Macroscopic Characteristics and Stroma
The thyroid gland is located on the anterior surface of the trachea. Anatomically, it consists of two lateral lobes, an isthmus, and a pyramidal lobe (present in 30–50% of cases).
Externally, the organ is covered by a connective tissue capsule. Septa extend inward from the capsule, dividing the parenchyma into lobules. The interfollicular stroma features a rich blood supply: a network of fenestrated capillaries envelops up to 50% of the follicular surface, ensuring intensive metabolism. Wide lymphatic capillaries and autonomic sympathetic nerve fibers are also present in the stroma (their stimulation enhances secretion, though less potently than TSH action).
Note: Histological sections may occasionally include fragments of the parathyroid glands adjacent to thyroid structures, which do not belong to the thyroid parenchyma.
Histological Structure of the Follicle
The primary structural component of the parenchyma is the follicle—a rounded structure whose wall consists of a single layer of glandular epithelium (thyrocytes). Clusters of extrafollicular epithelium are sometimes found in the parenchyma, though these are often merely artifacts (tangential sections of a follicular wall).
The follicular lumen is filled with a homogeneous colloid, whose chemical backbone is the glycoprotein thyroglobulin. Follicular cells are connected by tight junctions, desmosomes, and gap junctions. Tight junctions play a crucial barrier role: they seal the lumen and prevent thyroglobulin from entering the bloodstream. Compromising this barrier causes the body to recognize the protein as foreign, triggering an autoimmune attack on the gland.
Cellular Populations
Three main cell types are distinguished within the thyroid gland:
- Follicular cells (Thyrocytes): Constitute the vast majority. They rest on the basement membrane, with their apical pole bearing microvilli facing the follicular lumen. They synthesize thyroid hormones (thyroxine and triiodothyronine), which stimulate tissue growth, differentiation, and accelerate energy metabolism.
- Parafollicular cells (C cells, calcitoninocytes): Account for about 0.1%. They lie within the follicular wall (without reaching the lumen) or in groups within the stroma. They develop from the neural crest (APUD series). They synthesize calcitonin, a hormone that lowers blood $Ca^{2+}$ levels. Unlike thyrocytes, they do not take up iodine.
- Oxyphilic Hürthle cells (Askanazy cells): Large cells with eccentric hyperchromatic nuclei. Their number increases with age, though their exact function remains unclear.
Secretory Cycle of the Thyrocyte
The process of hormone formation is divided into two key phases.
Production phase (proceeds from the basal pole to the apical pole):
- The cell actively takes up amino acids, monosaccharides, and iodine ions from the blood.
- Polypeptide chains of thyroglobulin and the enzyme thyroid peroxidase are synthesized in the rough endoplasmic reticulum.
- Vesicles containing the protein are transported via the Golgi apparatus to the apical membrane and secreted into the colloid.
- At the colloid interface, thyroid peroxidase oxidizes iodine. Iodine atoms attach to tyrosine, forming thyroxine ($T_4$) and triiodothyronine ($T_3$) directly within the thyroglobulin molecule.
Excretion phase (proceeds from the apical pole to the basal pole):
- Stimulated by thyroid-stimulating hormone (TSH), pseudopodia appear on the apical surface of the thyrocyte.
- Colloid endocytosis occurs. Visually, this manifests as resorption vacuoles (light spaces within the colloid).
- Vesicles fuse with lysosomes. Lysosomal enzymes break down thyroglobulin.
- Free hormones ($T_3$ and $T_4$) exit through the basement membrane into blood capillaries via diffusion.
Morphological Signs of Glandular Activity
Follicular structure changes depending on the organ's activity, primarily linked to the rate of colloid resorption.
- During hyperfunction: The rate of resorption exceeds production. Thyrocytes increase in volume and become tall (columnar). The number of microvilli rises sharply, and mitotic activity is elevated. Follicles decrease in size, and the colloid becomes more fluid, containing numerous large resorption vacuoles.
- During hypofunction: A picture of stasis is observed. Thyrocytes flatten, and the number of microvilli drops. Follicles distend, the volume of colloid increases, and it becomes dense. Resorption vacuoles disappear, and cellular mitotic activity decreases.
Embryogenesis
Gland development originates from several embryonic primordia:
- Epithelium of the pharyngeal floor: Gives rise to typical thyrocytes (forming follicles).
- Epithelium of the 4th pharyngeal pouches (ultimobranchial bodies): Forms atypical follicles with heterogeneous contents.
- Neural crest: Neuroblasts migrate into the gland and differentiate into C cells.
- Mesenchyme: Forms the capsule, stromal septa, and vascular network.