Hyperthyroid disorders

Question 1

What are the classes of drugs used in the treatment of hyperthyroidism

Answer 1

Thionamides e.g. propylthiouracil (PTU), carbimazole
Potassium iodide
Radioiodine
beta-blockers

Question 2

What are the aims of the classes of hyperthyroidism drugs

Answer 2

Thionamides, potassium iodide, radioiodine reduce thyroid hormone synthesis

Beta blockers help with symptoms

Question 3

What are thionamides used for

Answer 3

Daily treatment of conditions: Graves’ , Toxic thyroid nodule/toxic multi nodular goitre
Treatment prior to surgery
Reduction of symptoms while waiting for radioactive iodine to act

Question 4

Describe the thyroid hormone synthesis mechanism

Answer 4

1. TSH binds to TSH receptor
2. Iodide Trapping using NIS (Na-I Symporter) – secondary active transport. Sodium conc. gradient maintained via Na+ K+ ATPase
3. Iodide pumped into colloid using Pendrin Pump (I-/Cl- antiporter)
4. Thyroglobulin synthesised and diffuses to colloid
5. I- is rapidly oxidised to I* via the enzyme thyroid peroxidase (TPO) in the presence of H2O2.
6. I* attaches to a tyrosine on a molecule of TG. Also catalysed by TPO
7. 1 I* added = 3-mono-iodotyrosine (MIT). 2 I* added = 3,5-di-iodotyrosine (DIT).
8. Coupling occurs: TPO and H2O2 combine a DIT from one TG to either an MIT or another DIT on another TG = T3/4
9. Lysozome moves towards the apical membrane and takes up T3/4 via endocytosis
10. Proteolysis cleaves T3 and T4 from the TG.
11. The T3/T4 diffuse towards the basolateral membrane

Question 5

What is the mechanism of action of thionamides

Answer 5

Inhibition of thyroid peroxidase
May suppress antibody production in graves’ disease
Reduces conversion of T4 to T3 in peripheral tissues

Question 6

Why is propranolol given with thionamides

Answer 6

Rapidly reduces tremor and tachycardia

Question 7

What are the unwanted actions of thionamides

Answer 7

Agranulocytosis (usually reduction in neutrophils) - rare and reversible on withdrawal of drug.
rashes (relatively common)

Question 8

Describe the pharmacokinetics thionamides

Answer 8

Orally active
Carbinmazole is pro-drug which first has to converted to methimazole
Crosses the placenta, secreted in breastmilk (

Question 9

Describe the follow up to thionamide treatment

Answer 9

Stop anti-thyroid drug treatment after 18 months

Review patient periodically including thyroid function tests for remission/relapse

Question 10

What is the role of beta blockers in thyrotoxicosis

Answer 10

Several weeks of anti-thyroid drugs to have an effect
Beta blockers are non-selective (propranolol)
Achieves reduced tremor, slower heart rate, less anxiety

Question 11

What is iodide used for

Answer 11

Usually KI
Preparation of hyperthyroid patients for surgery
Severe thyrotoxic crisis (thyroid storm)

Question 12

What is the mechanism of action for KI

Answer 12

Inhibits iodination of thyroglobulin

Inhibits H2O2 generation and thyroperoxidase

Question 13

-

Answer 13

-

Question 14

What are the unwanted actions of KI

Answer 14

Allergic reactions e.g. rashes, fever, angio-oedema

Question 15

What are the pharmacokinetics for KI

Answer 15

Given orally in Lugol’s solution (aqueous iodine)

Max effects after 10 days continuous administration

Question 16

Describe radioiodine

Answer 16

treats hyperthyroidism (graves, toxic nodular disease, thyroid cancers)
Accumulates in the colloid, emits beta particles and destroys follicular cells

Question 17

What are the pharmacokinetics of radioiodine

Answer 17

Discontinue anti-thyroid drugs 7-10 days prior to radioiodine treatment
Administer as a single oral dose 
Graves’ disease:  approx 500 MBq 
Thyroid cancer:   circa 3,000 MBq
Radioactive half life of 8 days
Radioactivity negligible after 2 months

Question 18

What are the cautions for radioiodine

Answer 18

Avoid close contact with small children for several weeks after receiving radioiodine.
Contra-indicated in pregnancy and breast feeding

Question 19

How long does the biochemical and clinical effect of thionamides take

Answer 19

biochemical - hours

Clinical effect - weeks (due to thyroxine remaining in the blood)