(Study type: Blood collected in a gold-, red-, or red/gray-top tube; related body system: Endocrine system. The specimen should be promptly transported to the laboratory for processing and analysis. The sample should be placed in an ice slurry immediately after collection. Information on the specimen label should be protected from water in the ice slurry by first placing the specimen in a protective plastic bag.)

There are four parathyroid glands located near or embedded in tissue at the back of the thyroid gland. Parathyroid hormone (PTH) is secreted by the parathyroid glands in response to changes in circulating levels of calcium. PTH regulates calcium levels in a complex feedback cycle of interactions also involving phosphorus and vitamin D. Therefore, interpretation of PTH testing is commonly performed in conjunction with serum calcium (total), creatinine (related to identifying kidney dysfunction as the cause of hypercalcemia), phosphorus (decreased in the presence of hypercalcemia often associated with primary hyperparathyroidism), and vitamin D (related to vitamin D deficiency often associated with primary hyperparathyroidism). A 24-hr urine calcium level may be requested to help distinguish primary hyperparathyroidism from familial hypocalciuric hypercalcemia (autosomal dominant inheritance pattern), which is a disorder of the kidney’s calcium-sensing receptors that can mimic primary hyperparathyroidism. Some laboratories have developed nomograms using total calcium and intact PTH, vitamin D and intact PTH, or one that combines all three variables. The nomograms are used to distinguish normal findings from atypical combinations of findings that point to a diagnosis of primary hyperparathyroidism. For additional information regarding regulation of calcium levels via feedback cycles also involving calcitonin, calcium, and phosphorus, refer to the studies titled “Calcitonin”; “Calcium, Blood, Total and Ionized and Urine”; “Phosphorus, Blood and Urine”; and “Vitamin Studies.”

Intact PTH is the form of PTH normally measured. In healthy individuals, intact PTH has a circulating half-life of about 5 min. N-terminal PTH has a circulating half-life of about 2 min and is found in minute quantities. Intact and N-terminal PTH are the only biologically active forms of the hormone. Ninety percent of circulating PTH is composed of inactive C-terminal and midregion fragments. PTH is cleared from the body by the kidneys. Patients who are diagnosed with primary hyperparathyroidism are usually scheduled for parathyroidectomy of a single parathyroid adenoma (in most cases). There are a number of different imaging modes used to preoperatively identify the target site and to assist intraoperatively during removal of the parathyroid gland of interest. For additional information regarding imaging and surgical removal (parathyroidectomy), refer to the study titled “Parathyroid Scan.” A 50% decrease or more in postoperative (30 min) PTH from baseline measurements can predict successful treatment.

A rapid PTH assay has been developed specifically for intraoperative monitoring of PTH in the surgical treatment of primary hyperparathyroidism. Rapid PTH assays have proved valuable because the decision whether the hyperparathyroidism involves one or multiple glands depends on measurement of circulating PTH levels. Surgical outcomes indicate that a 50% decrease or more in intraoperative (10 min) PTH from baseline measurements can predict successful treatment with up to 97% accuracy. An intraoperative decrease of less than 50% indicates the need to identify and remove additional malfunctioning parathyroid tissue.

Normal PTH response to low calcium level

PTH assists in regulating serum calcium (and phosphorus) levels by

• Enhancing production of active vitamin D (calcitriol) metabolites by the kidney, which increases absorption of calcium and phosphate in the small intestine
• Promoting renal tubular reabsorption of calcium and increased excretion of phosphate
• Stimulating the release of calcium and phosphate from bone into the bloodstream

Normal PTH response to high calcium level

Increased blood calcium and vitamin D levels initiate a negative feedback loop by signaling the parathyroid glands to stop release of PTH.

Hyperparathyroidism

Dysfunction of one or more parathyroid glands results in unregulated overproduction of PTH that leads to hypercalcemia and hypophosphatemia. There are three types of hyperparathyroidism:

• Primary hyperparathyroidism: oversecretion of PTH characterized by hypercalcemia and hypophosphatemia and related development of abdominal and bone pain, depression, formation of kidney stones, and polyuria. More common in females than males. Approximately 85% to 90% of cases are related to adenoma in a single gland; 10% to 15% are related to adenoma involving multiple glands; cancerous tumors of the parathyroids are rare.
• Secondary hyperparathyroidism: chronic oversecretion of PTH secondary to hypocalcemia; generally the result of vitamin D deficiency or chronic kidney disease.
• Tertiary hyperparathyroidism: development of excessive autonomous PTH secretion, often involving all four glands. Etiology is not well understood, but tertiary hyperparathyroidism is observed in patients with unresolved secondary hyperparathyroidism who have been on kidney dialysis for years or in patients with hyperparathyroidism that continues following kidney transplantation. Many patients with tertiary hyperparathyroidism have normal blood calcium levels and remain hypercalcemic after cessation of calcium and vitamin D therapy.

Hypoparathyroidism

Hypoparathyroidism is a relatively rare condition marked by PTH deficiency. It is also the natural result when the parathyroid glands are surgically removed.