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Bexarotene, a retinoic acid–like substance, inhibits thyrotropin secretion in normal subjects
The background of the study. Bexarotene is a retinoic acid–like substance that is approved for treatment of patients with cutaneous T-cell lymphoma. It has caused central (low serum thyrotropin [TSH]) hypothyroidism in patients treated for several weeks or longer. This study was done to assess the acute effects of a single dose of bexarotene in normal subjects.
How the study was done. The study group consisted of six normal subjects. They were given, in random order, 400 mg/m2 of bexarotene or placebo by mouth after an overnight fast. Blood samples for measurements of serum TSH, thyroxine (T4), triiodothyronine (T3), and T3-resin uptake were obtained at base line and at frequent intervals for 48 hours. Serum free T4 index and free T3 index values were calculated as the product of the serum total T4 or total T3 and the T3-resin uptake.
The results of the study. The average serum TSH concentration decreased from 1.4 mU/ml at base line to a nadir of 0.3 mU/L 24 hours after bexarotene administration (a decrease of 78 percent), after which it increased slightly (Table). There was a transient decrease in serum TSH concentrations from 1.5 to approximately 0.8 mU/L in the first 8 hours after administration of placebo, after which the values were similar to the base-line value.
| Table. Mean Serum TSH Concentrations after Administration of Bexarotene or Placebo in Six Normal Subjects.* | ||
| Serum TSH (mU/L) | Bexarotene |
Placebo |
| Base Line | 1.4 |
1.5 |
| 4 hours | 0.7 |
0.9 |
| 8 hours | 0.6 |
0.8 |
| 12 hours | 0.5 |
1.2 |
| 24 hours | 0.3 |
1.5 |
| 48 hours | 0.5 |
1.7 |
| *Most values were extrapolated from Figure 1 of the paper. | ||
As compared with placebo, the mean serum free T4 index value was lower 48 hours and the mean serum free T3 index values were lower 12, 24, and 48 hours after bexarotene administration.
Conclusion Bexarotene has a thyroid hormone–like action to inhibit TSH secretion in normal subjects.
The original article. Golden WM, Weber KB, Hernandez TL, Sherman SI, Woodmansee WW, Haugen BR. Single-dose rexinoid rapidly and specifically suppresses serum thyrotropin in normal subjects. J Clin Endocrinol Metab 2007;92:124-30.
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| Thyroid Digest Index | | | March 2007 Thyroid Digest |
