The Parathyroids

Functional Anatomy Are characteristically located adjacent and posterior to the thyroid gland. Are characteristically located adjacent and posterior to the thyroid gland. Most individuals have 4 parathyroid glands (80-90%), 2 on each side. Most individuals have 4 parathyroid glands (80-90%), 2 on each side.

Functional Anatomy The paired superior glands arise from the 4 th branchial pouch in close proximity to the origin of the thyroid gland. The paired superior glands arise from the 4 th branchial pouch in close proximity to the origin of the thyroid gland.

Functional Anatomy The paired inferior glands arise from the third branchial pouch along with the thymus (parathymus gland), migrate further, and thus are more likely to be found in ectopic locations such as the anterior mediastinum. The paired inferior glands arise from the third branchial pouch along with the thymus (parathymus gland), migrate further, and thus are more likely to be found in ectopic locations such as the anterior mediastinum. Other potential sites include intrathyroid, posterior mediastinum, central compartment of neck. Other potential sites include intrathyroid, posterior mediastinum, central compartment of neck.

Arterial Supply and Drainage All the glands are supplied by the inferior thyroid artery. Occasionally, the superior glands are supplied by the superior thyroid artery. All the glands are supplied by the inferior thyroid artery. Occasionally, the superior glands are supplied by the superior thyroid artery. Venous drainage is via the superior, middle and inferior thyroid veins. Venous drainage is via the superior, middle and inferior thyroid veins. The superior,middle thyroid veins drain directly into the IJ. The inferior into the innominate. The superior,middle thyroid veins drain directly into the IJ. The inferior into the innominate.

PTH Functions Secreted in response to calcium levels, not under pituitary control. Secreted in response to calcium levels, not under pituitary control. Increased mobilization of calcium and phosphate from bone by increasing osteoclastic activity. Increased mobilization of calcium and phosphate from bone by increasing osteoclastic activity. Directly promotes active calcium reabsorption in distal nephron. Directly promotes active calcium reabsorption in distal nephron.

PTH Functions Directly inhibits phosphate reabsorption in proximal tubule. Directly inhibits phosphate reabsorption in proximal tubule. Stimulates 1,25 dihydroxyvitamin D and increasing gut absorption of calcium and phosphorus. Stimulates 1,25 dihydroxyvitamin D and increasing gut absorption of calcium and phosphorus.

Causes of Primary Hyperparathyroidism Excessive, abnormally regulated secretion of PTH, resulting in hypercalcemia. Excessive, abnormally regulated secretion of PTH, resulting in hypercalcemia. Peaks between ages of 50-60, with a female:male ration of 3:1. Peaks between ages of 50-60, with a female:male ration of 3:1. A small percentage have a history of radiation exposure as a child. A small percentage have a history of radiation exposure as a child.

Etiology and Pathology Adenomas, single in 80-85% of patients. Adenomas, single in 80-85% of patients. 2-4% incidence of multiple adenomas. 2-4% incidence of multiple adenomas. Histologically, a proliferation in chief cells in a single focus with a compressed rim of surrounding normal tissue. Histologically, a proliferation in chief cells in a single focus with a compressed rim of surrounding normal tissue.

Etiology and Pathology Diffuse hyperplasia of all 4 glands occurs in 15% of patients. Diffuse hyperplasia of all 4 glands occurs in 15% of patients. May be associated with MEN 1 in 25-35%. May be associated with MEN 1 in 25-35%. Histologically diffuse chief cell hyperplasia is seen with cords or sheets of chief cells. Histologically diffuse chief cell hyperplasia is seen with cords or sheets of chief cells. Parathyroid carcinoma occurs in % of patients. Parathyroid carcinoma occurs in % of patients.

Causes of Hypercalcemia Malignancy Malignancy Primary hyperparathyroidism Primary hyperparathyroidism Familial hypocalciuric hypercalcemia Familial hypocalciuric hypercalcemia Immobilization Immobilization Granulomatous disease, Addisons disease Granulomatous disease, Addisons disease Vitamin D and A excess Vitamin D and A excess Milk-Alkali syndrome Milk-Alkali syndrome Drugs- thiazides, lithium Drugs- thiazides, lithium

Clinical Manifestations Most are asymptomatic. Most are asymptomatic. Symptoms are related to the magnitude and rate of rise. Symptoms are related to the magnitude and rate of rise. Hypercalcemia of malignancy is often associated with a rapid rise and is frequently symptomatic. Hypercalcemia of malignancy is often associated with a rapid rise and is frequently symptomatic.

Clinical Manifestations Neuromuscular: confusion, fatigue, coma, lethargy, weakness, depression, apathy. Neuromuscular: confusion, fatigue, coma, lethargy, weakness, depression, apathy. Renal: Stones most common manifestation of primary hyperparathyroidism. Renal: Stones most common manifestation of primary hyperparathyroidism.

Clinical Manifestations Cardiovascular: HTN, short QT, heart block. Cardiovascular: HTN, short QT, heart block. Skeletal: Bone pain, radiographic evidence (1- 2%) is uncommon. Subperiosteal resorption middle phalanx of 2-3 finger. Salt and pepper pattern on skull x-ray. Skeletal: Bone pain, radiographic evidence (1- 2%) is uncommon. Subperiosteal resorption middle phalanx of 2-3 finger. Salt and pepper pattern on skull x-ray. GI: Nausea, vomiting, anorexia, constipation, PUD, pancreatitis. GI: Nausea, vomiting, anorexia, constipation, PUD, pancreatitis.

Diagnosis Hypercalcemia and elevated PTH, >60mEq/mL are hallmarks of primary hyperparathyroidism. Hypercalcemia and elevated PTH, >60mEq/mL are hallmarks of primary hyperparathyroidism. True hypercalcemia is characterized by decreased ionized calcium level, which accurately reflect functional extracellular calcium levels despite hypoalbuminemia. True hypercalcemia is characterized by decreased ionized calcium level, which accurately reflect functional extracellular calcium levels despite hypoalbuminemia.

Diagnosis For every 1 mg/dL drop in serum albumin, total serum calcium drops 0.8mg/dL. For every 1 mg/dL drop in serum albumin, total serum calcium drops 0.8mg/dL. Hypophosphatemia occurs in 35% of patients. Hypophosphatemia occurs in 35% of patients.

Diagnosis Elevated urinary cAMP and urinary calcium may be present in 35%. Elevated urinary cAMP and urinary calcium may be present in 35%. Preoperative localization with ultrasound or nuclear medicine is rarely indicated for primary disease, but frequently needed for reoperation. Preoperative localization with ultrasound or nuclear medicine is rarely indicated for primary disease, but frequently needed for reoperation.

Treatment of Primary Hyperparathyroidism Surgery is the only definitive treatment of symptomatic disease. Surgery is the only definitive treatment of symptomatic disease. Cure rate is 90-95% at initial operation. Cure rate is 90-95% at initial operation.

Treatment of Primary Hyperparathyroidism Location and number of glands may be highly variable. Location and number of glands may be highly variable. To rule out lesions in multiple glands, bilateral neck exploration may be required, with identification of all 4 glands. To rule out lesions in multiple glands, bilateral neck exploration may be required, with identification of all 4 glands.

Treatment of Primary Hyperparathyroidism To confirm the presence or absence of parathyroid tissue, FS should be performed. To confirm the presence or absence of parathyroid tissue, FS should be performed. FS is not helpful in differentiating normal from diseased tissue, only that it is gland. FS is not helpful in differentiating normal from diseased tissue, only that it is gland. Intraoperative measurement of venous PTH also being done to confirm removal of functional parathyroid lesion. Intraoperative measurement of venous PTH also being done to confirm removal of functional parathyroid lesion.

Treatment of Adenomas Single or multiple enlarged glands are removed leaving normal glands. Single or multiple enlarged glands are removed leaving normal glands. If only three normal glands are identified, after a thorough exploration, ipsilateral thyroidectomy is often performed on the side of the missing gland. If only three normal glands are identified, after a thorough exploration, ipsilateral thyroidectomy is often performed on the side of the missing gland. In this setting 96% are intrathyroidal. In this setting 96% are intrathyroidal.

Multiglandular Hyperplasia Subtotal parathyroidectomy, or 3.5 glands removed. Subtotal parathyroidectomy, or 3.5 glands removed. Total parathyroidectomy, is followed by auto transplantation of gland fragments to the nondominant forearm or sternocleidomastoid. Makes reoperation for recurrence easier. Total parathyroidectomy, is followed by auto transplantation of gland fragments to the nondominant forearm or sternocleidomastoid. Makes reoperation for recurrence easier. Permanent hypoparathyroidism in 5%. Permanent hypoparathyroidism in 5%.

Persistent or Recurrent Disease Occurs in less than 5% post op. Occurs in less than 5% post op. Related to a single diseased gland remaining in the neck. Related to a single diseased gland remaining in the neck. Recurrent disease often related to regrowth of diseased tissue, inadvertent microscopic implantation during resection, parathyroid cancer must be part of differential. Recurrent disease often related to regrowth of diseased tissue, inadvertent microscopic implantation during resection, parathyroid cancer must be part of differential.

Preoperative Localization Recommended for recurrent disease. Recommended for recurrent disease. Adhesions make reoperation more difficult. Adhesions make reoperation more difficult. Ectopic location of gland more likely in this setting. Ectopic location of gland more likely in this setting.

Preoperative Localization US, CT& MRI (great for ectopic adenomas, deeper structures, mediastinum), Technetium-99m-Sestamibi scan. US, CT& MRI (great for ectopic adenomas, deeper structures, mediastinum), Technetium-99m-Sestamibi scan. Invasive localization with selective angiography, venous sampling with measurement of PTH can be combined with angiography. Invasive localization with selective angiography, venous sampling with measurement of PTH can be combined with angiography.

Surgical Reexploration 60-80% success rate % success rate. Increased risk of complications; nerve injury 5- 10%, hypoparathyroidism 10-20%. Increased risk of complications; nerve injury 5- 10%, hypoparathyroidism 10-20%. Median sternotomy and mediastinal exploration is necessary in 1-2%. Median sternotomy and mediastinal exploration is necessary in 1-2%. The superior parathyroids may be posterior to the esophagus and as superior as the pharynx. The superior parathyroids may be posterior to the esophagus and as superior as the pharynx.

Secondary Hyperparathyroidism A consequence of chronic renal failure. A consequence of chronic renal failure. These patients are unable to synthesize the active form of vitamin D, which results in hypocalcemia and a compensatory elevation of PTH. These patients are unable to synthesize the active form of vitamin D, which results in hypocalcemia and a compensatory elevation of PTH.

Secondary Hyperparathyroidism Untreated patients become symptomatic with bone demineralization, calcification of soft tissues, accelerated vascular calcification, pruritis, painful skin ulcerations from calcium deposition in skin “calciphylaxis”. Untreated patients become symptomatic with bone demineralization, calcification of soft tissues, accelerated vascular calcification, pruritis, painful skin ulcerations from calcium deposition in skin “calciphylaxis”. Treatment is medical with dialysis with high calcium baths, phosphate binding antacids, calcium supplements. Treatment is medical with dialysis with high calcium baths, phosphate binding antacids, calcium supplements. Surgical treatment is rarely indicated. Surgical treatment is rarely indicated.

Tertiary Hyperparathyroidism Associated with hypercalcemia and elevated PTH levels. Associated with hypercalcemia and elevated PTH levels. Persistent disease in patients with secondary hyperparathyroidism despite renal transplant secondary to dysregulated parathyroid function. Persistent disease in patients with secondary hyperparathyroidism despite renal transplant secondary to dysregulated parathyroid function. Treatment often requires surgical resection with subtotal parathyroidectomy. Treatment often requires surgical resection with subtotal parathyroidectomy.

Parathyroid Cancer Younger, equal male:female ration when compared to adenomas. Younger, equal male:female ration when compared to adenomas. More frequently symptomatic, with elevated PTH, calcium and alkaline phosphatase. More frequently symptomatic, with elevated PTH, calcium and alkaline phosphatase. Capsular invasion, angioinvasion on path. Capsular invasion, angioinvasion on path.

Parathyroid Cancer Often adherent to adjacent structures. Often adherent to adjacent structures. Treatment is resection of the involved gland, ipsilateral thyroid lobe, regional lymph nodes. Treatment is resection of the involved gland, ipsilateral thyroid lobe, regional lymph nodes. Recurrence is 50%, prognosis poor, chemoradiation of no benefit. Recurrence is 50%, prognosis poor, chemoradiation of no benefit.