Inter-individual differences in thyroid hormone bioactivity: the effect of genetic variation

Adequate levels of thyroid hormone are essential for normal development and growth, since thyroid hormone plays an important role in virtually all metabolic processes in the human body. This is clearly demonstrated in patients with thyroid hormone disorders. Hyperthyroidism leads to high circulating serum thyroid hormone levels. Patients complain of palpitations, excessive sweating, weight loss and can display swelling of thyroid gland, known as goiter. In contrast, decreased serum thyroid hormone levels due to hypothyroidism can result in weight gain, depression, atherosclerosis and hypertension. Even subtle changes in serum thyroid parameters in patients with subclinical thyroid disease can have important consequences on thyroid hormone related end-points, such as atherosclerosis, heart rate, depression and osteoporosis. Therefore, it is likely that small variations in genes involved in thyroid hormone metabolism that result in altered thyroid hormone bioactivity can also have effects on clinical end-points. This thesis focuses on the effect of thyroid hormone pathway genes on serum thyroid hormone levels and clinical endpoints using a candidate gene approach. In addition, associations between serum thyroid parameters and clinical endpoints, such as osteoporosis and hypertension are studied.