What is the purpose and procedure of a Sestamibi (Technetium-99m-sestamibi) scan in diagnosing parathyroid adenoma or hyperplasia?

Sestamibi Scan for Parathyroid Localization

Purpose and Clinical Role

Sestamibi scanning is a nuclear medicine imaging technique used exclusively for preoperative localization of parathyroid adenomas or hyperplasia in patients with biochemically confirmed hyperparathyroidism—it has no role in diagnosing hyperparathyroidism itself. 1, 2

The scan serves to guide surgical planning by identifying the location of abnormal parathyroid tissue before parathyroidectomy, particularly for minimally invasive approaches. 3, 2

Imaging Technique and Protocols

Standard Dual-Phase Protocol

The most commonly utilized technique involves:

• Injection of 20-30 mCi (740-1110 MBq) of Technetium-99m sestamibi intravenously 4, 5
• Early imaging at 15-20 minutes post-injection to capture initial uptake in both thyroid and parathyroid tissue 3, 5
• Delayed imaging at 90-120 minutes to demonstrate differential washout (sestamibi washes out faster from normal thyroid tissue than from hyperfunctioning parathyroid tissue) 3, 5
• Both planar and SPECT or SPECT/CT imaging should be performed, as SPECT significantly improves sensitivity 3, 5

Alternative Dual-Tracer Subtraction Technique

An alternative approach combines:

• Sestamibi with I-123 sodium iodide thyroid scanning, allowing simultaneous acquisition in a dual-energy window 3
• Reported sensitivity ranges from 75% to 94% for this technique, with one large study of 2,681 patients showing 87% sensitivity and 92% positive predictive value 3
• The European Association of Nuclear Medicine expressed preference for this dual-tracer technique, citing improved sensitivity for multigland disease and better distinction of sestamibi-avid thyroid nodules from parathyroid lesions 3

Diagnostic Performance

Primary Hyperparathyroidism (Single Adenoma)

For solitary parathyroid adenomas, sestamibi with SPECT/CT demonstrates the highest sensitivity:

• Meta-analysis data shows pooled sensitivity of 86% for dual-phase sestamibi with SPECT/CT, compared with 74% for SPECT alone and 70% for planar imaging alone 3
• Individual studies report sensitivity ranging from 67% to 86% when SPECT or SPECT/CT is added to dual-phase imaging 3
• Positive predictive value ranges from 91% to 96% 3

Factors That Decrease Sensitivity

Performance is significantly reduced in several clinical scenarios:

• Multigland disease (hyperplasia): Sensitivity drops to 24-66% 3
• Smaller adenomas (particularly <500 mg) 3
• Concomitant thyroid disease with retained radionuclide in thyroid tissue 3
• Ectopic glands: Sensitivity as low as 29% for ectopic locations in secondary/tertiary hyperparathyroidism 3

Secondary and Tertiary Hyperparathyroidism

Sestamibi performance is notably inferior in multigland disease:

• Per-patient sensitivity of 85% reported in one study of secondary hyperparathyroidism 3
• Per-lesion sensitivity only 59-62% for detecting individual hyperplastic glands 3
• For ectopic glands in tertiary hyperparathyroidism, sensitivity drops to 29-36% 3

Reoperative Cases

In patients with persistent or recurrent hyperparathyroidism after prior surgery:

• Sensitivity ranges from 33% to 86% depending on whether SPECT/CT is utilized 3
• Addition of SPECT/CT improves sensitivity from 74% to 86% in reoperative cases 3

Critical Algorithmic Approach

Step 1: Confirm Biochemical Diagnosis First

Never order sestamibi scanning without biochemical confirmation of hyperparathyroidism (elevated or inappropriately normal PTH with elevated serum calcium). 1, 2

Step 2: Choose Optimal Imaging Protocol

For primary hyperparathyroidism with suspected single adenoma:

• Order dual-phase sestamibi with SPECT/CT as first-line imaging 3, 2
• Consider adding ultrasound for complementary localization (concordant results increase surgical confidence) 2

For suspected multigland disease (secondary/tertiary hyperparathyroidism):

• Recognize that sestamibi sensitivity is substantially lower 3
• Consider combining with ultrasound and potentially 4D-CT for comprehensive evaluation 2

For reoperative cases:

• SPECT/CT is essential (not optional) given lower sensitivity in post-surgical anatomy 3

Step 3: Interpret Results in Clinical Context

Positive scan with concordant ultrasound: Proceed with targeted/minimally invasive parathyroidectomy 2

Negative or equivocal scan: Does not exclude parathyroid disease—proceed with bilateral neck exploration based on biochemical diagnosis 1

Common Pitfalls and How to Avoid Them

Pitfall 1: Using Imaging to Diagnose Hyperparathyroidism

Sestamibi has no role in confirming or excluding the diagnosis of hyperparathyroidism—this is a biochemical diagnosis only. 1, 2 Always obtain PTH and calcium levels first.

Pitfall 2: Ordering Planar Imaging Without SPECT/CT

Planar imaging alone has significantly lower sensitivity (42% vs 67%) compared to when SPECT is added. 3, 5 One study demonstrated that SPECT detected parathyroid hyperplasia that was completely missed by planar imaging. 3

Pitfall 3: Relying on Sestamibi Alone in Multigland Disease

In secondary or tertiary hyperparathyroidism, per-lesion sensitivity is only 29-62%, meaning many hyperplastic glands will be missed. 3 Use complementary imaging modalities and plan for bilateral exploration.

Pitfall 4: Assuming Negative Scan Rules Out Disease

A negative sestamibi scan does not exclude parathyroid pathology, particularly in cases of small adenomas, multigland disease, or ectopic locations. 3 Surgical exploration should be guided by biochemical diagnosis, not imaging results.

Pitfall 5: Misinterpreting Thyroid Nodule Uptake

Sestamibi-avid thyroid nodules can mimic parathyroid adenomas. 3 The dual-tracer technique with I-123 subtraction helps distinguish these entities more reliably than dual-phase imaging alone. 3