Residency · Residency · Nuclear Medicine
Parathyroid Scintigraphy
Introduction
Parathyroid scintigraphy is a key preoperative localization tool for patients with primary hyperparathyroidism (PHPT) who are surgical candidates. The most widely used technique employs Tc-99m sestamibi imaging, which exploits the differential washout of radiotracer between thyroid and parathyroid tissue. Accurate localization enables minimally invasive parathyroidectomy, reducing operative time, morbidity, and the need for bilateral neck exploration.
Clinical Context
Primary Hyperparathyroidism
PHPT has a prevalence of approximately 1 in 500 adults, with a female predominance. A solitary adenoma accounts for 80-85% of cases, multigland hyperplasia for 10-15%, and carcinoma for less than 1%. The biochemical hallmark is hypercalcemia with an inappropriately elevated or non-suppressed PTH level. Surgery is the only definitive treatment, and preoperative imaging guides the surgical approach.
Indications for Parathyroid Scintigraphy
The study is performed for preoperative localization before initial parathyroidectomy, for localization in reoperative cases after prior failed surgery, and when ectopic parathyroid tissue is suspected in mediastinal, retroesophageal, or intrathyroidal locations. It may also contribute to multigland disease assessment when used in combination with other modalities.
Radiopharmaceuticals and Mechanisms
Tc-99m Sestamibi
Tc-99m sestamibi is a lipophilic cationic agent taken up by mitochondria-rich cells. Parathyroid adenomas are packed with mitochondria, leading to avid and prolonged radiotracer uptake. Normal thyroid tissue also takes up sestamibi but washes out faster. This differential washout kinetics forms the basis of dual-phase imaging.
Tc-99m Pertechnetate (for Subtraction Imaging)
Tc-99m pertechnetate is trapped by thyroid follicular cells via the sodium-iodide symporter but is not taken up by parathyroid tissue. In the subtraction technique, a pertechnetate image representing thyroid tissue alone is digitally subtracted from a sestamibi image representing both thyroid and parathyroid uptake, revealing isolated parathyroid activity.
Imaging Protocols
Dual-Phase (Washout) Technique
A single injection of Tc-99m sestamibi (740-925 MBq, or 20-25 mCi) is administered intravenously. Early images obtained at 10-15 minutes show uptake in both thyroid and parathyroid tissue. Delayed images at 1.5-3 hours show washout from thyroid while the parathyroid adenoma retains activity. Persistent focal activity on delayed images localizes the adenoma. Pinhole collimator views improve spatial resolution for neck imaging, and SPECT/CT at either phase improves anatomic localization.
Dual-Isotope Subtraction Technique
This approach uses sequential or simultaneous acquisition of Tc-99m sestamibi and I-123 (or Tc-99m pertechnetate). The I-123 images represent thyroid tissue only, while sestamibi images represent thyroid plus parathyroid tissue. Digital subtraction of the thyroid image from the sestamibi image isolates parathyroid activity. The advantage of this method is that it does not depend on differential washout kinetics and can detect adenomas that wash out rapidly.
SPECT/CT
SPECT/CT improves sensitivity from approximately 70% with planar imaging to 85-90% for solitary adenomas. It provides precise three-dimensional localization (superior versus inferior pole, depth relative to the thyroid), distinguishes intrathyroidal parathyroid adenomas from thyroid nodules, and is essential for localizing ectopic glands in mediastinal, retroesophageal, or carotid sheath locations.
4D CT as Complementary Modality
Four-dimensional CT uses multiphasic contrast imaging to demonstrate differential enhancement and washout patterns of parathyroid tissue. It is increasingly used as a first-line or complementary modality, offering higher spatial resolution than scintigraphy but at the cost of greater radiation dose and iodinated contrast exposure.
| Technique | Principle | Sensitivity (Solitary Adenoma) | Advantage | Limitation |
|---|---|---|---|---|
| Dual-phase sestamibi (planar) | Differential washout | 60–70% | Simple, widely available | Misses rapid-washout adenomas |
| Dual-phase sestamibi (SPECT/CT) | Differential washout + anatomy | 85–90% | 3D localization; ectopic glands | Still dependent on washout kinetics |
| Dual-isotope subtraction | Sestamibi minus I-123/pertechnetate | 80–90% | Independent of washout | Requires two tracers; registration |
| 4D CT | Multiphasic enhancement | 85–92% | High spatial resolution | Radiation dose; contrast required |
| Ultrasound | Hypoechoic nodule adjacent to thyroid | 70–80% | No radiation; real-time | Operator-dependent; misses ectopic |
| F-18 Fluorocholine PET/CT | Choline kinase activity | 90–95% | Highest sensitivity | Cost; availability |
Interpretation
Positive Findings
A positive study shows focal retained activity on delayed images that does not correspond to thyroid tissue, or focal activity on subtraction images after removal of the thyroid component. SPECT/CT confirms the location relative to the thyroid, trachea, esophagus, and major vessels. Reports should specify laterality, craniocaudal position, and relationship to the thyroid gland.
Sensitivity and Specificity
For solitary adenomas, sensitivity is 80-90% with SPECT/CT and specificity is approximately 90-95%. However, for multigland disease, sensitivity drops markedly to 30-50%, representing the most significant limitation of the technique. Combining scintigraphy with ultrasound improves concordance and surgical confidence.
Causes of False Negatives
Multigland hyperplasia produces symmetric uptake that may be indistinguishable from normal thyroid. Small adenomas weighing less than 500 mg may fall below detection threshold. Concomitant thyroid nodules with sestamibi uptake (such as follicular adenomas) can mask parathyroid activity. Oxyphil-poor adenomas with fewer mitochondria take up less sestamibi, and some adenomas wash out rapidly, negating the advantage of dual-phase imaging.
Causes of False Positives
Thyroid nodules, particularly follicular adenomas, Hurthle cell neoplasms, and papillary carcinomas, represent the most common cause of false-positive studies. Metastatic lymph nodes, reactive cervical nodes, and brown tumors of bone (in severe hyperparathyroidism) can also mimic parathyroid adenomas.
Ectopic Parathyroid Glands
Ectopic glands are present in approximately 5-10% of patients. Common locations include the anterior mediastinum (within the thymus), the aortopulmonary window, the retroesophageal space, the carotid sheath, and within the thyroid parenchyma. SPECT/CT is critical for ectopic localization because planar imaging alone cannot reliably define depth or relationship to mediastinal structures. Mediastinal ectopic glands may require thoracoscopic or sternotomy approaches for removal.
Special Considerations
Secondary and Tertiary Hyperparathyroidism
In secondary and tertiary hyperparathyroidism, multigland hyperplasia predominates, and sestamibi sensitivity is limited. Imaging may still help identify a dominant gland for subtotal parathyroidectomy. Ultrasound and sestamibi are typically used in combination, and post-transplant tertiary hyperparathyroidism may benefit from localization before surgery.
Parathyroid Carcinoma
Parathyroid carcinoma is rare, accounting for less than 1% of PHPT. Sestamibi uptake is typically intense. Markedly elevated PTH and calcium levels raise clinical suspicion, but imaging cannot reliably distinguish carcinoma from adenoma. En bloc resection, rather than simple adenomectomy, is required for carcinoma.
Clinical Pearls
The dual-phase technique relies on differential washout between thyroid tissue (faster) and parathyroid adenoma (slower), and SPECT/CT substantially improves both sensitivity and anatomic localization compared to planar imaging alone. The most important limitation of parathyroid scintigraphy is its poor sensitivity (30-50%) for multigland hyperplasia, which is also the most common cause of false-negative studies. Thyroid nodules, particularly follicular adenomas and Hurthle cell neoplasms, are the most common source of false-positive sestamibi studies and should always be correlated with ultrasound. SPECT/CT is essential when ectopic parathyroid tissue is suspected, as it provides the three-dimensional localization required for surgical planning.
References
- Greenspan BS, et al. "SNM Practice Guideline for Parathyroid Scintigraphy 4.0." J Nucl Med Technol. 2012;40(2):111-118.
- Treglia G, et al. "Diagnostic Performance of Tc-99m-MIBI Scintigraphy in Primary Hyperparathyroidism: A Meta-Analysis." Endocrine. 2012;41(1):36-45.
- Cheung K, et al. "Comparison of Tc-99m Sestamibi SPECT/CT, 4D-CT, and Ultrasound for Preoperative Localization of Parathyroid Adenomas." Ann Surg Oncol. 2012;19(2):577-583.
- Wilhelm SM, et al. "The AAES Guidelines for Definitive Management of Primary Hyperparathyroidism." Ann Surg. 2016;264(6):e29-e35.