Pseudohypoparathyroidism

Definition

The parathyroid hormone (PTH) test is a blood test performed to determine the serum levels of a hormone secreted by the parathyroid gland. The parathyroid glands are small paired glands located near the thyroid gland at the base of the neck. Most people have four glands, two on each side of the neck. PTH regulates calcium and phosphorus levels in the body. It is secreted in response to low blood ionized calcium levels, causing bone to release calcium into the blood stream. In addition, it promotes the renal reabsorption of calcium and excretion of phosphorus.

Purpose

The PTH level is measured to evaluate the cause of an abnormal serum or plasma calcium. It is routinely monitored in patients with a kidney disorder called chronic renal failure (CRF). These patients lose calcium via the kidneys which stimulates release of PTH. This can lead to bone demineralization. The PTH test is also used to distinguish between primary hyperthyroidism and malignancies that result in high ionized calcium via secretion of a protein called parathyroid hormone-related protein. This stimulates the PTH receptor of bone causing increased plasma ionized calcium. PTH is also used to distinguish between hypoparathyroidism and a condition called pseudohypoparathyroidism, which results from a poor renal response to the hormone. Persons with primary hypoparathyroidism have a low ionized calcium because the parathyroid glands fail to produce enough PTH. Persons with pseudohypoparathyroidism have a low ioninzed calcium but have a normal or elevated level of PTH.

Description

Measurement of PTH is used for the differential diagnosis of hyperparathyroidism. Primary hyperparathyroidism is most often caused by a benign tumor (adenoma) in one or more of the parathyroid glands. It is rarely caused by parathyroid malignancy. Patients with this condition have high plasma PTH and ionized calcium levels and low plasma inorganic phosphorus. Primary hyperparathyroidism is treated by surgical removal of the tumor(s). The PTH test is used to measure the plasma hormone level during surgery. Complete removal of the tumor is signaled by a return to normal plasma PTH levels.

Secondary hyperparathyroidism is often seen in patients with chronic renal failure (CRF). The kidneys fail to excrete sufficient phosphate and do not reabsorb calcium. The parathyroid gland secretes PTH in an effort to raise the plasma ionized calcium level. Because of the constant stimulation of the parathyroid, CRF patients have high PTH and normal or slightly low calcium levels.

Tertiary hyperparathyroidism occurs when CRF causes proliferation of the parathyroids that does not respond to normal suppression by ionized calcium. Patients with this condition have high plasma PTH and calcium levels and low plasma inorganic phosphorus.

Specific PTH assays

Some PTH is split into peptide fragments by enzymes in the parathyroid gland prior to being released into the blood. Therefore, in addition to intact PTH, three smaller fragments are also present, an amino or N-terminal fragment, a midregion fragment, and a carboxy or C-terminal fragment. Only the intact hormone and fragments containing the amino terminal end of the molecule are physiologically active. A two-site enzyme immunoassay was recently developed to measure PTH. This method measures only the intact PTH and active fragments and is preferred over other assays that detect the inactive fragments.

Precautions

Drug interactions

Some prescription drugs affect the results of PTH tests. Drugs that increase PTH levels include phosphates, anticonvulsants, steroids, isoniazid, lithium, and rifampin. Drugs that decrease PTH include cimetidine and propranolol.

Timing

PTH levels are subject to diurnal variation. The plasma level peaks at around 2:00 A.M. and is lowest around 2:00 P.M. Specimens are usually drawn at 8:00 A.M. The laboratory should be notified if the patient works the night shift so that this difference in biological rhythm can be taken into account.

Related blood tests

Due to the relationship between PTH and calcium, ionized calcium and inorganic phosphorus levels should be tested at the same time as PTH. In addition, creatinine and other tests of renal function are helpful in identifying those patients who have secondary hyperparathyroidism caused by renal loss of calcium.

Preparation

The PTH test is performed on a sample of the patient's blood, withdrawn from a vein. The procedure, which is called a venipuncture, takes about five minutes. When performing this procedure, the nurse or phlebotomist should follow universal precautions for the prevention of transmission of bloodborne pathogens. The patient should have nothing to eat or drink starting at midnight of the day of the test.

Complications

Risks for this test are minimal, but may include slight bleeding from the puncture site, a small bruise or swelling in the area, or fainting or feeling lightheaded.

Results

Reference ranges for PTH tests vary somewhat depending on the specificity of the antibodies used in the assay to detect the hormone. Results should always be interpreted in association with calcium results. The following ranges are typical:

• intact PTH: 10-65 pg/mL

• PTH N-terminal (includes intact PTH): 8-24 pg/mL

• PTH C-terminal (includes C-terminal, intact PTH, and midmolecule): 50-330 pg/mL.

Abnormally high PTH values may indicate primary, secondary, or tertiary hyperparathyroidism. Causes of secondary hyperparathyroidism include chronic renal failure, malabsorption syndrome, and vitamin D deficiency. Abnormally low PTH levels indicate primary hypoparathyroidism or hypercalcemia. Primary hypoparathyroidism is less common than hyperthyroidism and may result from surgical removal of the glands (during thyroidectomy) or chronic inflammatory (autoimmune) disease. Malignancies producing parathyroid hormone-related protein are common causes of low PTH induced by high ionized calcium.

Health care team roles

This test is ordered by a physician. The blood sample is collected by a nurse or phlebotomist. PTH levels are usually analyzed by clinical laboratory scientists/medical technologists. If abnormal results occur, the patient is usually referred to an endocrinologist for further evaluation and treatment.

Key Terms

Assay

An analysis of the chemical composition or strength of a substance.

Hypercalcemia

Abnormally high levels of blood calcium.

Hyperparathyroidism

Overactivity of the parathyroid glands. Symptoms include generalized aches and pains, depression, and abdominal pain.

Hypoparathyroidism

Insufficient production of parathyroid hormone, which results in low levels of blood calcium.