Thyroid Disorders - cdn.ymaws.com · 1. (RX) Describe the signs and symptoms associated with...

3/14/19

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Thyroid DisordersNGOC-YEN PHAM, PHARMDUNMH PGY-1 PHARMACY RESIDENTAPRIL 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

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Hypothyroidism Pathway Result:

TSH: _____________

TH: ______________

How does this affect the body?

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

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Alteration of thyroid labs TSH Thyroid Gland

Decrease - Glucocorticoids- Metformin- Opiates- Interleukin-6

Increase- Interleukin-2 - Amphetamine - Ritonavir - St. John’s wort

Iodine uptake - Amiodarone- Contrast - Iodine

Hormone production - Amiodarone - Sulfonylureas - Sulfonamides

Secretion - Lithium - Iodine- Amiodarone

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

Thyroid Laboratory

Total T4Free T4 Total T3 TSH

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


Hypothyroidism

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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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Severe long-standing

hypothyroidism

Congenital deficiency of

thyroid hormone

Hypertrophy of thyroid gland

Iodine deficiency

Autoimmune destruction of thyroid gland

HypothyroidDecreased thyroid hormone

secretion/production

Endemic goiter

Cretinism Hashimoto’s thyroiditis

Myxedema Coma

HypothyroidismDecreased thyroid

hormone secretion/production


Signs and Symptoms


CaseA 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. HyperthyroidB. Hypothyroid

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What laboratory abnormalitieswould 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§ Eliminate symptoms

§ Normalize TSH & T4 levels

§ Shrink goiter (Hashimoto’s)

§Thyroid replacement therapy§ Natural hormones

§ Synthetic

§Available agents § Levothyroxine (T4)

§ Liothyronine (T3)

§ Desiccated thyroid (ArmourThyroid)


Levothyroxine

Synthroid (levothyroxine) [prescribing information] 2017.

Patient Dose

Healthy adults 1.6mcg/kg/day

Adults >50 years w/o evidence of coronary heart disease

50mcg/day

Adults with cardiac disease 12.5 to 25 mcg/day

Pregnant patients 1.6 mcg/kg/day (severe) 1 mcg/kg/day (mild)

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Antacids: Al/Mg Bile acid

sequestrantsCalcium carbonate

Ferrous sulfateProton pump

inhibitorsSucralfate

SoybeanFiber

supplementation Coffee

Grapefruit juice Ingestion of meals

RifampinCarbamazepine

AmiodaroneSertraline

Levothyroxine Pharmacokinetics


Impairs absorption Dietary Increase

clearance

Levothyroxine


Titration

• Based on TSH levels

• 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

Under treatmentLow T4Elevated TSHHypothyroid Sx↑ CholesterolIncrease dose 25 -50 mcg/day

OvertreatmentSx of hyperthyroid

↑ HR↑ Urinary Na excretion

↑ LFTs↓ cholesterol

↑ bone resorptionReduce dose by

25mcg/day

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Check-in QuestionWhat 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

Delirium/ComaAdvanced

hypothyroid symptoms

IV levothyroxine

IV hydrocortisone

Supportive therapy

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HypothyroidDecreased thyroid hormone


Hyperthyroidism (thyrotoxicosis)

Increased thyroid hormone



Thyroid Adenoma

Thyroid Storm

Grave’s Disease

Drug induced Hyperthyroidism

Amiodarone

Iodine induced

Inflammatory thyroiditis

ThionamidesRadioactive iodine

Prednisone 40mg daily for 6 to 12

weeks

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

Signs and Symptoms

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Signs and Symptoms

Onycholysis Exopthalmos

Pretibial myxedema Thyroid acropachy

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

Reduction of thyroid hormone

Reversing the cause of

thyrotoxicosis

Surgery

Radiation

Medications


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Pharmacological Agents

THIOUREAS (THIONAMIDES)

ADRENERGIC BLOCKERS

RADIOACTIVE IODINE

IODINE


Thionamides : Methimazole (MMI)

Mechanism of action

• Inhibits thyroid peroxidase

Indications

• Thyroid storm • Preferred in

pregnancy

Dosing

• 10 – 40mg once daily


Thionamides : Prophylthiouracil (PTU)

Mechanism of action

• Inhibits thyroid peroxidase and peripheral conversion of T4 to T3

Preference

• First trimester of pregnancy

• Thyroid storm

• Intolerance to methimazole

Dosing

• 150-600mg/day TID-QID


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Thionamides

Adverse effects

Common:

• Rash/urticaria

• Fever

• Arthralgia

Rare:

• Hepatitis

• SLE-like syndrome

• Agranulocytosis

• Cholestatic jaundice

Monitoring

• TSH, T3, T4, LFTS

• WBC + differential

• Repeat Q4-6 weeks after start

or change in doses


Iodine Mechanism of

Action

• Blocks thyroid hormone release

Uses

• Grave’s disease • Severely

thyrotoxic• Post-radioactive

iodine therapy

Adverse effects

• Hypersensitivity reaction

• Salivary gland swelling

• “Iodism”


Radioactive iodine (I131)

Indications

• Prior thyroid surgery

• Poor surgical risk

• Failed thionamide therapy

Details

• Contraindicated in pregnancy/breastfeeding

• Slow onset

• Preferred treatment for Graves’


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Radioactive iodine (I131)

Considerations

• Pre-treatment with methimazole in older patients

• Acute hyperthyroid post-treatment • First line treatment in younger patients

Adverse Effects

• Carcinogenic • Leukemia • Genetic damage• Hypothyroidism


Beta-Blockers •Provide relief of increased sympathetic tone

• Palpitations, tachycardia, anxiety

•Beta-blockers can also reduce peripheral conversion of T4 à T3

•Propranolol 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


Thyroid Storm (medical emergency!)

Burch-Wartofsky Point Scale (BWPS) for Thyrotoxicosis

Cardiovascular (tachycardia, Afib, CHF) GI/Hepatic (diarrhea, abdominal pain, jaundice) CNS (agitation à seizure/coma) Precipitant history (storm previously) 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

Hydrocortisone

PTU + iodine

Anti-adrenergic treatment


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CaseMN, a 41-year-old male presented to the ED with confusion, rightsided numbness and tingling, slurred speech, dizziness, and facial edema. BP = 90/60 mm Hg, HR = 50 beats/min T = 95.7 degrees F Abnormal Labs: CK = 439 IU/L SCr = 1.6 mg/dLTSH = 126.4 microIU/mL ↑↑↑↑FT4 = 0.29 ng/dL ↓↓↓↓

Which of the following should be administered to MN immediately?A. Aspirin 325mg B. metoprolol + methimazoleC. 500mcg IV levothyroxine + hydrocortisone 100mg IV

CaseWhat is your medication recommendation for pharmacological treatment of AA’s hyperthyroidism?

A. Propranolol and MethimazoleB. Atenolol and Iodine

C. PTU and Atenolol

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 ↓↓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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