Thyroid disease mediated by molecular defects in cell surface and nuclear receptors.

The proposed mechanisms of RTH are not mutually exclusive. In fact, there is considerable experimental evidence that many if not all of these complex receptor interactions with elements of the transcriptional unit are involved in RTH. Several aspects of RTH remain unclear, in particular on a clinical level. We still do not completely understand the seeming paradox of a tight distribution of receptor mutations and wide variability in phenotypic presentation. The discovery that many of the RTH receptors have defects in corepressor interaction makes it tempting to speculate that the variability in RTH phenotype within kindreds is secondary to differences in corepressor expression. These issues may be better understood as research further proceeds into cofactors and their control of transcription. We also need better tools to determine thyroid status at a peripheral level. Basal metabolic rate, serum measurement of thyroid-responsive gene products, echocardiographic techniques, and other clinical measures have for the most part been unhelpful in determining thyroid status of specific organ systems. Consequently, therapeutic interventions for RTH are directed toward normalizing biochemical indices of thyroid homeostasis, without really knowing whether these efforts correct imbalances within crucial tissues. These studies, and the more widespread investigation of hormone receptor action in general, are moving at a breathtaking pace, and there is a keen interest in applying these principals to understanding the pathophysiologic mechanism of a variety of diseases.