Migration of the thyroid, parathyroids, and pharyngeal pouch derivatives . The thyroid, parathyroid glands, and ultimobranchial bodies migrate inferiorly from their origin in the embryo. Courtesy of Tim Phelps © JHU/AAAM 2004, Department of Art as Applied to Medicine, The Johns Hopkins University School of Medicine
(a) The upper (IV) and lower (III) parathyroids exchange position as they migrate; parathyroid III becomes the inferior parathyroid, whereas parathyroid IV becomes the superior parathyroid. (b) The inferior parathyroid has a more variable location due to its longer migration and may commonly be found in the thyrothymic ligament or the thymus itself. Courtesy of Tim Phelps © JHU/AAAM 2004, Department of Art as Applied to Medicine, The Johns Hopkins University School of Medicine
To elaborate and consider this in further detail, the entire head and neck region is derived from ectoderm, mesoderm, endoderm, and neural crest-derived cells. During the fourth and fifth weeks of development, the pharyngeal, or branchial arches arise from a core of mesoderm that is lined internally by endoderm of the primitive foregut and externally by surface ectoderm. Bars of mesenchymal tissue become separated by deep grooves known as branchial clefts. Simultaneously, five pairs of outpockets develop along the lateral walls of the most cranial portion of the foregut, the pharyngeal gut. These outpockets are known as the pharyngeal pouches (Figs. 1.1 and 1.2). Unique to both the third and fourth pharyngeal pouches, dorsal and ventral wings develop bilaterally [4–7].
During the fifth week of embryogenesis, the endodermally derived epithelium of the third pouch differentiates. The dorsal wing becomes the right and left inferior parathyroid glands, respectively, while the ventral wing forms a portion of the thymus that will later coalesce. Bilaterally, the gland primordia lose their connection with the pharyngeal wall in order to allow migration in a caudal and medial direction. The rapid movement of the paired thymic counterparts toward the anterior mediastinum in the thorax draws the inferior parathyroid glands with them (Fig. 1.2). Upon arrival in the thorax, the thymic counterparts fuse to form the final gland. Occasionally, this fails to occur completely, and a tail of thymic remnant may persist in the thyroid gland (derived as noted from an outpouching of the pharyngeal endoderm; foramen cecum in the adult) or as an independent island of thymic tissue in the neck. As the thymus descends, the inferior parathyroid glands migrate to their final location most commonly along the inferoposterior aspect of the thyroid gland. However, the migration is highly variable and the glands can be found at any location from intrathyroidally to along the thyrothymic ligament to within the thymus if the dorsal and ventral wings of the third pouch fail to separate. This variability of each parathyroid gland is independent of the migration of the contralateral gland, thereby resulting in significant variability in adults. Nonetheless, the lower parathyroid gland is typically located anterior to the recurrent laryngeal nerve.
Similar to the third pouch, the fourth pharyngeal pouch also divides into a dorsal and ventral wing. Again, the dorsal wing forms parathyroidal nests that give rise to the superior parathyroid glands bilaterally. The ventral wings develop into the ultimobranchial body , which will later become incorporated into the thyroid gland and become the parafollicular or C cells that secrete calcitonin. The superior parathyroid glands invaginate and attach themselves to the caudally migrating thyroid gland (Figs. 1.1 and 1.2). Ultimately, the bilateral superior parathyroid glands usually locate symmetrically, either in close association with the superior pole of the thyroid gland or occasionally within the thyroid gland itself. A majority of the superior glands are posterolateral in location and lie just above or just below the intersection of the inferior thyroid artery and the recurrent laryngeal nerve but posterior to the recurrent nerve.
It is the numerous variations in embryologic pharyngeal pouch development that result in the wide variability and the “predictable unpredictability” of parathyroid gland anatomy ranging from supernumerary glands and variable locations within the neck to intrathyroidal and, occasionally, ectopic sites such as those in the mediastinum. As a result of these substantial variations, the treatment of hyperparathyroidism may be complicated by recurrent or refractory disease.
Applied Anatomy and Embryology: Clinically Relevant Abnormalities
As a result of the embryologic development discussed above, parathyroid glands are often found in abnormal or ectopic locations or may be supernumerary (Fig. 1.3). The inferior parathyroids have the greatest irregularity in their position, based on their long path of descent. Ectopic inferior glands may be found in the lower pole of the thyroid lobes, or they may continue to descend with the thymus and continue into the mediastinal structures such as the thymus or thyrothymic ligament. Alternatively, the inferior parathyroid glands may fail to descend beyond the angle of the mandible or be along their proximal path of descent along or in the carotid sheath. Conversely, ectopic superior glands are usually within two centimeters of their expected location and usually found in a more dorsal position than the inferior glands; the superior glands are often found in such positions as the retropharyngeal or retroesophageal spaces (Fig. 1.3). The single most common site of missed glands in a large series was in the tracheoesophageal groove in the posterior superior mediastinum (27%). The most common ectopic sites for parathyroid adenomas are also in the thymus (17%), intrathyroidal (10%), undescended glands (8.6%), carotid sheath (3.6%), and the retroesophageal space (3.2%) .