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Thyroid Disorders NGOC-YEN PHAM, PHARMD UNMH PGY-1 PHARMACY RESIDENT APRIL 1, 2019

Learning objectives

1. (RX) Describe the signs and symptoms associated with thyroid disorders

2. (RX) Identify the medications available for treatment of thyroid disorders

3. (RX) Describe the mechanism of action, drug-drug and drug-food interactions, contraindications, and adverse effects of pharmacological agents used in thyroid disorders

4. (RX) Given a case, formulate a treatment plan for the different thyroid disorders including medication selection and monitoring of therapy

Hypothyroidism Pathway Result: TSH: ______TH: ______

How does this affect the body?

3 DiPiro, et al. Pharmacotherapy: A Pathophysiologic Approach, 10e

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Alteration of thyroid labs TSH Thyroid Gland Decrease uptake - Glucocorticoids - Amiodarone - Metformin - Contrast - Opiates - Iodine - Interleukin-6 Hormone production Increase - Amiodarone - Interleukin-2 - Sulfonylureas - Amphetamine - Sulfonamides - Ritonavir - St. John’s wort Secretion - Lithium - Iodine - Amiodarone

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751.

Thyroid Laboratory

Free T4 Total T3 TSH Total T4 Normal 4.5–10.9 mcg/dL 0.8–2.7 ng/dL 60–181 ng/dL 0.5–4.7 milli- international units/L

Hyperthyroid ↑↑ ↑↑ ↑↑↑ ↓↓ Hypothyroid ↓↓ ↓↓ ↓ ↑↑ Increased TBG ↑ Normal ↑ Normal

DiPiro, et al. Pharmacotherapy: A Pathophysiologic Approach, 10e

Hypothyroidism WHAT ARE YOU DOING MAGGOT! WE NEED MORE THYROID HORMONE!

I’m s…s…sorry sir. There isn’t much out there. This is all I could find

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Hypothyroidism Hypertrophy of Decreased thyroid Severe long- thyroid gland hormone standing secretion/production Iodine deficiency Hypothyroidhypothyroidism Decreased thyroid hormone Hashimoto’s secretion/production Cretinism thyroiditis

Endemic Myxedema goiter Coma

Autoimmune Congenital destruction of deficiency of thyroid gland thyroid hormone

DiPiro, et al. Pharmacotherapy: A Pathophysiologic Approach, 10e

Signs and Symptoms

DiPiro, et al. Pharmacotherapy: A Pathophysiologic Approach, 10e

Case

A 60-year-old African American woman presents with a complaint of rapid weight loss despite a voracious appetite and heart palpitations. Physical examination reveals pulse rate 110 bpm, fine moist skin, symmetrically enlarged thyroid, mild bilateral quadriceps muscle weakness, and fine tremor.

These findings suggest: A. Hyperthyroid B. Hypothyroid

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What laboratory abnormalities would be expected?

A. High free T4 and high TSH B. High free T4 and low TSH C. Low free T4 and high TSH D. Low free T4 and low TSH

Treatment Guidelines §Goals of therapy §Available agents § Eliminate symptoms § (T4)

§ Normalize TSH & T4 levels § (T3) § Shrink goiter (Hashimoto’s) § Desiccated thyroid (Armour Thyroid) §Thyroid replacement therapy § Natural hormones § Synthetic

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751.

Levothyroxine Patient Dose Healthy adults 1.6mcg/kg/day Adults >50 years w/o evidence of 50mcg/day coronary heart disease

Adults with cardiac disease 12.5 to 25 mcg/day Pregnant patients 1.6 mcg/kg/day (severe) 1 mcg/kg/day (mild)

Synthroid (levothyroxine) [prescribing information] 2017.

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Levothyroxine Pharmacokinetics

Impairs Increase Dietary absorption clearance

Antacids: Al/Mg Soybean Rifampin Bile acid Fiber Carbamazepine sequestrants supplementation Amiodarone Calcium carbonate Coffee Sertraline Ferrous sulfate Grapefruit juice Proton pump Ingestion of meals inhibitors Sucralfate

Synthroid (levothyroxine) [prescribing information] 2017.

Levothyroxine

• Based on TSH levels Titration • 12.5 to 25mcg/day every 4 – 6 weeks

Monitoring • TSH & Free T4 at 4 – 6 weeks • Resolution of symptoms

Improvement • 2 weeks to several months

Synthroid (levothyroxine) [prescribing information] 2017.

Under treatment Overtreatment Low T4 Sx of hyperthyroid Elevated TSH ↑ HR Hypothyroid Sx ↑ Urinary Na excretion ↑ Cholesterol ↑ LFTs Increase dose 25 -50 mcg/day ↓ cholesterol ↑ bone resorption Reduce dose by 25mcg/day

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Check-in Question What dose of Levothyroxine would you recommend for a 75 yo (50kg) women with no history of heart disease?

A. 88 mcg po daily B. 25 mcg po daily C. 75 mcg po daily D. 12.5 mcg po daily

Case A 25-year-old African American woman presents with a complaint of rapid weight loss despite a voracious appetite and heart palpitations. Physical examination reveals pulse rate 110 bpm, fine moist skin, symmetrically enlarged thyroid, mild bilateral quadriceps muscle weakness, and fine tremor.

What pharmacological options should be used to manage this patient?

Myxedema Coma

Hypothermia IV levothyroxine

IV hydrocortisone

Advanced hypothyroid Delirium/Coma symptoms Supportive therapy

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Hyperthyroidism Hypothyroid (thyrotoxicosis) Decreased thyroid hormone Grave’s secretion/production Thyroid Increased thyroid hormone Disease Adenoma secretion/production Thyroid Storm

DiPiro, et al. Pharmacotherapy: A Pathophysiologic Approach, 10e

Drug induced Hyperthyroidism

Amiodarone

Thionamides Iodine induced Radioactive iodine

Prednisone 40mg Inflammatory thyroiditis daily for 6 to 12 weeks

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751. DiPiro, et al. Pharmacotherapy: A Pathophysiologic Approach, 10e

Signs and Symptoms

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Signs and Onycholysis Exopthalmos Symptoms

Thyroid acropachy Pretibial myxedema

Case A 23-year-old woman presents with palpitations. Over the past 6 months, she has reported loose stools, a 10-lb (4.5-kg) weight loss despite a good appetite and food intake, and increased irritability. She appears to be anxious. Thyroid gland is diffusely and symmetrically enlarged to twice the normal size, and it is firm and nontender; She has an eyelid lag, but no periorbital edema. HR = 119 bpm, BP = 137/80 mmHg TSH = 0.02 microU/ml (0.5-5.0 microU/L) FT4 = 4.10 ng/dl (0.89 to 1.76ng/dl).

Treatment Goals

Relief of symptoms

Medications Surgery Reduction of thyroid hormone

Reversing the Radiation cause of thyrotoxicosis

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751. DiPiro, et al. Pharmacotherapy: A Pathophysiologic Approach, 10e

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Pharmacological Agents

THIOUREAS (THIONAMIDES) IODINE

RADIOACTIVE ADRENERGIC IODINE BLOCKERS

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751. DiPiro, et al. Pharmacotherapy: A Pathophysiologic Approach, 10e

Thionamides : Methimazole (MMI)

Mechanism of Indications Dosing action

• Inhibits thyroid • Thyroid storm • 10 – 40mg once peroxidase • Preferred in daily pregnancy

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751.

Thionamides : Prophylthiouracil (PTU)

Mechanism of Preference Dosing action

• Inhibits thyroid • First trimester of • 150-600mg/day peroxidase and pregnancy TID-QID peripheral • Thyroid storm conversion of T4 • Intolerance to to T3 methimazole

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751.

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Thionamides

Adverse effects Monitoring

Common: • TSH, T3, T4, LFTS • Rash/urticaria • WBC + differential • Fever • Arthralgia • Repeat Q4-6 weeks after start Rare: or change in doses • Hepatitis • SLE-like syndrome • Agranulocytosis • Cholestatic jaundice

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751.

Iodine

Mechanism of Uses Adverse effects Action

• Blocks thyroid • Grave’s disease • Hypersensitivity hormone release • Severely reaction thyrotoxic • Salivary gland • Post-radioactive swelling iodine therapy • “Iodism”

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751.

Radioactive iodine (I131)

• Prior thyroid surgery Indications • Poor surgical risk • Failed thionamide therapy

• Contraindicated in pregnancy/breastfeeding Details • Slow onset • Preferred treatment for Graves’

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751.

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Radioactive iodine (I131)

• Pre-treatment with methimazole in older patients Considerations • Acute hyperthyroid post-treatment • First line treatment in younger patients

• Carcinogenic Adverse • Leukemia Effects • Genetic damage • Hypothyroidism

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751.

Beta-Blockers •Provide relief of increased sympathetic tone • Palpitations, tachycardia, anxiety •Beta-blockers can also reduce peripheral conversion of T4 à T3 • IR may be preferred due to short half-life • Patient can self-titrate dose to ameliorate symptoms •IV esmolol is used for symptomatic treatment of thyroid storm • Rapid onset, short half-life

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751.

Thyroid Storm (medical emergency!)

Burch-Wartofsky Point Scale (BWPS) for Thyrotoxicosis Hydrocortisone

Cardiovascular (tachycardia, Afib, CHF) GI/Hepatic (diarrhea, abdominal pain, jaundice) CNS (agitation à seizure/coma) Precipitant history (storm previously) PTU + iodine Thermoregulatory dysfunction (temp)

• BWPS ≥45 is highly suggestive of thyroid storm • BWPS 25-44 suggests impending thyroid storm • BWPS <25 is unlikely to represent thyroid storm Anti-adrenergic treatment

Jonklaas J. Thyroid. 2014 Dec;24(12):1670-751.

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Case MN, a 41-year-old male presented to the Which of the following should be ED with confusion, rightsided numbness administered to MN immediately? and tingling, slurred speech, dizziness, and facial edema. A. Aspirin 325mg BP = 90/60 mm Hg, HR = 50 beats/min T B. metoprolol + methimazole = 95.7 degrees F C. 500mcg IV levothyroxine + Abnormal Labs: CK = 439 IU/L SCr = 1.6 hydrocortisone 100mg IV mg/dL TSH = 126.4 microIU/mL ↑↑↑↑ FT4 = 0.29 ng/dL ↓↓↓↓

Case A 23-year-old woman presents with What is your medication palpitations. Over the past 6 months, she has recommendation for reported loose stools, a 10-lb (4.5-kg) weight pharmacological treatment of AA’s loss despite a good appetite and food intake, hyperthyroidism? and increased irritability. She appears to be anxious.Thyroid gland is diffusely and symmetrically enlarged to twice the normal A. Propranolol and Methimazole size, and it is firm and nontender; She has an B. Atenolol and Iodine eyelid lag, but no periorbital edema. C. PTU and Atenolol HR = 119 bpm, BP = 137/80 mmHg TSH = 0.02 microU/ml ↓↓ FT4 = 4.10 ng/dl ↑↑

Key Points

1) Thyroid hormone is essential in regulating cardiac function, bone growth, and maintaining metabolism

2) The goal of treatment is to normalize TSH and eliminate symptoms

3) Levothyroxine is the mainstay of treatment in hypothyroidism

4) Thyroid storm is a medical emergency that requires prompt treatment

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