WHITE CAP: Intra-operative Parathyroid Tissue Sensor (PTS)-Guided Assessment of Parathyroid Viability and Surgical Decision-Making

Background and Rationale Near-infrared autofluorescence (NIRAF) highlights parathyroid tissue at a wavelength of 820 nm. Several devices, including Fluobeam LX and PTeye®, have FDA 510(k) clearance for intra-operative identification of parathyroid glands. In \~70 % of single-gland disease, NIRAF shows a viable rim of normal tissue partially encasing the adenoma. Retrospective data conflict on whether rim preservation reduces transient hypocalcaemia or increases recurrence. No prospective randomized evidence exists.

Objectives Primary: Compare the incidence of transient hypocalcaemia (albumin-corrected Ca < 2.00 mmol·L-¹ or need for calcium/vit-D supplementation) within 48 h post-operative between preservation and en-bloc strategies.

Secondary: (i) Permanent hypocalcaemia at 6 months; (ii) PTH ≥ 15 pg·mL-¹ at 24 h; (iii) operative time and blood loss; (iv) biochemical or clinical recurrence up to 24 months; (v) correlation of quantitative NIRAF intensity with gland viability.

Study Design Multicentre, parallel-group, 1:1 randomized controlled trial (RCT). Block randomisation (size 4) stratified by centre and baseline vitamin-D status. Total sample 120 participants (60 per arm, includes 10 % attrition). Single-blind: outcome assessors and laboratory staff remain unaware of allocation.

Interventions Preservation arm: After adenoma excision, surgeon confirms NIRAF-positive rim and leaves it in situ; only minimal defatting to ensure vascularity.

En-bloc arm: Adenoma plus NIRAF-positive rim excised en bloc. If fewer than two normal glands remain in the neck, a 30 mg fragment is minced and autotransplanted into the non-dominant brachioradialis.

Eligibility Inclusion: age 18-75 y; biochemically confirmed primary hyperparathyroidism; imaging (MIBI or 4D-CT) concordant with a solitary adenoma; written informed consent.

Exclusion: multiple endocrine neoplasia, >1 enlarged gland on imaging, eGFR < 30, pregnancy, neck re-exploration, planned concomitant total thyroidectomy.

Outcome Assessments Serum Ca, phosphate, Mg, PTH measured pre-op; 6 h, 24 h, 48 h; Day 7; Months 1, 6, 12, 24. Laryngoscopy if voice change occurs. Recurrence defined as Ca above upper limit plus PTH > 65 pg·mL-¹ after Month 12. NIRAF intensity recorded (arbitrary units) using standard ROI software.

Statistical Plan Transient hypocalcaemia expected 30 % in en-bloc vs 10 % in preservation. With α = 0.05, 1-β = 0.80, needs 54 per arm; rounded to 60. Intent-to-treat analysis. Risk ratios with 95 % CI; secondary continuous outcomes by mixed-effects ANCOVA. Interim safety review at 50 % recruitment (O'Brien-Fleming boundary).

Regulatory and Ethics PTS devices are FDA-cleared; study classified as non-significant-risk device research exempt from IDE (21 CFR 812.2(b)). All centres have IRB approval. Data stored in REDCap, anonymised, GDPR-compliant. A three-member DSMB (endocrine surgeon, endocrinologist, biostatistician) will monitor AEs; trial pause if permanent hypocalcaemia exceeds 15 %.

Data Sharing De-identified participant data and analytic code will be available upon reasonable request 6 months after primary publication.

• Near-Infrared Parathyroid Tissue Sensor Imaging (PTS) (Device): FDA-cleared imager (e.g., Fluobeam LX/PTeye) providing real-time autofluorescence to identify parathyroid tissue during surgery; no dye or radiation.
• Rim-Preservation Technique (Procedure): Surgical excision of adenoma while leaving the NIRAF-positive rim of normal parathyroid tissue in situ; minimal defatting to ensure perfusion.
• En-bloc Resection Technique (Procedure): Surgical excision of adenoma together with the surrounding NIRAF-positive rim; autotransplant fragment if < 2 normal glands remain in neck.

Primary outcomes

• Incidence of Transient Hypocalcaemia [Baseline to 48 hours after surgery (Post-op Day 0-2)]: Proportion of participants whose albumin-corrected serum calcium falls < 2.00 mmol/L or who require oral/IV calcium ± active vitamin D to maintain normocalcaemia within 48 h post-operatively. Blood samples at 6 h, 24 h, and 48 h will be analysed by a blinded central laboratory.

Secondary outcomes

• Permanent Hypocalcaemia [6 months (±14 days) post-op]: Need for ongoing calcium ± calcitriol to maintain normocalcaemia at ≥ 6 months after surgery.
• Parathyroid Hormone (PTH) Recovery ≥ 15 pg/mL [24 hours post-op]: Percentage of patients with serum PTH ≥ 15 pg/mL at 24 h, indicating preserved parathyroid function.
• Operative Time [Intra-operative (minutes)]: Skin incision to skin closure, recorded by anaesthesia time stamp.
• Estimated Blood Loss [Intra-operative (mL)]: Calculated from suction canister minus irrigation plus soaked swab weight.
• Biochemical or Clinical Recurrence [12 to 24 months post-op]: Recurrence defined as serum calcium above lab upper limit of normal + PTH > 65 pg/mL and/or imaging-confirmed adenoma regrowth.
• Correlation of NIRAF Intensity with PTH Recovery [Intra-op & 24 hours post-op]: Spearman correlation between quantitative NIRAF counts (ROI) and 24-h PTH value.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Age 18 to 75 years, able to give informed consent.
* Biochemically proven primary hyperparathyroidism (elevated serum calcium and inappropriately high PTH).
* Pre-operative imaging (sestamibi scan, 4-phase CT, or ultrasound) concordant with a single parathyroid adenoma.
* Planned minimally invasive parathyroidectomy using near-infrared parathyroid tissue sensor (PTS) guidance.

Exclusion Criteria:

* Multiple endocrine neoplasia (MEN 1 or 2) or suspicion of multi-gland disease (>1 enlarged gland on imaging).
* Prior parathyroid or extensive neck surgery causing distorted anatomy.
* Need for simultaneous total thyroidectomy or other major neck procedure.
* Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m².
* Pregnancy or breastfeeding.
* Inability to tolerate general anaesthesia or contraindication to intra-operative PTS imaging.