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eMedicine Specialties > Radiology > Head/Neck

Parathyroid Adenoma

, Staff Physician, Staff Physician, Department of Radiology, Harbor Medical Center, University of California at Los Angeles
Fred S Mishkin, MD, Professor of Radiology in Residence, University of California at Los Angeles School of Medicine; Director, Division of Nuclear Medicine, UCLA-Harbor Medical Center; Panukorn Vasinrapee, MD, Assistant Clinical Professor of Radiology, University of California at Los Angeles School of Medicine; Associate Chief, Nuclear Medicine, Department of Radiology, Harbor-UCLA Medical Center

Updated: Mar 5, 2010

Introduction

Background

Primary hyperparathyroidism (HPT) is a condition characterized by an inappropriate excess of parathyroid hormone (PTH) secretion. The elevated PTH levels result in hypercalcemia and hypophosphatemia. Primary HPT is caused by parathyroid adenoma in 80-85% of patients, by multiple parathyroid adenomas in 2-3%, by parathyroid hyperplasia in 10-15%, and by parathyroid carcinoma in 2-3% of patients.[1 ]

For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education article Thyroid Problems.

Recent studies

Powell et al measured results and outcomes in patients who underwent reoperations for persistent or recurrent sporadic parathyroid adenoma. Reoperation resulted in long-term resolution of hypercalcemia in 92%. Adenomas were in entopic locations in 32%, and the most frequent ectopic location was the thymus (20%). Sestamibi scanning and ultrasonography were the most successful noninvasive imaging studies (positive predictive value, 96% and 84%, respectively). In 44% of patients, reoperation was based solely on noninvasive imaging. Of invasive procedures, arteriography resulted in the best localization (positive predictive value, 92%). Permanent recurrent laryngeal nerve injury occurred in 1.8%.[2 ]

Kandil et al evaluated intact PTH (iPTH) baseline levels in patients undergoing parathyroid surgery for primary HPT to determine effect on severity and outcome. A total of 304 patients had baseline iPTH values of at least 150 pg/mL (high baseline group), and 143 patients had baseline iPTH values lower than 150 pg/mL (low baseline group). Patients in the high baseline group had higher baseline levels of serum calcium, serum alkaline phosphatase, and parathyroid adenoma weights and lower serum 25-hydroxyvitamin D levels. Sestamibi scans were more likely to localize an adenoma in the high baseline group (83.7%) than in the low baseline group (68.9%). However, despite a lower rate of positive preoperative sestamibi scans for the low baseline group, these patients had a similar rate of disease cure as patients with higher baseline levels. Therefore, according to the authors, baseline iPTH levels should not be used as a criterion to perform parathyroidectomy in patients with primary HPT.[3 ]

Tublin et al evaluated the use of sonography alone, versus sonography and technetium-99m sestamibi SPECT, for parathyroid localization before minimally invasive parathyroidectomy. Parathyroidectomy was performed in 144 of 172 patients evaluated by both modalities. The sensitivity, specificity, and positive predictive value of sonography in identifying abnormal parathyroid glands were 74%, 96%, and 90%, respectively. In 112 of 144 patients (78%), sonography correctly localized a single adenoma or suggested multiglandular disease. The sensitivity, specificity, and positive predictive value of SPECT were 58%, 96%, and 89%. SPECT correctly predicted an adenoma or multiglandular disease in 88 of 144 patients (61%). SPECT identified uniglandular disease in 5 patients with negative sonographic findings. The authors concluded that elective use of Tc-99m sestamibi SPECT (ie, when sonographic findings are negative or equivocal) would have decreased the cost of imaging by 53%.[4 ]

Pathophysiology

The primary function of the parathyroid glands is to help regulate calcium homeostasis by producing PTH in response to hypocalcemia. PTH stimulates bone resorption, which in turn releases calcium. In primary HPT, excess PTH release results in hypercalcemia. Hypercalcemia is believed to be responsible for the clinical manifestations of the disease.

Frequency

United States

Primary HPT affects approximately 1 person per 500-1000 population.[5 ]

Mortality/Morbidity

  • Most patients with primary HPT present with asymptomatic hypercalcemia.
  • Common clinical presentations are believed to result from bone resorption and high serum concentrations of calcium. Common findings include nephrolithiasis, bone pain, arthralgias, muscular aches, peptic ulcer disease, pancreatitis, fatigue, depression, anxiety, and other mental disturbances.
  • The symptoms can be remembered with the following expression: stones, bones, groans, and psychic overtones.

Sex

  • Primary HPT is 2-4 times more common in women than in men.
  • Clark and Duh estimated that 1 woman in 500 and 1 man in 2000 older than 40 years are affected by this entity.[6 ]

Age

  • Primary HPT most commonly affects middle-aged adults; it is rare in children.
  • Reportedly, 1 woman in 500 and 1 man in 200 who are older than 40 years have primary HPT.[6 ]

Anatomy

Most individuals (83%) have 4 parathyroid glands: 2 superior glands and 2 inferior glands. Akerstrom et al report that approximately 13% of individuals have more than 4 glands, and 3% have only 3 glands.

Normal glands are encapsulated, soft, ovoid, yellowish-white organs surrounded by fat. According to Higgins, each gland measures approximately 5 X 3 X 1 mm and weighs approximately 40 mg. Glands receive most of their blood supply from branches of the paired inferior thyroid arteries. The paired superior thyroid arteries, thyroidea ima artery, and branches of the laryngeal and tracheoesophageal arteries may also supply the parathyroid glands.

Embryologically, the superior parathyroid glands are derived from the fourth pharyngeal pouch, and the inferior parathyroid glands are derived from the third pharyngeal pouch. The inferior thyroid glands develop in conjunction with the thymus and usually descend into the lower neck with the thymus. Most commonly, the superior parathyroid glands come to lie posterior to the upper-mid pole of the thyroid glands, and the inferior parathyroid glands usually lie on the anterolateral or posterolateral surface of the lower thyroid pole.

Akerstrom et al reported ectopic parathyroid glands in 20% of patients.[7 ]The inferior parathyroid glands tend to be more variable and ectopic. They can be found anywhere along the thymus line of descent.

Notable ectopic locations for the inferior parathyroid glands include the following: (1) near the hyoid bone, (2) within the carotid sheath, (3) superior to the thyroid gland, (4) intrathyroidal, (5) intrathymic, and (6) mediastinal.

Common ectopic locations for the superior parathyroid glands include the following: (1) tracheoesophageal groove, (2) retroesophageal space, (3) carotid sheath, and (4) posterosuperior mediastinum.

Presentation

Common clinical presentations include nephrolithiasis, bone pain, arthralgias, muscular aches, peptic ulcer disease, pancreatitis, fatigue, depression, anxiety, and other mental disturbances.

Preferred Examination

Indications for imaging

Imaging studies should be performed only after the diagnosis of primary HPT is established on the basis of biochemical findings. In patients with primary HPT who have not undergone previous neck surgery, preoperative localization imaging is controversial. Experienced surgeons have a 90-95% cure rate in patients with primary HPT who undergo neck exploration for the first time, as Salti reported.[8 ]

Shaha et al describe the following patients in whom preoperative imaging studies are warranted[9 ]:

  • Asymptomatic patients with mild hypercalcemia
  • Patients in hypercalcemic crisis in whom urgent diagnosis is needed
  • Patients with associated malignancies
  • Obese patients with short necks
  • Patients with cervical spinal problems in whom neck extension may be difficult
  • Patients with associated palpable thyroid abnormalities
  • High-risk patients in whom operative time is crucial or in whom local anesthesia must be used

Levin and Clark reported that the most common reasons for missed parathyroid glands during surgery are the presence of multiple abnormal glands, ectopic parathyroid glands, and surgical inexperience.[10 ]These are additional reasons for the use of preoperative localization studies.

In general, preoperative localization studies should be performed in patients who have undergone unsuccessful neck exploration, in contrast to patients who have not. Surgical success rates with repeat exploration are significantly lower than those with primary surgery.

Available imaging studies

Several noninvasive and invasive studies are available. Noninvasive studies include scintigraphy, ultrasonography (US), CT, and MRI. Perform the noninvasive studies first.

If the findings of the noninvasive studies are equivocal or nondiagnostic, perform the invasive procedures, such as parathyroid selective arteriography and/or selective parathyroid venous sampling. Currently, the preferred examination is dual-phase scintigraphy with the radiopharmaceuticals technetium Tc 99m sestamibi or technetium Tc 99m tetrofosmin.

Limitations of Techniques

One limitation common to all noninvasive and invasive studies is their low sensitivity in detecting small parathyroid adenomas. Limitations of each study are discussed in the following relevant sections.

Differential Diagnoses

Thyroid Nodules

Other Problems to Be Considered

Hyperplastic parathyroid gland
Parathyroid carcinoma
Thyroid nodules
Enlarged lymph nodes
Sarcoid granulomas
Neurofibromas
Other neck masses

Computed Tomography

Findings

A typical CT protocol for assessing parathyroid adenomas involves the acquisition of contiguous axial 2- to 3-mm images with a small field of view from the hyoid bone down to the carina, after the intravenous (IV) administration of contrast material. Nonenhanced images can also be obtained.

Prior to the IV administration of contrast material, parathyroid adenomas have an attenuation similar to that of muscle. Parathyroid adenomas tend to be hypervascular structures with variable contrast enhancement, as Cates et al described.[11 ]An enlarged, enhancing soft-tissue mass near the expected location of the parathyroid glands is considered to represent a parathyroid adenoma.

The disadvantages of CT include the following: (1) The use of ionizing radiation is required. (2) Intravenous administration of contrast material is required, and this injection is accompanied by associated risks. (3) Streak artifacts may be present at the thoracic inlet. (4) Previously placed surgical clips may cause metallic artifacts.

Degree of Confidence

In several reports, the sensitivity of CT in detecting parathyroid adenomas is 40-90%.

False Positives/Negatives

Cates et al describe some pitfalls of CT imaging.[11 ]False-positive findings may occur if a thyroid nodule, tortuous vessel, or laterally displaced esophagus is misidentified as an abnormal parathyroid gland.

False-negative findings result from small or ectopic parathyroid glands, poor visualization of neck structures as a result of streak artifact or distorted neck anatomy due to prior surgery, and misinterpretation of a parathyroid adenoma for a thyroid nodule. Also, thyroid goiters can obscure parathyroid adenomas.

Magnetic Resonance Imaging

Findings

MRI protocol

A typical MRI protocol involves the acquisition of axial images through the neck and mediastinum. Coronal and sagittal views can also be acquired. A Helmholtz-design surface neck coil is used to image the neck, and a torso phased-array ECG-gated coil is used to image the mediastinum.

Images are obtained from the hyoid bone to the lung apices by using T1-weighted spin-echo sequences (short recovery time [TR], short echo time [TE]) followed by T2-weighted spin-echo sequences (long TR, long TE). A section thickness of 3 mm with a 0.5-1 mm intersection gap is usually selected, and images are acquired by using 2 excitations, a 256 X 128 or 256 X 256 matrix, and a 12- to 16-cm field of view.

Superior and inferior presaturation pulses also are used to suppress blood-flow- artifact, McDermott and Spritzer described.[12 ]Faster imaging can be performed by using fast spin-echo techniques, which help reduce motion artifact that results from respiration and patient movement, according to Lee. IV contrast enhancement with gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) at a dose of 0.1 mmol/kg is optional. Seelos et al suggest that T1-weighted images with and without contrast enhancement may be used in lieu of standard T1-weighted and T2-weighted images when motion artifact may be a factor.[13 ]T1-weighted imaging times are shorter than T2-weighted imaging times. Other optional techniques include fat-suppression sequences and gradient-echo sequences.

Gadolinium-based contrast agents have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.

MRI findings

Normal parathyroid glands usually are not seen on MRIs. Parathyroid adenomas are identified on MRIs as soft-tissue masses in the expected normal and ectopic locations of the parathyroid glands. They commonly have low-to-medium signal intensity on T1-weighted images and high signal intensity on T2-weighted images, as Auffermann et al and Lee et al reported.[14 ]Seelos et al report that, if Gd-DTPA is administered, abnormal parathyroid glands have substantially enhancement on T1-weighted images, but not more than that achieved with conventional T2-weighted imaging.[13 ]

Approximately 30% of abnormal parathyroid glands do not have typical MRI signal intensity characteristics. Atypical patterns include high signal intensity on T1-weighted images and low-to-medium signal intensity on T2-weighted images, low signal intensity on both T1- and T2-weighted images, and high signal intensity on both T1- and T2-weighted images. Auffermann et al correlated the typical signal intensity characteristics with the histopathologic findings.[14 ]Low signal intensity on both T1- and T2-weighted images reflects cellular degenerative changes, old hemorrhage with hemosiderin-laden macrophages, and fibrosis in the abnormal gland. High signal intensity on both T1- and T2-weighted images indicates acute hemorrhage without significant degenerative or fibrotic changes.

Degree of Confidence

Several investigators report that the sensitivity for MRI is 57-100%. MRI is especially useful in detecting ectopic mediastinal glands, with reported sensitivities of 88-96%. A few groups report that MRI has a specificity of 87-100%.

False Positives/Negatives

False-positive findings are reported to result from the misidentification of the following as parathyroid adenomas: enlarged lymph nodes, thyroid nodules (adenomas and/or exophytic colloid cysts), enlarged cervical ganglia, and other neck masses such as sarcoid nodules and neurofibromas. Enlarged lymph nodes have signal intensity characteristics similar to those of abnormal parathyroid glands. Higgins notes that abnormal parathyroid glands are expected to be medial to the carotid sheath, whereas lymph nodes are most frequently situated around or lateral to the sheath.

False-negative findings most commonly result from small parathyroid glands. Stevens et al reported that the mean volume of detected abnormal glands is 3.5 cm3 and that the mean volume of missed glands is 1.4 cm3. They did not define a minimal threshold size for detection. Other reported false-negative findings result from concomitant thyroid disease, anatomic distortion due to prior surgery, ectopic glands (especially intrathyroidal glands), and atypical signal intensity characteristics.

Ultrasonography

Findings

A high-frequency (7.5- or 10-MHz) linear transducer should be used. Hopkins and Reading report that a lower frequency transducer can be used to obtain adequate depth penetration in obese patients, in those with large necks, and in those with thyromegaly.[15 ]The patient should be supine with his or her neck hyperextended. Gooding recommends that the examination should proceed from the carotid bifurcation superiorly to the sternal notch inferiorly and the carotid artery/internal jugular vein laterally.[16 ]

Normal-sized parathyroid glands are usually not visualized with US. On gray-scale images, parathyroid adenomas appear as a discrete, oval, anechoic or hypoechoic masses located posterior to the thyroid gland; anterior to the longus colli muscles; and, frequently, medial to the common carotid artery, as Gooding reported.[16 ]Hopkins and Reading report that an echogenic line that separates the thyroid gland from the enlarged parathyroid gland can usually be seen.[15 ]Randel et al report that larger adenomas as more likely to have cystic changes, lobulations, increased echogenicity due to fatty deposition, and occasional calcifications.[17 ]

Color Doppler US has been used to localize enlarged parathyroid glands. Parathyroid adenomas tend to be hypervascular lesions. Lane et al found that an extrathyroidal artery led to a parathyroid adenoma in 83% of their patients.[18 ]They further reported that a parathyroid adenoma was not visualized on gray-scale images in 5 of their patients but that the extrathyroidal feeding vessel provided a road map to the otherwise inconspicuous gland. However, Gooding points out that color Doppler sonograms of parathyroid adenomas may not show increased vascularity until the lesions are 1 cm in size.[16 ]

Degree of Confidence

Several authors report that the sensitivity of US in detecting parathyroid adenomas is 55-83%. US is especially limited in the mediastinum; in this area, its sensitivity is as low as 29%, as Rodriquez et al reported.[19 ]Several authors report that the specificity of US in detecting parathyroid adenomas is 40-98%.

False Positives/Negatives

False-positive findings result when thyroid nodules, enlarged lymph nodes, the esophagus, longus colli muscles, and perithyroid veins are mistaken for enlarged parathyroid glands.

False-negative findings result from small parathyroid glands; ectopic locations (especially in the mediastinum); and poor visualization of neck structures due to previous surgery, thyromegaly, or the patient's body habitus, as Hopkins and Reading reported.[15 ]

Localization of adenomas in the mediastinum is limited because of the lack of an acoustic window and the difficulty in visualizing structures posterior to the air-filled trachea and esophagus, according to Higgins. If an intrathyroidal lesion is detected, the lesion cannot be differentiated as a parathyroid adenoma or thyroid nodule. Aspiration biopsy is required.

Nuclear Imaging

The image below was obtained by using technetium-99m methoxyisobutyl isonitrile.

Left: Image obtained by using technetium Tc 99m m...

Left: Image obtained by using technetium Tc 99m methoxyisobutyl isonitrile (99mTc MIBI). Early images show uptake in the thyroid gland. The left lower pole is slightly more prominent, but the level of uptake is not different from the rest of the thyroid. Right: Delayed 99mTc-MIBI image shows delayed washout from a parathyroid adenoma near the lower pole of the left thyroid lobe. The radiopharmaceutical agent in thyroid gland itself has washed out, and the gland shows minimal activity.



Findings

Radiopharmaceutical agents

Several radiopharmaceutical agents can be used to evaluate the parathyroid glands. The use of different agents and methods has evolved over the last 2 decades.[4,20,21,22 ]

In the late 1970s, Coakley et al introduced the use of thallium Tl 201 as a parathyroid imaging agent.[23 ]Subsequently, Ferlin et al introduced the thallium Tl 201–technetium Tc 99m pertechnetate (thallium-pertechnetate) subtraction method.[24 ]This thallium-pertechnetate subtraction method was the first widely accepted method for radionuclide imaging of the parathyroid glands.

Thyroid tissue takes up both201 Tl and99m Tc pertechnetate. Abnormal parathyroid tissue, such as parathyroid adenomas, hyperplastic parathyroid glands, and parathyroid carcinoma, take up201 Tl but not99m Tc pertechnetate. Separate201 Tl and99m Tc pertechnetate images are obtained in a single session without moving the patient. Then, the99m Tc-pertechnetate image is subtracted from the thallium image by using computer processing. Any remaining activity usually indicates abnormal parathyroid tissue. This subtraction method was the traditional scintigraphic method for parathyroid imaging until the early 1990s, when99m Tc sestamibi and99m Tc tetrofosmin were introduced.

Coakley et al first recommended the use of99m Tc sestamibi for parathyroid imaging in 1989, at which time99m Tc sestamibi was substituted for201 Tl in the subtraction method.[23 ]In a landmark 1992 study, Taillefer et al introduced the use of99m Tc sestamibi as a single agent in a dual-phase technique.[25 ]Then, in 1995, Ishibashi et al found that99m Tc tetrofosmin is useful in parathyroid imaging because its imaging characteristics are similar to those of99m Tc sestamibi.[26 ]

201 Tl–99m Tc pertechnetate (thallium-pertechnetate) protocol

Zwas and Czerniak described a typical protocol for thallium-pertechnetate imaging.[27 ]Note that either201 Tl or99m Tc pertechnetate can be administered first. The protocol is as follows:

  • Use a pinhole collimator for neck imaging.
  • Use a parallel-hole all-purpose collimator for mediastinal imaging.
  • Set energy windows for201 Tl imaging at 80 keV ± 16.
  • Place the patient in a supine position with his or her neck slightly hyperextended beneath the gamma camera.
  • Ensure that the patient remains immobilized for both image acquisitions.
  • Intravenously administer 1-3 mCi201 Tl.
  • After 1 minute, obtain 6 anterior 5-minute images of the neck and mediastinum.
  • During the sixth image acquisition, switch the energy windows to 140 keV ± 28 for99m Tc pertechnetate imaging.
  • Administer 2 mCi of99m Tc pertechnetate.
  • After 10 minutes, obtain 2 anterior 5-minute images of the neck and mediastinum.
  • Sum the first 5201 Tl images. Then subtract the99m Tc pertechnetate images from the201 Tl images.
  • Residual201 Tl activity is indicative of parathyroid pathology.

The technical aspects of the procedure vary. Instead of99m Tc pertechnetate, sodium iodide I 123 can be used as the subtraction agent. Taillefer reports that disagreement exists regarding which radiotracer should be used as the subtraction agent (99m Tc pertechnetate vs sodium iodide I 123), the order of injection of the radiotracers, the injected activities of the radiotracers, the value of computer subtraction techniques, computer alignment, and display procedures.[25 ]In addition, a major disadvantage of the dual-isotope procedure is that the patient must remain motionless during both image acquisitions.

99m Tc sestamibi imaging

Soon after the introduction of99m Tc sestamibi, it was substituted for201 Tl in subtraction scintigraphy. Technetium Tc 99m sestamibi was first introduced as a myocardial perfusion agent; it was combined with either sodium iodide I 123 or99m Tc pertechnetate. Technetium Tc 99m sestamibi is taken up by both thyroid tissue and abnormal parathyroid tissue, whereas sodium iodide I 123 and99m Tc pertechnetate are taken up by only thyroid tissue. The sodium iodide I 123 or99m Tc-pertechnetate image is subtracted from the99m Tc-sestamibi image.

In 1992, Taillefer et al made one of the most recent important advances in parathyroid imaging by introducing the dual-phase technique with99m Tc sestamibi as the sole imaging agent.[25 ]Both thyroid tissue and abnormal parathyroid tissue take up99m Tc sestamibi within a few minutes. The examination is based on the differential washout of99m Tc sestamibi from thyroid tissue compared with abnormal parathyroid tissue. The rate of washout from abnormal parathyroid tissue, such as parathyroid adenoma, is much slower than that of normal thyroid tissue.

According to Taillefer et al, a typical protocol involves the IV injection of 20-25 mCi of99m Tc sestamibi and then the acquisition of early and delayed images of the neck and upper thorax and/or mediastinum. The initial early image is obtained 10-15 minutes after the injection; this step is called the thyroid phase of the study because99m Tc sestamibi is rapidly concentrated in the thyroid gland at this time. The delayed image is obtained 1.5-3 hours after the injection; this step is called the parathyroid phase. The parathyroid phase emphasizes the differential washout of99m Tc sestamibi from abnormal parathyroid glands.[25 ]

Optional techniques include the acquisition of right and left anterior oblique images to better depict the relationship of the parathyroid glands and thyroid gland. In addition,99m Tc pertechnetate or sodium iodide I 123 can be administered in difficult cases (eg, multinodular thyroid glands). Lastly, early single-photon emission CT (SPECT) imaging can be performed. Chen et al reported that late SPECT imaging has not been proven to add additional information.[28 ]Taillefer described a typical protocol for dual-phase scintigraphy with99m Tc sestamibi or99m Tc tetrofosmin, as follows[1 ]:

  • Examine the patient's neck for palpable thyroid or other neck masses.
  • Place the patient in a supine position with his or her neck hyperextended under the gamma camera.
  • Set energy windows to 140 keV ± 28.
  • Intravenously inject 20-25 mCi of99m Tc sestamibi or99m Tc tetrofosmin.
  • Use a camera with a large field of view and a high-resolution collimator.
  • Obtain anterior images of the neck and upper thorax and/or mediastinum. Image acquisition time is 10 minutes.
  • Obtain early thyroid-phase images 10-15 minutes after the injection.
  • Obtain delayed parathyroid-phase images 1.5-3 hours after the injection.

Optional imaging procedures include the following:

  • Right and left anterior oblique views can be obtained.
  • If nodules are palpable, delayed images can be obtained after 5-6 hours.
  • 99m Tc pertechnetate can be injected after delayed imaging.
  • Sodium iodide I 123 images may be obtained in a second examination on the next day.
  • SPECT can be performed.

One of the more recent uses of99m Tc sestamibi is in minimally invasive parathyroid surgery, which can be performed on an outpatient basis. The agent is injected prior to surgery, and a hand-held gamma probe is used to guide the incision and localize the abnormal gland. In a number of centers, this technique has been successful.

99m Tc tetrofosmin imaging

The most recently introduced radiopharmaceutical agent or parathyroid imaging is99m Tc tetrofosmin. Similar to99m Tc sestamibi,99m Tc tetrofosmin was used first as a myocardial perfusion imaging agent. It has imaging characteristics similar to those of99m Tc sestamibi, although it has a slightly different mechanism of uptake. The imaging protocols are similar. IV injections of 20-25 mCi of99m Tc tetrofosmin are used. Immediate and delayed anterior images of the neck and upper thorax and/or mediastinum are obtained 10-30 minutes and 1.5-3 hours after the99m Tc-tetrofosmin injection. Optional techniques include the acquisition of left and right anterior oblique images and the acquisition of separate thyroid images with99m Tc pertechnetate or sodium iodide I 123 in patients with more complex conditions. A typical protocol for99m Tc tetrofosmin is shown above in the protocol for99m Tc sestamibi.

One significant difference between99m Tc tetrofosmin and99m Tc sestamibi is the differential washout of the radiotracer from the thyroid gland. According to Lind, the thyroid washout rates are slower for99m Tc tetrofosmin than for99m Tc sestamibi.[29 ]In their study, Vallejos et al concluded that earlier imaging findings are more diagnostic than delayed imaging findings.[30 ]Irrespective of these differences, dual-phase imaging with either99m Tc sestamibi or99m Tc tetrofosmin is clearly superior to the traditional thallium-pertechnetate subtraction method. In addition, SPECT imaging may also be used with either99m Tc tetrofosmin or99m Tc sestamibi.

Degree of Confidence

In an extensive review of the literature about thallium-pertechnetate subtraction scintigraphy, Hauty et al reported an accumulated sensitivity of 82% in the detection of parathyroid adenomas.[31 ]

Several authors report that the sensitivity of the99m Tc-sestamibi,99m Tc-pertechnetate, or sodium iodide I 123 dual-isotope techniques in detecting parathyroid adenomas is 90-100%. Other authors report that the sensitivity of dual-phase planar imaging with99m Tc sestamibi in the detection of abnormal parathyroid tissue is 70-100%. Early SPECT imaging has a reported sensitivity of 91-96%. The reported sensitivity of dual-phase imaging with99m Tc tetrofosmin in detecting parathyroid adenomas is 77.3-100%.

False Positives/Negatives

Taillefer reported that the most common cause of false-positive localization in thallium-pertechnetate imaging is uptake in thyroid adenomas.[25 ]According to Hauty et al, small parathyroid glands are major factors that contributing to false-negative results.[31 ]

False-positive findings in99m Tc-sestamibi dual-phase imaging include uptake in coexisting thyroid nodules, which are interpreted as parathyroid adenomas. False-negative findings include parathyroid lesions, which are too small to be detected, and unusually rapid washout from a parathyroid adenoma. Pedunculated mobile glands may make precise localization of the gland difficult. Hyperplasia with one dominant gland may be misinterpreted as an adenoma, as Gordon et al reported. In the first few weeks after neck surgery, washout from the gland may be incomplete on delayed images. This finding, which is most likely the result of postoperative inflammation, makes the diagnosis of a parathyroid adenoma more difficult, as Gordon et al reported.[32 ]

False-positive and false-negative findings with99m Tc-tetrofosmin imaging are similar to those with99m Tc sestamibi.

Angiography

Findings

Invasive examinations, such as parathyroid arteriography and parathyroid venous sampling, can be considered when the findings of noninvasive imaging modalities are nondiagnostic.

Endocrine tumors, such as parathyroid adenomas, tend to be hypervascular. Parathyroid adenomas have a characteristic appearance on angiograms. They are round or oval lesions with smooth margins that display an intense vascular blush called a stain, according to Miller.[33 ]Typically, the paired inferior thyroid arteries supply the parathyroid glands; however, parathyroid gland blood supply can also be derived from the superior thyroid arteries; small branches of the laryngeal and tracheoesophageal arteries; and, occasionally, a thyroidea ima artery. The superior thyroid arteries are branches of the external carotid arteries. The inferior thyroid arteries are branches of the thyrocervical trunk.

Digital subtraction angiography (DSA) and/or conventional arteriography can be used to localize a parathyroid adenoma. Miller et al recommend selective arteriography of both thyrocervical trunks, both internal mammary arteries, and both common carotid arteries. The thyrocervical trunks are examined to assess intrathyroid glands, juxtathyroid glands, and glands that have descended into the superior mediastinum in the tracheoesophageal groove. The internal mammary arteries are studied to identify ectopic, anterior, mediastinal or thymic glands. The common carotid arteries are injected to detect parathymic or juxtathyroid glands. Superselective catheterization of the superior thyroid arteries may be performed, as Miller described.[33 ]Occasionally, arteriography of the aortic arch, and possibly the innominate artery, is performed to search for a thyroidea ima artery if findings from the aforementioned selective angiograms are negative, as Krudy et al reported.

The risks of parathyroid arteriography are stroke and spinal cord injury (eg, paralysis). Arteriography of the common carotid arteries and, especially, superselective catheterization of the superior thyroid arteries often require extensive manipulation of the guidewires and catheters in the region of the carotid bifurcation. This manipulation increases the risk of embolic stroke or dissection. The costocervical trunk, a neighboring branch of the thyrocervical trunk, supplies the cervical and upper thoracic segments of the spinal cord. Inadvertent injection into the costocervical trunk may cause spinal cord damage, as Miller reported.

Selective venous sampling and PTH measurements are performed to determine the general location of a parathyroid adenoma. A parathyroid arteriogram should be performed first because this serves as a guide or road map to the more variable parathyroid venous pathways, according to Miller. An end-hole catheter without side holes should be used to prevent the mixing of blood from adjacent veins. Sampling of small veins is the goal. Attempts should be made to sample the right and left thymic veins, inferior thyroid veins, and vertebral veins (if the middle and inferior thyroid veins were ligated in a previous operation). After each sample is obtained, a small amount of contrast material is injected, and a spot image is obtained to document the location of the catheter tip and sampling site. Lastly, a peripheral vein sample is obtained. A 2-fold gradient between the PTH concentration in the sampled vein and that of the peripheral vein must be observed, as Miller described.

With modifications, this technique has also been used during surgery to confirm success in removing the source of increased PTH production.

Degree of Confidence

Miller reported that the sensitivity of DSA is 49%; that of conventional arteriography is 60%. Miller also reported that the sensitivity of parathyroid venous sampling is 70-80%.[33 ]

Intervention

The primary treatment for parathyroid adenomas is surgical removal via bilateral neck exploration, unilateral neck exploration, or minimally invasive, radiologically guided parathyroidectomy. Other radiologic interventions include parathyroid adenoma angiographic ablation with IV administration of contrast material and US-guided ablation with ethanol. Generally, radiologic procedures are selected when the patient is a high-risk surgical candidate.

In angiographic ablation, the feeding artery is superselectively catheterized and high-osmolar ionic contrast material is injected to induce ischemia and infarction of the gland. This procedure should be performed only if the patient is known to have other normally functioning parathyroid tissue. Otherwise, permanent hypocalcemia can occur, as Miller reported.[33 ]Opponents of angiographic ablation base their opposition on the fact that no parathyroid tissue is available for histologic examination, no tissue is available for cryopreservation or autotransplantation, and recurrent disease is more common in these patients than in others, according to Rodriguez.[19 ]

In US-guided ethanol ablation, approximately 0.5-1 mL of 95% ethanol is injected into the parathyroid adenoma to cause tissue necrosis, as Karstrup et al reported.[34 ]Recurrence can be a problem. The major complication is recurrent laryngeal nerve damage.

Medicolegal Pitfalls

  • Failure to determine if the patient has other normally functioning parathyroid tissue before angiographic ablation can result in permanent hypocalcemia.
  • Opponents of angiographic ablation base their opposition on the following:
    • No parathyroid tissue is available for histologic examination.
    • No tissue is available for cryopreservation or autotransplantation.
    • Recurrent disease is more common in these patients than in others.
  • Failure to consider that recurrence can be a problem with US-guided ethanol ablation.
    • The procedure may have to be repeated several times.
    • The major complication is recurrent laryngeal nerve damage.

Multimedia

Left: Image obtained by using technetium Tc 99m m...

Media file 1: Left: Image obtained by using technetium Tc 99m methoxyisobutyl isonitrile (99mTc MIBI). Early images show uptake in the thyroid gland. The left lower pole is slightly more prominent, but the level of uptake is not different from the rest of the thyroid. Right: Delayed 99mTc-MIBI image shows delayed washout from a parathyroid adenoma near the lower pole of the left thyroid lobe. The radiopharmaceutical agent in thyroid gland itself has washed out, and the gland shows minimal activity.

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Keywords

parathyroid adenoma, HPT, primary hyperparathyroidism, excess parathyroid hormone, PTH, hypercalcemia, hypophosphatemia

Contributor Information and Disclosures

Author

, Staff Physician, Staff Physician, Department of Radiology, Harbor Medical Center, University of California at Los Angeles
, Staff Physician is a member of the following medical societies: American College of Radiology
Disclosure: Nothing to disclose.

Coauthor(s)

Fred S Mishkin, MD, Professor of Radiology in Residence, University of California at Los Angeles School of Medicine; Director, Division of Nuclear Medicine, UCLA-Harbor Medical Center
Fred S Mishkin, MD is a member of the following medical societies: American College of Angiology, American College of Radiology, American Heart Association, American Medical Association, California Medical Association, and Society of Nuclear Medicine
Disclosure: Nothing to disclose.

Panukorn Vasinrapee, MD, Assistant Clinical Professor of Radiology, University of California at Los Angeles School of Medicine; Associate Chief, Nuclear Medicine, Department of Radiology, Harbor-UCLA Medical Center
Panukorn Vasinrapee, MD is a member of the following medical societies: American Roentgen Ray Society, Radiological Society of North America, and Society of Nuclear Medicine
Disclosure: Nothing to disclose.

Medical Editor

Hussein M Abdel-Dayem, MD, Chief, Nuclear Medicine Service, Department of Radiology, Professor of Radiology, St Vincent's Catholic Medical Centers of New York
Disclosure: none None None

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

C Douglas Phillips, MD, Director of Head and Neck Imaging, Division of Neuroradiology, Weill Medical College of Cornell University/New York Presbyterian Hospital
C Douglas Phillips, MD is a member of the following medical societies: American College of Radiology, American Medical Association, American Society of Head and Neck Radiology, American Society of Neuroradiology, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Resolution Imaging Medical Corporation
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

Eugene C Lin, MD, Consulting Radiologist, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, and Society of Nuclear Medicine
Disclosure: Nothing to disclose.

Further Reading

Related eMedicine topics

 Hyperparathyroidism, Primary (from Radiology)

Hyperparathyroidism (from Endocrinology)

Hyperparathyroidism (from Emergency Medicine)

Hypercalcemia

Hypophosphatemia

Clinical guidelines

 The American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons Position Statement on the Diagnosis and Management of Primary Hyperparathyroidism
Procedure Guideline for Parathyroid Scintigraphy

Clinical trials

 The Effects of Alendronate After Cure of Primary Hyperparathyroidism (AlenPostPara)
Primary Hyperparathyroidism: Non-Classical Manifestations

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