Drugs in thyroid disease

Thyroid dysfunction
• Hypothyroidism
– Thyroxine replacement

• Hyperthyroidism
– Antithyroid drugs
– Radioactive iodine
– Surgery
 Levothyroxine
• Oral bioavailability 65 – 85%

• Half-life 7 days

• Given daily on empty stomach (mane)

• Metabolised in target tissues (deiodination)

 Levothyroxine
• Replacement therapy
– TSH normal range
– 50-150 μg daily

• Suppressive therapy
– TSH <0.01 mU/l
– Thyroid cancer, iodine deficiency goitre
– 150-200 μg daily
 Reduced thyroxine absorption
• Drug interactions
– Iron
– Calcium carbonate
– Cholestyramine

• Comorbid conditions
– Disorders causing malabsorption
– Previous small bowel surgery
 Increased thyroxine clearance
• Drug interactions
– Phenytoin
– Carbamazepine
– Phenobarbitone
– Rifampicin

• Coexisting conditions
– Pregnancy
– Nephrotic syndrome
 Antithyroid drugs
• Thionamides
– Carbimazole (rapidly metabolised to methimazole)
– Propylthiouracil

• Supersaturated potassium iodide

• Radioactive iodine
• Beta adrenoceptor antagonists
 Thionamides: mechanism of action
• Interfere with thyroid peroxidase-
mediated iodination of tyrosine
residues in thyroglobulin

• Propylthiouracil blocks conversion

of T4 to T3

• Immunomodulating effects
– ↓antithyrotropin-receptor antibodies
– apoptosis of intrathyroidal lymphocytes
 Thionamides: pharmacokinetics

• Rapidly absorbed from the GI tract

• Actively concentrated by the thyroid gland
• Plasma concentrations do not correlate with
antithyroid activity
 Thionamides: pharmacokinetics

• Carbimazole, Methimazole
– Long duration of action; once-daily dosing
– Not bound to plasma proteins

• Propylthiouracil
– Short duration of action; b.d. or t.d.s. dosing
– Bound to albumin; less likely to cross placenta
 Thionamides: adverse effects

• Minor
– Skin reactions (urticaria, macular rashes)
– Arthralgia
– Dyspepsia
• Major
– Polyarthritis
– Agranulocytosis
– Hepatitis
– Vasculitis
 Skin reactions
• May resolve with antihistamines

• Cross reactivity about 50%

• May need discontinuation

 Agranulocytosis
• Absolute count < 500 / mm3
• 0.1–0.5%
• Usually within first 3 months
• Autoimmune basis
• Warning: fever, sore throat, mouth ulcers
• Routine blood counts not necessary
• G-CSF enhances recovery
 Hepatotoxicity
• Carbimazole, Methimazole
– Intrahepatic cholestasis
– Resolves after discontinuation

• Propylthiouracil
– Allergic hepatitis with hepatocellular necrosis
– Recovery variable
 Vasculitis
• Mainly caused by propylthiouracil

• ANCA-positive

• Acute renal dysfunction, arthritis, skin ulceration,

vasculitic rash, respiratory symptoms

• May need immunosuppressive treatment

 Pregnancy & lactation

• Antithyroid drugs cross the placenta

• Risk of neonatal hypothyroidism

• No significant differences in neonatal thyroid

function between drugs
 Pregnancy & lactation

• Congenital anomalies with carbimazole,

methimazole
– Aplasia cutis
– Choanal or oesophageal atresia
– Umbilical abnormalities

• Propylthiouracil preferred in first trimester

• Safe during breast feeding

 Supersaturated potassium iodide
• Excess intrathyroidal iodine inhibits thyroid
hormone synthesis ( ? inhibition of thyroid
peroxidase)
• Effect lasts 1-2 weeks
• Reduced vascularity
• Same effect with iodinated contrast agents,
amiodarone, topical povidone–iodine
 Supersaturated potassium iodide
• For rapid control of hyperthyroidism
– thyroid storm
– preparation for surgery
– severe cardiac disease
 Radioiodine
• Sodium iodide (Na131I) liquid or capsule
• Taken up by thyroid cells
• β emission causes tissue necrosis over 6-18
weeks
• Adverse effects
– Radiation thyroiditis
– Hypothyroidism
• Contraindicated in pregnancy & lactation