comments: More sensitive of the 2 antibodies

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5
Q

Test of autoimmunity: TRAb

A

Measures: Thyroid receptor stimulating antibody
Reference: variable
Comments: Confirms Grave’s disease

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6
Q

Hyperthyroidism

A

Thyroid hormone excess
HYPERmetabolic state
Tachycardia, warm, insomnia
Higher metabolism
Palpitation, nervousness, anxiety
LOW TSH
T3, T4 high

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7
Q

Hyperthyroidism: Drug-induced Etiology

A

Excessive thyroid supplementation:
-Iodinated compounds:
-Ex: iodinated glycerol, potassium iodide, and providone iodine
Amiodarone (12 mg of free iodine/400 mg dose)
-Recommended dietary iodine intake = 150 mcg/day
-Optimal daily allowance = 250 mcg/day
Interferons (a and B)
Lithium

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8
Q

Hyperthyroidism: Treatment options

A

Thioamides:
-Propylthiuracil
-Methimazole
Radioactive Iodine (RAI)
Surgery (thyroidectomy)

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9
Q

Thioamides Comparison:

A

T1/2: PTU: 1-2.5 hours; Methimazole: 6-9 hours
Dosing: PTU: Q 8-12h; Methimazole: daily
Blocks T4->T3 conversion: PTU: Yes; Methimazole: No
Pregnancy: PTU: Not used; Methimazole: 2nd + 3rd trimester (start after 16 weeks)
Lactation: PTU: No; Methimazole: -
Potency: PTU: 1; Methimazole: ~10
Black Box Warning: PTU: - Methimazole: No (acute pancreatitis) (liver warning)

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10
Q

Thioamides comparison: Initial Dosing

A

Initial dosing: PTU: 50-150mg TID
Methimazole: Free T4 1-1.5x ULN: 5-10mg/day
Free T4 > 1.5-2x ULN: 10-20mg/day
Free T4 > 2x ULN; 20-40mg/day

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11
Q

Thioamides comparison: Maintenance dosing

A

PTU: 50mg BID or TID
Methimazole: 5-10mg/day

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12
Q

Thioamides comparison: Maximal dose

A

PTU: 1,200mg/day
Methimazole: 60mg/day

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13
Q

Thioamides - interactions with pregnancy

A

Methimazole - still crosses placenta, but less than PTU
Second trimester (16 weeks - convert PTU to methimazole

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14
Q

Thioamides dosing explained:

A

Depends on T4 levels
-Decrease dose 30% per month
Maintenance dose - lower

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15
Q

Drug of choice for thioamides

A

Methimazole - used exclusively unless patient is pregnant

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16
Q

Thioamides: Adverse Effects - GI upset: N/V

A

Take with meals, divided doses

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17
Q

Thioamides: Adverse Effects - Rash

A

Maculopapular, no systemic symptoms
-Treat with diphenhydramine, other antihistamines
-May try another thioamide
Wheals, hives, SOB:
Rash w/o wheezing: diphenhydramine
Anaphylactic reactions: Wheals, hives, SOB

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18
Q

Thioamides: Adverse Effects: Agranulocytosis (0.5-6%)

A

<500/mm^3 of neutrophils
Normally, 700-800 neutrophils to function too few neutrophils = immunocompromised
√WBC with differential
Cross reactivity ~50%
D/C thioamides immediately (reversible)

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19
Q

Warning signs of agranulocytosis

A

Fever > 101 >2 days
Flu like symptoms > 2 days
Mouth sores
Sore throat

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20
Q

Thioamides: Adverse Effects: Hepatitis (0.1-0.2%):

A

Obtain baseline LFT and PRN
Discontinue thioamides, give RAI or surgery

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21
Q

Thioamides: Efficacy Monitoring: √T4, T3, TSH initially Q4-6 weeks until euthyroid

A

Use w/minimal dose of medication
Then √Q3-6 months while on thioamides
TSH can be misleading - remain suppressed after T4 and T3 normalize

22
Q

Thioamides: Efficacy Monitoring: Remission rate

A

After 1-2 years of tx: ~40%
After 5-10 years of tx: ~80%

23
Q

Thioamides: Efficacy Monitoring: Once D/C thioamide

A

√Q4-6 weeks for first 3-4 months
Then yearly thereafter

24
Q

Radioactive iodine (RAI)

A

Slow destruction of thyroid gland with 131I radioactive isotope
Contraindicated in pregnancy, lactation, planning pregnancy < 6 months
Given dissolved in water or as a capsule. Colorless and tasteless
Avoid physical contact and secretion > 5 days
Euthyroid delayed (3-6 months)
Hypothyroidism (50-100%)
Graves’ orbitopathy (new or worsening)
Not recommended for moderate-severe orbitopathy
? Cancer

25
Surgery (Thyroidectomy)
For large glands (obstructive symptoms), multinodular goiter, cancer, medication failure, ophthalmopathy, pregnancy (2nd trimester) Risks: Vocal cord damage, removal of parathyroid glands Evaluate 2 months post surgery
26
Hyperthyroidism: B-blockers
**Adjunctive treatment ONLY** Short term use = alleviate symptoms Use in patients w/ HR > 90 bpm Prefer cardioselective B-blockers to maintain HR 60-90 BPM
27
Cardioselective BB (Preferred)
Atenolol 25-100mg daily metoprolol 25-50mg BID Propranolol 10-40mg PO Q6 or Q8H *Partially blocks peripheral T4->T3 conversion but VERY slow onset (7-10 days)
28
Calcium channel blockers (BB alternative)
Diltiazem or verapamil
29
BB: avoid agents with intrinsic sympathomimetic activity:
Acebutolol, careteolol, penbutolol, pindolol
30
Should patient OL be placed on a cardio-selective beta-blocker for her hyperthyroidism
Yes - BP greater than 90;
31
Hypothyroidism
Thyroid hormone deficiency HYPOmetabolic state Cold, exhaustion, fatigue, depression, weight gain (decreased metabolism)
32
Hypothyroidism: drug induced etiology
Amiodarone Lithium Interferons Management: Ideally D/c; if not able to - monitor, educate patient, check lab work annually
33
Hypothyroidism: Thyroid supplements:
**Levothyroxine (T4): Tirosint (cap); Tirosint-SOL (solution); Ermeza (solution); Thyquidity (solution); Synthroid; Levoxyl, Unithroid ^^MAIN FOCUS **Liothyronine (T3)**: Cytomel, Triostat **Desiccated thyroid**: Armour Thyroid
34
Main replacement in hypothyroidism
Levothyroxine (T4) should be first choice in replacement therapy for all hypothyroid patients -Cheap -Little allergenic rxn -uniform potency, stable, consistent, good bioavailability -Once a day dosing
35
Levothyroxine Black Box Warning:
In euthyroid patients, thyroid supplement within the range of daily hormonal requirements are **ineffective for weight reduction. High doses may produce serious/life threatening toxic effects, particularly when used with some anorectic drugs (sympathomimetic amines)** **Heart attack, heart failure**
36
Levothyroxine process
Peripheral T4->T3 conversion Provides necessary hormone w/o bolus effects of T3 Long T1/2 allows daily dosing **available as mcg strength** 12 different doses - based on titration schedule **regardless of manufacturer, strength color is always the same** **Narrow Therapeutic index**
37
Levothyroxine (T4 bioequivalence)
Bioequivalence = ? therapeutic equivalence Best to maintain on same product with every refill Any changes need monitoring **Narrow therapeutic index** Counseling: take on empty stomach (60 minutes before breakfast) or Bedtime (4 hours after dinner)
38
Drug interactions: Lower T4 absorption:
Bile acid sequestrations Al(OH)3 antacids Ferrous sulfate Sucralfate Calcium supplements
39
Drug interactions: Increase T4 requirement
Enzyme inducers: Phenytoin (PHT), carbamazepien (CBZ), rifampin, phenobarbital (PB)
40
Drug interactions: In crease serum TBG Concentration
Estrogen
41
Drug interactions: Disease-drug interaction
Warfarin
42
Levothyroxine dosing: uncomplicated (healthy) adult:
1.6 mcg/kg/day Average starting dose is 100mcg/day Increase by 12.5-25 mcg Q6-8 weeks **TSH levels obtained before SS can be VERY misleading**
43
Levothyroxine dosing: Elderly (>age 60):
<1.6 mcg/kg/day **Start at 25-50mcg/day increase by 12.5-25 mcg Q6-8 weeks as tolerated Initiate T4 cautiously Elderly may require less than younger due to decreased clearance of T4 Sensitive to small doses
44
Levothyroxine dosing: Cardiovascular disease, angina (CAD)
**Start 12.5-25mcg/day)** increase by 12.5-25 mcg Q6-8 weeks as tolerated Patients are very sensitive to CV effects of T4 Even subtherapeutic doses can precipitate severe angina, MI, or death Replace thyroid deficit slowly
45
Levothyroxine dosing: Longstanding hyperthyroidism (..1 year)
Dose slowly Start 12.5-25mcg/day) increase by 12.5-25 mcg Q6-8 weeks as tolerated
46
Levothyroxine dosing: Pregnant patients
May require 45% increase in dose Maintain normal TSH and FT4 in upper normal range to prevent fetal hypothyroidism
47
Liothyronine (T3):
Rapid absorption of T3 can cause hyperthyroid symptoms **Cardiac Toxicities** Short T1/2 necessitates BID-QID More $$ than T4 Main use: -Short term hormone replacement Diagnostic agent in T3 suppression test
48
Desiccated thyroid USP:
Natural product derived from pork thyroid glands Unpredictable potency result in over- and under- supplementation -"Potency" based on iodine content, not T4 and T3 Risk: allergic reactions to animal protein **No justification to use this product!** -1 grain (60mg) = 100mcg levothyroxine
49
Hypothyroidism: Efficacy Monitoring
Attain and maintain Euthyroid state -Normal TSH and FT4
50
Hypothyroidism: What to monitor:
√TSH, FT4, and clinical symptoms Q6-8 weeks -6-8 weeks after any dose or product change Until TSH normalized, then √Q3-6 months for the 1st year, then yearly Reversal of signs/symptoms in 203 weeks (max 4-6 weeks); anemia, hair, skin changes may take 6 months
51
Pregnancy
Essential to continue throughout pregnancy -Levothyroxine Require higher dose: -Increase T4 Turnover(?) Adjust by 25mcg, √TSH Q trimester Resumes to pre-pregnancy dose immediately after delivery Re √TSH in 6-8 weeks
52
Hypothyroidism Replacement therapy - Clinical pearl
Poor Adherence Drug-Food Interaction Drug- Drug Interaction *lead to patients with high or fluctuating TSH despite high levothyroxine dose (>200mcg/day)*