Surgical anatomy of the parathyroid glands

INTRODUCTION — The parathyroid glands were first identified by Sir Richard Owen in the Great Indian Rhinoceros in 1850 [1]. They were identified in humans by Ivar Sandstrom, a Swedish medical student, in 1880 [2]. The first parathyroidectomy was reported by Felix Mandl in 1929, 30 years prior to the isolation of human parathyroid hormone [3].

The success of the surgical management of parathyroid disease is based on accurate biochemical diagnosis and the surgeon's understanding of the significant embryologic variations in parathyroid anatomy. An expert knowledge of the unusual anatomic locations for enlarged parathyroid glands is crucial to operative success during both initial and reoperative parathyroid surgical exploration. The wide range of parathyroid anatomic variations may make it difficult to predict a patient's anatomy preoperatively.

Parathyroid anatomy is discussed here. The indications for parathyroidectomy, treatment of multiglandular disease, and surgical techniques are discussed elsewhere. (See "Primary hyperparathyroidism: Management", section on 'Candidates for surgery' and "Parathyroid exploration for primary hyperparathyroidism", section on 'Focused parathyroid exploration'.)

FUNCTION — The parathyroid glands are usually in close approximation with, but function independently of, the thyroid gland. The parathyroid glands produce parathyroid hormone (PTH), which is one of the two major hormones modulating calcium and phosphate homeostasis; the other hormone is calcitriol (1,25-dihydroxyvitamin D). PTH also stimulates the conversion of calcidiol (25-hydroxyvitamin D) to calcitriol in renal tubular cells, thereby stimulating intestinal calcium absorption. The function and regulation of PTH and the diagnosis and management of hyperparathyroidism are discussed in detail elsewhere. (See "Parathyroid hormone secretion and action" and "Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation" and "Primary hyperparathyroidism: Management".)

EMBRYOLOGY — The parathyroid glands arise from endodermal epithelial cells, in conjunction with the thymus (figure 1). The superior parathyroid glands are derived from the fourth branchial pouch. These glands are closely associated with the lateral lobes of the thyroid and have a short line of embryologic descent [4].

The inferior parathyroid glands are derived from the third branchial pouch. These glands are closely associated with the thymus and have a longer line of embryologic descent, which leads to more variability in their anatomic position [4]. Inferior parathyroids can be found as high in the neck as the carotid sheath and can also be found in the anterior mediastinum or even the pericardium. However, the majority of inferior parathyroids are found near the inferior pole of the thyroid.

The locations of ectopic parathyroid glands are related to the common origins of parathyroid, thyroid, and thymic tissue. The third branchial pouch contributes to thymus development as well as parathyroid and thyroid development. Both the third and fourth branchial pouches also contribute to thyroid development. (See "Surgical anatomy of the thyroid gland".)

SIZE AND LOCATION — Normal parathyroid glands are approximately the size of a grain of rice or a lentil. Normal glands are usually approximately 5 by 4 by 2 millimeters in size and weigh 35 to 50 milligrams (picture 1). Enlarged parathyroid glands can be 50 milligrams to 20 grams in weight, most typically weighing approximately 1 gram and 1 centimeter in size (picture 2).

The appearance of parathyroid glands can vary considerably [5,6]. The color varies from light yellow to reddish brown. Most parathyroid glands (83 percent) are oval, bean shaped, or spherical, but they can also be elongated (11 percent). Other variations such as teardrop, pancake, rod-like, sausage, and leaf-shaped parathyroid glands have been described [6]. Occasionally the glands are bilobated (5 percent) or multilobated (1 percent).

Most (84 percent) patients have four parathyroid glands, two superior and two inferior glands [5]. Additional glands are found in 13 percent of patients and only three glands in a very small number of patients (≤3 percent) [5]. The terms "superior" and "inferior" refer to a gland's embryologic origin, rather than the gland's location in the neck. During parathyroid exploration, deductive reasoning based on the embryologic origin of identified parathyroid glands helps the surgeon identify missing glands (figure 2).

The parathyroids are usually in close association with the thyroid [5]. Although there is significant variability in the position of the glands, they are usually symmetric. The superior glands are symmetric in 80 percent of cases, and inferior glands are symmetric 70 percent of the time [5].

Superior parathyroid glands — Normal superior parathyroid glands are usually located on the posterior-lateral surface of the middle to superior thyroid lobe. They lie under the thyroid superficial fascia, posterior to the recurrent laryngeal nerve, and can be visualized by carefully dissecting the thyroid capsule in this region. These glands also can reside inside the thyroid capsule, just superior and medial to the posterior tubercle of Zuckerkandl of the thyroid lobe. (See "Surgical anatomy of the thyroid gland", section on 'Tubercle of Zuckerkandl'.)

The recurrent laryngeal nerve is always anterior to the superior parathyroid gland. The superior parathyroid glands are usually 1 to 2 centimeters cranial to the junction of the recurrent laryngeal nerve with the inferior thyroid artery and within 1 centimeter of the entry point for the recurrent laryngeal nerve into the ligament of Berry and the cricoid cartilage [5].

Superior parathyroid glands can be undescended or can be parapharyngeal, retropharyngeal, or retrotracheal within the middle cervical/mediastinal compartment. Enlarged parathyroid glands can travel straight down the tracheoesophageal groove or the retropharyngeal space into the chest.

Inferior parathyroid glands — The two inferior parathyroid glands reside in the anterior mediastinal compartment, anterior to the recurrent laryngeal nerve. They are most often found in the thyrothymic tract or just inside the thyroid capsule on the inferior portion of the thyroid lobes.

Ectopic parathyroid glands — Ectopic parathyroid glands occur because parathyroid tissue may co-locate with tissues that have a similar embryologic development. An ectopic parathyroid gland that fails to have full migration during normal development is termed "undescended." The ectopic gland may be one of the four parathyroid glands, or it may be a supernumerary gland. In one series of 102 patients with persistent or recurrent hyperparathyroidism who required reoperation, ectopic glands were found in the paraesophageal position (28 percent), in the mediastinum (26 percent), intrathymically (24 percent), intrathyroidally (11 percent), in the carotid sheath (9 percent), and in a high cervical position (2 percent) [7]. These percentages will vary depending whether the ectopic gland is superior or inferior in origin.

●Ectopic superior parathyroid glands – Most often, a missing superior parathyroid gland will originate in a normal position but is difficult to find because caudal growth has moved the body of the adenoma to the paraesophageal or retroesophageal space. An ectopic superior parathyroid gland may be undescended and located at the piriform sinus. Superior parathyroid glands can be also be intrathyroidal, but less commonly than inferior parathyroid glands.

●Ectopic inferior parathyroid glands – Enlarged parathyroid glands can be undescended at the carotid bulb. More typically, they will be found lateral and inferior to the middle to lower thyroid lobe adjacent to the thyrothymic tract, which extends inferiorly from the inferior thyroid poles. They may be subcapsular or completely intrathyroidal or may reside within or in close proximity to the cervical or anterior mediastinal thymus. Ectopic inferior parathyroid glands are most often found in the thymus or mediastinum (9 percent) [8]. An undescended inferior parathyroid gland may be located anywhere within the carotid sheath (2 percent). They can also be located intrathyroidally (1 percent).

Supernumerary parathyroid glands — Supernumerary (more than four) parathyroid glands occur in 2.5 to 15 percent of individuals [5,9]. The majority of supernumerary glands are small, rudimentary, or divided. However, when enlarged, these additional glands may be responsible for persistent hyperparathyroidism after failed parathyroid exploration, especially in patients with secondary hyperparathyroidism or hyperparathyroidism associated with familial syndromes [5,10,11]. In one series of 137 cases of persistent hyperparathyroidism after parathyroidectomy, supernumerary glands were found in 15 percent of cases [9]. They can range from five to eight in number [6].

Supernumerary glands can reside anywhere from behind the thyroid down to and including within the thymus, representing the line of descent of thymic tissue during embryologic development. The most common location is within the thymus or in relation to the thyrothymic ligament (two-thirds of cases) [6,11]. The remaining supernumerary glands are usually found in the vicinity of the mid-thyroid lobe between two other glands.

BLOOD SUPPLY — In most patients, the inferior and superior parathyroid glands will both be supplied by branches of the inferior thyroid artery. Each parathyroid gland usually has its own end-artery [4]. Most parathyroid glands have a single arterial supply (80 percent), some have a dual artery supply (15 percent), and a minority have multiple arterial supply (5 percent) [12]. The venous drainage of the parathyroid glands consists of the superior, middle, and inferior thyroid veins that drain into the internal jugular vein or the innominate vein. (See "Surgical anatomy of the thyroid gland", section on 'Blood supply'.)

During thyroid surgery, the surgeon should try to preserve all of the parathyroid glands in situ with adequate blood supply whenever possible. However, the blood supply may not be adequate following dissection of the thyroid gland, and the parathyroids are not always clearly identified. It can be difficult to make a reliable intraoperative determination of individual parathyroid function, and patients may experience transient hypoparathyroidism despite having all four parathyroid glands preserved.

●Superior parathyroid glands – The superior parathyroid glands receive most of their blood supply from the inferior thyroid artery and also are supplied by branches of the superior thyroid artery in 15 to 20 percent of patients. A superior parathyroid gland that is supplied by the superior thyroid artery will usually be located in close proximity to the superior pole of the thyroid. A subcapsular dissection on the posterior lateral surface can assist in the identification of parathyroid glands.

●Inferior parathyroid glands – The inferior parathyroid glands receive their end-arterial blood supply from the inferior thyroid artery. Therefore, gentle medial mobilization of the parathyroid rim from the thyroid capsule and preservation of the lateral arteriole going to the parathyroid gland are important for preserving functioning inferior parathyroid glands. Ligation of the branches of the inferior thyroid artery close to the thyroid parenchyma and medial to the recurrent laryngeal nerve may help preserve intact parathyroid vascularity.

MISSING PARATHYROID GLANDS — A missed parathyroid adenoma is the most common cause for a failed initial parathyroid operation and persistent hyperparathyroidism [13]. During exploration for primary hyperparathyroidism, understanding the embryology and anatomy of the parathyroid glands will help determine which one of the four parathyroid glands is missing or whether a supernumerary gland is present. Surgical exploration for a missed or ectopic parathyroid gland is discussed in detail elsewhere. (See "Parathyroid exploration for primary hyperparathyroidism", section on 'Surgical management'.)

SUMMARY AND RECOMMENDATIONS

●The success of the surgical management of parathyroid disease is based on accurate biochemical diagnosis and the surgeon's expert understanding of the significant embryologic variations in parathyroid anatomy. Knowledge of the unusual anatomic locations for enlarged parathyroid glands is crucial to operative success during both initial and reoperative parathyroid surgery. (See 'Introduction' above.)

●The superior parathyroid glands are derived from the fourth branchial pouch. The inferior parathyroid glands are derived from the third branchial pouch. (See 'Embryology' above.)

●Most (84 percent) individuals have four parathyroid glands, two superior and two inferior glands. The terms "superior" and "inferior" refer to a gland's embryologic origin, rather than the gland's location in the neck. During parathyroid exploration, deductive reasoning based on the embryologic origin of identified parathyroid glands helps the surgeon identify missing glands. (See 'Size and location' above.)

●Ectopic parathyroid glands occur because parathyroid tissue may co-locate with tissues that have a similar embryologic development. The ectopic gland may be one of the four parathyroid glands, or it may be a supernumerary gland. (See 'Ectopic parathyroid glands' above.)

●Supernumerary (more than four) parathyroid glands may be responsible for persistent hyperparathyroidism after failed parathyroidectomy. Supernumerary glands can reside anywhere from behind the thyroid down to and including within the thymus, representing the line of descent of thymic tissue during embryologic development. The most common location is within the thymus or in relation to the thyrothymic ligament. (See 'Supernumerary parathyroid glands' above.)

●In most patients, the inferior and superior parathyroid glands will both be supplied by branches of the inferior thyroid artery. Each parathyroid gland usually has its own end-artery. (See 'Blood supply' above.)

●A missed parathyroid adenoma is the most common cause for a failed initial parathyroid operation and persistent hyperparathyroidism. Understanding the embryology and anatomy of the parathyroid glands will help determine which one of the four parathyroid glands is missing or if it is a supernumerary gland. (See "Parathyroid exploration for primary hyperparathyroidism", section on 'Missing gland'.)