Ex 4. L4 Thyroid Hormones 2 (38) Flashcards
TSH test
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
Free T4 test
Direct measurement of free thyroxine
Reference range: 0.7-1.9ng/dL
Comments: Most accurate. May be normal in mild thyroid disease
Test of Autoimmunity: ATgA
Measures: Antibodies to thyroglobulin
Reference range: Variable
Comments: + in autoimmune thyroid disease: Undetectable during remission
Test of autoimmunity: TPO-Ab
Measures: Thyroperoxidase antibodies
Reference range: variable
Comments: More sensitive of the 2 antibodies
Test of autoimmunity: TRAb
Measures: Thyroid receptor stimulating antibody
Reference: variable
Comments: Confirms Grave’s disease
Hyperthyroidism
Thyroid hormone excess
HYPERmetabolic state
Tachycardia, warm, insomnia
Higher metabolism
Palpitation, nervousness, anxiety
LOW TSH
T3, T4 high
Hyperthyroidism: Drug-induced Etiology
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
Hyperthyroidism: Treatment options
Thioamides:
-Propylthiuracil
-Methimazole
Radioactive Iodine (RAI)
Surgery (thyroidectomy)
Thioamides Comparison:
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)
Thioamides comparison: Initial Dosing
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
Thioamides comparison: Maintenance dosing
PTU: 50mg BID or TID
Methimazole: 5-10mg/day
Thioamides comparison: Maximal dose
PTU: 1,200mg/day
Methimazole: 60mg/day
Thioamides - interactions with pregnancy
Methimazole - still crosses placenta, but less than PTU
Second trimester (16 weeks - convert PTU to methimazole
Thioamides dosing explained:
Depends on T4 levels
-Decrease dose 30% per month
Maintenance dose - lower
Drug of choice for thioamides
Methimazole - used exclusively unless patient is pregnant
Thioamides: Adverse Effects - GI upset: N/V
Take with meals, divided doses
Thioamides: Adverse Effects - Rash
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
Thioamides: Adverse Effects: Agranulocytosis (0.5-6%)
<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)
Warning signs of agranulocytosis
Fever > 101 >2 days
Flu like symptoms > 2 days
Mouth sores
Sore throat
Thioamides: Adverse Effects: Hepatitis (0.1-0.2%):
Obtain baseline LFT and PRN
Discontinue thioamides, give RAI or surgery
Thioamides: Efficacy Monitoring: √T4, T3, TSH initially Q4-6 weeks until euthyroid
Use w/minimal dose of medication
Then √Q3-6 months while on thioamides
TSH can be misleading - remain suppressed after T4 and T3 normalize
Thioamides: Efficacy Monitoring: Remission rate
After 1-2 years of tx: ~40%
After 5-10 years of tx: ~80%
Thioamides: Efficacy Monitoring: Once D/C thioamide
√Q4-6 weeks for first 3-4 months
Then yearly thereafter
Radioactive iodine (RAI)
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
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
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
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)
Calcium channel blockers (BB alternative)
Diltiazem or verapamil
BB: avoid agents with intrinsic sympathomimetic activity:
Acebutolol, careteolol, penbutolol, pindolol
Should patient OL be placed on a cardio-selective beta-blocker for her hyperthyroidism
Yes - BP greater than 90;
Hypothyroidism
Thyroid hormone deficiency
HYPOmetabolic state
Cold, exhaustion, fatigue, depression, weight gain (decreased metabolism)
Hypothyroidism: drug induced etiology
Amiodarone
Lithium
Interferons
Management:
Ideally D/c; if not able to - monitor, educate patient, check lab work annually
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
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
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
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
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)
Drug interactions: Lower T4 absorption:
Bile acid sequestrations
Al(OH)3 antacids
Ferrous sulfate
Sucralfate
Calcium supplements
Drug interactions: Increase T4 requirement
Enzyme inducers: Phenytoin (PHT), carbamazepien (CBZ), rifampin, phenobarbital (PB)
Drug interactions: In crease serum TBG Concentration
Estrogen
Drug interactions: Disease-drug interaction
Warfarin
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
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
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
Levothyroxine dosing: Longstanding hyperthyroidism (..1 year)
Dose slowly
Start 12.5-25mcg/day)
increase by 12.5-25 mcg Q6-8 weeks as tolerated
Levothyroxine dosing: Pregnant patients
May require 45% increase in dose
Maintain normal TSH and FT4 in upper normal range to prevent fetal hypothyroidism
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
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
Hypothyroidism: Efficacy Monitoring
Attain and maintain Euthyroid state
-Normal TSH and FT4
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
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
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)
