Lec 1 Thyroid and Antithyroid Medications

Thyroid Hormone Physiology

Thyroid synthesizes thyroxine (T4) and triiodothyronine (T3)
o Iodide in blood follicular cell, thyroid peroxidase binds iodine to tyrosine residues of thyroglobulin
o Iodinated tyrosine combine to form T4 and T3
o T4 and T3 are transported to bloodstream by proteins
o T4 is converted in peripheral tissues to T3(liothyronine), the metabolically active thyroid hormone
T4 is more abundant
Picture: Iodine from the dietiodine are made into thyroglobulin and
brought back into the cell and exported out as T3 and T4.

Regulation of Thyroid Hormones

TSH from anterior pituitary regulates thyroid hormones
TSH under control of circulating free thyroid hormone (negative feedback) and TRH
from hypothalamus
Drugs, illness(lead to problem in the pituitary & hypothalamus), pregnancy can affect
thyroid hormones
Actions of Thyroid Hormones
T3 produces most effects related to thyroid hormones
o T3 is the active form
o Control DNA transcription and protein synthesis brain growth
o Increased Oxygen consumption stimulation of heart, skeletal muscle, liver, kidney
(calorigenic effects)
o Stimulation of the heart
Hyperthyroidism
Excessive amounts of T4 and T3
Clinical presentation
o Heat intolerance, weight loss despite increased appetite, nervousness, palpitations
o Increased bowel movements
o Warm, smooth and Moist skin, fine hair
o Exophthalmus and lid lag
o Edema of lower extremities
o Tachycardia
o Tremor and hyperactive DTRs
Hyperthyroidism is m/c caused by graves disease(autoimmune dz)
Thyrotoxicosis
Most commonly caused by Graves disease
Antithyroid Drugs (2 drugs that interfere the production of T3 and T4)
o Propothiouracil
o Methimazole
Radioactive Iodine (not everyone can do this)
Beta blockers (to control heart rate and palpitation sxs)
Antithyroid Drugs Propothiouracil (PTU)
Thiourea meds
o *Propylthiouracil MOA:
inhibit biosynthesis of thyroid hormone by serving as substrates for thyroid peroxidase and prevents
incorporation of iodide into iodotyrosines
Inhibit coupling of monoiodothyronine and diiodothyronine to form T4 and T3

 Inhibits peripheral conversion of T4 to T3 ( methimazole doesnt do this)

Pharmacology:
PTU shorter half life (TID-QID dosing) 300-600mg day divided into four doses
PTU inhibits peripheral conversion of T4 to T3
PTU is safer in pregnancy / lactation (than methimazole)(so use PTU for pt that is pregnant or
lactating)
Immediate effect
o Dosing and monitoring
Continuous therapy for 12-24 months remission (can occur after 24 months depends on the size of
the goiter and depends on the amount of antibodies they have)(tx of remission is oral drug again or
radioactive iodine)
Monitor frequently and make regular changes
Reduce dose slowly when euthyroid is achieved
Antithyroid Drugs- Methimazole
o *Methimazole:
most non-pregnant pt will start on methimazole b/c it is more potent
Inhibits incorporation of iodide and inhibits coupling of iodotyrosines to form T3 and T4
More potent than PTU (30mg-60mg /day three divides doses)
Average remission rates 40-50%
4-8 weeks symptoms diminish and T4 normalizes months later (3)
Monitor (free thyroxine index and total T3 will decrease) and clinical every 2 months
Monitor Free T4, total T3 and TSH
Doesnt work at quickly as PTU (use PTU when pt is having thyroid storm b/c it is faster)
Antithyroid Drugs Thioureas and Side Effects
Transient leukopenia is common
Rash is common (maculopapular and pruritic) (b/c sulfate derivative)
Agranulocytosis is most serious adverse effect (0.5-6%) (but rare)
o First 3 months of therapy
o Fever, throat infection, malaise and gingivitis
o Granulocytes < 250/mm
o Discontinue and improvement over weeks
Adverse Effects of Thioureas
Benign leukopenia (If the pts WBC is low, need to be hospitalized for the risk of sepsis)
Rashes
Arthralgias
GI intolerance
Serious adverse effects
o Agranulocytosis (most serious, suspect when pt comes in with fever or gingivitis and just started on the drug)
o Arthralgias and lupus like syndrome
o

Iodides
Used as adjunctive therapy with thioureas to prepare Graves pt (euthyroid)(or any cause of hyperactive thyroid) for
surgery
Given 7-14 prior to surgery (in the beginning it might raise the production of thyroid hormone but after a day or two
large quantity of iodide can shut down the production of thyroid hormone)
Used to quickly block thyroid hormone release in severe thyrotoxicosis
Protect thyroid against radioactive iodine following nuclear situation
o Daily Iodide will reduce uptake of radioactive iodine

MOA:
o Initially high doses of iodide inhibit synthesis of iodotyrosine and iodothyronine and inhibit the release of
thyroid hormone

Unknown mechanism
Available as
o Potassium Iodide Saturated solution (lugols solution)
o Used preoperatively
o Used 3-7 days after RAI therapy (radioactive iodine)
AE: (short-lived)
o Hypersensitivity reactions
o Salivary gland swelling (pain and irritation of the mouth and gum)
o Iodism

Radioactive Iodine
Sodium Iodide 131 (radioactive isotope; tasteless and colorless solution)
MOA: taken up and incorporated into thyroid hormones and thyroglobulin
Efficacy (usually one dose)
o Single dose 60% are euthyroid in 6 months or less and 40% become euthyroid within 1 year after two or more
doses. It is 95% or higher effective after 2nd dose
Monitor free thyroxine (FTI) levels
AE:
o Hypothyroid (#1 side effect)(over time)
30% of pt will develop hypothyroidism later in life after treated with radioactive iodine)
o CONTRAINDICATED IN PREGNANCY
o Mild thyroid tenderness and dysphagia
Take home message: Most pt treated with radioactive iodine with need to be treated with thyroid hormone therapy to prevent
hypothyroidism.
Need to take oral contraceptive for 6 months to one year to prevent pregnancy and Stay away from relatives for five days after
treatment. (pt is radioactive!)
Beta Blockers
Used to alleviate symptoms of hyperthyroidism (tremor, palpitation, tachycardic, anxiety, heat intolerance)
Used as adjunctive therapy with RAI, thioureas, or iodides
Propranolol is commonly used
AE: (AE of beta blocker)
Thyroid Storm
Medical emergency with severe thyrotoxicosis
o Extremely high heart rate, high blood pressure
o Thyroid storm is uncommon but may result from infection, trauma, withdraw form thyroid meds with high fever,
tachypnea, delirium , dehydration, coma vomiting and diarrhea
Clinical manifestations
Medical treatment
o Large doses of PTU (initiate treatment b/c it works quickly)
o Followed by iodines (to block the production of thyroid hormone)
o Esmolol (IV beta blocker to control heart rate and HTN)
o Corticosteroids (steroid to decrease pituitary production of TSH)
o Supportive care (cooling, Tylenol)
Hypothyroidism (more straight forward to treat)
Decreased thyroid hormone production
Most common is autoimmune thyroiditis or Hashimotos thyroiditis
Elevated TSH and low free T4 and T3 for primary hypo (thyroid itself is the problem)
Clinical manifestations: (opposite of hyperthyroidism)
o Dry skin, constipation
o Cold intolerance, weight gain, fatigue
o Cold and dry skin
o Periorbital puffiness (puffy eyes)
o Slow speech
o Bradycardia
Pharmacological Therapy
Synthetic thyroid hormones
o Most commonly used is levothyroxine (Synthroid, Levothyroid)* (preferred tx of choice)

Data shows plain levothyroxine is more easily to monitor and to work with. So the guideline now is to
prescribe levothyroxine either in brand synthroid or levothyroid.
o Others (but more complicated)
Synthetic T3 (Cytomel) and mixed T3 and T4 (Liotrix) and desiccated thyroid (Armour)
Dosing and monitoring
o Average maintenance is 110-120 MICROGRAMS/ day
For average healthy pt with hypo usually start 110-120 mcg of levothyroxine oral daily
o Initial starting dosage is 25-50mcg/day in older patients higher in younger, healthy pts
Start low to prevent side effect in elderly
Thyroid Supplements
The approximate equivalent doses for different thyroid supplements are: Armour Thyroid 1 grain (60 mg)=1 Thyrolar
(U.S. only)=25 mcg Cytomel=100 mcg levothyroxine (e.g., Synthroid, etc).
o FDA prohibits the usage of Armour thyroid due to high risk of contamination from animal products so the best
treatment for hypo is levothyroxine

Monitoring
TSH and free T4 (mostly TSH) guides therapy and should be checked every 6 weeks until euthyroid
o TSH is most sensitive
o The average daily levothyroxine replacement dose is 1.6 mcg/kg of body weight. However, the initial starting
dose should be based on the patient's age, weight, and cardiac status.
o Thyroid stimulating hormone (TSH) level should be checked approximately six to eight weeks after starting or
changing levothyroxine therapy to assess the appropriateness of the dose.
o The goal TSH level is between 0.3 to 3 micro IU/mL. In patients with thyroid cancer, the TSH goal may be
lower (i.e., <1 micro IU/mL).3
Monitor for signs of under or overdosages (if the dose is too high, pt will get tremor, anxiety and palpitation,
hyperactive, ect)(adjust down in 5-10 mcg range)
Use lower dosages in elderly patients and those with cardiac disease
Adverse Effects
Excessive doses may cause heart failure, myocardial ischemia
Start low (in elderly and sick pts) and titrate every 4-6 weeks as needed
Overdosage with suppression of TSH may cause reduced bone density
o More common in postmenopausal women
o b/c hypothyrodiam in women, make sure dont give too much levothyroxine which causes osteoclast breaking
down of bonerisk of osteoporosis so make sure to keep and monitor TSH in range.
Myxedema Coma
Life-threatening severe hypothyroidism
Clinical manifestations:
IV thyroxine (tx for myxedema coma)
Hydrocortisone (increase blood pressure which is low)
Blood pressure and cardiac support as needed
Special Situations
Pregnant hyperthyroid patients should be treated with PTU(lower dose)
Pregnant hypothyroid pts should be treated with levothyroxine
o Women with hypothyroid can cause infertility, monitor free T4 and TSH to work with the dose
Elderly hypothyroid patients requires lower initial dosages of synthetic thyroxine due to potential cardiac stress
Hypothyroidism and Medications
Increased sensitivity to digitalis (also opiate)
o monitor serum levels and clinical
May cause excessive anticoagulation in patients taking Coumadin
o Monitor INR closely
Opioids and other respiratory depressants