Editorial: Deafness and Goiter: Molecular Genetic Considerations

Profound deafness is one of the most striking features of certain congenital thyroid diseases. In addition, lesser defects in auditory function, albeit of uncertain incidence and severity, have been described in acquired thyroid disorders in later life. Numerous reports in the medical literature have indicated a link between the function of the thyroid gland and the development and possibly the maintenance of function of the auditory system. Deafness can occur, for example, in sporadic cretinism or in congenital hypothyroidism in any given population. It is also common in a majority of the cases of neurological cretinism arising in geographical regions where endemic iodine deficiency prevails. It is perhaps ironic that, despite this clear association and the fact that severe deafness is an obvious symptom, we know so little about the mechanisms that connect the functions of the endocrine and auditory systems. It is only comparatively recently that unfolding events have indicated that progress is being made in understanding the underlying molecular mechanisms. Deafness has long been associated with thyroid gland abnormalities. Indeed, this connection had been recognized before the identification of thyroid hormone, when the function of the thyroid gland still remained enigmatic. Reports dating from the latter half of the 19th century referred to deafness occurring in both sporadic and endemic cretinism and in a distinct condition of deaf-mutism with goiter, later termed Pendred’s syndrome (1). The first hints that thyroid hormone was essential for auditory function followed the advent of replacement therapy with thyroid extracts, originally pioneered by G.R. Murray in 1891, which was later reported to be capable of improving the hearing as well as the growth and mental development of infants suffering from cretinism. The requirement for thyroid hormone has since been substantiated in animal models. A further intriguing link has been provided by study of the more recently described syndrome of resistance to thyroid hormone (RTH), which is associated with defects in the thyroid hormone receptor p (TRS) gene. RTH is characterized by goiter and elevated levels of thyroid hormone but resistance of the pituitary and other organs to its actions (2). It is accompanied by a variable array of recognized symptoms, although these have generally not included deafness. However, as reported by Brucker-Davis et al. (4) in this issue of JCEM (see page 2768-2772), an incidence of hearing loss is now revealed that may have escaped previous notice (3,4). Despite the ostensible similarity of congenital hypothyroidism, RTH, and Pendred’s syndrome, in their association with deafness and goi-