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The parathyroid glands are a group of endocrine glands located on the posterior thyroid. These glands are responsible for the secretion of parathyroid hormone (PTH), and play a role in calcium homeostasis. Typically, there are four glands divided into pairs - the superior parathyroid glands and the inferior parathyroid glands. The superior parathyroids generally are located superior to the inferior thyroid artery and posterolaterally to the recurrent laryngeal nerve, bilaterally. The inferior parathyroids are most commonly near the inferior pole of the thyroid and anteromedially to the recurrent laryngeal nerve, bilaterally. Branches of the inferior thyroid artery deliver arterial blood supply. Venous drainage is via the thyroid veins (superior, middle, inferior).[1] The number and location of the parathyroid glands can be variable, with patients presenting with anywhere from three to eight parathyroid glands. Ectopic glands generally appear along the path of embryologic descent, within the carotid sheath, inside the thyroid gland, or within the superior mediastinum.[2] Embryologically, the parathyroid glands derive from the endoderm of the third and fourth pharyngeal pouches. The third pharyngeal pouch gives rise to the inferior parathyroid glands, while the superior parathyroids arise from the fourth pharyngeal pouch. Due to their relatively long course of descent, the final location of the inferior glands is more variable.

Hyperparathyroidism Primary Hyperparathyroidism [14] - This occurs when 1+ parathyroid glands secrete PTH autonomously, regardless of serum calcium levels. This condition is often discovered incidentally on routine labs, with mild elevations in serum calcium. Occasionally, patients can present with symptoms of hypercalcemia.[15] The most common cause is a parathyroid adenoma (approximately 85% of cases), followed by parathyroid hyperplasia (about 15%) and parathyroid carcinoma (less than 1%).[16] Typically, parathyroid adenomas affect a single gland (but can be multiple in rare cases), while parathyroid hyperplasia is multi-glandular. In primary hyperparathyroidism, both serum calcium and PTH are elevated. Secondary hyperparathyroidism - occurs most frequently in patients with chronic renal failure. Impaired renal function leads to an inability to reabsorb calcium or excrete phosphate properly. Potentially compounding this is a failure to activate vitamin D, further disrupting calcium homeostasis. Other, less common causes include severe vitamin D deficiency, malabsorption syndromes, and inadequate sun exposure. In secondary hyperparathyroidism, serum PTH is elevated, but serum calcium is low-normal to decreased. Tertiary Hyperparathyroidism - Most commonly occurs when hyperplastic parathyroid glands in secondary hyperparathyroidism patients begin to secrete PTH autonomously. This condition is often discovered when the chronic process causing secondary disease has resolved, e.g., in a renal transplant patient with a persistent increase in PTH. Lab results in tertiary hyperparathyroidism mimic primary hyperparathyroidism, with increases in both PTH and serum calcium. Hypoparathyroidism [17] - This can occur secondary to a variety of causes, most commonly following head/neck surgery, but can also occur due to abnormal parathyroid development, severe hypomagnesemia, autoimmune destruction of the parathyroids and other causes. This condition most commonly presents with symptoms of hypocalcemia, including perioral paresthesias, tetany/muscle cramps, and Chvostek's sign (facial muscle spasm in response to mechanical stimulation).[18][19] In patients receiving bilateral thyroidectomy, low intraoperative PTH levels can be a good predictor for postoperative hypocalcemia.[20]

Hypoparathyroidism [17] - This can occur secondary to a variety of causes, most commonly following head/neck surgery, but can also occur due to abnormal parathyroid development, severe hypomagnesemia, autoimmune destruction of the parathyroids and other causes. This condition most commonly presents with symptoms of hypocalcemia, including perioral paresthesias, tetany/muscle cramps, and Chvostek's sign (facial muscle spasm in response to mechanical stimulation).[18][19] In patients receiving bilateral thyroidectomy, low intraoperative PTH levels can be a good predictor for postoperative hypocalcemia.[20] DiGeorge Syndrome  [21] - a development defect caused by a microdeletion at 22q11, which can lead to a failure of the development of the third and fourth pharyngeal pouches, affecting the thymus and parathyroid glands. Poor thymic development leads to abnormal immune system development and deficiencies in T-cells. Improper parathyroid gland development leads to hypocalcemia. Patients with DiGeorge Syndrome can also present with congenital cardiac defects (particularly of the outflow tracts), abnormal facial development, and cleft palates. Multiple Endocrine Neoplasia - a rare, genetically inherited syndrome, leading to proliferative lesions in various endocrine organs. There are several forms defined by the genes involved, but all have an autosomal dominant inheritance pattern. MEN 1 [22] - Aka Wermer syndrome, this syndrome results from a mutation in the MEN1 tumor suppressor gene on chromosome 11. Approximately 90% of cases are inherited, and 10% are due to random mutation. This mutation can lead to lesions of the '3 Ps' - the parathyroids, pancreas, and pituitary. The most common parathyroid lesion is an adenoma. Pancreatic tumors are most commonly gastrinomas, but insulinomas and glucagonomas can also present. Pituitary adenomas most commonly secrete prolactin. MEN 2A [23] - Aka Sipple syndrome, this syndrome results from a mutation in the RET oncogene, a tyrosine-kinase localized to chromosome 10q11. MEN 2A can also affect the parathyroids, but more commonly causes parathyroid hyperplasia than adenomas. This syndrome also presents with medullary thyroid carcinoma and pheochromocytoma;100% of patients with (+) RET mutation will develop medullary thyroid cancer in their lifetime, so prophylactic thyroidectomy is the recommendation.

MEN 2A [23] - Aka Sipple syndrome, this syndrome results from a mutation in the RET oncogene, a tyrosine-kinase localized to chromosome 10q11. MEN 2A can also affect the parathyroids, but more commonly causes parathyroid hyperplasia than adenomas. This syndrome also presents with medullary thyroid carcinoma and pheochromocytoma;100% of patients with (+) RET mutation will develop medullary thyroid cancer in their lifetime, so prophylactic thyroidectomy is the recommendation. MEN 2B [23] - This also results from a mutation in the RET oncogene, located at chromosome 10q11. MEN 2B can lead to medullary thyroid carcinoma, pheochromocytomas, similarly to MEN2A. It can also present with marfanoid body habitus and mucosal neuromas of the skin, oral mucosa, and intestines. 100% of patients with (+) RET mutation will develop medullary thyroid cancer in their lifetime, so here again, the recommendation is for prophylactic thyroidectomy.