The Parathyroid Glands: Small but Significant
Most people have four parathyroid glands, each about the size of a grain of rice, located behind the thyroid gland in the neck. Despite their small size, these glands play a critical role in regulating calcium levels in the blood. They produce parathyroid hormone (PTH), which controls how much calcium is released from bones, absorbed from food, and retained by the kidneys.
When one or more parathyroid glands become overactive, a condition called hyperparathyroidism, they produce too much PTH. This leads to elevated calcium levels in the blood (hypercalcaemia), which can cause a range of symptoms including fatigue, bone pain, kidney stones, abdominal discomfort, depression, and difficulty concentrating.
The most common cause of primary hyperparathyroidism is a parathyroid adenoma, a benign tumour in one of the four glands. Less commonly, more than one gland is enlarged (multigland hyperplasia), or rarely, a parathyroid carcinoma is responsible.
What Is a Sestamibi Scan?
A sestamibi scan (also called a parathyroid sestamibi scan or Tc-99m sestamibi scintigraphy) is a nuclear medicine imaging test designed to locate overactive parathyroid tissue. The tracer used, Tc-99m sestamibi, is taken up by cells with high metabolic activity, particularly those with abundant mitochondria.
Parathyroid adenomas have significantly more mitochondria than normal parathyroid tissue, and they retain the sestamibi tracer longer than surrounding thyroid tissue. This differential retention is the basis of the scan: the overactive gland “holds onto” the tracer while normal tissue washes it out.
How the Scan Works
There are two main protocols used for parathyroid sestamibi scanning, and some centres use a combination of both for higher accuracy.
Dual-Phase (Wash-Out) Protocol
In this approach, a single tracer (Tc-99m sestamibi) is injected, and images are taken at two time points:
Early phase: Images are acquired 15 to 20 minutes after injection. At this point, both the thyroid gland and any parathyroid adenoma take up the tracer.
Delayed phase: Images are repeated at 2 to 3 hours after injection. By this time, the thyroid has largely washed out the tracer, but the parathyroid adenoma retains it. The result is a persistent focus of tracer uptake that stands out against the now-faded thyroid background.
Subtraction Protocol
This method uses two tracers: Tc-99m sestamibi (taken up by both thyroid and parathyroid) and a second tracer that is taken up only by the thyroid (such as Tc-99m pertechnetate or I-123). By digitally subtracting the thyroid-only image from the combined image, the remaining signal represents the parathyroid adenoma.
The subtraction technique can be particularly useful when a parathyroid adenoma sits close to or behind the thyroid, making it hard to distinguish on the dual-phase images alone.
SPECT/CT
Many centres now add SPECT/CT (single-photon emission computed tomography combined with CT) to the sestamibi scan. This provides three-dimensional localisation of the adenoma and shows its relationship to surrounding anatomical structures. For the surgeon, SPECT/CT images can be extremely valuable in planning a minimally invasive approach.
The Scan Procedure
Preparation: No special preparation is typically required. You do not need to fast. Inform the nuclear medicine team if you are taking any thyroid medications or if you have had recent imaging with iodinated contrast, as these can affect the scan.
Injection: The tracer is injected into a vein in the arm. The injection is brief and feels like a standard blood draw.
Imaging: You lie on the imaging table with a gamma camera positioned over your neck and upper chest. The camera captures planar images (flat 2D images) and, in most centres, SPECT/CT images as well. You need to remain still during image acquisition, which takes about 20 to 30 minutes per phase.
Waiting period: Between the early and delayed phases, there is a wait of approximately 1.5 to 2.5 hours. You can leave the imaging area during this time and return for the delayed images.
Total time: Plan for approximately 3 to 4 hours at the imaging centre, including the waiting period between phases.
What the Scan Reveals
The nuclear medicine physician analyses the images looking for a focus of persistent tracer uptake that corresponds to an overactive parathyroid gland. The report will describe:
- The location of the abnormal gland (right or left, upper or lower pole, or ectopic position)
- Whether one gland or multiple glands appear affected
- The relationship of the gland to the thyroid and other neck structures
A positive scan showing a single adenoma is the most common result in primary hyperparathyroidism and supports a minimally invasive surgical approach (focused parathyroidectomy). When the scan is negative or shows multiple areas of uptake, the surgical approach may be different, often involving bilateral neck exploration.
The Connection to Surgical Planning
Surgery is the definitive treatment for primary hyperparathyroidism caused by a parathyroid adenoma. The sestamibi scan plays a direct role in surgical planning in several ways:
Minimally invasive surgery: When the scan clearly identifies a single adenoma, the surgeon can perform a targeted operation through a small incision, removing just the abnormal gland. This approach has a shorter operative time, less anaesthesia, and a quicker recovery compared to a full bilateral neck exploration.
Ectopic glands: In about 10-15% of patients, a parathyroid gland is located in an unusual position, such as deep in the neck, behind the oesophagus, in the mediastinum (chest), or within the thyroid gland itself. The sestamibi scan, particularly with SPECT/CT, can identify these ectopic glands before surgery, preventing a frustrating search during the operation.
Re-operative cases: For patients who have had previous neck surgery and develop recurrent or persistent hyperparathyroidism, the sestamibi scan helps locate the remaining abnormal tissue in a surgically altered anatomy.
Limitations of the Scan
No imaging test is perfect, and the sestamibi scan has known limitations:
- Small adenomas (under 500 mg) may not retain enough tracer to be detected
- Multigland hyperplasia can be harder to identify than a single adenoma, as the uptake pattern is less distinct
- Coexisting thyroid nodules can mimic parathyroid adenomas, leading to false positive results
- Sensitivity varies across studies, ranging from about 70% to 90% depending on patient selection and imaging technique
For these reasons, the sestamibi scan is often used in combination with neck ultrasound, and sometimes 4D CT, to increase the overall accuracy of pre-operative localisation.
When Is a Sestamibi Scan Needed?
A sestamibi scan is recommended when blood tests confirm primary hyperparathyroidism (elevated calcium with elevated or inappropriately normal PTH) and surgery is being considered. The scan is not used to diagnose hyperparathyroidism; that diagnosis comes from blood work. The scan’s role is to locate the abnormal gland so the surgeon knows where to operate.
If you have been diagnosed with hyperparathyroidism and your doctor has recommended a sestamibi scan, it means surgery is being considered and the scan will help determine the surgical approach. Discuss the results with your endocrinologist and surgeon to understand how the findings apply to your specific situation.