Pharm - Thyroid Disorders

How much T4 is produced in a day?

100mcg

How much T3 is produced in a day?

30mcg

What is the half life of T3?

About 1 day

What is the half life of T4?

About 7 days

When do you treat hypothyroidism?

TSH >4 WITH symptoms or TSH >10 regardless of symptoms

What are the treatment goals for hypothyroidism treatment?

Achieve euthyroid state, decrease signs and symptoms and avoid overtreatment.

What is the drug of choice for hypothyroidism?

Levothyroxine (cheap, most evidence)

What hormone does Levothyroxine replace synthetically?

T4

When do treat hypothyroidism if TSH is 4-9?

Symptoms present

Age <60

Planning pregnancy or pregnant

Presence of anti-TPO antibodies

TSH progressively rising on serial checks

When do you usually NOT treat hypothyroidism?

Age >60

Mild elevation of TSH (4-7) w/o symptoms

Concurrent acute illness

Euthyroid sick syndrome

Which drug is a synthetic T3 replacement and is used with caution for thyroid replacement?

Liothyronine (has greater CV risks and harder to monitor)

What is the 2nd or 3rd line treatment for hypothyroidism?

Dessicated Thyroid (T4+T3 in about 4:1 ratio; derived from pig thyroid)

What are the ADE of thyroid replacement meds?

CV (tachycardia, HTN, palpitations)

Weight loss

Sweating

Diarrhea

Anxiety

What is the black box warning for thyroid replacement meds?

DO NOT use to treat obesity or for weight loss in patients that are euthyroid. Also drug has a narrow therapeutic index.

What are some counseling points for patients on levothyroxine?

Take 30-60 minutes before breakfast on an empty stomach

Symptoms may not improve for several weeks

Stick to the same brand

Thyroid replacement is FOR LIFE

What is the dosing of Levothyroxine in a healthy adult?

1.6mcg/kg/day. Round to nearest available strength

What is the dosing of Levothyroxine in a >60 year old?

25-50mcg/day. Start low, go slow

What is the dosing of Levothyroxine if CVD is present?

12.5-50mcg/day.

What is the dosing of Levothyroxine for maintenance?

Add 12.5-25mcg (very low amount), check q4-6 weeks. Titrate to goal TSH.

What is the relationship between IV dose of Levo and PO Levo?

IV is ~75% of oral dose.

What is the DOC for pregnant patients with hypothyroidism?

Levo. Increase dose 20-30% (2 extra tablets/week) when pregnancy is confirmed, adjust q4 weeks PRN.

What is the 1st trimester TSH goal?

<2.5

What are the 2nd and 3rd trimester TSH goals?

<3.0

What happens if hypothyroidism goes untreated in pregnancy?

Increased risk of miscarriage and development issues.

What is the dosing for an infant aged 1-3 months (for Levo)?

10-15mcg/kg/day

What is the dosing for an infant aged 3-6 months (for Levo)?

8-10mcg/kg/day

What should be used to calculate Levothyroxine dose for obese patients?

Lean body weight.

What is the initial treatment for Myxedema coma?

IV Bolus Levothyroxine 200-400mcg and Liothyronine 5-20mcg

What is the maintenance dose after Mxyedema coma treatment?

Levothyroxine 50-100mcg IV daily and Liothyronine 2.5-10mcg q 8hrs.

When do you switch from IV meds to PO meds in myxedema coma?

Once clinically stable. Liothyronine continued until there is clinical improvement (stopped due to increased risk of CV and death)

What other non thyroid medication is given during myexedma coma?

Hydrocortisone 100mg IV q8h until adrenal insufficiency is ruled out.

How does hypothyroidism affect digoxin metabolism?

Decreases clearance, increases serum concentration.

How does hypothyroidism affect insulin metabolism?

Decrease glucose metabolism and increases insulin resistance.

How does hypothyroidism affect warfarin metabolism?

Decreases clotting factor catabolism, less anticoagulation needed

How does hypothyroidism affect opoid metabolism?

Decreases respiratory drive, decreases muscle tone and increases risk of respiratory depression.

What medications can cause hyperthyroidism?

Amiodarone, excess iodine, and excess levothyroxine.

Which treatments for hyperthyroidism lead to permanent hypothyroidism?

Radioactive iodine and surgery.

Which drugs are highlighed as thionamides?

Methimazole and PTU.

What is the MOA of Methimazole?

Inhibits TPO, blocks T3/T4 synthesis

What is the MOA of PTU?

Inhibits TPO and blocks peripheral T4 to T3 conversion.

Is Methimazole or PTU first line for hyperthyroidism?

Methimazole

Is Methimazole or PTU preferred in 1st trimester pregnancy?

PTU! Methimazole is teratogenic

Is Methimazole or PTU preferred in 2nd and 3rd trimesters of pregnancy?

Methimazole! PTU has hepatotoxicity risk (black box!!)

Is Methimazole or PTU preferred for thyroid storm treatment?

PTU! Blocks T4 to T3 conversion.

What are the ADE of Thionamides?

GI, ageusia, bleeding, hepatotoxicity, agranulocytosis, congenital malformations (w/ Methimazole in 1st trimester)

What can be done to decrease the GI ADE with Methimazole?

Split doses >30mg/day (basically take less at once)

What should be monitored when taking a thionamide?

S/sx of acute illness or jaundice, baseline CBC, TSH and FT4 q4-6 weeks after dose changes, then q2-3 months once euthyroid.

What is the initial dosing of PTU?

100mg q8hr initially, then 50mg q8hr.

What is the Methimazole dosing for a patient with Free T4 1-1.5x ULN?

5-10mg daily

What is the Methimazole dosing for a patient with Free T4 1.5-2x ULN or iodine-induced thyrotoxicosis?

10-20mg daily

What is the Methimazole dosing for a patient with Free T4 >2x ULN?

20-40mg/day (divided in 2-3 doses)

What is the Methimazole dosing for a patient with amiodarone-induced thyrotoxicosis?

30-40mg/day (divided in 2-3 doses)

What is the MOA of Radioactive Iodine?

Emits radiation that destroys overactive follicular cells.

Can Amiodarone cause hypo or hyperthyroidism?

Both! Can either inhibit conversion of T4 to T3, or increases thyroid hormone release.

What is the most reliable guide in a patient using amiodarone?

TSH

What drugs are used as adjunctive therapies?

Iodide and beta blockers (propranolol preferred)

What is the MOA of iodide (SSKI- Potassium iodide)?

Blocks organification, blocks thyroid hormone release, blocks T4 to T3 conversion.

When is the max effect of iodide?

10-15 days, thyroid "escapes" so only indicated for short-term use.

What are the uses of iodide?

Preop thyroidectomy, thyroid storm, nuclear radiation emergency.

What are the ADE of iodide?

Metallic taste, rash, GI, allergic reaction, and iodine toxicity

When should iodide be avoided?

Pregnancy and patients with goiters.

What is the MOA of beta-blockers?

Block beta receptors to control CV symptoms; propranolol also blocks peripheral T4 to T3.

When are beta-blockers indicated?

Symptom management; NOT a defintive therapy.

What is the target HR for beta-blocker therapy?

<90bpm

When should atenolol or metoprolol be used instead of propranolol?

In asthma/COPD patients

What are the CI for beta-blocker therapy?

Decompensated HF, cardiogenic shock, bradycardia, heart block.

What adjunct therapy is used as an alternative to methimazole/PTU?

Lithium

What is the MOA of Lithium?

Inhibits iodine uptake, inhibits thyroid hormone synthesis, and inhibits conversion of T4 to T3.

What are the ADE of Lithium?

Serotonin syndrome, arrhythmias, acne, psoriasis, GI

What are the signs of Lithium toxicity?

Tremor, confusion, tinnitus, nausea, diarrhea, coma, death

What are suggestive symptoms of hyperthyroidism in pregnancy?

Failure to gain weight despite good appetite, persistent tachycardia, excessive anxiety or tremors, heat intolerance.

What is the treatment for thyroid storm?

PTU 500mg-1g loading dose, then 200-500mg q4h. Beta blocker to control adrenergic tone. Iodide to decrease release of thyroid hormone (give 1hr after PTU). Glucocorticoids (dexamethasone) to block T4 to T3 conversion. Bile acid sequestrant to reduce enterohepatic recycling

What is the pre-op preparation for thyroidectomy?

Achieve euthyroid state with methimazole/PTU first

Iodide 1-2 weeks pre-op to decrease vascularity of gland

Beta-blocker for cardiac stability

What is the process for a post-op thyroidectomy patient?

Initiate levothyroxine 1.6 mcg/kg/day. Monitor Ca levels for hypoparathyroidism. Monitor TSH at 6 weeks, then 6 months, then annually.