Pathogenesis of thyroid nodules in multinodular goiter

American Journal Of Pathology (Impact Factor: 4.59). 12/1982; 109(2):215-23.
Source: PubMed

ABSTRACT Pathogenesis of nodule formation was studied in over 100 nodular goiters from a subendemic area. 60 surgical specimens were autoradiographed. Only one classical, well-encapsulated adenoma was detected. All other nodules were incompletely encapsulated and consisted of follicles that were morphologically and functionally identical to those of nonnodular parenchyma. Most characteristic was the tremendous interfollicular heterogeneity appearing on autoradiographs. Nodular goiters contain multiple foci and strands of fibrous tissue, which result from scarring of multiple hemorrhagic necroses occurring during goiter growth. Therefore, the slowly growing number of newly formed follicles has to squeeze into the meshes of an inelastic network of connective tissue. Nodular growth pattern is the inevitable consequence. Some particular nodules expand because of excessive accumulation of colloid. We conclude that most thyroid nodules in long-standing goiters consist of ordinary, polyclonal goiter follicles which expand in nodular fashion because they replicate within a mold made out of a poorly extensible network of connective tissue.

36 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Clinics in Endocrinology and Metabolism 06/1985; 14(2):351-72. DOI:10.1016/S0300-595X(85)80038-4
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Functional and morphologic heterogeneity of human multinodular goiters was investigated in 300 samples from "cold" and "hot" regions of 20 goiters transplanted onto nude mice. Transplants were labeled with [3H]thymidine and radioiodine, while the host's thyroid-stimulating hormone (TSH) secretion was either stimulated or suppressed. Proliferation and function of follicular cells were assessed in whole follicles reconstructed from autoradiographs of serial sections. Hot transplants had a higher autonomous iodine uptake than those of cold tissue in TSH-suppressed hosts. Functional autonomy widely varied among the follicles, but even more so among individual cells. Hot grafts differed from cold ones only by a comparatively larger fraction of autonomous cells. Intercellular differences of iodinating activity were not abolished by TSH. Grafts faithfully reproduced the individual growth pattern of the original tissue. Between 0.5% and 7% of all follicular cells replicated despite suppression of TSH. Up to 70% of these cells were clustered, forming scattered foci of autonomously growing tissue. Other cells only started replicating after long-term TSH stimulation. Thus, goiters contained subsets of cells with high and others with low growth response. Progenies of replicating cells remained clustered, sometimes budding outwards to form new follicles. Autonomy of growth and autonomy of function are independent traits of epithelial cells. Epithelial cells have their individual growth pattern, replication rate, and functional capacity. These traits are passed on from a mother cell to its progeny during follicle neogenesis. To this main mechanism accounting for the morphologic and functional heterogeneity of human goiters, inheritable modifications of gene expression must probably be added.
    Journal of Clinical Investigation 12/1985; 76(5):1992-2002. DOI:10.1172/JCI112199 · 13.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In a prospective investigation, thyroid function was studied in 43 patients before and after surgery on a nontoxic nodular goiter. Prior to surgery, 11 patients displayed a flat thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH), suggesting subclinical hyperthyroidism. Thyroid autoantibodies (microsomal/thyroglobulin) were found in low titers in 7 of 43 patients, and in no patient were TSH-receptor antibodies found. Three months following surgery, 32 patients were chemically euthyroid and 11 patients had elevated TSH values. Seven of the latter had additional signs of hypothyroidism and were given continuous thyroxine substitution. Starting 3 months after surgery, increasingly higher doses of thyroxine were administered to patients with a normal TRH test until an abnormal TSH response was observed. Four patients had a flat TSH response to TRH without administration of thyroxine and in 9 patients a daily dose of only 0.1 mg resulted in such a response. The 32 euthyroid patients developed flat TSH responses at an average dose of 123 μg of thyroxine. The data indicate that following surgery, the thyroid hormone production from the nonnodular thyroid remnant has low suppressibility, suggesting that, in nodular goiter, tissue with abnormal hormone production is widely distributed within the gland. It appears then that thyroxine medication in nodular goiter has a place mainly in patients developing hypothyroidism following surgery.
    World Journal of Surgery 07/1986; 10(3):481-7. DOI:10.1007/BF01655315 · 2.64 Impact Factor
Show more


36 Reads
Available from