PTH

What is being tested?
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 increases or decreases in calcium and PTH levels and lead to symptoms of hypercalcaemia or hypocalcaemia.

PTH is produced by four parathyroid glands located in the neck behind the thyroid. Normally these glands secrete PTH into the bloodstream in response to low blood calcium levels. Parathyroid hormone then works in three ways to help raise blood calcium levels back to normal. It releases calcium from the bones, stimulates the activation of vitamin D in the kidneys (which in turn increases calcium absorption by the intestine) and suppresses the excretion of calcium in the urine (while encouraging the excretion of phosphate). As calcium levels in the blood start to rise, PTH normally falls.

Parathyroid hormone itself is made up of 84 amino acids (sometimes called PTH (1-84)). Once released from the parathyroid gland into the bloodstream, it has a very short life: levels fall by half in less than 5 minutes. This fall is caused mainly by the breakdown of PTH into smaller fragments, mainly PTH (35-84) and PTH (7-84). Although these fragments were once thought to be inactive, they are in fact active but act differently from PTH (1-84). These fragments (especially PTH (7-84)) seem to do the opposite of PTH: they lower serum calcium and prevent calcium from being removed from bone.

How is it used?
When is it requested?
What does the test result mean?
Is there anything else I should know?

How is it used?
PTH is requested to help diagnose the reasons for a high or low calcium level and to help distinguish between parathyroid and non-parathyroid causes. It may also be requested to monitor the effectiveness of treatment when a patient has a parathyroid condition. PTH is requested together with calcium. It is not only the blood levels that matter, but the balance between them and the response of the parathyroid glands to changes in calcium levels. Doctors are usually concerned either about severe imbalances in calcium regulation, which may require medical intervention, or about persistent imbalances that point to an underlying problem.

High calcium levels, called hypercalcaemia, may be due to hyperparathyroidism, a group of conditions characterised by overproduction of PTH by the parathyroid glands. Hyperparathyroidism is classified as primary, secondary or tertiary. Primary hyperparathyroidism is in most cases due to a parathyroid tumour (usually benign) that secretes PTH without feedback control. This keeps PTH permanently switched on, which can cause hypercalcaemia and kidney stones, calcium deposits in organs and bone loss. With this type of hyperparathyroidism, patients usually have high calcium and PTH levels, while phosphate levels are often low. Secondary hyperparathyroidism is usually due to kidney failure. In patients with kidney disease and/or kidney failure, phosphate may not be excreted efficiently, upsetting its balance with calcium. Kidney disease can also prevent the patient from producing the active form of vitamin D, which means they will not be able to absorb calcium from the diet properly. As phosphate levels rise and calcium levels fall, PTH is secreted. Secondary hyperparathyroidism can also be caused by any other condition that lowers calcium, such as calcium malabsorption due to intestinal disease and vitamin D deficiency. In secondary hyperparathyroidism, patients usually have high PTH levels and low or normal calcium levels. Sometimes people with secondary hyperparathyroidism develop high serum calcium while also having high PTH; this is sometimes called tertiary hyperparathyroidism.

Low calcium levels, called hypocalcaemia, may be due to hypoparathyroidism, i.e. the inability of the parathyroid gland to produce enough PTH. Hypoparathyroidism can be due to a variety of conditions and can be persistent, progressive or temporary. Causes include autoimmune disorders, damage to the parathyroid glands or their surgical removal, genetic conditions and serious illnesses. Affected patients usually have low PTH and calcium levels and also high phosphate levels.

When is it requested?
PTH may be requested when a calcium test is abnormal. It may also be requested when there are symptoms of hypercalcaemia, such as tiredness, nausea, abdominal pain and thirst. It is also requested when there are symptoms of hypocalcaemia, such as abdominal pain, muscle cramps and tingling in the fingers. The doctor may request PTH, together with calcium, from time to time when a patient has been treated for diseases or conditions affecting calcium regulation, such as removal of a parathyroid tumour, or when there is a chronic condition such as kidney disease.

When a person has hyperparathyroidism, the usual treatment is surgery to remove the enlarged gland or glands. In about 85-90% of cases of primary hyperparathyroidism, only one parathyroid gland is abnormal, but in the remaining cases two or more glands are abnormal. In secondary hyperparathyroidism, all four parathyroid glands are usually affected. During surgery, it is important for the surgeon to make sure that all abnormal glands have been removed. If all are abnormal, this usually means removing three glands completely and part of the fourth, leaving just enough parathyroid tissue to prevent hypoparathyroidism. One way to make sure all abnormal tissue has been removed is to measure PTH before and after an apparently abnormal gland is removed. If all the abnormal tissue has been removed, PTH levels will fall by more than 50% within 10 minutes. For this to be useful, the laboratory must be able to provide results quickly (this is known as rapid or intraoperative PTH measurement).

What does the test result mean?
The doctor will decide whether calcium and PTH levels are in balance as they should be. If both levels are normal, the body’s calcium regulation system is probably working properly.

Low PTH levels may be due to conditions that cause hypercalcaemia, or to a problem with PTH production that causes hypoparathyroidism. Excess PTH secretion may be due to hyperparathyroidism, which is very often caused by a benign parathyroid tumour.

Calcium–PTH relationship

If calcium levels are low and PTH levels are high, the parathyroid glands are responding as they should and are producing appropriate amounts of PTH. Depending on the degree of hypocalcaemia, the doctor may investigate the low calcium further by measuring vitamin D, phosphorus and magnesium levels.
If calcium levels are low and PTH levels are normal or low, PTH is not responding and the cause is probably hypoparathyroidism.
If calcium levels are high and PTH levels are also high, the parathyroid glands are producing inappropriate amounts of PTH. The doctor may order X-rays or other imaging tests to check the cause and severity of the hyperparathyroidism.
If calcium levels are high and PTH levels are low, the parathyroid glands are responding appropriately, but the doctor will probably investigate further to look for non-parathyroid causes of the high calcium level.

Is there anything else I should know?
Because there are many PTH fragments, PTH tests may measure one or more fragments. None of the intact PTH assays measures PTH (35-84), which is actually the PTH fragment present in the greatest amount in the blood. Many intact PTH assays also measure PTH (7-84). In most people this fragment is present in much smaller amounts than PTH (1-84), so this is not a problem. In kidney failure, a common reason for measuring PTH levels, PTH (7-84) levels increase relative to PTH (1-84), and sometimes more than half of what is measured as PTH is this fragment. Some PTH assays (often called “bio-intact” or “PTH (1-84)” tests) do not measure this fragment. There is currently no clear evidence that tests that do not measure PTH (7-84) fragments are actually more useful for patients with kidney failure than tests that measure both PTH (1-84) and PTH (7-84); however, results are always lower with tests that measure only PTH (1-84).

PTH levels vary during the day, peaking at around 2 a.m. Samples are usually taken at around 8 a.m.

Medicines that can increase PTH levels include phosphates, anticonvulsants, steroids, isoniazid, lithium and rifampicin.

1. Can I have an abnormal PTH level without having symptoms?
2. What does vitamin D have to do with PTH?

1. Can I have an abnormal PTH level without having symptoms?
Yes. If the calcium level changes slowly, you may have no noticeable symptoms. In this case, the imbalance will most likely be discovered when an abnormal calcium level is found during a routine check-up, followed by a PTH test.

2. 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. Excess or deficiency of vitamin D can upset calcium metabolism.