Complications of anti thyroid drugs

Agranulocytosis is an idiosynchratic reaction which may occur with any anti thyroid drug. Rashes and itch are also common with anti thyroid drugs and are not usually severe. Abnormalities of liver function are common with carbimazole, but severe hepatitis may occur with propyl thiouracil. Vasculitis and arthralgia are also occasionally seen with both agents.

Stop anti thyroid medication immediately if a severe drug reaction is suspected

Propyl thiouracil or carbimazole are both associated with agranulocytosis and must be stopped if this complication is suspected, and only restarted if a blood count has confirmed that the white cell count is in fact normal.

With confirmed new abnormalities or deterioration in liver function, stop anti thyroid drugs, though an alternative anti thyroid drug may be used subsequently if indicated.

With confirmed vasculitis, stop anti thyroid drugs, but with rash, it is usually possible to continue the anti thyroid drug.

Neutrophil count confirmed as 1-1.5 x 10 1.5x10(9)

 This level of mild neutropaenia may be associated with thyrotoxicosis itself, and will be a normal finding in some individuals. 

Continue therapy, but remind the patient of the symptoms that might suggest agranulocytosis, and institute regular monitoring of blood counts.

Neutrophil count less than 1 x 10(9) in a patient who is otherwise well

Stop the anti thyroid drug.

Warn the patient of the symptoms of neutropaenic sepsis and to attend immediately if they develop a fever, sore throat or otherwise feel unwell.

Monitor blood count daily.

Asymptomatic agranulocytosis usually responds well to withdrawal of the causative drug.

Do not rechallenge the patient with the same or alternative anti thyroid drugs in future.

Arrange definitive treatment of their thyrotoxicosis once their blood count has recovered e.g. radioactive iodine or surgery.  

Neutropaenia below 1 x 10(9) with suspected sepsis or in an unwell patient

Stop the anti thyroid drug. 

Take blood and urine cultures and arrange a chest radiograph.

Admit the patient to hospital and follow local guidelines and take local haematology and or microbiology advice for the treatment of neutropaenic sepsis. This will include administration of intra venous fluids, and broad spectrum antibiotics. Pseudomonas is a commonly implicated organism in these patients. 

Monitor blood count 12 hourly initially, then daily if this is increasing.

Take advice from local haematologists. They may wish to perform a bone marrow trephine biopsy to guide whether to use granulocyte-colony stimulating factor (G-CSF). If the white cell count is not recovering haematologists may recommend G-CSF which may accelerate recovery in patients not responding after withdrawal of the offending drug, though this does not change eventual outcomes.  

Do not rechallenge the patient with the same or alternative anti thyroid drugs in future. This is a life threatening complication, and there is significant cross reactivity between the two commonly used anti thyroid agents.

Arrange definitive treatment of their thyrotoxicosis once their blood count has recovered e.g. radioactive iodine or surgery.  The patient may require medical preparation e.g. with beta blockers for radioactive iodine or with beta blockers and lugol's iodine for surgery if their thyrotoxicosis is not already well controlled. 

Skin reactions

Itch is a common feature of untreated thyrotoxicosis, and usually settles as thyroid function improves.

Typical drug rashes are also common with anti thyroid drugs and usually respond to topical treatments, antihistamines. If the rash is severe, switch to an alternative anti thyroid drug using a dose equivalence of 5mg carbimazole to 50mg propyl thiouracil. 

Arthraligia and vasculitis 

Arthralgia and vasculitis are very rare with carbimazole but are seen more frequently with propylthiouracil treatment.

If this is suspected, stop the anti thryoid drug. Perform an autoantibody screen, particularly a full ANCA screen, for drug-induced lupus and discuss with rheumatology and/ or renal medicine. 

Do not rechallenge the patient with an alternative anti thyroid drug, but in stead a definitive treatment e.g. radioactive iodine or surgery should be arranged.

Hepatitis and other liver blood test abnormalities 

Mild abnormalities of liver function are common with thyrotoxicosis, so a baseline assessment prior to treatment is useful. Mild hepatitis with an increase in transaminases to 1.6x upper limit of normal also commonly occurs after around 3 months treatment with propylthiouracil. This is usually transient and requires no treatment so routine monitoring is not recommended unless the baseline function was abnormal.
 
Allergic hepatitis causing submassive hepatic necrosis occurs in ~0.1-0.2% of patients treated with propylthiouracil. Stop propylthiouracil and involve hepatology immediately if this condition is suspected.
 
Carbimazole is not associated with allergic hepatitis. However, carbimazole treatment may be associated with the development of a cholestatic pattern of abnormal liver function. Withdraw the drug and inform hepatology if this condition is suspected, though complete recovery is usual after the drug is withdrawn.