To determine the cause of calcium imbalances; to evaluate parathyroid function; to diagnose and differentiate between primary, secondary, and tertiary hyperparathyroidism; to diagnose hypoparathyroidism; during surgery for hyperparathyroidism to confirm removal of the gland(s) causing the problem
Parathyroid Hormone (PTH)
When calcium blood levels are higher or lower than normal; when you are having surgery for hyperparathyroidism; when your healthcare practitioner wants to determine how well your parathyroid glands are functioning
A blood sample drawn from a vein in your arm
Current practices do not require fasting. PTH levels peak during sleep hours and are lowest during mid-morning to late afternoon hours, the period when most samples are drawn. There may be seasonal fluctuations in PTH due to its inverse relationship with vitamin D. Talk to your healthcare practitioner about sample timing.
Parathyroid hormone (PTH) helps the body maintain stable levels of calcium in the blood. It is part of a feedback loop that includes calcium, PTH, vitamin D, and, to some extent, phosphorus (phosphate) and magnesium. Conditions and diseases that disrupt this feedback loop can cause inappropriate elevations or decreases in calcium and PTH levels and lead to symptoms of hypercalcemia or hypocalcemia. This test measures the amount of PTH in the blood.
PTH is produced by four button-sized parathyroid glands that are located in the neck behind the thyroid gland. Normally, these glands secrete PTH into the bloodstream in response to low blood calcium levels. The hormone works in three ways to help raise blood calcium levels back to normal (two are direct and one is indirect):
- PTH directly promotes the release of calcium from bones into the bloodstream.
- It directly acts on the kidneys to reduce the elimination of calcium in the urine while promoting the elimination of phosphorus in the urine.
- The indirect effect stimulates the kidneys to convert vitamin D from the inactive to the active form, which in turn increases the absorption of calcium from food in the intestines.
As calcium levels begin to increase in the blood, PTH normally decreases.
Parathyroid hormone itself is composed of 84 amino acids (sometimes called PTH (1-84)). Intact and fragmented hormone is present in and secreted by the parathyroid gland. The intact hormone represents a smaller fraction, but its portion is increased when calcium levels are low and decreased when calcium levels are high.
Once released into the bloodstream, PTH has a very short life span; levels fall by half in less than 5 minutes due to uptake and cleavage in the liver and kidneys. The fragments are referred to as C-terminal fragments and are variably sized, missing anywhere from 6 amino acids to more than half the N-terminal portion of the molecule. C-terminal fragments have a longer half-life, exist in much higher concentrations, and are eventually cleared by the kidneys.
Although it was originally thought that the C-terminal fragments were inactive, it now appears that certain fragments may have biologic activities that are able to oppose those of intact PTH.
- How is it used?
The so-called intact PTH is the most frequently ordered parathyroid hormone test. It is used to help diagnose the cause of a low or high calcium level and to help distinguish between parathyroid-related and non-parathyroid-related causes. It may also be used to monitor the effectiveness of treatment when an individual has a parathyroid-related condition. PTH is routinely monitored for people with chronic kidney disease or who are on dialysis.
A calcium test is almost always ordered along with a PTH test. It is not just the level in the blood that is important but the balance between calcium and PTH and the response of the parathyroid glands to changing levels of calcium. Usually, healthcare practitioners are concerned about either severe imbalances in calcium regulation that may require medical intervention or persistent imbalances that indicate an underlying problem.
PTH levels can be used to monitor people who have conditions or diseases that cause chronic calcium imbalances or to monitor those who have had surgery or another treatment for a parathyroid tumor.
- When is it ordered?
A PTH test may be ordered when a test for calcium is abnormal. It may be ordered when someone has symptoms associated with increased calcium, such as:
- Abdominal pain
PTH may also be ordered when a person has symptoms associated with decreased calcium, such as:
- Abdominal pain
- Muscle cramps
- Tingling fingers or toes
A healthcare practitioner may order a PTH test along with a calcium test at intervals when someone has been treated for a disease or condition that affects calcium regulation, such as the removal of a parathyroid tumor, or when a person has end-stage renal disease.
Sometimes, an intraoperative PTH test will be ordered when someone who has hyperparathyroidism is undergoing surgery to have abnormal parathyroid tissue removed to ensure removal of all of the abnormal glands, which can occasionally vary in number and location.
- What does the test result mean?
A healthcare practitioner will evaluate both calcium and PTH results together to determine whether the levels are appropriate and are in balance as they should be. If both PTH and calcium levels are normal, then it is likely that the body's calcium regulation system is functioning properly.
Low levels of PTH may be due to conditions causing increased calcium or to an abnormality in PTH production causing hypoparathyroidism.
Excess PTH secretion may be due to hyperparathyroidism, which is most frequently caused by a benign parathyroid tumor. In rare cases, it may be caused by cancer.
The table below summarizes results that may be seen:
Calcium PTH Interpretation Normal Normal Calcium regulation system functioning normally Low High PTH is responding correctly; may run other tests to check for other causes of decreased calcium Low Normal or Low PTH not responding correctly; probably have hypoparathyroidism and secondary hypocalcemia High High Parathyroid gland producing too much PTH; may do imaging studies to check for hyperparathyroidism High Low PTH is responding correctly; may run other tests to check for non-parathyroid-related causes of elevated calcium Normal High Mild hyperparathyroidism
Calcium - PTH Relationship
- If calcium levels are low and PTH levels high, then the parathyroid glands are responding appropriately, producing appropriate amounts of PTH. Depending on the degree of hypocalcemia, a healthcare practitioner may investigate a low calcium level further by measuring vitamin D, phosphorus, and magnesium levels.
- If calcium levels are low and PTH levels are normal or low, then PTH is not responding properly and the person tested probably has hypoparathyroidism. Hypoparathyroidism is a failure of the parathyroid glands to produce sufficient PTH. It may be due to a variety of conditions and may be persistent, progressive, or transient. Causes include an autoimmune disorder, parathyroid damage or removal during surgery, a genetic condition, or a severe illness. Those affected will generally have low PTH levels, low calcium levels, and high phosphorus levels.
- If calcium levels are high and PTH levels are high, then the parathyroid glands are producing inappropriately high amounts of PTH. A healthcare practitioner may order X-rays or other imaging studies to help determine the cause and evaluate the severity of hyperparathyroidism. Hyperparathyroidism is a group of conditions characterized by an overproduction of PTH by the parathyroid glands that is separated into primary, secondary, and tertiary hyperparathyroidism. (See Parathyroid Diseases for more on this.)
- If calcium levels are high and PTH levels are low, then the parathyroid glands are responding properly, but a healthcare practitioner is likely to perform further investigations to check for non-parathyroid-related reasons for the elevated calcium, such as rare mutations in calcium receptors or tumors that secrete a peptide that has PTH-like activity and increases calcium concentration, which in turn decreases PTH.
- Is there anything else I should know?
Currently, the most prevalent assay for PTH is the intact PTH assay, which typically measures the whole molecule (PTH 1-84) and the larger fragments (predominantly PTH 1-74). While this assay is known as the "intact" assay, it measures large fragments that are slightly smaller than the truly intact hormone. There are less common but newer assays that detect only the whole molecule, which has the greatest bioactivity. The "intact" and "whole or bioactive" assays have different reference ranges, but typically their results yield similar interpretations. The effects of fragmentation and disease are still being studied, and there are instances when the two assays may yield a different interpretation.
Drugs that may increase PTH levels include phosphates, anticonvulsants, steroids, isoniazid, lithium, and rifampin.
Parathyroid cancers may be associated with familial hyperparathyroidism and MEN- I syndromes.
- Can I have an abnormal PTH level without having symptoms?
Yes, if your calcium level changes slowly, you may not have any noticeable symptoms. In this case, the imbalance will most likely be detected by finding an abnormal calcium level during a regular health check, then checking your PTH level.
- What does vitamin D have to do with PTH?
If you do not have enough vitamin D, your body will not be able to absorb calcium properly. Vitamin D regulates the intestinal absorption of calcium, while PTH regulates the activation of vitamin D. Too much or too little vitamin D can cause an imbalance in calcium metabolism. During winter months with less sun exposure, especially further from the equator, vitamin D levels are typically lower and PTH levels may therefore be higher. Diet and illness may affect the magnitude of these changes.
- What is intraoperative PTH and why is it done?
An "intraoperative PTH" is a PTH test done on a person while that person is undergoing parathyroid gland surgery. When someone has hyperparathyroidism, the usual treatment is surgery to remove an enlarged parathyroid gland or glands. About 85-90% of the time in primary hyperparathyroidism, only one abnormal parathyroid gland is present, but in the remaining cases (and in secondary and tertiary hyperparathyroidism), two or more of the glands are abnormal.
During surgery, it is important for the surgeon to make sure that all of the abnormal glands have been removed. If all are abnormal, typically three glands are completely removed along with part of the fourth, leaving behind just enough parathyroid tissue to prevent hypoparathyroidism.
One way to be sure that all of the abnormal tissue has been removed is to measure PTH before and after a suspected abnormal gland has been removed. If all of the abnormal tissue is gone, PTH levels will fall by over 50% within 10 minutes. To be useful, this requires that the laboratory be able to provide the test results quickly. This is often called rapid or intraoperative PTH measurement.
- What other tests could be useful in assessing PTH?
Other testing may include:
- Total and ionized calcium
- Phosphorus (phosphate)
- Vitamin D (25-(OH) vitamin D and 1,25-(OH)2 vitamin D)