Autofluorescence and Indocyanine Green to Avoid Hypocalcemia After Thyroidectomy

Study Overview
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Brief Summary
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Hypoparathyroidism (and the resulting hypocalcemia) remains the most common morbidity after a total thyroidectomy. The identification and preservation of parathyroid glands during neck surgery has always been challenging but is crucial to avoid postoperative hypocalcemia. Recently, the specific autofluorescent characteristics of endogenous fluorophores in the parathyroid tissue have been used to detect and confirm parathyroid glands during thyroid surgery. Injecting indocyanine green and using its fluorescent characteristics has the advantage of adding information about the vascular supply of the parathyroid glands. This randomized clinical trial aims to investigate whether using autofluorescence and indocyanine green during thyroid surgery can predict or prevent postoperative hypocalcemia.

Detailed Description
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Hypoparathyroidism (and the resulting hypocalcemia) remains the most common morbidity after a total thyroidectomy. When defined as corrected serum calcium levels below 2.10 mmol/L, the temporary rates of hypocalcemia after a total thyroidectomy excluding lymph node neck dissection still easily exceed 20% (BAETS fifth national audit report, 2017). When extending the follow-up period to more than six months after surgery, late or permanent hypocalcemia is seen in over 5% of patients after a total thyroidectomy. These British numbers have been confirmed in large European and American databases. A large, Belgian, single-center analysis, including redo-surgery and lymph node neck dissections, confirmed temporary and permanent rates of hypocalcemia of 32% and 3%, respectively. While temporary hypocalcemia results in a reduced quality of life, additional medical costs to the patients and the society, and hypocalcemia-related symptoms, permanent hypocalcemia adds an increased risk of developing renal failure, basal ganglia calcifications, neuropsychiatric derangements, and infections. The identification and preservation of parathyroid glands during neck surgery has always been challenging but is crucial to avoid postoperative hypocalcemia. The visual evaluation of parathyroid gland vascularization is even more challenging, prone to subjectivity, and depending on surgical experience and surgical volume. Moreover, even experienced endocrine surgeons appear to be unreliable in using visual scores to assess the viability of parathyroid glands. Recently, the specific autofluorescent characteristics of endogenous fluorophores in the parathyroid tissue have been used to detect and confirm parathyroid glands during thyroid surgery. However, this signal does not provide any information on viability and vascularization of the parathyroid glands. Injecting indocyanine green (ICG) and using its fluorescent characteristics has the advantage of adding information about the vascular supply of the parathyroid glands. The combined technique of autofluorescent and ICG-enhanced imaging suffers from lack of standardization, optimal technique, dosage, and timing of the ICG administration, and still must prove its possible benefit in a clinical setting. Hence, this randomized clinical trial aims to investigate whether using autofluorescence (AF) and indocyanine green during thyroid surgery can predict or prevent postoperative hypocalcemia. By using parathyroid gland detection via autofluorescence imaging and verifying their viability after ICG injection, the authors aim to identify patients at risk of hypocalcemia.

Official Title
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The Use of Autofluorescence and Indocyanine Green to Avoid Hypocalcemia After Total Thyroidectomy: A Randomized Clinical Trial

Conditions
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Thyroid Disease, Hypoparathyroidism Postprocedural

Intervention / Treatment
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* Drug: Autofluorescent detection + Injection of indocyanine green
* Procedure: Gold standard of visual identification and evaluation of viability of the parathyroid glands.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All adult patients undergoing a total thyroidectomy without previous neck surgery. Exclusion Criteria: Children and teenagers (<18 years old) Patients refusing participation or unable/unwilling to sign the informed consent Patients with a completion thyroidectomy Patients with planned central and lateral neck lymph node dissections (thyroid cancer) Patients with previous neck surgery Patients with a known allergy/hypersensitivity to indocyanine green

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-center, comparative, randomized, single-blind, controlled trial against the gold standard of visual identification and viability evaluation.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autofluorescent detection and injection of indocyanine green<br>Drug: indocyanine green (ICG) Autofluorescence detection of the parathyroid glands and injection of indocyanine green at two predefined timepoints will be performed to evaluate the vascularization of the parathyroid glands. | Drug: Autofluorescent detection + Injection of indocyanine green<br>* All four parathyroid glands will be actively sought for in every case selected for the use of AF/ICG, with AF verification of parathyroid tissue. The timepoints of AF will be: 1 = after lateral dissection side 1 (side 1) 2= after lateral dissection side 2 (side 2) The timepoints of ICG injection will be: 1 = after the first thyroid lobectomy (side 1) 2 = after the second thyroid lobectomy (side 2) Scoring of the viability of parathyroid glands (adapted from Vidal Fortuny et al., 2016): 1 = black = not viable/vascularized 2 = grey = moderately viably/ moderately vascularized 3 = white = viable/well-vascularized<br>* Other names: ICG Injection;|
| Placebo Comparator: Control group<br>Gold standard of visual identification and evaluation of viability. | Procedure: Gold standard of visual identification and evaluation of viability of the parathyroid glands.<br>* Gold standard of visual identification and evaluation of viability of the parathyroid glands.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative hypocalcemia | Defined as parathyroid hormone (PTH) levels <15 pg/mL, serum calcium levels <2.10 mmol/L, or the intake of calcium or activated vitamin D supplements after total thyroidectomy. | One week after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of identified parathyroid glands | Visual identification and confirmation with autofluorescence | 1 hour after surgery | 
| The number of reimplanted parathyroid glands | Visual identification and decision to re-implant after ICG | 1 hour after surgery | 
| The presence of late or permanent hypocalcemia | Defined as persistent PTH levels <15 pg/mL, persistent serum calcium levels <2.10 mmol/L, or continued intake of calcium or activated vitamin D supplements more than six months after surgery. | Six months after surgery |