Preoperative Lugol's Solution in Graves' Disease and Toxic Nodular Goiter

Hyperthyroidism Clinical Trial

Official title:

Preoperative Lugol's Solution in Graves' Disease and Toxic Nodular Goiter

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04856488
• Other study ID #: LugolProtocol001
• Status: Recruiting
• Phase: Phase 3
• Start date: November 18, 2021
• Est. completion date: August 2025

Study information

• Verified date: October 2023
• Source: Karolinska University Hospital
• Contact: Jan Calissendorff, MD, PhD
• Phone: +46(0)8 51770000
• Email: jan.calissendorff[@]regionstockholm.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess if preoperative treatment with Lugol's solution prior to thyroidectomy can reduce the surgical complications hypoparathyroidism and laryngeal nerve palsy

Description:

Current practice in Sweden before thyroidectomy due to hyperthyroidism is preoperative treatment with antithyroid drugs (ATD) to all patients with Graves' disease and in cases of toxic nodular goiter with pronounced hyperthyroidism. Iodine solution is administered preoperatively in selected cases of Graves' disease where ATD is intolerable. In the cases where iodine is used it is in the form of extemporaneous prepared iodine potassium iodide solution (Lugol 5%). The dose varies in clinical studies. In American and Swedish guidelines the dose is 5-10 drops 3 times per day for 10 days prior to surgery. American guidelines recommend iodine as preoperative treatment i Graves' disease but this is based on sparse evidence. Iodine as preoperative treatment in toxic nodular goiter has yet not been studied.

The purpose of this study is to assess if preoperative treatment with Lugol's solution prior to thyroidectomy due to hyperthyroidism reduce the surgical complications hypoparathyroidism and laryngeal nerve palsy.

Before including toxic nodular goiters accepted for surgery, a pilot study will be performed on 20 patients with toxic nodular goiter. They will receive Lugol solution 3 times per day for ten days and thyroid hormone levels will be measured day 0, day 3-4, day 6-7 and after 10 days of Lugol treatment. Heart rate assessed and ThyPRO39 filled out before and after treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 182
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Hyperthyroidism accepted for thyroidectomy due to toxic nodular goiter with free T4 <30 pmol/L or Graves' disease

• Signed informed consent

Exclusion Criteria:

• Unstable coronary artery disease

• Previous thyroid surgery

• Congestive heart failure

• Renal insufficiency

• Hepatic failure

• Current infection

• Treatment with steroids or anticoagulants

• Thyroid associated orbitopathy CAS > 2

• Diabetes mellitus type 1

• Active cancer

• Severe psychiatric illness

• Amiodarone treatment

• Pregnancy

• Breast feeding

• Women of child bearing potential not using contraceptive

• Inability to comprehend the meaning of the study

• Iodine hypersensitivity

Related Conditions & MeSH terms

• Goiter, Nodular
• Graves Disease
• Hyperthyroidism

Intervention

Drug:
• Iodine-Potassium Iodide 5%-10% Oral and Topical Solution
Iodine Potassium Iodide 5% oral solution, administered 3 times per day for 10 days

Locations

Country	Name	City	State
Sweden	Department of Endocrinology, Karolinska University Hospital	Solna	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Jan Calissendorff

Country where clinical trial is conducted

Sweden, 

References & Publications (11)

Calissendorff J, Falhammar H. Lugol's solution and other iodide preparations: perspectives and research directions in Graves' disease. Endocrine. 2017 Dec;58(3):467-473. doi: 10.1007/s12020-017-1461-8. Epub 2017 Oct 26. — View Citation

Calissendorff J, Falhammar H. Rescue pre-operative treatment with Lugol's solution in uncontrolled Graves' disease. Endocr Connect. 2017 May;6(4):200-205. doi: 10.1530/EC-17-0025. Epub 2017 Mar 21. — View Citation

Huang SM, Liao WT, Lin CF, Sun HS, Chow NH. Effectiveness and Mechanism of Preoperative Lugol Solution for Reducing Thyroid Blood Flow in Patients with Euthyroid Graves' Disease. World J Surg. 2016 Mar;40(3):505-9. doi: 10.1007/s00268-015-3298-8. — View Citation

Kaur S, Parr JH, Ramsay ID, Hennebry TM, Jarvis KJ, Lester E. Effect of preoperative iodine in patients with Graves' disease controlled with antithyroid drugs and thyroxine. Ann R Coll Surg Engl. 1988 May;70(3):123-7. — View Citation

Marigold JH, Morgan AK, Earle DJ, Young AE, Croft DN. Lugol's iodine: its effect on thyroid blood flow in patients with thyrotoxicosis. Br J Surg. 1985 Jan;72(1):45-7. doi: 10.1002/bjs.1800720118. — View Citation

Nauman J, Wolff J. Iodide prophylaxis in Poland after the Chernobyl reactor accident: benefits and risks. Am J Med. 1993 May;94(5):524-532. doi: 10.1016/0002-9343(93)90089-8. No abstract available. — View Citation

Randle RW, Bates MF, Long KL, Pitt SC, Schneider DF, Sippel RS. Impact of potassium iodide on thyroidectomy for Graves' disease: Implications for safety and operative difficulty. Surgery. 2018 Jan;163(1):68-72. doi: 10.1016/j.surg.2017.03.030. Epub 2017 Nov 3. — View Citation

Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct;26(10):1343-1421. doi: 10.1089/thy.2016.0229. Erratum In: Thyroid. 2017 Nov;27(11):1462. — View Citation

Spallek L, Krille L, Reiners C, Schneider R, Yamashita S, Zeeb H. Adverse effects of iodine thyroid blocking: a systematic review. Radiat Prot Dosimetry. 2012 Jul;150(3):267-77. doi: 10.1093/rpd/ncr400. Epub 2011 Oct 20. — View Citation

Whalen G, Sullivan M, Maranda L, Quinlan R, Larkin A. Randomized trial of a short course of preoperative potassium iodide in patients undergoing thyroidectomy for Graves' disease. Am J Surg. 2017 Apr;213(4):805-809. doi: 10.1016/j.amjsurg.2016.07.015. Epub 2016 Aug 4. — View Citation

Yilmaz Y, Kamer KE, Ureyen O, Sari E, Acar T, Karahalli O. The effect of preoperative Lugol's iodine on intraoperative bleeding in patients with hyperthyroidism. Ann Med Surg (Lond). 2016 Jun 16;9:53-7. doi: 10.1016/j.amsu.2016.06.002. eCollection 2016 Aug. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from Baseline in Quality of Life on the Thyroid Specific Patient Reported Outcome 39 (ThyPRO 29) questionnaire	ThyPRO 39 is a validated thyroid specific Quality of Life form. Self reported questionnaire filled out before and after surgery. ThyPRO consists of 39 items grouped in 11 scales. Each item is is rated from 0 to 5 on a 5 point Likert scale. Increasing scores indicating decreasing quality of life. Lower scores indicating better quality of life.	6 months postoperatively
Primary	Temporary hypoparathyroidism	Numbers of participants with signs of hypoparathyroidism measured as hypocalcemia, low parathormone (PTH), supplementation with per oral vitamin D or calcium.	1 month postoperatively
Secondary	Temporary laryngeal nerve palsy	Number of patients with postoperative signs of vocal chord damage via clinical assessment or laryngoscopy.	1 month postoperatively
Secondary	Permanent laryngeal nerve palsy	Number of patients with postoperative signs of vocal chord damage via clinical assessment or laryngoscopy.	6 months postoperatively
Secondary	Permanent hypoparathyroidism	Numbers of participants with signs of hypoparathyroidism measured as hypocalcemia, low PTH, supplementation with per oral vitamin D or calcium.	6 months postoperatively