Altered binding of serum thyroid hormone to thyroxine-binding globulin in women with functional hypothalamic amenorrhea

Abstract

Objective: To further characterize hypothyroidemia with decreased serum concentrations of total triiodothyronine and total T 4 in women with functional hypothalamic amenorrhea. Design: Cohort study. Setting: University of California San Diego Clinical Research Center. Patient(s): 8 women with functional hypothalamic amenorrhea (hypogonadotropic or normogonadotropic amenorrhea of at least 6 months duration) and 9 normal cycling women in the early follicular phase of their cycles. Intervention(s): 24-hour frequent blood sampling. Main Outcome Measure(s): Comparison of levels of thyroid hormones and binding proteins between functional hypothalamic amenorrhea and normal cycling women. Measurements of serum free T 4, free triiodothyronine, total T 4, total triiodothyronine, reverse triiodothyronine, thyroid-binding globulin, albumin, and prealbumin levels and determination of T 4 binding and binding affinity to each of the three binding proteins. Result(s): The results confirmed reduced levels of total triiodothyronine and total T 4, but revealed no significant difference in free triiodothyronine and free T 4, as well as reverse triiodothyronine, levels between functional hypothalamic amenorrhea and normal cycling women. Although serum levels of thyroid hormone-binding proteins were similar between normal cycling women and functional hypothalamic amenorrhea, a significant decrease in T 4 bound to thyroid binding globulin along with a decrease in apparent affinity of thyroid-binding globulin for T 4 was present in functional hypothalamic amenorrhea. No differences in prealbumin-or albumin-T 4 interactions were found. Conclusion(s): In functional hypothalamic amenorrhea, a reduced thyroid-binding globulin binding affinity appears to explain the disparity between normal levels of free triiodothyronine, free T 4, and binding proteins in the face of reduced levels of total triiodothyronine and total T 4.