Intra-Operative Parathyroid Hormone Measurement

Definition
Demographic
Description
How IOPTH Measurement is Performed
IOPTH Measurement for Predicting Post-operative Hypoparathyroidism
Risks Associated with IOPTH Measurement

Definition

Intra-Operative Parathyroid Hormone (IOPTH) Measurement is a method of monitoring the blood for levels of parathyroid hormone (PTH) during surgery to remove abnormal parathyroid glands (parathyroidectomy ). The blood level of PTH drops after the abnormal parathyroid glands are removed, and indicates to the surgeon that the diseased glands have all been found

Demographic

IOPTH measurement can be done on any patient having a parathyroidectomy. This procedure is done because of one or more abnormal parathyroid glands. The surgical procedure and IOPTH measurement are usually performed on patients with parathyroid adenomas (benign tumors). Parathyroid cancer is considered extremely rare, and adenomas make up most of the demographic for IOPTH measurement during parathyroidectomy.

Description

IOPTH is measured to monitor the activity of hyperfunctional parathyroid glands during a parathyroidectomy. IOPTH measurement helps surgeons determine whether they have removed all pathological tissue (abnormal parathyroid glands).

Calcium and the Parathyroid Glands

The regulation of calcium is an important aspect of our physiology because it has significant impact on many body systems. Calcium is necessary for nervous system function. It is responsible for the electrical impulses that travel along our nerve endings. Calcium is also critical for muscle contraction, including the heart muscle. Additionally calcium stored in the bones increases their strength. Calcium levels are very tightly regulated in the body, because too much or too little may have a serious impact on health. For this reason calcium is the only mineral present in our bodies that has its own set of glands to regulate blood levels called the parathyroid glands.

The parathyroid glands are located in the neck area usually behind or within the thyroid gland. There are usually four glands located in parallel pairs around the superior and inferior portion of the trachea. There may be up to six glands in an individual, but this is unusual and only one is necessary to maintain body physiology. The glands are tiny, usually between the size of a grain of rice and a pea. Parathyroid glands are part of the body’s endocrine system, and release hormones necessary for modulation of calcium in normal physiological functioning. The sole function of the parathyroid glands is to keep calcium levels within a narrow, safe, and functional range in the blood. The parathyroid glands monitor present levels of blood calcium and use PTH to increase or decrease levels as necessary throughout the day. PTH impacts the release of calcium from the bones and the absorption of calcium back into the bones to modulate the blood level.

Normal Parathyroid Function

A normal blood calcium level is 8.4 to 10.2 mg/dl. Blood calcium levels are always kept in this narrow range by PTH. The parathyroid gland releases PTH in response to low blood calcium. Accordingly, PTH release is decreased in response to high blood calcium. PTH travels to the skeletal system and causes the release of calcium from bone, to supply the muscles and nervous system. PTH also travels to the intestine, where it influences the absorption of calcium from ingested food. A normal blood PTH level ranges from 14 to 65 pg/ml.

Abnormal Parathyroid Function

One form of abnormal parathyroid function is hyperparathyroidism. In this disorder, one or more of the parathyroid glands secretes too much PTH despite high blood calcium levels. The normal regulatory mechanisms have lost control, and calcium levels fluctuate wildly. The most common cause of hyperparathyroidism is a parathyroid adenoma. An adenoma is a benign tumor and is not cancerous. It is merely a group of cells that grows and behaves without the normal regulatory control mechanisms. Parathyroid adenomas may grow to the size of a walnut. With some parathyroid adenomas, blood levels may exceed 200 pg/ml, while others may be present with blood PTH still within the normal range. While hyperparathyroidism may present with levels of PTH within the normal range, the diseased glands do not down regulate their activity even when blood calcium levels are high. Hyperparathyroidism causes a variety of medical problems such as damage to the kidneys, liver, and skeletal system. Patients may develop kidney stones, osteoporosis, high blood pressure, depression, difficulty sleeping, fatigue, and irritability. The heart rhythm is also affected, and heart complications such as arrhythmias may ensue.

IOPTH Measurement and Scanning for Pathology

Parathyroid glands can be very difficult to locate. Approximately 85% of parathyroid glands are found behind the thyroid gland, but they can be located anywhere between the jaw and the chest (very rarely). Their variation in size, number, and location make them very difficult for surgeons to find for parathyroidectomy, with more experienced surgeons having a higher success rate. The preferred way to scan for a parathyroid adenoma is through a sestamibi scan. A sestamibi scan is a type of radioimaging used to visualize certain types of abnormal cells in the body. One of the uses for a sestamibi scan is identification of a parathyroid adenoma. Sestamibi scans identify overactive parathyroid glands rather than larger sized ones. Pre-operative identification of the abnormal gland allows for a less invasive surgical procedure than an exploratory one would have been.

While sestamibi scanning is an important part of finding the location of abnormal parathyroid glands that need parathyroidectomy, it is often coupled with IOPTH measurement for confirmation that no glands were missed during the procedure. IOPTH measurement is done during surgery because parathyroid adenomas release excessive amounts of PTH. The half-life (amount of time is takes for half the present hormone to be metabolized or excreted) of PTH is less than 5 minutes. Because it takes so little time for the hormone to be metabolized, when the original source of the PTH is taken away, the remaining PTH takes very little time to drop off. When an abnormal adenoma is removed during a parathyroidectomy, a drop in PTH is observed in 10 to 15 minutes. If the PTH does drop off, it is likely that the surgeon removed all the abnormal parathyroid tissue. If the PTH level does not drop off into the expected range, then there is an additional abnormal parathyroid gland present in the body. If an additional abnormal gland was missed during the sestamibi scan, the IOPTH measurement has identified the mistake. More invasive types of surgery may be necessary to find the remaining abnormal tissue. Since parathyroid adenomas are often singular, IOPTH measurement often prevents unnecessary exploratory surgical procedures. IOPTH measurement may be done until all the abnormal glands are found and removed.

QUESTIONS TO ASK YOUR DOCTOR

• Why do I need a parathyroidectomy?
• What symptoms do I have that are indicative of hyperparathyroidism?
• How experienced is my surgeon with this procedure?
• How often does the radiology department do sestamibi scans successfully?
• What are the chances that the IOPTH will find any abnormal glands that may have been missed in the scan?
• What are the risks associated with the procedure?

How IOPTH Measurement is Performed

IOPTH measurement is done from blood drawn during the surgical procedure, and sent it to the hospital’s lab for quick analysis. A response from the lab is called into the operating room in a timely manner, while the surgery is ongoing. The blood samples required for IOPTH assays are usually taken from an indwelling intravenous catheter. The concentration of PTH is relatively constant in most peripheral veins. Which vein the blood is drawn from does not matter, as long as the same location is used for all the blood draws. After the anesthesia is administered, the blood is tested for a baseline value of PTH to use as comparison to PTH levels after the abnormal tissue is removed. Additional blood samples are taken at 5,10, and 15 minutes post-removal. A decrease of greater than or equal to 50% of baseline within 10 to 15 minutes after removal is usually indicative of successful removal of the abnormal tissue.

IOPTH Measurement for Predicting Post-operative Hypoparathyroidism

IOPTH is also a useful tool in predicting the occurrence of symptomatic hypocalcemia following parathyroidectomy. In chronic hyperparathyroidism the normal parathyroid glands become inactive over time in response to the high levels of calcium in the blood caused by excretion of excessive of PTH from the parathyroid adenoma. When the parathyroid adenoma is removed, the remaining healthy glands do not immediately return to normal function and secretion of PTH. Because the abnormal hormone-secreting parathyroid gland has been removed and the remaining normal glands are relatively inactive, many patients experience

KEY TERMS

Adenoma— A benign tumor that may contain many uncontrolled and overly active cells, but which is not cancerous.

Catheter— A flexible tube inserted into the body to allow passage of fluids in or out.

Hyperparathyroidism— An endocrine disorder involving secretion of excessive amounts of PTH by the parathyroid gland.

Hypoparathyroidism— An endocrine disorder involving a deficiency of secretion of PTH from the parathyroid gland.

Parathyroidectomy— A surgical procedure in which one or more parathyroid glands are removed.

Radioimaging— The process of using a radioactively labeled compound to visualize specific types of body tissue.

Sestamibi— A type of radioimaging pharmaceutical compound that has been deemed medically safe to use in the human body for sestamibi scans.

a temporary state of blood calcium deficiency. Having a level of calcium in the blood that is too low is called hypocalcemia. If the levels are low enough, it can cause medically adverse effects.

To predict whether a patient will have post-operative symptomatic hypocalcemia, an IOPTH measurement is done following skin closure at the end of the surgical procedure. Studies have shown that a post-operative PTH level less than 10 pg/ml is predictive of symptomatic hypocalcemia. Patients with PTH levels this low are immediately given calcium and vitamin D supplementation. This supplementation is continued until the normal parathyroid glands return to full function. Measuring blood calcium levels after parathyroidectomy may also correlate with symptomatic hypocalcemia. However, the high levels of calcium that may be present from the excised parathyroid adenoma take longer to decrease than the PTH. Blood calcium measurement is usually not useful until 12 to 24 hours after surgery, and such a delay in calcium therapy may be detrimental. IOPTH is an effective predictive tool that has provided the necessary information before the patient leaves the operating room.

Risks Associated with IOPTH Measurement

There is very little risk associated with having blood drawn for an IOPTH measurement. Most people have no side effects from a blood draw, or a small bruise. However, with any blood draw there is a small chance that the area around the punctured vein may develop phlebitis, the inflammation of a vein. Phlebitis may also involve a bacterial infection if the site of the blood draw was not appropriately cleaned before the needle was inserted. Phlebitis can be locally painful but usually resolves in a short period of time. Additionally, patients with disorders involving the inability of the blood to form normal blood clots should discuss their condition and their medications with the physician before the procedure is done.

Resources

BOOKS

Cecil Essentials of Medicine, Sixth Edition. Saunders, Elsevier 2004.

Chaundhry H., et al. Fundamentals of Clincal Medicine. Lippincott Williams & Wilkins 2004.

Costanzo, Linda S. Physiology, Third Edition. Elsevier Health Sciences, 2006.

Harrison’s Principles of Internal Medicine, Sixteenth Edition. McGraw-Hill, 2005.

Kumar, Vinay, Nelson Fausto, and Abul Abbas. Robbins & Cotran: Pathologic Basis of Disease, Seventh Edition. Saunders, Elsevier, 2005.

Le T., et al. First Aid for the Wards. McGraw-Hill, 2003. Maxwell Quick Medical Reference, Fourth Edition. Maxwell Publishing Company 2002.

PERIODICALS

Bergson, Eric J., Laura A. Sznyter, Sanford Dubner, Christopher J. Palestro, and Keith S. Heller. “Sestamibi Scans and Intraoperative Parathyroid Hormone Measurement in the Treatment of Primary Hyperparathyroidism.” Arch Otolaryngol Head Neck Surg. 2004;130:87–91.

Yen, Tina W. F., Stuart D. Wilson, Elizabeth A. Krzywda, and Sonia L. Sugg. “The role of parathyroid hormone measurements after surgery for primary hyperparathyroidism.” Surgery 2006;140:665–74.

ORGANIZATIONS

American Academy of Otolaryngology—Head and Neck Surgery, One Prince Street, Alexandria, Virginia, 22314-3357, (703)836-4444, http://www.entnet.org/contactus.cfm.

American Association of Endocrine Surgeons, 3550 Terrace Street, Pittsburgh, Pennsylvania, 15261, (412)647-0467, (412)648-9551, http://www.endocrinesurgery.org/contact/contact.html.

Maria Basile, PhD

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