Histology of the Thyroid Gland
Histology of the Thyroid Gland
The thyroid gland is a bilobular endocrine gland that is found in the neck, anterior and inferior to the larynx. Grossly, the gland appears brownish-red and the left and right lobes are connected by an isthmus. The main purpose of this organ is to produce, store and secrete the iodine-based hormones triiodothyronine (T3) and thyroxine (T4). These hormones have various effects on fat, protein and carbohydrate metabolism, as well as on the development especially central nervous system and general growth.
The thyroid hormones are regulated by the Hypothalamus-Pituitary-Thyroid axis (HPT) via thyroid regulating hormones (TRH; from hypothalamus) and thyroid stimulating hormone (TSH; from pituitary gland). Although this article is primarily focused on the histology of the thyroid gland, some basic embryology and gross anatomy will also be discussed for completion. Furthermore, clinically significant points relating to the histology of the thyroid gland will also be addressed.
The thyroid gland is of endodermal origin, arising from the floor of the pharynx, posterior to the tuberculum impar (central enlargement posterior to the first pharyngeal arch) and anterior to the copula linguae (swelling formed by parts of the second, third and fourth pharyngeal arches). Its site of origin also corresponds to the foramen cecum of the tongue (along the sulcus terminalis, which separates the posterior third from the anterior two thirds of the tongue).
As the thyroid is formed, it descends anterior to the pharyngeal pouches as a bilobed diverticulum, while maintaining an attachment to the tongue via the thyroglossal duct. This duct typically disappears, but may persist and present as a thyroglossal cyst. At the end of seventh gestational week, the thyroid is anteroinferiorly related to the trachea, which is its final destination and has its classical bilobular shape. By the end of the third gestational month, the gland has visible histologically functional units.
The thyroid gland is situated opposite C5 and T1 vertebra in the anterior neck region. There is some degree of variability in the mass of the gland, particularly between males and females. The exception to the sex dichotomy of thyroid size is between the ages of eight months to the onset of menarche.
Since the organ of discussion is an endocrine gland, it is highly vascularized to facilitate rapid access of the hormones to the blood stream. Its arterial supply is mainly derived from the superior and inferior thyroid arteries. The branches of these arteries form many anastomoses to ensure adequate perfusion. The anterior and posterior divisions of the superior thyroid artery supplies anterior and medial aspects of the gland, respectively. It should also be noted that the posterior branch also supplies the lateral surface of the gland. The inferior thyroid artery also bifurcates into an ascending superior division and an inferior division. The former supplies the inferior part of the gland while the latter carries blood to the gland’s posterior aspect. An inconstant, but important vessel may arise from the brachiocephalic trunk or directly from the aortic arch, which may be problematic during tracheostomies or thyroidectomies. This vessel is known as the thyroid ima artery. It may act as a collateral vessel in cases where perfusion to the gland is suboptimal.
Equally important is the venous drainage, which is achieved by the inferior, middle and superior thyroid veins. The superior thyroid vein travels with the superior thyroid artery from the superior part of the gland. The inferior vein forms a glandular venous plexus that empties blood from both the superior and middle thyroid veins to the brachiocephalic vein. Finally, the middle thyroid veins drain the lateral surface of the gland to the inferior vena cava.
Typically, cells of an endocrine gland have a cord-like arrangement and their products to be secreted are kept within the individual cells. The thyroid gland is an exception to this rule.
It is encased by a thin connective tissue capsule that enters the substance of the lobes to further subdivide the gland into irregular lobular units. Each lobule contains a cluster of follicles, which are the structural and functional units of the thyroid gland.
A follicle is surrounded by thin connective tissue stroma rich in fenestrated capillaries (along with the sympathetic nerves that innervate them) and lymphatics. Follicular epithelium is a simple epithelium consisting of low columnar, cuboidal or squamous cells depending on the level of activity of the follicle. When they are active, they appear cuboidal to low columnar, but when they are inactive the cells are squamous. These follicular (principal) cells take up the necessary amino acid precursors and iodine at its basolateral surface and release the final product into the blood stream at its apical end. Follicular cells are responsible for producing thyroglobulin (an iodine rich, inactive form of the thyroid hormones), which is then stored as a semi-solid substance (colloid) in the lumen of the follicles. The colloid stains pink with haematoxylin and eosin (H&E) staining, while the follicular cells have a purple appearance. The degree of activity of a follicle can also be assessed based on the amount and appearance of colloid it contains. Inactive follicular lumina are larger; colloid is abundant and appears solid. In contrast, active follicular lumina are smaller and there is little to no colloid present.
Another cell type that can be identified on histological preparations of thyroid tissue is parafollicular cells, also known as C (clear) cells. C-cells appear clear due to the fact that they are lightly stained on H&E preparation. They can be found within the basal lamina of the thyroid follicles without extending into the follicular lumen or between thyroid follicles in the interfollicular space, either singly or in the form of groups. Parafollicular cells are a subtype of neuroendocrine cells (amine precursor uptake and decarboxylation – AUPD – system) that produce thyrocalcitonin (calcitonin). This hormone aide in the regulation of blood calcium levels by downregulating bone resorption (breakdown of bone and subsequent release of minerals into the blood) and limiting calcium reuptake in the kidneys.
Thyroid hormone synthesis begins with recognition of thyroid stimulating hormones (TSH) by TSH-receptors at the basolateral region of the follicular cells. Simultaneously, iodine is taken into the cell via Na+/I- symporters (the excess Na+ is removed by Na+/K+-ATPase pumps). Iodine is used in the organification of tyrosine in the follicular lumen to form monoiodotyrosine (MIT). MIT can then be organified to form diiodotyrosine (DIT). The enzyme thyrosine peroxidase (TPO), can subsequently link a MIT and a DIT molecule to form triiodothyronine (T3) or two DIT molecules to form thyroxine (T4).