A new review of tar­geted ther­a­pies’ and immunother­a­pies’ adverse effects on the thy­roid gland, includ­ing rec­om­men­da­tions for screen­ing and treat­ment, has been pub­lished. The study reported that the ther­a­pies are linked to thy­roid dys­func­tion in 20%–50% of patients, which can result in adverse effects on patients’ qual­ity of life.

The researchers found that anti­neo­plas­tic agents that pre­vent spe­cific cel­lu­lar processes to restrict the growth of can­cer calls can cause thy­roid dys­func­tion. Because of the com­plex­ity of the clin­i­cal pic­ture in indi­vid­u­als with can­cer, the side effect is often over­looked by health­care providers. Thy­roid dys­func­tion symp­toms such as mem­ory loss, fatigue, weak­ness, car­dio­vas­cu­lar effects, and depres­sion can be mis­tak­enly asso­ci­ated with the pri­mary disease.

The researchers reported that there are no known meth­ods to pre­vent thy­roid dis­ease in patients who are receiv­ing these agents. They said that screen­ing for the dis­ease is most likely ben­e­fi­cial but noted that their study had no screen­ing rec­om­men­da­tions for indi­vid­u­als who were asymp­to­matic. In the new review, researchers offered their own rec­om­men­da­tions for patients depend­ing on the abnor­mal­ity pat­tern of each agent.

• Tyro­sine kinase inhibitors: Rates of hypothy­roidism, usu­ally per­ma­nent, range from 5%–50%. Thyroid-​​stimulating hor­mone (TSH) level should be mea­sured at base­line, monthly for four months, and every two to three months thereafter.
• Bexarotene: Asso­ci­ated with a 40%–80% rate of hypothy­roidism. TSH level drops rapidly after ini­ti­a­tion of ther­apy and reverses after dis­con­tin­u­a­tion. Thy­roid hor­mone replace­ment should be ini­ti­ated when treat­ment is started and free thy­rox­ine (T4) level mon­i­tored for the first five to seven weeks of ther­apy, then every four to eight weeks after.
• Iodine-​​based ther­apy: Inci­dence rates range from 9%–41% for tosi­tu­momab and 12%–64% for I-​​131 ioben­guane. Hypothy­roidism may be pre­vented with the use of Lugol solu­tion or sat­u­rated potas­sium iodine. TSH should be mea­sured at base­line and semiannually.
• Interferon-​​alfa: Patients have a 2%–10% risk for hypothy­roidism related to autoim­mune thy­roidi­tis. Onset varies from 1–23 months (median, 4 months) and is per­ma­nent in 60% of patients. TSH and antithy­roid per­ox­i­dase anti­bod­ies (anti-​​TPO) should be mea­sured at base­line; TSH is mea­sured semi­an­nu­ally if the anti-​​TPO test result is neg­a­tive and every two months if it is positive.
• Interleukin-​​2: 10%–50% of patients develop thy­roid dis­ease asso­ci­ated with autoim­mune thy­roidi­tis lead­ing to hypothy­roidism and thy­ro­tox­i­co­sis. Patients should have TSH screen­ing before ther­apy and every two to three months dur­ing therapy.
• Ipil­i­mumab and treme­li­mumab: These agents have been asso­ci­ated with pitu­itary fail­ure. Treat­ment includes dis­con­tin­u­ing drug ther­apy and ini­ti­at­ing hor­mone replace­ment ther­apy. Free T4 and morn­ing cor­ti­sol lev­els should be mea­sured at base­line and then every two to three months if symp­toms such as headache, nau­sea, vom­it­ing, lethargy, or con­sti­pa­tion develop.
• Thalido­mide and lenalido­mide: 10%–20% of patients will develop either hypothy­roidism or thy­ro­tox­i­co­sis within one to six months after treat­ment is ini­ti­ated. TSH level should be mea­sured at base­line and every two to three months.

The researchers also sug­gested sev­eral areas for research, specif­i­cally under­stand­ing the bio­logic effects of these agents on the thy­roid, to iden­tify pre­ven­tion and screen­ing strate­gies. They rec­om­mended that large ran­dom­ized clin­i­cal tri­als of thy­roid dis­ease need to be con­ducted to assess improve­ments in fatigue and qual­ity of life of patients and to assess unex­pected effects of can­cer outcomes.

• Ham­n­vik, O.P., Larsen, P.R., & Mar­qusee, E. (2011). Thy­roid dys­func­tion from anti­neo­plas­tic agents. Jour­nal of the National Can­cer Insti­tute, 103, 1572–1587.