Parathyroid Scan (Sestamibi Scintigraphy)

Overview

Radiopharmaceutical & Mechanism

• Agent: 99mTc-sestamibi (a lipophilic cationic compound)
• Uptake: Diffuses passively across cell membranes and accumulates in mitochondria
• Both thyroid and parathyroid tissue take up sestamibi, but parathyroid adenomas (rich in oxyphil cells with high mitochondrial content) retain the tracer significantly longer
• Normal parathyroid glands are too small to be visualized on any form of scintigraphy
• Comparison of early images (10 min) and delayed images (2 hours) after injection reveals the parathyroid focus as persisting activity after thyroid washout

Imaging Modalities (Progression)

1. Planar Sestamibi Scintigraphy

• Traditional two-dimensional anterior-posterior (and sometimes lateral) views
• Provides limited anatomical detail
• Sensitivity: ~71-79% for single adenomas
• Negative result in 12-25% of patients

2. SPECT (Single Photon Emission Computed Tomography)

• 3-dimensional rotating images with higher resolution
• Better detection of deep cervical and ectopic glands
• Sensitivity: 87-91% for single adenomas; overall 92-98%
• Limited sensitivity for multigland disease (MGD)

3. Sestamibi SPECT/CT (Current Gold Standard)

• Fuses SPECT functional data with CT anatomical data
• Sensitivity: up to 96% for single adenomas
• Up to 60% more accurate than SPECT alone for MGD
• Delivers significantly less radiation than 4D-CT when using attenuated CT windows

4. Subtraction (Dual Isotope) Scintigraphy

• Useful when thyroid pathology (nodular goitre) complicates interpretation
• Patient receives sestamibi (thyroid + parathyroid uptake) AND a thyroid-specific tracer (¹²³I or 99mTc-pertechnetate)
• Computer software subtracts the thyroid image, revealing parathyroid tissue
• Limitation: motion artefact can degrade image quality

Classic Scan Finding

Predictive Factors for Scan Result

Causes of False Negative / Limitations

• Multigland disease (MGD): Major shortcoming - in one study, none of 15 patients with MGD were identified preoperatively
• Small gland size (<600 mg)
• Coexisting thyroid disease (nodules, goitre)
• Superior gland location (tends to be smaller)
• Calcium channel blockers: Interfere with sestamibi uptake by parathyroid cells
• Low oxyphil cell content

Indications

• Preoperative localization in primary hyperparathyroidism before first-time surgery
• Preoperative planning for minimally invasive parathyroidectomy (MIP) - requires concordant imaging
• Ectopic gland localization (mediastinal, intrathyroidal, retroesophageal) - sestamibi is superior to ultrasound for mediastinal glands
• Reoperative parathyroid surgery (with fine-cut CT windows)
• Localizing autotransplanted glands in the forearm

Intraoperative Use (Radioguided Surgery)

Comparison with Other Localizing Studies

• Fischer's Mastery of Surgery, 8th ed., pp. 1128-1130
• Scott-Brown's Otorhinolaryngology Head & Neck Surgery, Vol. 1, pp. 882-884
• Goldman-Cecil Medicine, p. (block 39 - Hyperparathyroidism diagnosis)

All Indications for Parathyroid Scan (Sestamibi Scintigraphy)

1. Primary Hyperparathyroidism (pHPT) - Preoperative Localization

• Before minimally invasive parathyroidectomy (MIP): Sestamibi scintigraphy (ideally SPECT/CT) is required to confirm single-gland disease and localize the adenoma to guide a focused, limited unilateral approach. MIP is considered when at least one preoperative study identifies a single suspicious gland.
• Before bilateral cervical exploration (BCE): Even when BCE is planned, preoperative imaging helps the surgeon anticipate gland position and reduces operative time.
• Important caveat: Imaging has no role in diagnosing pHPT or deciding whether to operate - it is purely to assist surgical planning in a patient already committed to surgery. (Fischer's Mastery of Surgery, 8th ed., p. 1163)

2. Ectopic Parathyroid Gland Localization

• Mediastinal adenomas (present in ~15% of persistent/recurrent cases) are frequently missed by ultrasound but detected on sestamibi scan, which surveys the whole body including the chest
• Retroesophageal / paratracheal / intrathyroidal locations
• Ectopic glands within the thyrothymic ligament or within the thymus
• Scan field of view should extend from the neck to the base of the heart to capture all possible ectopic sites

3. Persistent or Recurrent Hyperparathyroidism (Reoperative Surgery)

• After failed first parathyroid exploration, sestamibi scintigraphy is a first-line re-localization study alongside neck ultrasound
• In re-exploration, combined imaging (SPECT/CT + ultrasound ± 4D-CT ± MRI) is often required
• Fine-cut CT windows on SPECT/CT can be specifically used to assess candidacy for reoperation
• Invasive studies (selective arteriography, venous sampling) are only used if non-invasive localization has failed (Pye's Surgical Handicraft, p. 342)

4. Secondary Hyperparathyroidism (sHPT) - Selected Cases

• Routine preoperative scintigraphy is not standard for sHPT (bilateral open exploration is usually performed for renal HPT)
• However, sestamibi scan is indicated in sHPT when:
  • Planning revision surgery after failed prior parathyroidectomy for sHPT
  • Detecting ectopic or supernumerary glands (which influence the surgical plan)
  • Identifying the gland with the lowest MIBI uptake that may be partially autografted or preserved
  • Combination of cervical ultrasound + dual-tracer scintigraphy is recommended for localization in renal HPT undergoing surgery (EANM Practice Guidelines 2021)

5. Tertiary Hyperparathyroidism

• After renal transplantation, persistent autonomous hyperparathyroidism may require parathyroidectomy
• Sestamibi scan is used preoperatively for localization, particularly in re-exploration scenarios

6. Parathyroid Carcinoma - Preoperative Mapping

• When parathyroid carcinoma is suspected (very high PTH, palpable neck mass), scintigraphy helps map the primary lesion and identify potential metastatic or recurrent disease, though sensitivity is limited

7. Intraoperative Radioguided Parathyroidectomy

• 99mTc-sestamibi is injected preoperatively and a handheld gamma probe is used intraoperatively to confirm complete resection of the hyperfunctioning gland
• Particularly used when standard localization is uncertain or in reoperative cases
• Most centers now prefer this as an adjunct to intraoperative PTH (ioPTH) monitoring rather than as the primary guidance tool (Current Surgical Therapy 14e)

8. Autotransplanted Parathyroid Tissue - Function Assessment

• After total parathyroidectomy with forearm autotransplantation (for sHPT), sestamibi can localize functioning transplanted tissue in the forearm if hypercalcaemia recurs
• Confirms the autograft is hyperfunctioning and guides surgical re-excision

9. When Concordant Localization Is Needed for MIP Decision

• Patients with negative or discordant results on ultrasound: sestamibi scan is used as the second-line imaging modality
• Patients in whom a single-gland focus is identified concordantly on both ultrasound and sestamibi are the best candidates for MIP without bilateral exploration

Conditions Where Parathyroid Scan Is NOT Indicated

• Fischer's Mastery of Surgery, 8th ed., pp. 1163-1164
• Scott-Brown's Otorhinolaryngology Head & Neck Surgery, Vol. 1, pp. 882-884
• Pye's Surgical Handicraft, 22nd ed., p. 342
• EANM Practice Guidelines for Parathyroid Imaging (2021) - European Association of Nuclear Medicine

Protocol for Parathyroid Imaging

Step 1 - Patient Preparation

Clinical Checks (Before Booking)

• Confirm biochemical diagnosis of hyperparathyroidism (elevated PTH + hypercalcaemia) - imaging is only for localization, not diagnosis
• Review previous neck surgery notes and pathology reports
• Check for pregnancy / breastfeeding (absolute contraindications to radionuclide imaging)
• Check renal function if 4D-CT is being considered (contrast agent)

Drug Withholding

• Exception: If the patient is on thyroid hormone replacement, do NOT withdraw - instead switch to dual-phase sestamibi (rather than dual-tracer) to avoid hypothyroidism
• If total thyroidectomy has been performed: subtraction technique is not applicable - use dual-phase sestamibi only

Patient Positioning

• Patient supine with a sandbag placed under the shoulders to extend the neck - exactly as positioned on the operating table - under the gamma camera
• Neck hyperextension improves separation of thyroid from parathyroid tissue on images
• Patient must remain completely still especially during dual-tracer studies (motion artefact is the main source of error)
• Claustrophobic patients or those unable to remain still may require sedation

Step 2 - Radiopharmaceuticals

• Dose adjusted based on patient body mass and whether SPECT is planned
• 99mTc-tetrofosmin dual-phase is NOT recommended - it washes out too rapidly from parathyroid tissue to give reliable delayed images

Step 3 - Imaging Protocols

Protocol A: Dual-Phase 99mTc-Sestamibi (Standard / Most Widely Used)

1. IV injection of 99mTc-sestamibi (400-900 MBq)
2. Early images: 10-15 min post-injection
3. Delayed images: 90-150 min post-injection (some centres use 2-3 hours)
4. Both phases: large field of view from skull base to base of heart (to capture ectopic mediastinal glands)
5. Views: anterior + right and left anterolateral planar images

• Large field-of-view gamma camera
• Low-Energy High-Resolution (LEHR) collimators
• Energy window: 140 ± 10 keV
• Matrix size: 128×128 (minimum) or 256×256 (preferred)

Protocol B: Dual-Phase Sestamibi + SPECT/CT (Current Best Practice)

• After early or delayed planar images, perform SPECT/CT acquisition
• SPECT covers neck + upper mediastinum (skull base to heart base)
• CT: use lowest CT dose compatible with the purpose (attenuation correction CT at ~30 mA is sufficient for most cases; fine-cut diagnostic CT at ~120 mA for reoperative cases)
• Fusion of SPECT functional data with CT anatomical data on workstation
• Sensitivity: up to 96% for single adenomas; 88% patient-based pooled detection rate (EANM meta-analysis, 23 papers, 1236 patients)
• SPECT alone (without CT): sensitivity 92-98%

Protocol C: Dual-Tracer Subtraction Scintigraphy

C1: 99mTc-sestamibi / 99mTc-pertechnetate subtraction

• Option 1 (pertechnetate first):
  1. Inject 99mTc-pertechnetate → wait 30 min → acquire 10-min thyroid image
  2. Inject 99mTc-sestamibi → acquire 10-min image 10 min later
  3. Computer-subtract pertechnetate (thyroid) from sestamibi (thyroid + parathyroid)
• Option 2 (sestamibi first):
  1. Acquire early sestamibi image
  2. Inject pertechnetate → immobilize patient 15-30 min → acquire 10-min image
  3. Computer-subtract

C2: 99mTc-sestamibi / ¹²³I-iodide subtraction

• ¹²³I given orally (uptake imaging at 4-6 hours or next day)
• Then sestamibi injected IV; early image at 10-15 min
• Digital subtraction of ¹²³I thyroid image from sestamibi image
• Recommend 2-3 day waiting period between tracers to reduce administered activity/radiation
• Without iodine saturation for the thyroid scan

Protocol D: PET/CT with ¹⁸F-Choline or ¹¹C-Methionine (Emerging)

• Higher spatial resolution than SPECT
• Shorter imaging time (~1 hour total)
• Avoid vigorous exercise before scan (increases muscle uptake)
• No standardized dose/protocol yet per EANM 2021
• Increasingly used in Europe as second-line or even first-line at specialist centres

• Requires on-site cyclotron (limits availability)
• Useful in negative/equivocal sestamibi cases

Step 4 - Image Interpretation

Dual-Phase Sestamibi

• Positive: Focal area of retained activity at delayed phase that was present on early phase - site of hyperfunctioning parathyroid
• True positive pattern: Focus persists or becomes relatively more prominent at 2 hours compared to surrounding thyroid
• False negative: Small gland (<600 mg), rapid washout, thyroid nodule obscuring the focus, calcium channel blockers

SPECT/CT Interpretation

• Report should specify:
  • Which images showed the lesion (early, delayed, or both)
  • Location: Mediastinum vs thyroid bed (upper/lower pole, ectopic); laterality (right/left)
  • Depth and relationship to surrounding structures (enabled by CT)
  • Any confounding factors (patient motion, thyroid nodules, prior thyroidectomy)
  • Whether SPECT or SPECT/CT was used
  • CT parameters used (kVp, mA, pitch, beam width, scan length)

Subtraction Scans

• Residual activity after thyroid subtraction = parathyroid focus
• Limitation: Motion artefact can create false positives or obscure true positives

Step 5 - Radiation Dosimetry Summary

Step 6 - Reporting Checklist

• Patient demographics and clinical indication
• Radiopharmaceutical(s) used, dose, route, and order of administration
• Timing of image acquisition after injection
• Imaging type: planar / SPECT / SPECT-CT
• Projections acquired and region imaged (neck, mediastinum)
• CT parameters (kVp, mA, pitch, beam width, scan length) if CT used
• Presence/absence and location of focal retained activity
• Laterality and depth in relation to thyroid/anatomical landmarks
• Study limitations (motion, thyroid disease, prior surgery)
• Correlation with ultrasound findings if available

Quick Protocol Decision Tree

Primary hyperparathyroidism confirmed biochemically
        |
Is thyroid gland intact?
   |                     |
  YES                    NO (total thyroidectomy)
   |                          |
Is thyroid disease present?   Dual-phase sestamibi only
   |               |
  YES              NO
   |               |
Dual-tracer    Dual-phase sestamibi
subtraction    + SPECT/CT (standard)
+ SPECT/CT
        |
All negative or discordant?
        |
   4D-CT or ¹⁸F-Choline PET/CT

• EANM Practice Guidelines for Parathyroid Imaging (2021)
• SNMMI Practice Guideline for Parathyroid Scintigraphy 4.0
• Scott-Brown's Otorhinolaryngology Head & Neck Surgery, Vol. 1, pp. 882-884
• Fischer's Mastery of Surgery, 8th ed., pp. 1128-1130