Thyroid

Acute Oncology Guidelines
NHS Lothian

Approximately 5-10% of individuals treated with cancer immunotherapies will develop abnormal thyroid function and this may be either thyrotoxicosis or hypothyroidism. Immunotherapies may cause a destructive thyroiditis or precipitate the presentation of Graves’ disease or autoimmune hypothyroidism. Patients with pre-existing thyroid antibodies are at increased risk. Thyroiditis usually occurs during the first few cycles of therapy and the typical pattern is of transient hyperthyroidism followed by hypothyroidism.

Interpretation of thyroid function tests

TSH 

(0.2-4.5 mU/l)

fT4

(9-21 pmol/l)

fT3

(2.6-6.2 pmol/l)

 Interpretation
<0.01 >21 >6.2 Thyrotoxicosis
<0.01 High normal >6.2 T3 thyrotoxicosis
<0.01 High normal High normal Subclinical thyrotoxicosis
<0.01 <9 <2.6 Secondary hypothyroidism (pituitary cause)
<0.01 Low normal Low normal Subclinical secondary hypothyroidism (pituitary cause)
>4.5 <9 <2.6 Primary hypothyroidism
>4.5 Low normal Low normal Subclinical primary hypothyroidism

It is very important that low TSH levels are interpreted along with T4 and T3 levels, because a low TSH can occur in both thyrotoxicosis and secondary hypothyroidism.

Suggested monitoring

  • TSH and fT4 should be checked prior to commencement of the immunotherapy.   
  • If TFTs are abnormal then these results should be discussed with an endocrinologist before the immunotherapy is started.   
  • TSH and fT4 should be checked at least monthly while on the immunotherapy; after 6 months, the monitoring frequency can reduce to 3 monthly if the patient is asymptomatic. New symptoms, which could be indicative of thyroid dysfunction, should prompt earlier assessment of thyroid function. fT3 should be added on if TSH is low and fT4 high normal. 

Investigation and management of thyrotoxicosis

  • Thyrotoxicosis should be detected biochemically before symptoms occur. 
  • Most commonly this will be due to a destructive thyroiditis, in which case it should be self-limiting over a few weeks or months.  It is not mandatory to stop the immunotherapy, but it is likely that cessation of therapy will speed resolution of the thyrotoxicosis.  If the immunotherapy is to be continued, the case should be discussed with an endocrinologist. 
  • If symptomatic, commence propranolol (20-80 mg t.d.s) and continue until T4 normal.  Inderal LA is a once daily preparation of propranolol and is very useful – it is available in 80mg and 160 mg preparations and is administered once daily. 
  • Measure TRAb titres (TSH Receptor Antibodies – brown tube to Clinical Biochemistry).  Positive TRAbs confirms a diagnosis of Graves’ disease. 
  • If TRAbs are negative, arrange a thyroid scintigram with Nuclear Medicine.  
  • If thyroiditis confirmed, monitor TFTs every 4 weeks, watching out for development of hypothyroidism. 
  • Neck pain can be treated with NSAIDS. 
  • Severe episodes of thyroiditis (i.e. significant neck pain and/or thyrotoxicosis) may require additional therapy with Prednisolone (40mg daily) until T4 is normal. 
  • If TRAbs are positive or the thyroid scintigram shows evidence of Graves’ disease or nodular disease, refer to Endocrinology. 

Management of hypothyroidism

  • Hypothyroidism detected de novo may be due to autoimmune disease or, more commonly, is the tail-end of an episode of thyroiditis in which the hyperthyroid phase was not clinically evident. 
  • If TSH >10 and/or T4 <9, commence levothyroxine 100 ug/daily. If elderly or have pre-existing cardiac disease, discuss with endocrinologist as a lower starting dose should be used. 
  • If TSH 5-10 and T4 >9, treatment may not be necessary, unless symptomatic. 
  • Recheck TFTs after 4 weeks and adjust T4 dose according to TSH. 
  • It is usually not necessary to discontinue the immunotherapy when hypothyroidism is detected de novo.  
  • Hypothyroidism may not be permanent. After 4-6 months of levothyroxine therapy, it is always worth reducing the dose to 50 mcg.  If TSH is in the normal range 4 weeks later, discontinue the levothyroxine and recheck TFTs after another 4 weeks. An elevated TSH at any stage indicates an on-going requirement for levothyroxine. The risk of permanent hypothyroidism will be higher in those with positive anti-thyroid peroxidase antibodies.

Editorial Information

Last reviewed: 01/05/2017

Author(s): Strachan M.

Version: 1.0

Reviewer name(s): Stewart J.