Parathyroid hormone

PTH is requested to help diagnose the reason for a low or high calcium level, to help distinguish between parathyroid-related and non-parathyroid-related causes. It may also be ordered to monitor the effectiveness of treatment when a patient has a parathyroid-related condition. PTH is ordered along with calcium. It is not just the levels in the blood that are important, but the balance between them and the response of the parathyroid glands to changing levels of calcium. Usually doctors are concerned about either severe imbalance in calcium regulation that may require medical intervention, or in persistent imbalances that indicate an underlying problem.

High blood calcium levels, called hypercalcaemia, may be due to hyperparathyroidism, a group of conditions characterised by an overproduction of PTH by the parathyroid gland. Hyperparathyroidism is separated into primary and secondary hyperparathyroidism.

Primary hyperparathyroidism is most frequently due to a parathyroid tumour (usually benign), that secretes PTH without feedback control. This puts PTH constantly in the ‘ON’ position, where it can cause hypercalcaemia, and can lead to kidney stones, calcium deposits in organs and decalcification of bone. With primary hyperparathyroidism, patients will generally have high calcium and high PTH levels, while phosphate levels are often low.

Secondary hyperparathyroidism is usually due to kidney failure. In patients with kidney disease and/or failure, phosphate may not be excreted efficiently, disrupting its balance with calcium. Kidney disease may also make the patient unable to produce the active form of vitamin D and this in turn means that they are unable to absorb calcium properly from the diet. As phosphate levels build up and calcium levels fall, PTH is secreted.

Secondary hyperparathyroidism can also be caused by any other condition that causes low calcium, such as malabsorption of calcium due to intestinal disease and vitamin D deficiency. With secondary hyperparathyroidism, patients will generally have high PTH levels and low or normal calcium levels. Sometimes, patients with secondary hyperparathyroidism develop a high blood calcium and still have high PTH levels; this is sometimes called tertiary hyperparathyroidism.

Low blood calcium levels, called hypocalcaemia, may be due to hypoparathyroidism, where there is a failure of the parathyroid gland to produce PTH. Magnesium is required  for correct functioning of PTH, so low magnesium can be associated with hypocalcaemia. Hypoparathyroidism 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 thyroid surgery, a genetic condition, and severe illnesses. Affected patients will generally have low PTH levels and low calcium levels and will also have high phosphate levels.

PTH levels can also be used to monitor patients who have conditions or diseases that cause chronic calcium imbalances, and to monitor those who have had surgery or other treatment for parathyroid tumours.

Calcium should be monitored at the same time as PTH: it is not just the levels in the blood that are important, but the balance between the two, and the response of the parathyroid to changing levels of calcium. Usually doctors are concerned about either severe imbalances in calcium metabolism (that may require medical intervention) or in persistent imbalances (that indicate an underlying problem).

PTH may be requested when a test for calcium is abnormal. PTH may be requested when you have symptoms associated with hypercalcaemia, such as tiredness (fatigue), nausea, abdominal pain (stomach ache) and thirst. PTH may also be requested when you have symptoms associated with hypocalcaemia, such as abdominal pain, muscle cramps and tingling fingers. Your doctor may request a PTH, along with calcium (and other tests) at intervals when you have been treated for diseases or conditions that affect calcium regulation, such as the removal of a parathyroid tumour or when you have a chronic condition such as kidney disease.

When a person has hyperparathyroidism, the usual treatment is surgery to remove the enlarged gland or glands. About 85-90% of the time in primary hyperparathyroidism, only one abnormal parathyroid gland is present, but in the remaining cases two or more of the glands is abnormal. In secondary hyperparathyroidism, usually all four of the parathyroid glands are affected. During surgery, it is important for the surgeon to make sure that they have removed all of the abnormal glands. If all are abnormal, this usually means removing three glands completely and 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 an apparently abnormal gland has been removed. If all 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 results quickly (this is often called rapid or intraoperative PTH measurement).

Your doctor will determine whether calcium and PTH concentrations 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 hypercalcaemia 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 tumour

Calcium - PTH relationship

• If calcium levels are low and PTH levels high, then the parathyroid glands are responding as they should and producing appropriate amounts of PTH. Depending on the degree of hypocalcaemia, your doctor may investigate the low calcium further by looking at your vitamin D, phosphate and magnesium levels.
• If calcium levels are low and PTH levels are normal or low, then PTH is not responding and you probably have hypoparathyroidism
• If calcium levels are high and PTH levels are high, then your parathyroid gland is producing inappropriate amounts of PTH and your doctor may request X-rays or other imaging studies to check for the cause and severity of hyperparathyroidism.
• If calcium levels are high and PTH levels are low, then your calcium regulation system is working normally but your doctor will do further investigation to check for non-parathyroid related reasons for your elevated calcium.

	PTH	Interpretation
Normal	Normal	Calcium regulation system functioning OK
Low	High	PTH is responding correctly: may run other tests to check hypocalcaemia
Low	Normal/Low	PTH not responding correctly: probably have hypoparathyroidism
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 reasons for elevated calcium

• If calcium levels are low and PTH levels are 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 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 tansient. 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. Hyperparathryoidism is a group of conditions characterised 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 tumours that secrete a peptide that has PTH-like activity and increases calcium concentration, which in turn decreases PTH.

About Reference Intervals

'Intact’ PTH is broken down by the body (metabolised) into several molecular fragments and tests for PTH may measure one or more of these fragments. None of the assays for intact PTH measure PTH (35-84), which is actually the fragment of PTH present in highest amounts in blood. Many intact PTH assays measure PTH (7-84) as well. In most people, this fragment is present in much lower amounts than PTH (1-84), so this is not a concern.

In kidney failure, a common setting for measuring PTH levels, PTH (7-84) levels increase compared to PTH (1-84), and sometimes over half of what is measured as PTH represents this fragment. Some PTH assays (often called ‘biointact’ or ‘PTH (1-84)’ tests) do not measure this fragment. There is no clear evidence at present that tests that do not measure PTH (7-84) fragments actually are more helpful in kidney failure patients than tests that measure both PTH (1-84) and PTH (7-84), however, results are always lower with the tests that measure only PTH (1-84).

PTH levels will vary during the day, peaking at about 2 am. Specimens are usually taken at about 8 am and are generally collected with a fasting serum calcium level.

Drugs that may increase PTH levels include: phosphates, anticonvulsants, steroids, isoniazid, lithium, and rifampin.
Drugs that may decrease PTH include cimetidine and propranolol.

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 by checking your PTH level.

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 and too little vitamin D can cause calcium metabolism imbalances.