Physiological variations in thyroid hormones: physiological and pathophysiological considerations.

Thyroid hormone production is regulated via pituitary thyrotropin (TSH) modulation of thyroxine (T4) prohormone secretion by the thyroid gland and regulation of active triiodothyronine (T3) production in peripheral tissues via metabolic events influencing activities of the iodothyronine monodeiodinase enzyme systems. Control at both levels is developmentally regulated and modified in serious nonthyroidal illness (trauma, infection, cancer, metabolic diseases). Racial and gender differences are of little significance except for the effects of placental estrogens and chorionic gonadotropin during pregnancy. There is a circadian rhythm of TSH secretion, with peak values at the onset of sleep and nadir concentrations during the afternoon hours. Peak and nadir concentrations differ by approximately +/- 50%. The effect on circulating T4 and T3 concentrations is not significant because of the large size of the extrathyroidal T4 pool. In healthy subjects there is no significant impact of body weight, physical training, body habitus, posture, immobilization, exercise, or ambulatory status on thyroid function, and no significant geographic environmental variation. Nutrition also has a minimal impact except for variation in iodine intake. Subthreshold concentrations of iodine intake are associated with increased TSH secretion, goiter, increased thyroid iodine uptake, decreased T4 production, an increased T3/T4 secretion ratio, and an increased ratio of circulating T3/T4 concentrations. Excessive iodine intake can block thyroid hormone biosynthesis by inhibiting the enzymes involved in the biosynthetic process, resulting in reduced T4 secretion, increased TSH concentrations, goiter, and hypothyroidism if the iodine excess is chronic.