October 27, 2011 — A host of the newer anticancer drugs are associated with thyroid dysfunction and should be accompanied by routine testing for thyroid abnormalities, according to Ole-Petter Riksfjord Hamnvik, MD, and colleagues from Brigham and Women's Hospital in Boston, Massachusetts. In a review published online October 18 in the Journal of the National Cancer Institute, the authors point to tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide as drugs associated with thyroid damage.
Dr. Hamnvik told Medscape Medical News that his "interest arose after seeing patients presenting with profound hypothyroidism while taking antineoplastic agents. These patients had had symptoms of hypothyroidism for several months that had not been recognized as symptoms of hypothyroidism. Usually, their providers thought that they were just experiencing the side effects of the antineoplastic agents. When hypothyroidism was finally diagnosed, I was able to improve the quality of life of these patients with simple treatments. When reviewing the literature, I realized that these effects are quite common but largely unknown."
Focus on Patients Taking Newer Agents
Dr. Hamnvik warned that because any screening can lead to a large number of abnormal results that require follow-up, routine thyroid testing is not recommended unless the pretest probability of thyroid disease is high.
"Thyroid dysfunction is very common with some of these novel agents, but is really not seen with the older agents. I would therefore recommend screening only in patients who are taking the newer agents discussed in our review," Dr. Hamnvik said.
To understand the thyroid-related adverse effects of antineoplastic agents, Dr. Hamnvik and colleagues reviewed published articles on novel antineoplastic agents approved by the US Food and Drug Administration, and words relating to the thyroid gland such as "thyroid", "hypothyroidism", "hyperthyroidism", "thyrotoxicosis", and "Graves". Studies pertaining to the use of these drugs in treating thyroid cancer were excluded. The recommendations are based on published recommendations (when available), the authors' clinical experience, and the literature review.
Proposed Screening for New Antineoplastic Agents
LT4, levothyroxine; MRI, magnetic resonance imaging; T4, thyroxine; TSH, thyroid-stimulating hormone; TPO, thyroid peroxidase
Dr. Hamnvik said: "I think that a big barrier to routine screening for thyroid disease in these patients is the physicians' concerns about following up abnormal results. We have attempted to provide a framework on how to interpret and act on these results to help reduce this barrier. Luckily, cancer patients are seen frequently with routine blood draws, which can easily be expanded to include thyroid function tests."
Maya Lodish, MD, who reviewed the study for Medscape Medical News, echoed Dr. Hamnvik's recommendations and pointed out that treatment-related thyroid dysfunction can be even more devastating for pediatric cancer patients than for adults.
Dr. Lodish, who is assistant clinical investigator at The Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland, agrees that "adopting routine thyroid testing for patients on these chemotherapeutic agents is a very reasonable approach.... As a pediatric endocrinologist, I care for many patients on these agents who have developed abnormalities of thyroid hormone levels. In growing children, the early diagnosis and management of thyroid dysfunction is especially critical."
Dr. Hamnvik and Dr. Lodish have disclosed no relevant financial relationships.
J Natl Cancer Inst. Published online October 18, 2011. Abstract
Dr. Hamnvik told Medscape Medical News that his "interest arose after seeing patients presenting with profound hypothyroidism while taking antineoplastic agents. These patients had had symptoms of hypothyroidism for several months that had not been recognized as symptoms of hypothyroidism. Usually, their providers thought that they were just experiencing the side effects of the antineoplastic agents. When hypothyroidism was finally diagnosed, I was able to improve the quality of life of these patients with simple treatments. When reviewing the literature, I realized that these effects are quite common but largely unknown."
Focus on Patients Taking Newer Agents
Dr. Hamnvik warned that because any screening can lead to a large number of abnormal results that require follow-up, routine thyroid testing is not recommended unless the pretest probability of thyroid disease is high.
"Thyroid dysfunction is very common with some of these novel agents, but is really not seen with the older agents. I would therefore recommend screening only in patients who are taking the newer agents discussed in our review," Dr. Hamnvik said.
To understand the thyroid-related adverse effects of antineoplastic agents, Dr. Hamnvik and colleagues reviewed published articles on novel antineoplastic agents approved by the US Food and Drug Administration, and words relating to the thyroid gland such as "thyroid", "hypothyroidism", "hyperthyroidism", "thyrotoxicosis", and "Graves". Studies pertaining to the use of these drugs in treating thyroid cancer were excluded. The recommendations are based on published recommendations (when available), the authors' clinical experience, and the literature review.
Proposed Screening for New Antineoplastic Agents
| Antineoplastic Agent | Thyroid Test Recommendation |
| Tyrosine kinase inhibitors | TSH before treatment; monitor every 4 weeks and titrate LT4 as required; when stable, monitor every 2 months |
| Denileukin diftitox | TSH and anti-TPO antibodies before treatment, then TSH every month for first 3 months, then every 2 to 3 months |
| I-131-based therapies | TSH before treatment; pretreatment iodine to saturate thyroid; TSH every 6 months for life |
| Immunotherapies | TSH and anti-TPO antibodies before treatment; monitor TSH every 2 to 3 months if anti-TPO positive, otherwise every 6 months |
| Bexarotene | TSH and free T4 before treatment; start LT4 with treatment; monitor free T4 weekly for 5 to 7 weeks, then every 1 to 2 months |
| Ipilimumab, tremelimumab | Baseline pituitary MRI before treatment; TSH, free T4, 8 AM cortisol before treatment, then every 2 to 3 months |
| Alemtuzumab | TSH before treatment, then every 2 to 3 months |
| Interferon-α | TSH and anti-TPO antibodies before treatment; monitor TSH every 2 to 3 months if anti-TPO positive, otherwise every 6 months |
Dr. Hamnvik said: "I think that a big barrier to routine screening for thyroid disease in these patients is the physicians' concerns about following up abnormal results. We have attempted to provide a framework on how to interpret and act on these results to help reduce this barrier. Luckily, cancer patients are seen frequently with routine blood draws, which can easily be expanded to include thyroid function tests."
Maya Lodish, MD, who reviewed the study for Medscape Medical News, echoed Dr. Hamnvik's recommendations and pointed out that treatment-related thyroid dysfunction can be even more devastating for pediatric cancer patients than for adults.
Dr. Lodish, who is assistant clinical investigator at The Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland, agrees that "adopting routine thyroid testing for patients on these chemotherapeutic agents is a very reasonable approach.... As a pediatric endocrinologist, I care for many patients on these agents who have developed abnormalities of thyroid hormone levels. In growing children, the early diagnosis and management of thyroid dysfunction is especially critical."
Dr. Hamnvik and Dr. Lodish have disclosed no relevant financial relationships.
J Natl Cancer Inst. Published online October 18, 2011. Abstract
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