The ParathyroidsThe Parathyroids

Functional AnatomyFunctional Anatomy

Are characteristically located Are characteristically located adjacent and posterior to the thyroid adjacent and posterior to the thyroid gland.gland.

Most individuals have 4 parathyroid Most individuals have 4 parathyroid glands (80-90%), 2 on each side.glands (80-90%), 2 on each side.

Functional AnatomyFunctional Anatomy

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

Functional AnatomyFunctional Anatomy

The paired inferior glands arise from the The paired inferior glands arise from the third branchial pouch along with the third branchial pouch along with the thymus (parathymus gland), migrate thymus (parathymus gland), migrate further, and thus are more likely to be further, and thus are more likely to be found in ectopic locations such as the found in ectopic locations such as the anterior mediastinum.anterior mediastinum.

Other potential sites include intrathyroid, Other potential sites include intrathyroid, posterior mediastinum, central posterior mediastinum, central compartment of neck.compartment of neck.

Arterial Supply and Arterial Supply and DrainageDrainage

All the glands are supplied by the inferior All the glands are supplied by the inferior thyroid artery. Occasionally, the superior thyroid artery. Occasionally, the superior glands are supplied by the superior thyroid glands are supplied by the superior thyroid artery.artery.

Venous drainage is via the superior, Venous drainage is via the superior, middle and inferior thyroid veins.middle and inferior thyroid veins.

The superior,middle thyroid veins drain The superior,middle thyroid veins drain directly into the IJ. The inferior into the directly into the IJ. The inferior into the innominate.innominate.

PTH FunctionsPTH Functions

Secreted in response to calcium Secreted in response to calcium levels, not under pituitary control.levels, not under pituitary control.

Increased mobilization of calcium Increased mobilization of calcium and phosphate from bone by and phosphate from bone by increasing osteoclastic activity.increasing osteoclastic activity.

Directly promotes active calcium Directly promotes active calcium reabsorption in distal nephron.reabsorption in distal nephron.

PTH FunctionsPTH Functions

Directly inhibits phosphate Directly inhibits phosphate reabsorption in proximal tubule.reabsorption in proximal tubule.

Stimulates 1,25 dihydroxyvitamin D Stimulates 1,25 dihydroxyvitamin D and increasing gut absorption of and increasing gut absorption of calcium and phosphorus.calcium and phosphorus.

Causes of Primary Causes of Primary HyperparathyroidismHyperparathyroidism

Excessive, abnormally regulated Excessive, abnormally regulated secretion of PTH, resulting in secretion of PTH, resulting in hypercalcemia.hypercalcemia.

Peaks between ages of 50-60, with a Peaks between ages of 50-60, with a female:male ration of 3:1.female:male ration of 3:1.

A small percentage have a history of A small percentage have a history of radiation exposure as a child.radiation exposure as a child.

Etiology and PathologyEtiology and Pathology

AdenomasAdenomas, single in 80-85% of , single in 80-85% of patients.patients.

2-4% incidence of multiple 2-4% incidence of multiple adenomas.adenomas.

Histologically, a proliferation in chief Histologically, a proliferation in chief cells in a single focus with a cells in a single focus with a compressed rim of surrounding compressed rim of surrounding normal tissue.normal tissue.

Etiology and PathologyEtiology and Pathology

Diffuse hyperplasiaDiffuse hyperplasia of all 4 glands of all 4 glands occurs in 15% of patients.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 Histologically diffuse chief cell hyperplasia

is seen with cords or sheets of chief cells.is seen with cords or sheets of chief cells. Parathyroid carcinomaParathyroid carcinoma occurs in 0.5- occurs in 0.5-

1.0% of patients.1.0% of patients.

Causes of HypercalcemiaCauses of Hypercalcemia

MalignancyMalignancy Primary hyperparathyroidismPrimary hyperparathyroidism Familial hypocalciuric hypercalcemiaFamilial hypocalciuric hypercalcemia ImmobilizationImmobilization Granulomatous disease, Addisons diseaseGranulomatous disease, Addisons disease Vitamin D and A excessVitamin D and A excess Milk-Alkali syndromeMilk-Alkali syndrome Drugs- thiazides, lithiumDrugs- thiazides, lithium

Clinical ManifestationsClinical Manifestations

Most are asymptomatic.Most are asymptomatic. Symptoms are related to the Symptoms are related to the

magnitude and rate of rise.magnitude and rate of rise. Hypercalcemia of malignancy is often Hypercalcemia of malignancy is often

associated with a rapid rise and is associated with a rapid rise and is frequently symptomatic.frequently symptomatic.

Clinical ManifestationsClinical Manifestations

Neuromuscular: confusion, fatigue, Neuromuscular: confusion, fatigue, coma, lethargy, weakness, coma, lethargy, weakness, depression, apathy.depression, apathy.

Renal: Stones most common Renal: Stones most common manifestation of primary manifestation of primary hyperparathyroidism.hyperparathyroidism.

Clinical ManifestationsClinical Manifestations

Cardiovascular: HTN, short QT, heart Cardiovascular: HTN, short QT, heart block.block.

Skeletal: Bone pain, radiographic evidence Skeletal: Bone pain, radiographic evidence (1-2%) is uncommon. Subperiosteal (1-2%) is uncommon. Subperiosteal resorption middle phalanx of 2-3 finger. resorption middle phalanx of 2-3 finger. Salt and pepper pattern on skull x-ray.Salt and pepper pattern on skull x-ray.

GI: Nausea, vomiting, anorexia, GI: Nausea, vomiting, anorexia, constipation, PUD, pancreatitis.constipation, PUD, pancreatitis.

DiagnosisDiagnosis

Hypercalcemia and elevated PTH, Hypercalcemia and elevated PTH, >60mEq/mL are hallmarks of primary >60mEq/mL are hallmarks of primary hyperparathyroidism.hyperparathyroidism.

True hypercalcemia is characterized True hypercalcemia is characterized by decreased ionized calcium level, by decreased ionized calcium level, which accurately reflect functional which accurately reflect functional extracellular calcium levels despite extracellular calcium levels despite hypoalbuminemia.hypoalbuminemia.

DiagnosisDiagnosis

For every 1 mg/dL drop in serum For every 1 mg/dL drop in serum albumin, total serum calcium drops albumin, total serum calcium drops 0.8mg/dL.0.8mg/dL.

Hypophosphatemia occurs in 35% of Hypophosphatemia occurs in 35% of patients.patients.

DiagnosisDiagnosis

Elevated urinary cAMP and urinary Elevated urinary cAMP and urinary calcium may be present in 35%.calcium may be present in 35%.

Preoperative localization with Preoperative localization with ultrasound or nuclear medicine is ultrasound or nuclear medicine is rarely indicated for primary disease, rarely indicated for primary disease, but frequently needed for but frequently needed for reoperation.reoperation.

Treatment of Primary Treatment of Primary HyperparathyroidismHyperparathyroidism

Surgery is the only definitive Surgery is the only definitive treatment of symptomatic disease.treatment of symptomatic disease.

Cure rate is 90-95% at initial Cure rate is 90-95% at initial operation.operation.

Treatment of Primary Treatment of Primary HyperparathyroidismHyperparathyroidism

Location and number of glands may Location and number of glands may be highly variable.be highly variable.

To rule out lesions in multiple glands, To rule out lesions in multiple glands, bilateral neck exploration may be bilateral neck exploration may be required, with identification of all 4 required, with identification of all 4 glands.glands.

Treatment of Primary Treatment of Primary HyperparathyroidismHyperparathyroidism

To confirm the presence or absence of To confirm the presence or absence of parathyroid tissue, FS should be parathyroid tissue, FS should be performed.performed.

FS is not helpful in differentiating normal FS is not helpful in differentiating normal from diseased tissue, only that it is gland.from diseased tissue, only that it is gland.

Intraoperative measurement of venous Intraoperative measurement of venous PTH also being done to confirm removal of PTH also being done to confirm removal of functional parathyroid lesion.functional parathyroid lesion.

Treatment of AdenomasTreatment of Adenomas

Single or multiple enlarged glands Single or multiple enlarged glands are removed leaving normal glands.are removed leaving normal glands.

If only three normal glands are If only three normal glands are identified, after a thorough identified, after a thorough exploration, ipsilateral thyroidectomy exploration, ipsilateral thyroidectomy is often performed on the side of the is often performed on the side of the missing gland.missing gland.

In In this settingthis setting 96% are intrathyroidal. 96% are intrathyroidal.

Multiglandular HyperplasiaMultiglandular Hyperplasia

Subtotal parathyroidectomy, or 3.5 Subtotal parathyroidectomy, or 3.5 glands removed.glands removed.

Total parathyroidectomy, is followed Total parathyroidectomy, is followed by auto transplantation of gland by auto transplantation of gland fragments to the nondominant fragments to the nondominant forearm or sternocleidomastoid. forearm or sternocleidomastoid. Makes reoperation for recurrence Makes reoperation for recurrence easier.easier.

Permanent hypoparathyroidism in 5%.Permanent hypoparathyroidism in 5%.

Persistent or Recurrent Persistent or Recurrent DiseaseDisease

Occurs in less than 5% post op.Occurs in less than 5% post op. Related to a single diseased gland Related to a single diseased gland

remaining in the neck.remaining in the neck. Recurrent disease often related to Recurrent disease often related to

regrowth of diseased tissue, regrowth of diseased tissue, inadvertent microscopic implantation inadvertent microscopic implantation during resection, parathyroid cancer during resection, parathyroid cancer must be part of differential.must be part of differential.

Preoperative LocalizationPreoperative Localization

Recommended for Recommended for recurrentrecurrent disease. disease. Adhesions make reoperation more Adhesions make reoperation more

difficult.difficult. Ectopic location of gland more likely Ectopic location of gland more likely

in this setting.in this setting.

Preoperative LocalizationPreoperative Localization

US, CT& MRI (great for ectopic US, CT& MRI (great for ectopic adenomas, deeper structures, adenomas, deeper structures, mediastinum), Technetium-99m-mediastinum), Technetium-99m-Sestamibi scan.Sestamibi scan.

Invasive localization with selective Invasive localization with selective angiography, venous sampling with angiography, venous sampling with measurement of PTH can be measurement of PTH can be combined with angiography.combined with angiography.

Surgical ReexplorationSurgical Reexploration

60-80% success rate.60-80% success rate. Increased risk of complications; nerve Increased risk of complications; nerve

injury 5-10%, hypoparathyroidism 10-injury 5-10%, hypoparathyroidism 10-20%.20%.

Median sternotomy and mediastinal Median sternotomy and mediastinal exploration is necessary in 1-2%.exploration is necessary in 1-2%.

The superior parathyroids may be The superior parathyroids may be posterior to the esophagus and as superior posterior to the esophagus and as superior as the pharynx.as the pharynx.

Secondary Secondary HyperparathyroidismHyperparathyroidism

A consequence of chronic renal A consequence of chronic renal failure.failure.

These patients are unable to These patients are unable to synthesize the active form of vitamin synthesize the active form of vitamin D, which results in hypocalcemia and D, which results in hypocalcemia and a compensatory elevation of PTH.a compensatory elevation of PTH.

Secondary Secondary HyperparathyroidismHyperparathyroidism

Untreated patients become symptomatic Untreated patients become symptomatic with bone demineralization, calcification of with bone demineralization, calcification of soft tissues, accelerated vascular soft tissues, accelerated vascular calcification, pruritis, painful skin calcification, pruritis, painful skin ulcerations from calcium deposition in skin ulcerations from calcium deposition in skin “calciphylaxis”.“calciphylaxis”.

Treatment is medical with dialysis with Treatment is medical with dialysis with high calcium baths, phosphate binding high calcium baths, phosphate binding antacids, calcium supplements.antacids, calcium supplements.

Surgical treatment is rarely indicated.Surgical treatment is rarely indicated.

Tertiary Tertiary HyperparathyroidismHyperparathyroidism

Associated with hypercalcemia and Associated with hypercalcemia and elevated PTH levels.elevated PTH levels.

Persistent disease in patients with Persistent disease in patients with secondary hyperparathyroidism despite secondary hyperparathyroidism despite renal transplant secondary to renal transplant secondary to dysregulated parathyroid function.dysregulated parathyroid function.

Treatment often requires surgical Treatment often requires surgical resection with subtotal parathyroidectomy.resection with subtotal parathyroidectomy.

Parathyroid CancerParathyroid Cancer

Younger, equal male:female ration Younger, equal male:female ration when compared to adenomas.when compared to adenomas.

More frequently symptomatic, with More frequently symptomatic, with elevated PTH, calcium and alkaline elevated PTH, calcium and alkaline phosphatase.phosphatase.

Capsular invasion, angioinvasion on Capsular invasion, angioinvasion on path.path.

Parathyroid CancerParathyroid Cancer

Often adherent to adjacent Often adherent to adjacent structures.structures.

Treatment is resection of the Treatment is resection of the involved gland, ipsilateral thyroid involved gland, ipsilateral thyroid lobe, regional lymph nodes.lobe, regional lymph nodes.

Recurrence is 50%, prognosis poor, Recurrence is 50%, prognosis poor, chemoradiation of no benefit.chemoradiation of no benefit.