• Calcitonin is a hormone made by the thyroid gland.
• The calcitonin blood test is mainly ordered to help diagnose and manage C-cell hyperplasia or medullary thyroid cancer (MTC).
• These are two rare conditions caused by changes to certain cells inside the thyroid gland.
• These conditions cause calcitonin levels to rise.

Calcitonin is a hormone made by the thyroid, a small gland that sits at the base of the front of your neck. Calcitonin’s known role is in helping to regulate calcium levels circulating in the blood. However, in adults, calcitonin plays only a limited part in calcium control. People who have their thyroid removed, and therefore make no calcitonin, usually maintain normal calcium levels. The exact role of calcitonin is unclear and is still being studied.

The calcitonin blood test is mainly ordered to help diagnose and manage C-cell hyperplasia or medullary thyroid cancer (MTC). These are two rare conditions caused by changes to certain cells inside the thyroid gland. When these changes occur, these cells make large amounts of calcitonin.

• MTC is a rare form of thyroid cancer that originates from the C‑cells in the thyroid.
• C-cell hyperplasia is a benign (non-cancerous) condition that may or may not progress to become MTC.

The inside of the thyroid is called the medulla. It is made up of follicular cells, which take up iodine and make thyroid hormone, and cells called parafollicular C-cells, which make calcitonin.

Thyroid cancer is quite common and more than 90 percent start from thyroid follicular cells. However, MTC which makes up only about four percent of all thyroid cancers, and C-cell hyperplasia are different because they start in C-cells. These two conditions are rare.

For more on the thyroid, thyroid hormones and how they regulate many of your body functions (how fast you burn calories, your heart rate, blood pressure and body temperature) see Thyroid testing.

C-cell hyperplasia

In C-cell hyperplasia, C cells grow out of control and multiply (proliferate). This can sometimes be an early step toward medullary thyroid cancer. The cells look normal, but there are more of them. Because there are more C-cells, calcitonin levels in the blood rise.

C-cell hyperplasia can be:

• sporadic (not inherited from a parent) and due to chronic stimulation of C-cells, for example:
  • Long-term high calcium levels due to chronic kidney disease
  • Chronic thyroid disease
  • Autoimmune thyroid disease
  • Severe infections, such as sepsis
  • Certain medications such as proton pump inhibitors and GLP-1 receptor agonists (diabetes medications)
  • Ageing.
• inherited from a parent and this is seen in an inherited syndrome called MEN2 (Multiple Endocrine Neoplasia type 2) and familial medullary thyroid carcinoma (FMTC). In these settings, C-cell hyperplasia is considered an early detectable stage before cancer develops.

Medullary thyroid cancer (MTC)

Three in four cases of MTC are sporadic, meaning the cancer is acquired during a person’s lifetime and it is not inherited from a parent. About one in four cases are linked to the inherited syndrome, MEN2.

Multiple Endocrine Neoplasia type 2 (MEN2) syndrome

MEN2 is a syndrome caused by an inherited mutation (also known as a variant) in the RET gene. This syndrome is associated with several related disorders.

If your doctors suspect you may have MEN2, they may order genetic testing that focuses on the RET gene. This gene controls cell growth, and it is mutated in MEN2 syndrome. If you have the RET gene mutation (also called a variant), you can have preventive thyroid surgery to remove your thyroid gland before cancer develops.

RET gene variants are inherited in an autosomal dominant pattern. This means the altered gene can be inherited from only one parent. It does not need both parents to carry the variant and having one altered copy of the gene is enough to increase the risk of developing the cancer. Because of this, first‑degree relatives (parents, siblings, children) have a 50 percent chance of carrying the same variant and should be offered testing.

If you have a variant known to cause cancer, genetic testing will be recommended for your biological family members. Genetic testing can identify people with MEN2 before cancer develops, allowing preventive thyroid surgery in childhood in someone at high risk.

Monitoring treatment

Calcitonin testing is also used to monitor the effectiveness of treatment for MTC, and to check for recurrence.

Stimulation tests

Stimulation tests are more sensitive than calcitonin measurements alone. However, with modern high-sensitivity calcitonin assays, stimulation tests are used less often than they were in the past.

Used together with RET genetic testing, which can identify people at high risk even before calcitonin rises, calcitonin assays are very accurate.

Stimulation tests are most often used when results are uncertain or within the normal range, but clinical suspicions remain.

A stimulation test works by giving a substance that forces the C-cells to release calcitonin, then measuring how high the level rises.

• A baseline blood sample is taken to measure calcitonin.
• A stimulating drug is given intravenously.
• Blood samples are taken at several time points over a period of minutes.
• The rise in calcitonin is measured.

People with early C-cell hyperplasia or MTC will usually have significant increases in their levels of calcitonin during this test.

Other tests you may have

As well as tests that measure your levels of calcitonin you may have other types of testing, including:

• carcinoembryonic antigen (CEA). CEA levels are typically higher in people with MTC.
• Plasma and urine catecholamines and metanephrines to exclude phaeochromocytoma (a rare tumour of the adrenal gland) before surgery.
• Serum calcium and PTH to exclude primary hyperparathyroidism.

Sample

Blood.

Any preparation?

None.

Reading your test report
Your results will be presented along with those of your other tests on the same form. You will see separate columns or lines for each of these tests.

An elevated concentration of calcitonin means that excessive amounts are being produced.

With successful treatment for MTC (removal of the thyroid gland and often some surrounding tissues), calcitonin levels will usually fall to very low levels.

If levels stay low over time, then it is likely that the treatment is effective. In some cases, calcitonin levels will fall but remain moderately elevated after treatment. This means that some calcitonin-producing tissue remains. Doctors will monitor calcitonin and watch for increases over time. If calcitonin levels begin to rise, then it is likely that there is a recurrence of MTC.

Other thyroid tests, such as free T4, free T3, and TSH, are usually normal when calcitonin levels are elevated.

Significantly elevated levels of calcitonin are a good indicator of C-cell hyperplasia or MTC. However, other procedures, such as a thyroid biopsy, scan, and ultrasound, will be used to make a diagnosis.

Calcitonin levels are often used to help distinguish C-cell hyperplasia from MTC, although there is some overlap. In general, the higher the calcitonin level, the more likely it is that cancer is present.

Reference intervals - comparing your results to the healthy population

Your results will be compared to reference intervals (sometimes called a normal range).

• Reference intervals are the range of results expected in healthy people.
• They are used to provide a benchmark for interpreting a patient's test results.
• When compared against them, your results may be flagged high or low if they sit outside this range.
• Some reference intervals are harmonised or standardised, which means all labs in Australia use them.
• Others are not because for these tests, labs are using different instruments and chemical processes to analyse samples.
• Always compare your lab results to the reference interval provided on the same report.

If your results are flagged as high or low this does not necessarily mean that anything is wrong. It depends on your personal situation.

Reference intervals for calcitonin vary between laboratories so you will need to go through your results with your doctor, who will interpret the results based on the reference intervals provided by the laboratory.

The choice of tests your doctor makes will be based on your medical history and symptoms. It is important that you tell them everything you think might help.

You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely.

Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods or supplements. These may affect your results. Ask:

• Why does this test need to be done?
• Do I need to prepare (such as fast or avoid medications) for the sample collection?
• Will an abnormal result mean I need further tests?
• How could it change the course of my care?
• What will happen next, after the test?

Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.

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