82nd Annual Meeting of the American Thyroid Association:

What Is the Optimal L-T3 to L-T4 Ratio and Administration Plan for Thyroid Cancer Patients Undergoing Withdrawal?

For patients with thyroid cancer who are undergoing withdrawal for nuclear medicine procedures, liothyronine (L-T3) is used; it is the synthetic formulation of T3.  It may also be used in some hypothyroid patients—in combination with levothyroxine (L-T4).

It’s known that L-T3 has a narrow therapeutic index; it’s also known than L-T3 toxicity carries risk of serious adverse effects.  Therefore, an accurate understanding and estimation of the pharmacokinetics (PK) of L-T3 is essential, but currently-available PK data are contradictory.  Current PK data was also mostly derived from a single-dose measurement—in healthy volunteers.

Research funded by the NIDDK intramural research program was undertaken to better understand L-T3 PK in thyroid cancer patients.  It was a small study, but these results were presented at the American Thyroid Association 2012 Annual Meeting as a Short Call Oral Presentation.

How the Study Worked
There were 4 thyroid cancer patients in the study—2 men and 2 women.  Their age was 55.7 ± 9.6 years, and they were all undergoing TH withdrawal in order to have nuclear medicine procedures.

These patients were given L-T3 substituted at a 1:3 ratio for L-T4; it was a three-times daily administration. The average dose of L-T4 was 156.2 ± 23.9 µg; the average dose of L-T3 was 52.7 ± 8.8 µg. 

After one moth of this L-T3 administration, the patients were admitted.

After administration of the last dose, the PK parameters were estimated.

Serum T3 levels were measured in the patients at: 0, 30, 60, 90, 120, 150, 180, 210, 240, 360, 480, 600, and 720 minutes.  Then, for the next 10 days, serum T3 levels were measured every 12 hours.  TSH was also measured every 12 hours.

The baseline serum T3 was 194.7 ± 50.5 ng/dL (range: 162-270 ng/dL; normal range is 90-215 ng/dL).

Baseline TSH was 0.01 ± 0.01 µIU/mL (normal range is 0.4-4.0 µIU/mL).

At day 11—after L-T3 withdrawal—TSH levels were 47.5 ± 19.0 µIU/mL.

Cmax of T3 was 341.2 ± 74.1 ng/dL, and it was seen (Tmax) at 1.75 ± 0.29 hours.  There was an apparent half-life of T3 of 27.0 ± 12.0 hours.

Clinical Implications of This Pharmacokinetics Study
This study was done to see if the researchers could find a dose administration that would more nearly mimic the physiologic response that’s closer to normal.

This study shows that substituting L-T3 for L-T4 at a 1:3 ratio three-times daily can provide adequate suppressive therapy.  It can maintain mean T3 concentrations in the normal ranges, and it results in TSH concentrations that are adequate for nuclear medicine therapy.  Also, there are minimal hypothyroid symptoms.

This administration provides a more normal response than once-daily administration.

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