Elsevier

Endocrine Practice

Volume 23, Issue 5, May 2017, Pages 566-575
Endocrine Practice

Original Articles
Adverse Event Reporting in Patients Treated with Thyroid Hormone Extract

https://doi.org/10.4158/EP161584.ORGet rights and content

ABSTRACT

Objective: Thyroid hormone extract is used for the treatment of thyroid disorders, but limited data exist on adverse events commonly noted by the physicians associated with this use. The purpose of this survey was to report adverse events observed by expert physicians managing patients treated for thyroid disease with thyroid hormones.

Methods: Members of the American Thyroid Association, The Endocrine Society, and the American Association of Clinical Endocrinologists developed a survey instrument modeled on the U.S. Food and Drug Administration (FDA)'s reported adverse events for levothyroxine that would effectively assess the clinical experience of frequent prescribers of thyroid hormone. Survey links were emailed to physicians, and the websites of each society provided links to the data collection form.

Results: A total of 174 reports of adverse events occurring in patients on thyroid hormone extract were received. Ninety-one of these reports were accompanied by alterations in thyrotropin values and were further analyzed. Of these, 62 (68%) subjects had developed new symptoms associated with altered thyroid-stimulating hormone (TSH). A majority of TSH changes and symptoms described were consistent with thyrotoxicosis (65%), and 2 patients had developed arrhythmias. Reporters noted difficulty in dose adjustment by primary care providers due to confusion in interpreting thyroid function test results while on thyroid extract, which often necessitated subspecialty referrals.

Conclusion: These adverse event reports should stimulate consideration by the FDA to regulate and monitor thyroid hormone extract use and consider standardizing these extracts to meet current standards of manufacture, hormone content, availability, and shelf-life, like the rigor with which preparations such as levothyroxine are monitored.

Abbreviations

AE = adverse event

ATA = American Thyroid Association

FDA = Food and Drug Administration

LT3 = liothyronine

LT4 = levothyroxine

PTF = Pharmacovigilance Task Force

T3 = triiodothyronine

TSH = thyroid-stimulating hormone

Section snippets

INTRODUCTION

Oral thyroid hormone extract use for the treatment of hypothyroidism has been described since the 1890s in the English literature but dates as far back as the sixth century ce in Chinese writings (1,2). Prior to the development of radioimmune assays to measure both serum thyroxine (T4) and serum triiodothyronine (T3) levels in the early 1970s (3), extract doses were titrated based on a clinical assessment of wellbeing and avoidance of the signs of overt hyperthyroidism. Both T4 and T3 have been

METHODS

The PTF was created to assess potential adverse events (AEs) attributable to the use of thyroid hormone products. It used a survey tool that was created to gather data similar to that used by the FDA to change policy for LT4 (22,23). Members of the ATA, the American Association of Clinical Endocrinologists (AACE), and the Endocrine Society (TES) collaborated to survey the experience of physicians caring for patients with thyroid disease on LT3, thyroid extract, or LT4 therapy. The result of

RESULTS

Of the total 1,536 survey responses received, the majority (971 of 1,536 [63%]) reported no AEs. Since the physicians who responded to these surveys could have been members of all three organizations and had received multiple requests to respond, calculation of an accurate response rate was not possible.

A total of 565 completed AE reports (37% of total responses) were further reviewed. Of these, 335 (59%) reported on events occurring in LT4-treated patients, 174 (31%) reports were on

DISCUSSION

This survey of thyroid extract therapy documents 91 validated reports of AEs accompanied by objective changes in the thyroid function that were associated with the use of stable doses of thyroid extracts in compliant subjects in the U.S. It should be emphasized that nearly one-third of the reports received had been excluded (55 of 174 [32%]) from analysis, as the subjects had undergone dose adjustments between the two assessment occasions. Compared to a rate of only 8.9% reporting unstable

CONCLUSION

Although the manufacturers of thyroid hormone extract have made great strides to standardize the LT4 and LT3 content of their products, the preparations remain unregulated by the FDA. The responses documented in this survey raise clinical concerns. It is important to provide a broader understanding of issues that may arise from use of the thyroid extract products among physicians, pharmacists, and patients to achieve optimal treatment for hypothyroidism. Clinicians prescribing thyroid hormone

ACKNOWLEDGMENT

The study was supported by the American Thyroid Association. The Pharmacovigilance committee was chaired by Drs. Haugen and Levy by providing tele-conferencing support. The ATA, TES, and AACE provided for the distribution and collection of the data by the vendors. Other members of the task force were: Nicholas J. Sarlis, MBBS, MD, PhD; Matthew D. Ringel, MD; Irwin L. Klein, MD; Ernie Richardson, MD; Paul S. Jellinger, MD; James V. Hennessey, MD; Jeffrey R. Garber, MD; Ruth M. Belin, MD; Eric

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