Thyroid disorders are more common in women and some families, although the exact rate of inheritance is unknown (38,39). In geriatric populations, the incidence may be as high as 5% (40). The laboratory diagnosis of thyroid disease can be difficult because of altered hormonal states such as pregnancy and exogenous hormones. Thyroid hormones act in target tissues by binding to nuclear receptors, which induce change in gene expression. Extrathyroidal conversion of thyroxine (T4) to triiodothyronine (T3) takes place in target tissue. T3 binds the nuclear receptor with higher affinity than T4, which makes T3 more biologically active. Pituitary thyroid stimulating hormone (TSH) and hypothalamic thyrotropin-releasing hormone (TRH) regulate hormone production and thyroid growth by normal feedback physiology. Thyroid-stimulating immunoglobulins (TSI), once known as a long-acting thyroid stimulator (LATS), bind to the TSH receptor, which results in hyperthyroid Graves disease.
More than 99% of circulating T4 and T3 concentrations are bound by plasma proteins, predominately to thyroxine-binding globulin (TBG), and the remaining 1% of thyroid hormones are free. Free levels of thyroid hormones remain constant despite physiologic or pharmacologic alterations. Regardless of total serum protein levels, active thyroid hormone remains stable. In healthy women, transitions from puberty to menopause do not alter free thyroid hormone concentrations. Excess endogenous or exogenous sources of estrogen increase TBG plasma concentration by decreasing hepatic clearance. Androgens (especially testosterone) and corticosteroids have the opposite effect by increasing hepatic TBG clearance.
Thyroid function tests may be misleading in women receiving exogenous sources of estrogen because of altered binding characteristics. In euthyroid individuals, elevations of thyroid hormone concentrations arise from three mechanisms: (i) increased protein binding because of altered albumin and estrogen states, (ii) decreased peripheral conversion of T4 to T3,or (iii) congenital tissue resistance to thyroid hormones, which is rare. Postmenopausal hormonal therapy and pregnancy alter laboratory findings and complicate interpretation of thyroid function studies. Most laboratories compensate by reporting a free T4 level that mathematically corrects for physiologic alterations. If questions arise, a clinical pathologist should be consulted.