- Email: [email protected]
Lugol's iodine in Graves' disease – Revisited
International Journal of Surgery 36 (2016) 30e31
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.journal-surgery.net
Letter to the Editor
Lugol's iodine in Graves' disease e Revisited
Graves' disease (GD) is a genetically determined organ specific autoimmune disease characterized both by excessive production of thyroid hormones and a large diffuse hypervascular inflammatory thyroid gland. Although most patients with GD are treated with radioiodine or medically, surgery is recommended in specific group of patients [1]. Preoperative preparation is crucial to prevent intraoperative and post operative complications like thyroid storm and hemorrhage. Thyrotoxicosis can be adequately controlled by antithyroid drugs but increased gland vascularity resulting in excessive intraoperative bleeding still remains a potential problem. Huang et al. have shown that the higher the thyroid blood flow, the greater the intraoperative blood loss in Graves' disease [2]. This blood flow rate is primarily dependent upon the size and vascular density of the thyroid gland and directly proportional to the severity of Graves' disease. Preoperative treatment with Lugol's iodine for 7e10 days blocks the release of thyroid hormones as well as decreases the vascularity of the thyroid gland. Lugol's iodine contains 6.3mg of iodine per drop of solution. High concentrations of iodide have the capacity to limit their own transport. Acute transient inhibition of the synthesis of iodotyrosines and iodothyronines by high intracellular iodide concentrations is well known as the Wolff-Chaikoff effect. High plasma iodide concentrations result in inhibition of the release of thyroid hormone. The effects are exerted directly on the thyroid gland and are demonstrable both in the thyrotoxic as well as euthyroid patients [3]. Although some endocrine surgeons administer Lugol's iodine to decrease thyroid gland vascularity, there is still no agreement on its effectiveness. Evidence in favour of Lugol's iodine administration comes mainly from imaging studies assessing thyroid blood flow [4,5]. In the study by Ansaldo et al. [6], twenty five patients with diffuse toxic goiter (DTG) were treated with Lugol's iodine for 7 days, mean basal Doppler Resistance Index (RI) of intrathyroid arterial flow was significantly lower in patients with DTG compared with normal controls. Moreover, the RI was significantly increased in patients with DTG after Lugol's iodine treatment. In the study by Huang et al. [7], twenty-five euthyroid Graves' disease patients were preoperatively treated with Lugol's iodine for 10 days. On doppler ultrasonography, there was a 60% average reduction in blood flow on the operative day from the baseline blood flow. Although, the difference in physiological parameters like thyroidal blood flow after treatment with Lugol's iodine is well established, it is not clear whether this reduction in blood flow necessarily translate to a difference in clinical outcomes in terms
of blood loss rates. An older randomized controlled study by Coyle et al. showed no appreciable difference in blood loss at thyroidectomy whether or not Lugol's iodine was administered [8]. However, a recent randomized study by Erbil et al. did report a significance difference with administration of Lugol's iodine, as the patient becomes euthyroid after an antithyroid drug treatment, the additional effect of Lugol's iodine is a reduction of blood flow and of thyroid vascularity [9]. In this study, 36 patients with GD were randomly assigned either to pre-operative treatment with Lugol's iodine or to no treatment. The study demonstrated a statistically significant difference in intraoperative blood loss (54 ml in the Lugol's iodine group vs 108 ml in the control group, 9.33-fold decrease in Lugol's iodine group). The evidence for the utility of Lugol's iodine administration has been mixed, however recent studies have shown a significant decrease in thyroid gland blood flow and intraoperative blood loss even in Euthyroid GD [6,7,9]. Current American Thyroid Association (ATA) guidelines recommends Lugol's iodine in Grave's disease patients in the immediate preoperative period to reduce gland vascularity. Conclusion Lugol's iodine can be routinely used preoperatively in Hyperthyroid GD as it reduces hormone secretion as well as gland vascularity and is also recommended in Euthyroid GD as it definitely reduces the vascularity of the gland even in Euthyroid state. Conflicts of interest None. Sources of funding None. Ethical approval None. Author contribution
http://dx.doi.org/10.1016/j.ijsu.2016.10.018 1743-9191/© 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
Ashwini Reddy e study design, analysis and writing. Mayilvaganan Sabaretnam e study design, analysis and writing.
Letter to the Editor / International Journal of Surgery 36 (2016) 30e31
Guarantor Ashwini Reddy. Mayilvaganan Sabaretnam. References [1] D.S. Cooper, Hyperthyroidism, Lancet 362 (9382) (2003 Aug 9) 459e468. [2] S.M. Huang, N.H. Chow, H.L. Lee, et al., The value of color flow Doppler ultrasonography of the superior thyroid artery in the surgical management of Graves disease, Arch. Surg. 138 (2003) 146e151. [3] Goodman & Gilman's The Pharmacological Basis of Therapeutics. [4] J.F. Rodier, J.C. Janser, H. Petit, O. Schneegans, G. Ott, A. Kaissling, J.C. Grob, M. Velten, Effect of preoperative administration of Lugol's solution on thyroid blood flow in hyperthyroidism, Ann. Chir. 52 (3) (1998) 229e233. [5] D.C. Chang, M.H. Wheeler, J.P. Woodcock, I. Curley, J.R. Lazarus, H. Fung, R. John, R. Hall, A.M. McGregor, The effect of preoperative Lugol iodine on thyroid blood flow in patients with Graves' hyperthyroidism, Surgery 102 (1987) 1055e1061. [6] G.L. Ansaldo, F. Pretolesi, E. Varaldo, C. Meola, M. Minuto, G. Borgonovo, DerchiLE,Torre GC. Doppler evaluation of intrathyroid arterial resistances during preoperative treatment with Lugol's iodide solution in patients with diffuse toxic
31
goiter, J. Am. Coll. Surg. 191 (6) (2000 Dec) 607e612. [7] S.M. Huang, W.T. Liao, C.F. Lin, H.S. Sun, N.H. Chow, Effectiveness and mechanism of preoperative lugol solution for reducing thyroid blood flow in patients with Euthyroid Graves' disease, World J. Surg. 40 (3) (March 1 2016) 505e509. [8] P.J. Coyle, J.E. Mitchell, Thyroidectomy: is Lugol's iodine necessary? Ann. R. Coll. Surg.Engl. 64 (5) (Sep; 1982) 334e335. [9] Y. Erbil, Y. Ozluk, M. Giris, et al., Effect of lugol solution on thyroid gland blood flow and microvessel density in the patients with Graves' disease, J. Clin. Endocrinol. Metab. 92 (2007) 2182e2189.
Ashwini C. Reddy, Mayilvaganan Sabaretnam* Department of Endocrine and Breast Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, India *
Corresponding author. E-mail address: [email protected] (M. Sabaretnam). 27 June 2016 Available online 18 October 2016
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.journal-surgery.net
Letter to the Editor
Lugol's iodine in Graves' disease e Revisited
Graves' disease (GD) is a genetically determined organ specific autoimmune disease characterized both by excessive production of thyroid hormones and a large diffuse hypervascular inflammatory thyroid gland. Although most patients with GD are treated with radioiodine or medically, surgery is recommended in specific group of patients [1]. Preoperative preparation is crucial to prevent intraoperative and post operative complications like thyroid storm and hemorrhage. Thyrotoxicosis can be adequately controlled by antithyroid drugs but increased gland vascularity resulting in excessive intraoperative bleeding still remains a potential problem. Huang et al. have shown that the higher the thyroid blood flow, the greater the intraoperative blood loss in Graves' disease [2]. This blood flow rate is primarily dependent upon the size and vascular density of the thyroid gland and directly proportional to the severity of Graves' disease. Preoperative treatment with Lugol's iodine for 7e10 days blocks the release of thyroid hormones as well as decreases the vascularity of the thyroid gland. Lugol's iodine contains 6.3mg of iodine per drop of solution. High concentrations of iodide have the capacity to limit their own transport. Acute transient inhibition of the synthesis of iodotyrosines and iodothyronines by high intracellular iodide concentrations is well known as the Wolff-Chaikoff effect. High plasma iodide concentrations result in inhibition of the release of thyroid hormone. The effects are exerted directly on the thyroid gland and are demonstrable both in the thyrotoxic as well as euthyroid patients [3]. Although some endocrine surgeons administer Lugol's iodine to decrease thyroid gland vascularity, there is still no agreement on its effectiveness. Evidence in favour of Lugol's iodine administration comes mainly from imaging studies assessing thyroid blood flow [4,5]. In the study by Ansaldo et al. [6], twenty five patients with diffuse toxic goiter (DTG) were treated with Lugol's iodine for 7 days, mean basal Doppler Resistance Index (RI) of intrathyroid arterial flow was significantly lower in patients with DTG compared with normal controls. Moreover, the RI was significantly increased in patients with DTG after Lugol's iodine treatment. In the study by Huang et al. [7], twenty-five euthyroid Graves' disease patients were preoperatively treated with Lugol's iodine for 10 days. On doppler ultrasonography, there was a 60% average reduction in blood flow on the operative day from the baseline blood flow. Although, the difference in physiological parameters like thyroidal blood flow after treatment with Lugol's iodine is well established, it is not clear whether this reduction in blood flow necessarily translate to a difference in clinical outcomes in terms
of blood loss rates. An older randomized controlled study by Coyle et al. showed no appreciable difference in blood loss at thyroidectomy whether or not Lugol's iodine was administered [8]. However, a recent randomized study by Erbil et al. did report a significance difference with administration of Lugol's iodine, as the patient becomes euthyroid after an antithyroid drug treatment, the additional effect of Lugol's iodine is a reduction of blood flow and of thyroid vascularity [9]. In this study, 36 patients with GD were randomly assigned either to pre-operative treatment with Lugol's iodine or to no treatment. The study demonstrated a statistically significant difference in intraoperative blood loss (54 ml in the Lugol's iodine group vs 108 ml in the control group, 9.33-fold decrease in Lugol's iodine group). The evidence for the utility of Lugol's iodine administration has been mixed, however recent studies have shown a significant decrease in thyroid gland blood flow and intraoperative blood loss even in Euthyroid GD [6,7,9]. Current American Thyroid Association (ATA) guidelines recommends Lugol's iodine in Grave's disease patients in the immediate preoperative period to reduce gland vascularity. Conclusion Lugol's iodine can be routinely used preoperatively in Hyperthyroid GD as it reduces hormone secretion as well as gland vascularity and is also recommended in Euthyroid GD as it definitely reduces the vascularity of the gland even in Euthyroid state. Conflicts of interest None. Sources of funding None. Ethical approval None. Author contribution
http://dx.doi.org/10.1016/j.ijsu.2016.10.018 1743-9191/© 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.
Ashwini Reddy e study design, analysis and writing. Mayilvaganan Sabaretnam e study design, analysis and writing.
Letter to the Editor / International Journal of Surgery 36 (2016) 30e31
Guarantor Ashwini Reddy. Mayilvaganan Sabaretnam. References [1] D.S. Cooper, Hyperthyroidism, Lancet 362 (9382) (2003 Aug 9) 459e468. [2] S.M. Huang, N.H. Chow, H.L. Lee, et al., The value of color flow Doppler ultrasonography of the superior thyroid artery in the surgical management of Graves disease, Arch. Surg. 138 (2003) 146e151. [3] Goodman & Gilman's The Pharmacological Basis of Therapeutics. [4] J.F. Rodier, J.C. Janser, H. Petit, O. Schneegans, G. Ott, A. Kaissling, J.C. Grob, M. Velten, Effect of preoperative administration of Lugol's solution on thyroid blood flow in hyperthyroidism, Ann. Chir. 52 (3) (1998) 229e233. [5] D.C. Chang, M.H. Wheeler, J.P. Woodcock, I. Curley, J.R. Lazarus, H. Fung, R. John, R. Hall, A.M. McGregor, The effect of preoperative Lugol iodine on thyroid blood flow in patients with Graves' hyperthyroidism, Surgery 102 (1987) 1055e1061. [6] G.L. Ansaldo, F. Pretolesi, E. Varaldo, C. Meola, M. Minuto, G. Borgonovo, DerchiLE,Torre GC. Doppler evaluation of intrathyroid arterial resistances during preoperative treatment with Lugol's iodide solution in patients with diffuse toxic
31
goiter, J. Am. Coll. Surg. 191 (6) (2000 Dec) 607e612. [7] S.M. Huang, W.T. Liao, C.F. Lin, H.S. Sun, N.H. Chow, Effectiveness and mechanism of preoperative lugol solution for reducing thyroid blood flow in patients with Euthyroid Graves' disease, World J. Surg. 40 (3) (March 1 2016) 505e509. [8] P.J. Coyle, J.E. Mitchell, Thyroidectomy: is Lugol's iodine necessary? Ann. R. Coll. Surg.Engl. 64 (5) (Sep; 1982) 334e335. [9] Y. Erbil, Y. Ozluk, M. Giris, et al., Effect of lugol solution on thyroid gland blood flow and microvessel density in the patients with Graves' disease, J. Clin. Endocrinol. Metab. 92 (2007) 2182e2189.
Ashwini C. Reddy, Mayilvaganan Sabaretnam* Department of Endocrine and Breast Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, India *
Corresponding author. E-mail address: [email protected] (M. Sabaretnam). 27 June 2016 Available online 18 October 2016