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

OBJECTIVE

To further characterize hypothyroidemia with decreased serum concentrations of total triiodothyronine and total T4 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 T4, free triiodothyronine, total T4, total triiodothyronine, reverse triiodothyronine, thyroid-binding globulin, albumin, and prealbumin levels and determination of T4 binding and binding affinity to each of the three binding proteins.

RESULT(S): The results confirmed reduced levels of total triiodothyronine and total T4, but revealed no significant difference in free triiodothyronine and free T4, 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 T4 bound to thyroid-binding globulin along with a decrease in apparent affinity of thyroid-binding globulin for T4 was present in functional hypothalamic amenorrhea. No differences in prealbumin- or albumin-T4 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 T4, and binding proteins in the face of reduced levels of total triiodothyronine and total T4.