Parathyroid Scintigraphy (Sestamibi)

Parathyroid scintigraphy with technetium-99m sestamibi finds overactive parathyroid tissue in primary hyperparathyroidism. The tracer accumulates in the mitochondria of cells with high activity and is retained longer in abnormal parathyroid tissue than in the thyroid, which shows washout.

The patient receives 500 to 740 MBq of technetium-99m sestamibi intravenously. Planar images of the neck and chest are taken at 10 to 15 minutes (early) and at 2 to 3 hours (delayed).

The dual phase method looks for tracer that remains in a focus after the thyroid has washed out. Pinhole or parallel hole collimators are used.

SPECT or SPECT-CT of the neck and mediastinum improves localisation by depth and relation to the thyroid. A subtraction method uses a thyroid specific tracer (iodine-123 or technetium pertechnetate) and subtracts it from the sestamibi images, and some centres use a single phase technique with early SPECT-CT and 4D CT.

The examination takes 2 to 3 hours, with imaging of 30 to 60 minutes. The effective dose is about 6 to 9 mSv.

Primary hyperparathyroidism affects about 1 in 500 women and 1 in 2000 men, mostly in the older age group, and 85% is due to a single adenoma. Surgical removal cures 95 to 98%. Preoperative localisation allows a focused (minimally invasive) operation instead of four gland exploration.

Sestamibi has a sensitivity of about 70 to 90% for single adenomas, falling to 30 to 60% for multigland disease, with a specificity of 90%.

Indications.

• Biochemically proven primary hyperparathyroidism, before surgery, to localise an adenoma.
• Persistent or recurrent hyperparathyroidism after surgery (re-operation), including ectopic and mediastinal glands.
• Tertiary hyperparathyroidism and secondary hyperparathyroidism with persistent disease after renal transplantation (in selected cases).
• Normocalcaemic hyperparathyroidism with surgical indication.
• Familial and syndromic disease (multiple endocrine neoplasia), usually with other imaging.
• Intra-operative probe localisation (surgery with a gamma probe) in some centres.

Not for diagnosis of hyperparathyroidism (this is biochemical) and not when surgery is not planned.

Contraindications and precautions.

• Pregnancy: avoid, and use ultrasound. Breast feeding: interrupt for about 24 hours.
• Allergy to the tracer is rare.
• Recent thyroid disease, large goitres and thyroid nodules reduce accuracy.
• Thyroid hormone, antithyroid drugs and iodine affect subtraction methods only.
• Calcium channel blockers, vitamin D and calcium supplements may reduce uptake. Stop for 2 to 4 weeks only where the team advises.
• Confirm the biochemical diagnosis (raised calcium with raised or inappropriately normal parathyroid hormone) before the scan.
• Patients must lie still for the SPECT images.

Preparation and technique.

No fasting is needed. The patient drinks fluids. Metal jewellery is removed from the neck. For subtraction, a second tracer is given at the beginning or the end of the study.

After the injection, early images are taken at 10 to 15 minutes, and delayed images at 2 to 3 hours. Images cover from the mandible to the lower chest to include the mediastinum. SPECT-CT is taken at the early or late phase (or both) with a low dose CT for localisation.

Images are displayed in the planar form with early and late comparison, with SPECT-CT fused images, and with subtraction images if used. The report states the side, the level in relation to the thyroid (upper, middle, lower, behind or under), and any ectopic site.

Normal appearances.

Early images show uptake in the thyroid, salivary glands, heart and liver, with some activity in the muscles. On delayed images the thyroid washes out and the salivary glands fade, with no persistent focal uptake. Normal parathyroid glands are small (under 5 mm), and do not show.

Interpretation.

• Parathyroid adenoma: a focus of uptake that persists or increases on delayed images when the thyroid has washed out, usually behind the lower or upper pole of the thyroid. SPECT-CT shows its position, with a relation to the thyroid, oesophagus and trachea.
• Ectopic adenoma: foci in the mediastinum, behind the oesophagus (tracheo oesophageal groove), the carotid sheath, the thymus, the thyroid itself (intrathyroidal) and the anterior mediastinum. These explain failed surgery.
• Multigland hyperplasia: multiple or faint foci, or false negative, as the glands are small and have lower uptake. Sestamibi underestimates the extent.
• Parathyroid carcinoma: a large focus with intense uptake, though not specific.
• Thyroid nodules: adenomas and cancers can retain tracer and mimic parathyroid disease. Subtraction methods, ultrasound and SPECT-CT help.
• Lymph nodes, brown tumours, brown fat and metastases can show uptake.
• Negative scan: no focus. The scan does not exclude a gland, particularly small adenomas, deep glands, multiple gland disease, and glands with low mitochondrial content.
• Concordant imaging: sestamibi and ultrasound agreement on the same lateral and level raises confidence for a focused operation (positive predictive value of over 95%).
• Post-operative: persistent uptake suggests residual disease, and a negative scan with persistent hypercalcaemia needs 4D CT, MRI or venous sampling.
• Intra-operative: probe counts in the excised gland are over 20% of the background (the 20% threshold) to confirm a hyperfunctioning gland.

Critical values and findings needing immediate action.

• Severe hypercalcaemia (corrected calcium over 3.5 mmol/L) or hypercalcaemic crisis: urgent hydration, bisphosphonate and endocrine review, and surgery.
• Localisation of a large or suspicious gland (possible carcinoma): surgical referral for en bloc resection.
• Mediastinal adenoma: thoracic or endocrine surgical planning.
• Unexpected thyroid cancer or lymphoma found on scan: specialist review.
• Persistent post-operative hypercalcaemia with ectopic gland: re-operation planning at a specialist centre.

Limitations and artefacts.

• Sensitivity falls for small (under 500 mg) or deeply seated adenomas, for multigland hyperplasia and for glands with low oxyphil cell content.
• Thyroid nodules and goitres retain sestamibi (false positive) or hide a gland (false negative). Ultrasound correlation is essential.
• Washout rates vary. Some adenomas wash out as fast as the thyroid, and some thyroid tissue retains tracer.
• Early images alone are not reliable, so the dual phase or SPECT-CT method is used.
• The limited field may miss ectopic glands, so the chest should be included.
• Brown fat, muscle, lymph nodes, and salivary glands cause false positive uptake.
• Concurrent medicines and low serum parathyroid hormone reduce uptake.
• The method does not tell the difference between adenoma and hyperplasia, and hence the surgical plan uses biochemistry and the intra-operative parathyroid hormone assay.
• Radiation dose, and time cost, limit repeat use.

Special groups.

• Children and young adults: genetic syndromes and multigland disease are more likely, so imaging is less reliable.
• Patients with multiple endocrine neoplasia or familial disease: bilateral exploration is usually planned.
• Patients with renal failure: secondary and tertiary disease, with multigland hyperplasia, so sestamibi has lower value.
• Patients with prior neck surgery: 4D CT or ultrasound add value.
• Pregnant patients: ultrasound only, and medical treatment where possible.
• Regions: primary hyperparathyroidism is under diagnosed. Secondary disease in renal failure and vitamin D deficiency are common. Imaging is limited, so experienced surgeons perform bilateral exploration with biochemical direction and intra-operative parathyroid hormone testing where available.

Follow up tests.

• Neck ultrasound by an experienced operator.
• Four dimensional CT and MRI for ectopic and recurrent disease.
• Choline or fluorocholine PET-CT for difficult cases.
• Selective venous sampling for parathyroid hormone when imaging is negative.
• Calcium, phosphate, parathyroid hormone, 25-hydroxy vitamin D, creatinine, 24-hour urinary calcium.
• Bone density scan and kidney imaging for complications.
• Genetic testing (multiple endocrine neoplasia, familial hypocalciuric hypercalcaemia exclusion).
• Referral to endocrine surgery, endocrinology or nephrology.