Single-dose rexinoid rapidly and specifically suppresses serum thyrotropin in normal subjects.

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.

The use of a combination of galectin-3 and thyroid peroxidase for the diagnosis and prognosis of thyroid cancer.

In this retrospective histologic study, galectin-3 had a sensitivity of 92% (22/24) for papillary thyroid carcinoma and 44% (4/9) for follicular thyroid carcinoma. Thyroid peroxidase (TPO) had a sensitivity of 50% (12/24) for papillary and 11% (1/11) for follicular carcinoma. The combination of galectin-3 and TPO had a sensitivity of 96% (23/24) for papillary and 44% (4/9) for follicular carcinoma. From a prognostic standpoint, of patients whose papillary carcinomas expressed both markers, all became free of disease. Of those whose papillary carcinomas expressed galectin-3 but not TPO, 57% (4/7) became free of disease, 29% (2/7) had persistent disease, and 14% (1/7) had progressive disease. This study confirms previous observations that galectin-3 alone is highly sensitive for papillary carcinoma but not adequately sensitive for follicular carcinoma. TPO alone is not adequately sensitive for the evaluation of any thyroid lesion. The combination of galectin-3 and TPO is complementary as a diagnostic and prognostic tool for patients with papillary carcinoma.