Selection of Long-term Antithyroid Treatment Debated

A research team attempted to make a case for antithyroid medications as the most efficacy and desirable therapy for Grave's disease, but at least 1 US expert refuted the data.

With Ramin Malboosbaf MD, and commentary by Elena A Christofides, MD

To curb excess thyroid hormone production in Grave’s disease without radioactive iodine (RAI) treatment or surgery, clinicians typically prescribe antithyroid (AT) medications. The efficacy and safety of long-term AT treatment were examined in a meta-analysis,1 published in the journal, Thyroid.

Therapy for hyperthyroidism arising from Grave’s disease (GD) is not straightforward and involves complex decision-making,” said study co-author Ramin Malboosbaf MD, an endocrinologist at the Endocrine Research Center of Research Institute for Endocrine Sciences at Shahid Beheshti University of Medical Sciences in Tehran.

“There is no specific cure for this endocrine disease, and any therapeutic option can be associated with certain complications,” Dr. Malboosbaf told EndocrineWeb, “Several recent studies, for example, have reported inconsistent findings on the advantages and disadvantages of long-term (greater than 2 years) treatment with AT medications. We undertook a systematic review to clarify the numerous outcomes of long-term treatment with AT therapies.

Exploring the best treatment for Grave's disease.

Meta-Analysis of Grave’s Disease Treatments

The researchers identified 587 applicable articles of which only six fully met the study criteria.1 They defined long-term treatment as two years duration and excluded patients that withdrew due to side effects or poor compliance. The authors concluded that “AT treatment-induced remission in 61% of adults and 53% of non-adults overall, with a positive relationship between time and remission rate. Up to 70% of patients who discontinued AT therapy relapsed and smokers appeared to have significantly lower remission rates.”1

The study findings suggested that major complications were rare (no more than 1.5%), and included life-threatening agranulocytosis and hepatotoxicity, which tended to occur early in treatment and at higher doses. The overall complication rate of 19.1% reflected insignificant or temporary symptoms such as rash, gastric intolerance, and arthralgia. The authors suggested that clinicians discuss an apparent association of birth defects arising with AT medication use with women of childbearing age.1

The take-away message is that “long-term AT treatment is effective and safe, especially in adults, indicating that it should be considered as an alternative treatment for the management of Grave’s disease,” Dr. Malboosbaf said.

A Critical View of the Study Findings

Elena A Christofides, MD, FACE, a clinical associate professor of Endocrinology at Ohio University College of Medicine, and chief operating officers of Endocrinology Associates in Columbus, Ohio, found nothing new in this study. While she agreed that treatment planning for Grave’s disease may be difficult, she challenged the study authors' conclusions and any applicability of this study to current American patients.

“I understand the need to use precise criteria in a meta-analysis, but this was so restrictive that just 1% of available literature was included,” Dr. Christofides told EndocrineWeb. “In addition, the dataset for the US included only 43 patients and was from 1987, making it 30 years, a time when insurance and prescription coverage was dramatically different.” Because this study relied heavily on research outside the United States (US) with many patients having universal healthcare and coming from different ethnicities, populations, and cultural practices, she believed that the findings could not be generalized to the US.

“Even in the same office, or the same city in the US, treatment protocols vary dramatically based on economics and demographics,” she said. “The choice of AT treatment is patient-specific and culturally sensitive. To make her point, Dr. Christofides described three different women in the US, all 18 years old with differing life circumstances. For an 18 years old woman who planned to start a family shortly, ATA medications might be the most appropriate choice because radioactive iodine is unsafe for a fetus and the potential side effects of surgery could also affect the mother’s ability to become pregnant.

For an 18-year-old woman with no plans for a family and so could safely undergo radioactive iodine treatment, AT medications, might be less practical, according to Dr. Christofides. Finally, say said, an 18-year-old female who was serving in the armed forces wouldn’t want to be dependent on prescription medications, so AT medications would not be her choice, rather it would be a better choice for her to have low-dose radioactive iodine from that perspective.

“Simply put, this study’s data-set is not generalizable to a US population in 2017,” said Dr. Christofides.

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