Toxic nodular goitre.

Toxic nodular goitre is the late result of a slow growth process generating new daughter follicles from the mother follicles of a normal thyroid gland. Since the normal follicular shell is not built up by monoclonal epithelial cells, but rather by cells with widely variable functional equipment, daughter follicles generated by the preferential replication of particular mother follicular cells endowed with a high growth potential, may be different from mother follicles. For instance, the progeny of follicles may have a higher or lower iodine metabolism than their progenitor follicles. Some of the newly generated follicles have a high autonomous, i.e. TSH-independent, iodine turnover, while some others have a high autonomous growth potential. The degree of autonomous function is entirely independent of that of growth. In the process of goitrogenesis, newly generated follicles may, in addition, acquire new forms of expressing genetic functions. Such new traits, e.g. a particular growth pattern, may become inheritable and are then passed on from mother to daughter cells. The result is the most characteristic of all hallmarks of nodular goitres, which is the heterogeneity of structure and function between two diseased glands and even between closely adjacent follicles of the same gland. Greatly uneven intrinsic replication rates between different follicular cells and equally varying independency on growth stimuli account for regional differences in goitre growth. This, together with a network of fibrous scars interfering with unimpeded expansion of the growing follicle population, invariably produces a nodular growth pattern of the goitre. TSH certainly does not account for the growth of this type of goitre. Instead, a number of thyroid growth factors, including growth-stimulating immunoglobulins akin to those found in Graves' disease, have been discovered in recent years. Once the number of follicular cells with high intrinsic growth potential has become large enough under the impact of extrathyroidal growth stimuli, goitre growth may become autonomous and self-perpetuating. Whether or not a nodular goitre will produce thyrotoxicosis is a function of the number of follicles with high intrinsic iodine turnover which happen to be generated in the course of goitrogenesis. In contrast to thyrotoxicosis in Graves' disease, hyperthyroidism in nodular goitre is a very slowly progressing, insidiously evolving complication.