Thyroid

The thyroid gland is a key endocrine organ found in all vertebrates and plays an essential role in regulating metabolism, growth and development. In humans it is positioned in the anterior neck, just below the Adam’s apple, and is notable for its butterfly-like shape consisting of two lateral lobes joined by a narrow isthmus. Its microscopic structure, hormone production, embryological development and clinical significance make it one of the most widely studied glands in human physiology.

Structure and Location

The thyroid lies anterior to the larynx and upper trachea. Each of its two lobes measures approximately 5 cm in length, 3 cm in width and 2 cm in thickness, while the isthmus generally spans the second and third tracheal rings. The gland weighs around 25 grams in healthy adults, although its size varies with sex, age and physiological conditions; it becomes noticeably larger in women, especially during pregnancy.
The gland is enveloped by a thin fibrous capsule with inner and outer layers. The inner layer forms septa that divide the gland into microscopic lobules, while the outer layer is continuous with the pretracheal fascia. A thickened region of this fascia, known as Berry’s ligament, anchors the gland to the cricoid and thyroid cartilages, causing it to rise and fall during swallowing.
Multiple anatomical structures surround the thyroid. The infrahyoid muscles lie anteriorly, the sternocleidomastoid muscles laterally and the trachea, oesophagus, larynx and lower pharynx posteriorly. Close to the posterior aspect of each lobe run the recurrent laryngeal nerve and the inferior thyroid artery. Typically four parathyroid glands are embedded between the layers of the thyroid capsule behind the lobes.

Blood, Lymphatic and Nerve Supply

The thyroid gland receives a rich vascular supply, one of the most extensive in the body relative to its size. Arterial supply is mainly provided by:

• the superior thyroid artery, arising from the external carotid artery
• the inferior thyroid artery, arising from the thyrocervical trunk

In some individuals an additional vessel, the thyroid ima artery, supplies the gland. Thyroid veins form a network around the capsule and drain into the internal jugular and brachiocephalic veins via the superior, middle and inferior thyroid veins.
Lymphatic drainage passes through the prelaryngeal (Delphian), pretracheal and paratracheal lymph nodes before reaching the deep cervical chain. Sympathetic fibres arise from the cervical sympathetic ganglia, while parasympathetic innervation is supplied by branches of the superior and recurrent laryngeal nerves.

Anatomical Variations

Numerous variations occur in the morphology of the gland. A pyramidal lobe, a remnant of the embryonic thyroglossal duct, is present in many individuals and may extend upward from the isthmus or from one of the lobes, often on the left side. Small accessory thyroid tissues may appear anywhere along the original descent pathway of the thyroid from the tongue to the neck.
Another variant sometimes observed is Zuckerkandl’s tubercle, a posterior extension of thyroid tissue near the recurrent laryngeal nerve and inferior thyroid artery. A levator muscle of the thyroid may connect the isthmus to the hyoid bone.

Microanatomy and Histological Features

Under the microscope, the thyroid displays a highly specialised structure centred on its functional units, the thyroid follicles. These are spherical structures ranging from 0.02 to 0.9 mm in diameter and consist of:

• follicular cells (thyrocytes): a single epithelial layer surrounding the follicle; when stimulated by thyroid-stimulating hormone (TSH) they synthesise the thyroid hormones triiodothyronine (T₃) and thyroxine (T₄)
• follicular lumen: the central cavity filled with colloid, a concentrated solution of thyroglobulin that serves as a precursor for thyroid hormone synthesis
• parafollicular cells (C cells): scattered between follicles, these cells secrete the hormone calcitonin which regulates calcium homeostasis

Follicular cell morphology varies with activity, from squamous in inactive glands to columnar when stimulated.

Hormones and Physiological Functions

The thyroid produces three primary hormones:

• triiodothyronine (T₃)
• thyroxine (T₄)
• calcitonin

T₃ and T₄ influence the basal metabolic rate, protein synthesis and numerous metabolic pathways. They are essential for normal growth, neural development and overall homeostasis. Calcitonin contributes to calcium balance by decreasing blood calcium levels, opposing the actions of parathyroid hormone.
Thyroid hormone secretion is regulated through the hypothalamic–pituitary–thyroid axis. The hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary to release TSH. TSH, in turn, promotes hormone synthesis and secretion by the thyroid. Circulating thyroid hormones exert negative feedback on both the pituitary and hypothalamus.

Embryological Development

The thyroid is the first endocrine gland to develop during human embryogenesis. It appears during the third to fourth week of gestation as a midline epithelial thickening in the floor of the primitive pharynx, located between the median tongue bud and the copula. From this site, marked later by the foramen cecum, the thyroid descends through the neck connected by the thyroglossal duct.
Between weeks five and seven the thyroglossal duct normally degenerates, while the thyroid continues its migration to its definitive position anterior to the trachea. By week eleven measurable TSH is present, and by weeks eighteen to twenty sufficient T₄ is produced to support fetal development. T₃ levels remain relatively low until around week thirty. Adequate fetal thyroid function is crucial for neurodevelopment.

Disorders of the Thyroid Gland

A variety of disorders affect thyroid structure and function. These include:

• hyperthyroidism, most commonly caused by Graves’ disease
• hypothyroidism, often due to iodine deficiency or, in iodine-sufficient regions, Hashimoto’s thyroiditis
• thyroiditis, encompassing several forms of inflammation
• goitre, referring to thyroid enlargement
• thyroid nodules, which may be benign or malignant
• thyroid cancer, which includes several histological types

Iodine deficiency remains the leading preventable cause of intellectual disability in children globally. Conversely, autoimmune thyroid disease represents a major cause of thyroid dysfunction in developed regions.