thyroid -butler pa therapeutics ·
TRANSCRIPT
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Hypothyroidism 03.15.16
PA Therapeutics
Heather Folz, PharmDPGY2 Ambulatory Care
HYPOTHYROIDISM OBJECTIVES
§ Identify treatment goals § Outline therapeutic treatment approach for an
“uncomplicated” patient§ Briefly explain pharmacologic rationale§ List monitoring requirements§ Describe most relevant patient counseling
points§ Identify contraindications, precautions, and
drug interactions and their management§ Address treatment considerations for special
populations 2
PATHOPHYSIOLOGY
3http://emedicine.medscape.com/article/122393-‐overview
↑ TSH↓ T3, T4
HALLMARK SYMPTOMS
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https://i.ytimg.com/vi/b2Q-‐XumnVVY/maxresdefault. jpg
TREATMENT GOALS
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Normalized serum TSH levels
(0.4-‐4.0 mIU/L)
Restore clinically euthyroid state
Minimize adverse reactions
Prevent complications
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TREATMENT
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Levothyroxine
efficacious
long-‐termexperience
favorable side effect profile
ease of use
good absorption
long serum half-‐life
low cost
TREATMENT
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§ Levothyroxine (T4) (Levoxyl, Synthroid)– Synthetic form of thyroid secreted thyroxine– Converted to active L-triiodothyronine (T3)– Product bioavailability variance up to 14%– Narrow therapeutic index
TREATMENT
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Population Initial Dose (mcg/day) Comments
Healthy Adults <50 1.7mcg/kg/dayUsual range 100-‐125mcg>200mcg/day rarely required
Adults <50 with cardiac diseaseORHealthy Adults >50*
25-‐50mcg *Elderly pts may require <1mcg/kg/day
Adults >50 with cardiac disease
12.5-‐25mcgAdjust by 12.5-‐25mcg every 6-‐8 wks
Pediatrics Follow wt-‐based dosing
Pregnancy 100-‐150mcgIncrease dose 20-‐30% when pregnancy confirmed
APPLICATION
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Answer: Levothyroxine 100mcg/day (~1.7mcg/kg/day)
Rachel is a healthy 130lb, 29 yo female with no PMH except for a recent diagnosis of moderate hypothyroidism. What dose of levothyroxine would you initiate?
TREATMENT
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§ Liothyronine (T3) (Cytomel, Triostat)– Synthetic form of triiodothyronine (T3)
§ Desiccated Thyroid (Armour Thyroid, Nature-Throid)– T3 and T4
– Beers Criteria– Porcine derivative
MONITORING
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Significant T4 ↑ ~1-‐2 wks
Steady state TSH ~6 wks
TSH annually once stable
Consider monitoring T4 and TSH as early as 3 weeks if
symptomatic
↑ dose by 12.5-‐25mcg/day Q4-‐8wks until normalized TSH
Normal serum TSH (0.4-‐4.0mIU/L)
Change in levothyroxine formulation → Re-‐evaluate TSH in 6wks
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APPLICATION
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a. Naturally derivedb. Must be activated to T3c. Inexpensived. Reliable concentration/dose
Levothyroxine is preferred for all the following reasons EXCEPT?
PATIENT COUNSELING
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Take on empty stomach
Separate from vitaminsand supplements
Take with water Be consistent
Rule of Separation § At least 30-‐60 mins before food or 4 hours after
§ 4 hours from antacids, iron, and calcium supplements
APPLICATION
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a. Take levothyroxine at least 30 mins before breakfast and switch MV to evenings
b. Start taking levothyroxine in the evening 4 hours after dinner
c. Continue current administration, but stay consistentd. Switch to Armour Thyroid to avoid administration
interactions
Kristen’s TSH is therapeutic, but you learn that she is taking her levothyroxine in the morning with all other medications and daily multivitamin. How should you counsel her?
SAFETY
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Common
Palpitations
Alopecia, sweating
Weight loss
Diarrhea
Insomnia
Anxiety
Serious
MI
Decreased BMD/fractures
Micromedex (accessed 2/7/2016)
Increased cardiovascular risks if serum TSH <0.1mIU/L
SAFETY
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Boxed Warning for Weight Reduction
Do not use thyroid hormones, including levothyroxine, either alone or with other therapeutic agents, for the treatment of obesity or for weight loss. In euthyroid patients, doses within the range of daily hormonal
requirements are ineffective for weight reduction. Larger doses may produce serious or even life-‐threatening manifestations of toxicity, particularly when given in
association with sympathomimetic amines such as those used for their anorectic effects for weight reduction.
DRUG INTERACTIONS
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-‐Tricyclicantidepressants-‐Vitamin K antagonists
-‐Bile acid sequestrants-‐Calcium, magnesium, iron, MV/minerals
-‐Anticonvulsants-‐Estrogen-‐PPIsLe
vothyroxinemay in
crease
May decrease levothyroxine
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APPLICATION
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a. Counsel patient to separate timing of warfarin and levothyroxine dose as much as possible
b. Levothyroxine directly interferes with the INR test; order a different coagulation assay
c. Levothyroxine and warfarin should not be taken together; switch to novel oral anticoagulant
d. Levothyroxine can increase warfarin concentrations; decrease warfarin dose and monitor INR in 1-2 weeks
Jimmy’s INR came back elevated at 4.2. He denies any significant changes but you notice his dose of levothyroxine was ↑ 3 weeks ago. How should you proceed?
SAFETY
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When to Admit
1) Suspected myxedema crisis 2) Hypercapnia
When to Refer1) Unable to titrate to normal TSH or clinically euthyroid state 2) Significant coronary disease
HYPOTHYROIDISM WRAP UP
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Symptom ↓ ~2wks (full resolution ~months)
Report angina or tachycardia Take consistently
Monitor TSH ~4-‐8wks
Goal ~0.4-‐4.0mIU/L ↑ or ↓ 12.5-‐25mcg/day Q4-‐8wks
Levothyroxine = preferred treatment
1.7mcg/kg/day Start lower doses if >50or CVD
EXAMPLE DOSE ADJUSTMENT ALGORITHM
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TSH Level (milliunits/L) Change in mcg/day
4-‐10Add 12.5
*25 if current dose >150mcg/day
>10 Add 25
0.5-‐0.2Subtract 12.5
*25 if current dose >175mcg/day
<0.1 Subtract 25
Recheck TSH after ~6 weeks after dose change
GUIDELINES
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§ American Thyroid Association Task Force (2014)– Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines
for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 2014; 24:1670.
Hyperthyroidism
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HYPERTHYROIDISM OBJECTIVES
§ Identify treatment goals § Outline therapeutic treatment approach for an
“uncomplicated” patient§ Briefly explain pharmacologic rationale§ List monitoring requirements§ Describe most relevant patient counseling
points§ Identify contraindications, precautions, and
drug interactions and their management§ Address treatment considerations for special
populations25
PATHOPHYSIOLOGY
26http://emedicine.medscape.com/article/122393-‐overview
↓ TSH↑ T3, T4
HALLMARK SYMPTOMS
27
http://www.lloydhealthcare.org/wp-‐content/uploads/2015/02/Hyperthyroidism-‐symptoms..png
TREATMENT GOALS
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Normalized thyroid hormones
Restore clinically euthryoid state
Minimize adverse reactions
Prevent complications of disease progression
TREATMENT
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Beta blockersThiourea drugs (antithyroid
drugs)
Radioactive iodine (131I,
RAI)
Thyroid surgery
Beta blockers
TREATMENT
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Medication Dose (mg/day) CommentsPropranolol ER Initial: 60mg once or twice/day
Max: 320mg/day
Symptomrelief
Beta blocker relieves tachycardia, tremor, diaphoresis, and anxiety . . .
Does NOT effect hormone secretion
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TREATMENT
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Thiourea drugs: inhibits T3 and T4 synthesis
-‐Good response ino Mild disease
o Small goiterso Elderly
-‐Non-‐invasive-‐Low cost-‐Low risk hypothyroidism
-‐Agranulocytosis-‐Pancytopenia-‐Hepatotoxicity -‐Pruritus, allergic dermatitis, GI-‐Compliance
Goal: induce remission in 3-‐8wksNot curative
Thiourea drugs (thioamides)
Methimazole (MMI)
• Generally preferred• Initial: 15-‐60mg/day• Divided dosing• Pregnancy max =20mg/day
• Lower hepatotoxicity risk
Propylthiouracil (PTU)
• Favored in 1st
pregnancy trimester• Initial: 300-‐600mg/day• Divided dosing• Pregnancy max =200mg/day
TREATMENT
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MONITORING
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Baseline LFTs
WBC (fever, pharyngitis, or bleeding)
Monthly serum FT4
Re-‐assess PRN for hepatotoxicity
85% of agranulocytosis in 1st
90 days
TSH may remain low for several months
TREATMENT
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Radioactive iodine (131I, RAI): destroys thyroid tissue
-‐Curative
-‐Low cost
-‐60% euthyroid by 6mo
-‐One time PO dose
-‐May repeat in 6 months prn
-‐May worsen ophthalmopathy-‐↑ hyperparathyroidism
-‐May cause hypothyroidism-‐Thionamide/BB 1st if severe hyperthyroidism, elderly, or CVD
Harmful to fetus and children: Contraindicated in pregnancy and lactation
APPLICATION
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a. Curative therapy may cause hypothyroidismb. Methimazole is generally preferred over PTUc. Propranolol only controls symptomsd. Radioactive Iodine is preferred in pregnancy
Which hyperthyroidism treatment consideration is NOT accurate?
MONITORING
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Baseline pregnancy test
FT4 in 4-‐6wks
TSH Q6-‐12 months
Avoid RAI within 4 months of pregnancy
Best immediate indicator
Lifelong follow-‐up
Radioactive iodine (131I, RAI)
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Instruction to minimize radioactive exposure(http://www.thyroid.org/radioactive-‐iodine/)
Duration (days)
Sleep in a separate bed (~6 feet of separation) from another adult 1-‐11
Delay return to work 1-‐5
Maximize distance from children and pregnant women (6 feet) 1-‐5
Limit time in public places 1-‐3
Do not travel by airplane or public transportation 1-‐3
Do not travel on a prolonged automobile trip with others 2-‐3
Maintain prudent distances from others (~6 feet) 2-‐3
Drink plenty of fluids 2-‐3
Do not prepare food for others 2-‐3
Do not share utensils with others 2-‐3
Sit to urinate and flush the toilet 2-‐3 times after use 2-‐3
Sleep in a separate bed (~6 feet of separation) from pregnant partner, child or infant 6-‐23
Avoid conception 6-‐12 months
TREATMENT
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Thyroid surgery (thyroidectomy): resect one lobe
Option for:-‐Pregnant or planning on becoming pregnant-‐Large goiters-‐Severe opthalmopathy-‐MalignancyEuthyroid ~1month
-‐Hypoparathyroidism-‐Hypothyroidism-‐Risk of laryngeal nerve damage-‐Expensive-‐Scar
Achieve euthyroid state prior to surgery
APPLICATION
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a. Methimazole b. Propylthiouracil c. Radioactive Iodine d. Surgery
Kerry is a 41 yo female with mild graves disease. She is not planning on becoming pregnant. What is the best option to treat her hyperthyroidism?
SAFETY
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When to Admit
Thyroid crisis or "storm"
Hyperthyroidism-‐induced AF Thyroidectomy
APPLICATION
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a. Avoid methimazole during 1st trimesterb. Switch from PTU to methimazole at 2nd
trimesterc. Avoid conception for 6-12months post 131Id. Continue beta blockers for long-term
symptom treatment
Which pregnancy consideration statement is FALSE?
HYPERTHROIDISM WRAP UP
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• Only treats symptoms• Use with other treatmentsBeta blockers
• Short-‐term/not cure• Option for mild symptoms or before RAI/surgery• Methimazole preferred
Thiourea drugs
• Curative• Consider pregnancy and ophthalmopathy
Radioactive iodine
• Curative• Recommended for severe disease/very large goiter• Consider $ and complications
Thyroid surgery
Best treatment based on pt preference and symptoms
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GUIDELINES
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§ American Thyroid Association and American Association of Clinical Endocrinologists (2011)– Bahn Chair RS, Burch HB, Cooper DS, et al.
Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid 2011; 21:593.