Early postoperative levothyroxine initiation after total thyroidectomy for Graves’ disease
No evidence-based standards exist regarding levothyroxine (LT4) replacement therapy initiation timing in patients with hyperthyroid Graves’ disease undergoing total thyroidectomy. Although LT4 replacement from the first postoperative day has been the standard of care at our hospital, its clinical va...
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Published in | Endocrine Journal Vol. 72; no. 7; pp. 813 - 818 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Japan
The Japan Endocrine Society
01.01.2025
一般社団法人 日本内分泌学会 Japan Science and Technology Agency |
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ISSN | 0918-8959 1348-4540 1348-4540 |
DOI | 10.1507/endocrj.EJ25-0009 |
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Abstract | No evidence-based standards exist regarding levothyroxine (LT4) replacement therapy initiation timing in patients with hyperthyroid Graves’ disease undergoing total thyroidectomy. Although LT4 replacement from the first postoperative day has been the standard of care at our hospital, its clinical validity has not been thoroughly examined. This study investigated the perioperative kinetics of thyroid hormones to assess the safety and efficacy of early LT4 initiation. Thirty patients with Graves’ disease (18 hyperthyroid and 12 euthyroid) and 12 with thyroid nodules who underwent total thyroidectomy were included. Blood samples were collected from each patient for thyroid hormone measurement on the day before surgery (D-1), 15 min after surgery (D0), at 8:00 am on days 1 (D1) and 3 (D3), and 3 weeks (W3) and 3 months (M3) after surgery. In 18 patients with hyperthyroid Graves’ disease, serum free triiodothyronine (FT3) levels significantly decreased immediately after surgery and were within the normal range by D1. Although LT4 was started on D1, FT3 levels continued to decline by D3 and remained low at W3 and M3. Serum FT4 levels followed a slower decline but remained within the normal range for M3. In patients with euthyroid Graves’ disease and those with thyroid nodules, hormone levels stayed within or around the reference range throughout the observation period. In conclusion, initiating LT4 on the day after surgery is safe and effective for maintaining thyroid function in patients with hyperthyroid Graves’ disease undergoing total thyroidectomy. These results could inform future guidelines, supporting earlier postoperative LT4 initiation. |
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AbstractList | No evidence-based standards exist regarding levothyroxine (LT4) replacement therapy initiation timing in patients with hyperthyroid Graves’ disease undergoing total thyroidectomy. Although LT4 replacement from the first postoperative day has been the standard of care at our hospital, its clinical validity has not been thoroughly examined. This study investigated the perioperative kinetics of thyroid hormones to assess the safety and efficacy of early LT4 initiation. Thirty patients with Graves’ disease (18 hyperthyroid and 12 euthyroid) and 12 with thyroid nodules who underwent total thyroidectomy were included. Blood samples were collected from each patient for thyroid hormone measurement on the day before surgery (D-1), 15 min after surgery (D0), at 8:00 am on days 1 (D1) and 3 (D3), and 3 weeks (W3) and 3 months (M3) after surgery. In 18 patients with hyperthyroid Graves’ disease, serum free triiodothyronine (FT3) levels significantly decreased immediately after surgery and were within the normal range by D1. Although LT4 was started on D1, FT3 levels continued to decline by D3 and remained low at W3 and M3. Serum FT4 levels followed a slower decline but remained within the normal range for M3. In patients with euthyroid Graves’ disease and those with thyroid nodules, hormone levels stayed within or around the reference range throughout the observation period. In conclusion, initiating LT4 on the day after surgery is safe and effective for maintaining thyroid function in patients with hyperthyroid Graves’ disease undergoing total thyroidectomy. These results could inform future guidelines, supporting earlier postoperative LT4 initiation. No evidence-based standards exist regarding levothyroxine (LT4) replacement therapy initiation timing in patients with hyperthyroid Graves' disease undergoing total thyroidectomy. Although LT4 replacement from the first postoperative day has been the standard of care at our hospital, its clinical validity has not been thoroughly examined. This study investigated the perioperative kinetics of thyroid hormones to assess the safety and efficacy of early LT4 initiation. Thirty patients with Graves' disease (18 hyperthyroid and 12 euthyroid) and 12 with thyroid nodules who underwent total thyroidectomy were included. Blood samples were collected from each patient for thyroid hormone measurement on the day before surgery (D-1), 15 min after surgery (D0), at 8:00 am on days 1 (D1) and 3 (D3), and 3 weeks (W3) and 3 months (M3) after surgery. In 18 patients with hyperthyroid Graves' disease, serum free triiodothyronine (FT3) levels significantly decreased immediately after surgery and were within the normal range by D1. Although LT4 was started on D1, FT3 levels continued to decline by D3 and remained low at W3 and M3. Serum FT4 levels followed a slower decline but remained within the normal range for M3. In patients with euthyroid Graves' disease and those with thyroid nodules, hormone levels stayed within or around the reference range throughout the observation period. In conclusion, initiating LT4 on the day after surgery is safe and effective for maintaining thyroid function in patients with hyperthyroid Graves' disease undergoing total thyroidectomy. These results could inform future guidelines, supporting earlier postoperative LT4 initiation.No evidence-based standards exist regarding levothyroxine (LT4) replacement therapy initiation timing in patients with hyperthyroid Graves' disease undergoing total thyroidectomy. Although LT4 replacement from the first postoperative day has been the standard of care at our hospital, its clinical validity has not been thoroughly examined. This study investigated the perioperative kinetics of thyroid hormones to assess the safety and efficacy of early LT4 initiation. Thirty patients with Graves' disease (18 hyperthyroid and 12 euthyroid) and 12 with thyroid nodules who underwent total thyroidectomy were included. Blood samples were collected from each patient for thyroid hormone measurement on the day before surgery (D-1), 15 min after surgery (D0), at 8:00 am on days 1 (D1) and 3 (D3), and 3 weeks (W3) and 3 months (M3) after surgery. In 18 patients with hyperthyroid Graves' disease, serum free triiodothyronine (FT3) levels significantly decreased immediately after surgery and were within the normal range by D1. Although LT4 was started on D1, FT3 levels continued to decline by D3 and remained low at W3 and M3. Serum FT4 levels followed a slower decline but remained within the normal range for M3. In patients with euthyroid Graves' disease and those with thyroid nodules, hormone levels stayed within or around the reference range throughout the observation period. In conclusion, initiating LT4 on the day after surgery is safe and effective for maintaining thyroid function in patients with hyperthyroid Graves' disease undergoing total thyroidectomy. These results could inform future guidelines, supporting earlier postoperative LT4 initiation. |
ArticleNumber | EJ25-0009 |
Author | Daisuke Tatsushima Atsushi Yamaoka Hiroyuki Yamashita Takashi Fukuda Hiroshi Takahashi Seigo Tachibana Yusuke Mori Shinya Sato Kento Katsuyama Yuji Nagayama Hisakazu Shindo Misa Okamura |
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Cites_doi | 10.1097/SLA.0000000000003580 10.1186/s40463-018-0281-z 10.1067/msy.1998.91254 10.1172/JCI106835 10.1038/bmt.2012.244 10.1089/thy.2016.0229 10.1089/thy.1991.1.273 10.1001/jama.2023.19052 10.1089/thy.2022.0392 10.1210/en.2015-1848 10.7326/0003-4819-100-3-372 10.1210/jcem-23-11-1067 10.1007/s00268-020-05654-4 10.3803/EnM.2021.1198 10.1016/j.ijsu.2017.01.086 10.1210/jcem-41-2-354 10.3390/jcm11092416 10.1089/thy.2016.0456 10.1001/jama.299.7.769 10.1159/000490384 10.1089/thy.2019.0135 10.1210/jc.2007-0178 |
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Keywords | Levothyroxine Liothyronine Graves’ disease Hyperthyroidism Total thyroidectomy |
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References | 15 Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48: 452–458. 23 Wiersinga WM (1991) Propranolol and thyroid hormone metabolism. Thyroid 1: 273–277. 5 Al Jassim A, Wallace T, Bouhabel S, Majdan A, Hier M, et al. (2018) A retrospective cohort study: do patients with graves’ disease need to be euthyroid prior to surgery? J Otolaryngol Head Neck Surg 47: 37. 7 Hermann M, Richter B, Roka R, Freissmuth M (1994) Thyroid surgery in untreated severe hyperthyroidism: perioperative kinetics of free thyroid hormones in the glandular venous effluent and peripheral blood. Surgery 115: 240–245. 16 Takamatsu J, Sugawara M, Kuma K, Kobayashi A, Matsuzuka F, et al. (1984) Ratio of serum triiodothyronine to thyroxine and the prognosis of triiodothyronine-predominant Graves’ disease. Ann Intern Med 100: 372–375. 14 Inomata K, Yamamoto A, Yukishita M, Adachi M, Yamashita H, et al. (2004) Fundamental and clinical evaluation of ECLusys FT3 II and thyroid function related tests by automated electrochemiluminescence immunoassay system Modular Analytics . Igaku to Yakugaku 51: 187–196 (In Japanese). 6 Fazendin J, Zmijewski P, Allahwasaya A, McLeod C, Akhund R, et al. (2023) Surgical treatment of hyperthyroidism can be performed safely before a euthyroid state is achieved. Thyroid 33: 691–696. 2 Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, et al. (2016) 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 26: 1343–1421. 19 Jonklaas J, Davidson B, Bhagat S, Soldin SJ (2008) Triiodothyronine levels in athyreotic individuals during levothyroxine therapy. JAMA 299: 769–777. 10 Nicoloff JT, Low JC, Dussault JH, Fisher DA (1972) Simultaneous measurement of thyroxine and triiodothyronine peripheral turnover kinetics in man. J Clin Invest 51: 473–483. 20 Senese N, Lechien JR, Poppe K, Rodriguez A, Dequanter D (2022) Changes in TSH, T4, T3 and thyroglobulin levels throughout total thyroidectomy. J Clin Med 11: 2416. 11 Ohba K, Leow MK, Singh BK, Sinha RA, Lesmana R, et al. (2016) Desensitization and incomplete recovery of hepatic target genes after chronic thyroid hormone treatment and withdrawal in male adult mice. Endocrinology 157: 1660–1672. 21 Hsieh LB, Yen TWF, Dream S, Patel D, Evans DB, et al. (2020) Perioperative management and outcomes of hyperthyroid patients unable to tolerate antithyroid drugs. World J Surg 44: 3770–3777. 8 Hermann M, Roka R, Richter B, Freissmuth M (1998) Early relapse after operation for Graves’ disease: postoperative hormone kinetics and outcome after subtotal, near-total, and total thyroidectomy. Surgery 124: 894–900. 9 Beckers C, Vandenschrieck HG, Devisscher M (1963) Peripheral metabolism of labeled thyroid hormones in goitrous patients from the Uele endemic (Republic of the Congo). J Clin Endocrinol Metab 23: 1067–1073. 18 Ito M, Kawasaki M, Danno H, Kohsaka K, Nakamura T, et al. (2019) Serum thyroid hormone balance in levothyroxine monotherapy-treated patients with atrophic thyroid after radioiodine treatment for Graves’ disease. Thyroid 29: 1364–1370. 12 Ohba K, Sinha RA, Singh BK, Iannucci LF, Zhou J, et al. (2017) Changes in Hepatic TRβ protein expression, lipogenic gene expression, and long-chain acylcarnitine levels during chronic hyperthyroidism and triiodothyronine withdrawal in a mouse model. Thyroid 27: 852–860. 13 Yang S, Zhou L, Lu Z, Ma B, Ji Q, et al. (2017) Systematic review with meta-analysis of intraoperative neuromonitoring during thyroidectomy. Int J Surg 39: 104–113. 24 Williams DE, Chopra IJ, Orgiazzi J, Solomon DH (1975) Acute effects of corticosteroids on thyroid activity in Graves’ disease. J Clin Endocrinol Metab 41: 354–361. 17 Laurberg P, Vestergaard H, Nielsen S, Christensen SE, Seefeldt T, et al. (2007) Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases. J Clin Endocrinol Metab 92: 2149–2156. 3 Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, et al. (2018) 2018 European Thyroid Association Guideline for the management of Graves’ hyperthyroidism. Eur Thyroid J 7: 167–186. 4 Patel KN, Yip L, Lubitz CC, Grubbs EG, Miller BS, et al. (2020) The American Association of Endocrine Surgeons Guidelines for the definitive surgical management of thyroid disease in adults. Ann Surg 271: e21–e93. 22 Sabatino L, Vassalle C, Del Seppia C, Iervasi G (2021) Deiodinases and the three types of thyroid hormone deiodination reactions. Endocrinol Metab (Seoul) 36: 952–964. 1 Lee SY, Pearce EN (2023) Hyperthyroidism: a review. JAMA 330: 1472–1483. 11 22 12 23 13 24 14 15 16 17 18 19 1 2 3 4 5 6 7 8 9 20 10 21 |
References_xml | – reference: 9 Beckers C, Vandenschrieck HG, Devisscher M (1963) Peripheral metabolism of labeled thyroid hormones in goitrous patients from the Uele endemic (Republic of the Congo). J Clin Endocrinol Metab 23: 1067–1073. – reference: 14 Inomata K, Yamamoto A, Yukishita M, Adachi M, Yamashita H, et al. (2004) Fundamental and clinical evaluation of ECLusys FT3 II and thyroid function related tests by automated electrochemiluminescence immunoassay system Modular Analytics . Igaku to Yakugaku 51: 187–196 (In Japanese). – reference: 1 Lee SY, Pearce EN (2023) Hyperthyroidism: a review. JAMA 330: 1472–1483. – reference: 13 Yang S, Zhou L, Lu Z, Ma B, Ji Q, et al. (2017) Systematic review with meta-analysis of intraoperative neuromonitoring during thyroidectomy. Int J Surg 39: 104–113. – reference: 19 Jonklaas J, Davidson B, Bhagat S, Soldin SJ (2008) Triiodothyronine levels in athyreotic individuals during levothyroxine therapy. JAMA 299: 769–777. – reference: 5 Al Jassim A, Wallace T, Bouhabel S, Majdan A, Hier M, et al. (2018) A retrospective cohort study: do patients with graves’ disease need to be euthyroid prior to surgery? J Otolaryngol Head Neck Surg 47: 37. – reference: 22 Sabatino L, Vassalle C, Del Seppia C, Iervasi G (2021) Deiodinases and the three types of thyroid hormone deiodination reactions. Endocrinol Metab (Seoul) 36: 952–964. – reference: 6 Fazendin J, Zmijewski P, Allahwasaya A, McLeod C, Akhund R, et al. (2023) Surgical treatment of hyperthyroidism can be performed safely before a euthyroid state is achieved. Thyroid 33: 691–696. – reference: 21 Hsieh LB, Yen TWF, Dream S, Patel D, Evans DB, et al. (2020) Perioperative management and outcomes of hyperthyroid patients unable to tolerate antithyroid drugs. World J Surg 44: 3770–3777. – reference: 24 Williams DE, Chopra IJ, Orgiazzi J, Solomon DH (1975) Acute effects of corticosteroids on thyroid activity in Graves’ disease. J Clin Endocrinol Metab 41: 354–361. – reference: 7 Hermann M, Richter B, Roka R, Freissmuth M (1994) Thyroid surgery in untreated severe hyperthyroidism: perioperative kinetics of free thyroid hormones in the glandular venous effluent and peripheral blood. Surgery 115: 240–245. – reference: 23 Wiersinga WM (1991) Propranolol and thyroid hormone metabolism. Thyroid 1: 273–277. – reference: 10 Nicoloff JT, Low JC, Dussault JH, Fisher DA (1972) Simultaneous measurement of thyroxine and triiodothyronine peripheral turnover kinetics in man. J Clin Invest 51: 473–483. – reference: 3 Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, et al. (2018) 2018 European Thyroid Association Guideline for the management of Graves’ hyperthyroidism. Eur Thyroid J 7: 167–186. – reference: 18 Ito M, Kawasaki M, Danno H, Kohsaka K, Nakamura T, et al. (2019) Serum thyroid hormone balance in levothyroxine monotherapy-treated patients with atrophic thyroid after radioiodine treatment for Graves’ disease. Thyroid 29: 1364–1370. – reference: 17 Laurberg P, Vestergaard H, Nielsen S, Christensen SE, Seefeldt T, et al. (2007) Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases. J Clin Endocrinol Metab 92: 2149–2156. – reference: 20 Senese N, Lechien JR, Poppe K, Rodriguez A, Dequanter D (2022) Changes in TSH, T4, T3 and thyroglobulin levels throughout total thyroidectomy. J Clin Med 11: 2416. – reference: 4 Patel KN, Yip L, Lubitz CC, Grubbs EG, Miller BS, et al. (2020) The American Association of Endocrine Surgeons Guidelines for the definitive surgical management of thyroid disease in adults. Ann Surg 271: e21–e93. – reference: 11 Ohba K, Leow MK, Singh BK, Sinha RA, Lesmana R, et al. (2016) Desensitization and incomplete recovery of hepatic target genes after chronic thyroid hormone treatment and withdrawal in male adult mice. Endocrinology 157: 1660–1672. – reference: 16 Takamatsu J, Sugawara M, Kuma K, Kobayashi A, Matsuzuka F, et al. (1984) Ratio of serum triiodothyronine to thyroxine and the prognosis of triiodothyronine-predominant Graves’ disease. Ann Intern Med 100: 372–375. – reference: 15 Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48: 452–458. – reference: 8 Hermann M, Roka R, Richter B, Freissmuth M (1998) Early relapse after operation for Graves’ disease: postoperative hormone kinetics and outcome after subtotal, near-total, and total thyroidectomy. Surgery 124: 894–900. – reference: 12 Ohba K, Sinha RA, Singh BK, Iannucci LF, Zhou J, et al. (2017) Changes in Hepatic TRβ protein expression, lipogenic gene expression, and long-chain acylcarnitine levels during chronic hyperthyroidism and triiodothyronine withdrawal in a mouse model. Thyroid 27: 852–860. – reference: 2 Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, et al. (2016) 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid 26: 1343–1421. – ident: 4 doi: 10.1097/SLA.0000000000003580 – ident: 5 doi: 10.1186/s40463-018-0281-z – ident: 8 doi: 10.1067/msy.1998.91254 – ident: 10 doi: 10.1172/JCI106835 – ident: 15 doi: 10.1038/bmt.2012.244 – ident: 2 doi: 10.1089/thy.2016.0229 – ident: 23 doi: 10.1089/thy.1991.1.273 – ident: 1 doi: 10.1001/jama.2023.19052 – ident: 6 doi: 10.1089/thy.2022.0392 – ident: 11 doi: 10.1210/en.2015-1848 – ident: 16 doi: 10.7326/0003-4819-100-3-372 – ident: 9 doi: 10.1210/jcem-23-11-1067 – ident: 14 – ident: 21 doi: 10.1007/s00268-020-05654-4 – ident: 22 doi: 10.3803/EnM.2021.1198 – ident: 13 doi: 10.1016/j.ijsu.2017.01.086 – ident: 24 doi: 10.1210/jcem-41-2-354 – ident: 20 doi: 10.3390/jcm11092416 – ident: 12 doi: 10.1089/thy.2016.0456 – ident: 19 doi: 10.1001/jama.299.7.769 – ident: 3 doi: 10.1159/000490384 – ident: 7 – ident: 18 doi: 10.1089/thy.2019.0135 – ident: 17 doi: 10.1210/jc.2007-0178 |
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Snippet | No evidence-based standards exist regarding levothyroxine (LT4) replacement therapy initiation timing in patients with hyperthyroid Graves’ disease undergoing... No evidence-based standards exist regarding levothyroxine (LT4) replacement therapy initiation timing in patients with hyperthyroid Graves' disease undergoing... |
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SubjectTerms | Adult Aged Female Graves disease Graves Disease - blood Graves Disease - drug therapy Graves Disease - surgery Hormone Replacement Therapy - methods Humans Hyperthyroidism Levothyroxine Liothyronine Male Middle Aged Nodules Original Patients Postoperative Care - methods Postoperative Period Surgery Thyroid gland Thyroid hormones Thyroid Nodule - blood Thyroid Nodule - surgery Thyroidectomy Thyroxine Thyroxine - administration & dosage Thyroxine - blood Thyroxine - therapeutic use Total thyroidectomy Treatment Outcome Triiodothyronine Triiodothyronine - blood Young Adult |
Title | Early postoperative levothyroxine initiation after total thyroidectomy for Graves’ disease |
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ispartofPNX | Endocrine Journal, 2025, Vol.72(7), pp.813-818 |
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