A publication of the American Thyroid Association

Summaries for Patients from Clinical Thyroidology by Ernest Mazzaferri, MD MACP
Table of Contents


Abbreviations & Definitions

T4 is levothyroxine, a molecule that contains 4 iodine atoms.

T3 is triiodothyronine, a molecule that contains 3 iodine atoms.

FT4 is free thyroxine (a type of circulating thyroid hormone).

FT3 is free triiodothyronine (another type of circulating thyroid hormone)

Conversion of T4 to T3 The thyroid gland secretes considerably more T4 than T3 which is biologically much more potent than T4.

Deiodinases Enzymes that convert T4 to T3. Iodothyronine D-1 is mainly expressed in the liver, kidney, and thyroid gland and D-2, is mainly expressed in the brain, pituitary, cardiac and skeletal muscle, and placenta convert T4 to T3.

TSH is thyrotropin, thyroid stimulating hormone

What is the study about? Patients with large follicular thyroid cancers often develop T3 toxicosis. However, T3 is not commonly measured in patients with thyroid cancer.

The full article title: “3,5,3′-Triiodothyronine thyrotoxicosis due to increased conversion of administered levothyroxine in patients with massive metastatic follicular thyroid carcinoma.” It is in the June 2008 Issue of the Journal of Clinical Endocrinology and Metabolism (Volume 93 Issue 6, pages 2239-42). The authors are A Miyauchi, Y Takamura, Y Ito, A Miya, K Kobayashi, F Matsuzuka, N Amino,. N Toyoda, E Nomura, and M Nishikawa, M. The abstract can be obtained from:

What is known about the problem being studied? Patients with widely metastatic thyroid cancer may have triiodothyronine (T3) thyrotoxicosis due to increased D-1 and D-2 activity that converts thyroxine (T4) to T3 in amounts sufficient to cause thyrotoxicosis, but the prevalence, diagnosis, and treatment of this problem have not been fully elucidated.

What was the aim of the study? This study was aimed at identifying the prevalence and cause of T3 toxicosis in patients with thyroid cancer and the diagnostic clues for the diagnosis.

Who was studied? The study subjects were 58 patients with metastatic thyroid cancer measuring 2 cm or larger in diameter; 54% had papillary cancer, 35% had follicular cancer, and 12% had medullary thyroid cancer. Study controls were 17 patients with papillary thyroid cancer who had no sign of tumor recurrence after total thyroidectomy.

How was the study done? Frozen stored sera remaining from past measurements were used to measure FT3 to clarify the course of change in these patients. Three stored frozen tumors, two primary tumors and one metastatic subcutaneous tumor from two patients were studied for measurement of D-1 and D-3 activity.

What were the results of the study? In all, 20%) of 20 patients had T3 thyrotoxicosis; their mean age was 59.5 years. There were no statistical differences in the mean age, in levels of TSH and FT4. Analyses of stored sera from two patients with T3 thyrotoxicosis revealed that FT3 levels had started to increase about 2 to 4 years earlier while FT4 levels gradually declined but remained in the normal range. Also, in one patient both FT4 and FT3 declined to undetectable levels during a 1-month period in which L-T4 was stopped to facilitate 131I therapy.

Withdrawal of L-T4 in the four patients with thyrotoxicosis for 1 week resulted in a decrease of serum FT4 and FT3 levels in all four patients, indicating that the high T3 levels were not produced by functioning metastases but instead originated from increased conversion of T4 to T3 in tumor tissue. This was documented by measurement of D-1 and D-2 in tumor specimens that revealed high levels of these enzymes.

How does this compare with other studies? In 2003 Kim et al. first identified three patients with large or widely metastatic follicular thyroid cancer who had persistently increased T3/T4 ratios in the absence of T3 production by the tumor. They assayed D-1 and D-2 activity in a large follicular thyroid cancer resected from one of these patients and found that D-2 was 8-fold higher than in normal human thyroid tissue and resection of the tumor, leaving the left thyroid lobe intact, normalized the serum T3/T4 ratio. They concluded that this had probably come about by the increase in D-2 activity

What are the Limitations of this study? There are no potential limitations in this study.

What are the implications of this study? One in five patients with widely metastatic follicular thyroid cancer has T3 thyrotoxicosis from increased tumor deiodinase activity that can be identified by measuring serum T3 levels and stopping levothyroxine therapy

Table of Contents