Thyroid gland

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 (which occurs in 30–50% of cases).

Externally, the organ is covered by a connective tissue capsule. Septa extend inward from it, dividing the parenchyma into lobules. The interfollicular stroma is richly vascularized: a network of fenestrated capillaries entwines up to 50% of the follicular surface, ensuring an intensive metabolism. The stroma also contains wide lymphatic capillaries and autonomic sympathetic nerve fibers (their stimulation enhances secretion, but to a lesser extent than the action of TSH).

Note: In histological specimens, fragments of parathyroid glands may occasionally be found adjacent to the thyroid structures, which do not belong to its parenchyma.

Histological structure of the follicle

The main structural component of the parenchyma is the follicle, a rounded formation 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 an artifact (tangential section of the follicular wall).

The follicular cavity is filled with a homogeneous colloid, the chemical basis of which 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. Disruption of this barrier causes the body to perceive the protein as foreign, triggering an autoimmune attack on the gland.

Cell populations

Three main cell types are distinguished in the thyroid gland:

1. Follicular cells (thyrocytes): Constitute the vast majority. They rest on the basement membrane, with their apical portion bearing microvilli facing the follicular lumen. They synthesize thyroid hormones (thyroxine and triiodothyronine), which stimulate growth and tissue differentiation and accelerate energy metabolism.
2. Parafollicular cells (C cells, calcitoninocytes): Make up about 0.1%. Located in the follicular wall (without reaching the lumen) or in groups within the stroma. Develop from the neural crest (APUD series). Synthesize calcitonin, a hormone that lowers blood $Ca^{2+}$ levels. Unlike thyrocytes, they do not take up iodine.
3. Oxyphilic Hürthle cells (Askanazi cells): Large cells with an eccentric hyperchromatic nucleus. Their number increases with age, although 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 released into the colloid.
• At the border with the colloid, 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):

• Under the influence of thyroid-stimulating hormone (TSH), pseudopodia appear on the apical surface of the thyrocyte.
• Colloid endocytosis occurs. Visually, this manifests as resorption vacuoles (light cavities 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

The structure of follicles changes depending on the activity of the organ, which is primarily associated with the rate of colloid reabsorption.

• In hyperfunction: The rate of reabsorption exceeds production. Thyrocytes increase in volume and become tall (columnar). The number of microvilli increases sharply, and mitotic activity is elevated. Follicles decrease in size, and the colloid becomes more fluid, containing numerous large resorption vacuoles.
• In hypofunction: A picture of stasis is observed. Thyrocytes flatten, and the number of microvilli decreases. Follicles become distended, the volume of colloid increases, and it becomes dense. Resorption vacuoles disappear, and cellular mitotic activity decreases.

Embryogenesis

The development of the gland 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 layers, and vascular network.

Class and exam questions

What else to study on this topic

• Biochemical mechanisms of oxidation and iodination mediated by thyroid peroxidase
• The effect of thyroid-stimulating hormone (TSH) on the initiation of the secretory cycle
• Mechanisms of calcium homeostasis maintenance by the parathyroid glands and C cells
• Ultimobranchial follicles: structure and clinical significance

Other topics in the "Endocrine System" section

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