The thyroid angiofollicular units, a biological model of functional and morphological integration

The fundamental role of the thyroid gland is to ensure the biosynthesis of thyroid hormones whose primary role during embryonic development and the maintenance of homeostasis after birth is well known. The challenge here is double, as the hormone synthesis depends on both potentially toxic biochemical processes, as long as they are not fully contained, and the availability of a trace element, iodine, whose uptake may be extremely variable depending on the geographical location and the physiological status of individuals. The squaring of the circle has been resolved by the thyroid gland during its phylogenetic maturation by setting up angiofollicular units, morphological entities whose the perfect functional coherence between the different compartments within them (epithelial, endothelial and interstitial) results from a high level three-dimensional assemblage. This morphological and functional integration warrants adequate supplies of thyroid hormones whose mobilization must be triggered at any time when necessary. This functional requirement finds its expression in the morphological heterogeneity that ultimately culminates in the formation of nodules. Each angiofollicular unit is an individualized entity with its own genotypic and phenotypic asset that runs on the extrinsic control of TSH and a host of autocrine and paracrine factors. But subtle intrinsic mechanisms of self-regulation, operating out of any outside influences, constantly adjust the availability of players involved in the hormonal synthesis (iodine, thyroglobulin) within a biochemical entity (the thyroxisome) that is perfectly suited for this synthesis taking place without prejudice to the thyrocyte. The hormonal synthesis generates oxygen-derived substances as oxidative load or stress, though perfectly controlled in healthy thyrocytes. Any injury related to the nature, the amount, or where in the cell oxygen-derived substances are produced, may lead to morphological and functional breakdowns responsible for various disease processes, including those of autoimmune or even neoplastic nature.