Abstract
Thyroid hormone (TH) synthesis and release is under feedback regulation by the hypothalamic input to the pituitary via thyroid-stimulating hormone (TSH) and thyroid-releasing hormone (TRH) resulting in pituitary secretion of TSH. Clinicians generally diagnose thyroid disease based on the serum levels of the THs [l-3,3’,5-triiodothyronine (T3) and l-3,3’,5,5-tetraiodothyronine (thyroxine or T4)] in conjunction with the measurement of serum TSH. Patients with hypothyroidism have low serum T4 and high serum TSH concentrations. This is usually a result of reduced production of TH due to gland destruction (such as in autoimmune thyroid disease) or impaired biosynthesis of thyroid hormone (such as in organification defects). On the other hand, hyperthyroidism is usually diagnosed when the T4 and T3 are high and the TSH is suppressed. The latter is commonly seen in autoimmune hyperthyroidism or autonomous TH secreting adenomas of the thyroid gland. When there is loss of the inverse relationship between TH levels and TSH concentrations (e.g., high serum T3 and/or T4 but normal TSH as in TH resistance) or when T4 and T3 levels are markedly different (e.g., high T3 and low T4 in a TH transporter defect, or low T3 and high T4 as seen in TH metabolism defects), the clinician must consider a genetic defect in the differential diagnosis. Correct diagnosis can be made from clinical observations and confirmed by appropriate genetic testing, as discussed in this chapter. The correct diagnosis will lead to a rational therapy avoiding inappropriate thyroid gland ablation or hormone supplementation.