Embryology

The thyroid, the parathyroid glands, and the thymus originate from the embryonic pharyngeal region. The pharynx itself is initially an endodermally lined cul-de-sac that forms the cephalic extremity of the foregut. This is derived from a part of the yolk sac. The foregut diverticulum is divided into a more cranial pharynx and a more caudal proper foregut with the appearance of the primordium of the pulmonary apparatus as a small ventral outgrowth. When the embryo is approximately 26 days old, lateral walls of the pharynx show a nonuniform growth that forms five pairs of endodermally lined pouches.4

Only the first pouch persists as a large, hollow cavity to form at least the greater part of the middle ear cavity and the tympanic tube. The second pouch almost completely disappears. It is from the third and fourth pouches that the parathyroid and thymus glands develop, and they also contribute to the formation of the thyroid gland. The fate of the fifth pouch is uncertain. Each pair of parathyroid glands has a different origin. The inferior parathyroid glands originate from the third branchial pouch and, therefore, are designated as parathyroid III, whereas the superior parathyroid glands descend from the fourth branchial pouch and are referred to as parathyroid IV. Figure 38-1 schematically depicts the development and migration of the parathyroids.

Norris,5 basing his findings on a collection of 139 human embryos, fetuses, and newborn children, studied the morphogenesis of the parathyroid glands. He divided the developmental process into five stages, as described next.

Preprimordial Stage

The preprimordial stage is represented by embryos from 4 to 8 mm in length. This stage makes up the embryonic development between the time of the formation of the pharynx (foregut) and the earliest appearance of a recognizable parathyroid anlage. The third and fourth pouches show slight dorsal extensions. The third pouch, which has the form of a tubelike lateral expansion from the embryonic pharynx, makes contact with the ectoderm of the branchial cleft and then continues its growth downward in the ventral direction.

Early Primordial Stage

At this stage, the embryo is about 9 mm in length. The tissue destined to become the parathyroids can be recognized. Proliferation and differentiation of large, clear cells with sharply demarcated polygonal outlines occur in the third and four pouches. This proliferation results in a thickening of the third diverticulum wall. The early primordium of parathyroid IV adopts the form of a solid budlike nodule; the fourth pouch still exists as a tubular diverticulum from the pharynx.

Branchial Complex Stage

At this stage, paired derivatives of the third and fourth pouches become separated from each other to take up independent positions. During the early stage, the branchial pouches are joined to the pharynx; subsequently, the pharyngobranchial ducts become drawn out, narrowed, and finally divided so that at each side of the midline there is a pair of lobulated bodies. One pair represents the thymus and parathyroid III (third branchial complex), and the other represents the lateral thyroid and parathyroid IV (fourth branchial complex).

FIGURE 38-1. Origin of parathyroid glands from the third and fourth pharyngeal pouches.

The median thyroid, which descended in an earlier stage from a median diverticulum of the floor of the pharynx, begins to grow out laterally and cephalocaudally in the form of a flat plate that extends to both sides of the midline. This plate begins to bend dorsally at its lateral edges and extends more and more dorsally to intervene between the laterally placed third branchial complex and the more medially placed fourth branchial complex.

At the beginning of the branchial complex stage, the thymus primordium and the parathyroid primordium are intimately joined; however, the thymus enters into a period of rapid ventral growth until it makes contact with the pericardium. Parathyroid III, on the other hand, does not grow as rapidly as the thymus and remains as a budlike projection from the upper end of the thymus cord. Finally, parathyroid III takes a spherical shape, intimately attached to the cephalic pole of the thymus cord. At the end of this stage, the third branchial complex migrates through the entire extent of the embryonic neck, and separation of the parathyroid from the thymus begins.

The position of the fourth complex in relation to the median thyroid depends on changes in form, size, and position of the rapidly growing lateral lobe of the median thyroid. During this time, parathyroid IV is still attached to the lateral thyroid body. The brachial complex stage ends when the embryo is approximately 18 to 20 mm in length.

Isolation Stage

This stage is characterized by separation of each branchial complex. When the thymus and parathyroids have descended and parathyroid III is at about the level of the lower pole of the thyroid, parathyroid III increases in size and gradually becomes constricted at its base of attachment, and complete separation occurs. The two elements of the fourth complex also grow and become constricted until the interlobular stalk is divided. There is almost no descent of this complex, and the isolation of parathyroid IV occurs when the lateral and median thyroids become incorporated. The final position of parathyroid IV in relation to the thyroid gland is determined by the place at which the inclusion of the lateral thyroid body occurs. Isolation of the parathyroid glands is usually accomplished by the time the embryo is 20 mm in length.

Definitive Form Stage

This stage is the period from the end of the stage of isolation to the time when the parathyroids assume their definitive form. Alteration in form from a spherical or globular body toward an ellipsoid shape occurs. The form of the parathyroid glands is ultimately determined by their relation to adjacent structures.

This embryologic relationship of the parathyroids, the thyroid, and the thymus makes the location of most parathyroid glands predictable.

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