Embryology of the Thyroid and Parathyroids 

The thyroid gland is the first of the body's endocrine glands to develop, on approximately the 24th day of gestation. The gland originates as a proliferation of endodermal epithelial cells on the median surface of the developing pharyngeal floor. The site of this initial development lies between 2 key structures, the tuberculum impar and the copula, and is known as the foramen cecum. The thyroid initially develops caudal to the tuberculum impar, which is also known as the median tongue bud. This embryonic swelling arises from the first pharyngeal arch and occurs midline on the floor of the developing pharynx, eventually helping form the tongue as the 2 lateral lingual swellings overgrow it.

The foramen cecum begins rostral to the copula, also known as the hypobranchial eminence. This median embryologic swelling consists of mesoderm that arises from the second pharyngeal pouch (although the third and fourth pouches are also involved). The thyroid gland, therefore, originates from between the first and second pouches.

The initial thyroid precursor, the thyroid primordium, starts as a simple midline thickening and develops to form the thyroid diverticulum. This structure is initially hollow, although it later solidifies and becomes bilobed. The 2 lobes are located on either side of the midline and are connected via an isthmus.

An image of the superior parathyroids can be seen below.

The initial descent of the thyroid gland occurs anterior to the pharyngeal gut. At this point, the thyroid is still connected to the tongue via the thyroglossal duct. The tubular duct later solidifies and subsequently obliterates entirely (during gestational weeks 7-10). Nonetheless, in some individuals, remnants of this duct may still persist.

The foramen cecum represents the opening of the thyroglossal duct into the tongue; its remains may be observed as a small blind pit in the midline between the anterior two thirds and the posterior third of the tongue.

A pyramidal lobe of the thyroid may be observed in as many as 50% of patients. This lobe represents a persistence of the inferior end of the thyroglossal duct that has failed to obliterate. As such, the pyramidal lobe itself may be attached to the hyoid bone, similar to a thyroglossal duct cyst, or may be incorporated into a thyroglossal duct cyst.

Further descent of the thyroid gland carries it anterior (or ventral) to the hyoid bone and, subsequently, anterior (or ventral) to the laryngeal cartilages. As the thyroid gland descends, it forms its mature shape, with a median isthmus connecting 2 lateral lobes. The thyroid completes its descent in the seventh gestational week, coming to rest in its final location immediately anterior to the trachea.

For further reading, please see the Medscape Reference article Thyroid Anatomy.

Parafollicular cells are also known as C cells. These cells are a special subset of cells within the thyroid gland that secrete calcitonin, a hormone necessary for the regulation of calcium.

The parafollicular cells arise from the ultimobranchial body. This body represents the last structure derived from the branchial pouches, hence its name. The ultimobranchial body arises from the fifth pharyngeal pouch, which is alternately described as the ventral portion of the fourth pharyngeal pouch. (Whether fifth pharyngeal pouches actually exist is debatable.)

Migrating cells from the neural crest region infiltrate the ultimobranchial body. This structure is then incorporated into the thyroid gland, as the ultimobranchial body fuses with the thyroid gland and disseminates its cells into it. The C cells of the thyroid, therefore, are of neural crest origin.

If the thyroglossal duct does not atrophy, then the remnant can manifest clinically as a thyroglossal duct cyst. While half of these generally midline cystic masses are located at or just below the level of the hyoid bone, they may be located and can track anywhere from the thyroid cartilage up the base of the tongue. If the cyst ruptures, it may go on to form a thyroglossal duct sinus or a thyroglossal duct fistula that exits through the overlying skin. Because the hyoid bone develops in an anterior direction and may surround the thyroglossal duct, the surgeon should resect the central portion on the hyoid bone along with the cyst (the Sistrunk procedure), unless the thyroglossal duct tract can clearly be observed coursing away from the bone.^[1]

An aberrant or ectopic thyroid gland may occur anywhere along the path of initial descent of the thyroid, although it is most common at the base of the tongue, just posterior to the foramen cecum. In this location, an aberrant or ectopic thyroid gland is known as a lingual thyroid and represents a failure of the thyroid to descend. This failure to descend contrasts with the incomplete descent of the thyroid, in which case the resulting final resting point of the gland may be high in the neck or just below the hyoid bone.^[2]

Accessory thyroid tissue can also occur, arising from remnants of the thyroglossal duct. While the accessory thyroid tissue may be functional, it is generally insufficient for normal function if the main thyroid gland is entirely removed. This accessory tissue may appear anywhere along the path of the thyroglossal duct tract.

The inferior parathyroid glands are also known as parathyroid IIIs because they arise from the dorsal wing of the third pharyngeal pouch. The third brachial pouch differentiates at gestational weeks 5-6, with the ventral wing becoming the thymus. The thymus and parathyroids both lose their connections to the pharynx at gestational week 7. The thymus then migrates caudally and medially, pulling the parathyroids with it; therefore, parathyroid IIIs are further inferior than are parathyroid IVs. The parathyroid in turn loses its connection with the thymus. The inferior parathyroid glands usually stop at the dorsal surface of the thyroid gland, outside of the fibrous capsule of the gland itself.

An image of the inferior parathyroids can be seen below.

The superior parathyroid glands are also known as parathyroid IVs because they arise from the dorsal wing of the fourth pharyngeal pouch, differentiating at gestational weeks 5-6. At gestational week 7, the glands lose connections with the pharynx and attach themselves to the thyroid gland, which is migrating caudally, albeit far less a migration than the thymus (with parathyroid IIIs as described above). Because of the lesser length of migration, the superior parathyroid glands (IV) are in a more constant location than the inferior parathyroids (III). The superior parathyroids are generally located more posterior and medial than the inferior parathyroids, and their final resting point is usually on the dorsal surface of the thyroid gland, outside the fibrous capsule of the thyroid gland.

An image of the superior parathyroids can be seen below.

Accessory or supernumerary parathyroid glands are found in approximately 13% of individuals at autopsy. These glands most likely result from tissue fragmentation occurring during the migration of the glands rather than from an initial division of the primordia of the glands themselves.

Absence of parathyroids (ie, < 4 glands) is noted in approximately 3% of individuals at autopsy. This absence may result from a failure of the primordia to differentiate into the parathyroid glands or may be the result of parathyroid gland atrophy early in development.

Ectopic parathyroid glands occur in 15-20% of patients. The glands may be located anywhere near or even within the thyroid or thymus. For example, if parathyroid IVs do not descend entirely, they may be located as high as the bifurcation of the common carotid artery. Conversely, if parathyroid IVs do not release from the thymus, they may be located intrathoracically, as low as the aortopulmonary window. Other common ectopic locations include the anterior mediastinum, posterior mediastinum, and retroesophageal and prevertebral regions. However, even when the parathyroid glands are in an ectopic location, they still often are symmetrical from side to side, making localization somewhat easier.

After adhering to the thyroid capsule, the parathyroid gland may actually enter the thyroid gland and embed there rather than remaining outside the gland. This situation results in an intrathyroidal parathyroid gland.

DiGeorge syndrome manifests as congenital thymic aplasia and absent parathyroid glands. This syndrome results from failure of the third and fourth brachial pouches to differentiate. DiGeorge syndrome is also associated with facial abnormalities from abnormal development within first arch structures. No genetic cause is known, but teratogens are the assumed mechanism. Symptoms include neonatal tetany and impaired cellular immunity with normal humoral immunity.