CONTEXT: Retinoid X receptor agonists (rexinoids) have demonstrated benefit in patients with certain malignancies but appear to cause central hypothyroidism in some patients with advanced cancer. The influence of rexinoids on thyroid function in healthy subjects is not clear. OBJECTIVE: The objective of this study was to determine the effect of a single dose of bexarotene on levels of TSH, T4, and T3 in healthy subjects. DESIGN: This study was a randomized, double-blind, placebo-controlled, crossover trial. SETTING: This study was conducted at the General Clinical Research Center (University of Colorado Health Sciences Center, Aurora, CO). SUBJECTS:Six healthy adults (>18 yr old) were studied. INTERVENTION: Single-dose rexinoid (bexarotene, 400 mg/m2) or placebo, with TSH measurements at 0, 1, 2, 4, 8, 12, 24, and 48 h, were used. MAIN OUTCOME MEASURE: The main outcome was the serum TSH level at 24 h. RESULTS: Single-dose bexarotene suppressed serum TSH (P < 0.001) over time. Compared with placebo, levels of TSH were significantly lower by 12 h (P = 0.043); the nadir of 0.32 +/- 0.02 mU/liter (P < 0.001) was seen at 24 h. Free T4 index and free T3 index were also significantly lower than placebo over time (48 h) (P = 0.029; P = 0.004, respectively). Serum prolactin, cortisol, and triglycerides were not affected (P > 0.05 for all). There was no significant effect of single-dose bexarotene on rT3 or T3/rT3 ratio at 24 h. CONCLUSION: A single dose of a rexinoid can rapidly and specifically suppress serum TSH levels in healthy subjects. These data provide insight into the mechanisms by which rexinoids cause central hypothyroidism and potential ways this effect can be used for treatment of disorders such as thyroid hormone resistance and TSH-secreting pituitary tumors.
RCT Entities:
CONTEXT: Retinoid X receptor agonists (rexinoids) have demonstrated benefit in patients with certain malignancies but appear to cause central hypothyroidism in some patients with advanced cancer. The influence of rexinoids on thyroid function in healthy subjects is not clear. OBJECTIVE: The objective of this study was to determine the effect of a single dose of bexarotene on levels of TSH, T4, and T3 in healthy subjects. DESIGN: This study was a randomized, double-blind, placebo-controlled, crossover trial. SETTING: This study was conducted at the General Clinical Research Center (University of Colorado Health Sciences Center, Aurora, CO). SUBJECTS: Six healthy adults (>18 yr old) were studied. INTERVENTION: Single-dose rexinoid (bexarotene, 400 mg/m2) or placebo, with TSH measurements at 0, 1, 2, 4, 8, 12, 24, and 48 h, were used. MAIN OUTCOME MEASURE: The main outcome was the serum TSH level at 24 h. RESULTS: Single-dose bexarotene suppressed serum TSH (P < 0.001) over time. Compared with placebo, levels of TSH were significantly lower by 12 h (P = 0.043); the nadir of 0.32 +/- 0.02 mU/liter (P < 0.001) was seen at 24 h. Free T4 index and free T3 index were also significantly lower than placebo over time (48 h) (P = 0.029; P = 0.004, respectively). Serum prolactin, cortisol, and triglycerides were not affected (P > 0.05 for all). There was no significant effect of single-dose bexarotene on rT3 or T3/rT3 ratio at 24 h. CONCLUSION: A single dose of a rexinoid can rapidly and specifically suppress serum TSH levels in healthy subjects. These data provide insight into the mechanisms by which rexinoids cause central hypothyroidism and potential ways this effect can be used for treatment of disorders such as thyroid hormone resistance and TSH-secreting pituitary tumors.
Authors: Jennifer S Janssen; Vibha Sharma; Umarani Pugazhenthi; Celia Sladek; William M Wood; Bryan R Haugen Journal: Mol Cell Endocrinol Date: 2011-03-31 Impact factor: 4.102