Effects of the Environment, Chemicals and Drugs on Thyroid Function

The sensitive and tightly regulated feedback control system, thyroid gland autoregulation, and the large intrathyroidal and extrathyroidal storage pools of thyroid hormone serve to provide a constant supply of thyroid hormone to peripheral tissues in the face of perturbations imposed by the external environment, chemicals and drugs, and a variety of diseases processes. The thyroid is subject to a great number of exogenous and endogenous perturbations. The same agent may produce alterations in various aspects of thyroid hormone economy. For this reason, it is difficult to precisely classify all external and internal influences according to their mode of action. This chapter reviews effects on the thyroid produced by changes in the external environment, chemicals and drugs. The effects of non-thyroidal illness are reviewed in Chapter 5b. The effects of the more important factors and chemical agents and drugs are discussed individually. RESPONSES TO ALTERATIONS IN THE EXTERNAL ENVIRONMENT Environmental Temperature Changes in environmental temperature may cause alterations in TSH secretion and in the serum concentration of thyroid hormones and their metabolism. The changes are probably mediated through the hypothalamus and the pituitary and by peripheral effects on the pathways and rates of thyroid hormone degradation and fecal losses and alterations in thyroid hormone action. The in vitro effects of temperature on the firmness of binding of T4 to its transport serum proteins conceivably also play a role in vivo. The overall effects of environmental temperature have been more obvious and easier to demonstrate in animals than in humans but differences in thermal regulation 1a may mean that findings in animal models may not apply to humans. Additionally, studies of individuals with prolonged residence in Arctic and Antarctic regions may be confounded by other alterations in daylight, activity levels, living conditions and sleep deprivation. 1b,1c Effects of Cold Dramatic, although transient, increases in serum TSH levels have been observed in infants and young children during surgical hypothermia. Also, a prompt and important secretion of TSH occurs in the newborn, in the first few hours after birth, accompanied by an increase in thyroid hormone secretion and clearance. Since this TSH surge is partially prevented by maintaining infants in a warm environment, postnatal cooling appears to be responsible in part for the rise in TSH secretion. In most studies, exposure of adults to cold or even intensive hypothermia has produced no changes, or at best minimal increases in serum TSH. More prolonged exposure to cold generally results in maintenance of the total T4 (TT4) and free T4 (fT4) levels with maintenance of a normal or decreased total T3 (TT3) and free T3 (fT3) levels. 7a,7b , however, others have shown prolonged arctic residence leads the increase in TSH to be associates with an increase in, thyroglobulin and T3.. These alterations may be partly the consequence of a direct effect of temperature on the rate and pathways of