A Prognostic Model for Predicting the Probability of Remission of Toxic Diffuse Goiter
Objective of the Study: To develop an assessment scale for predicting the probability of remission of toxic diffuse goiter (TDG), to optimize treatment approaches.
Study Design: This investigation included retrospective analysis and a prospective, open-label, nonrandomized, noncontrolled study.
Materials and Methods: The investigation had two parts— retrospective analysis and a prospective study. The retrospective analysis was done on data collected from 515 patients with TDG (404 [78.5%] women and 111 [21.5%] men), who had been diagnosed between 1970 and 2010. The mean age of the enrolled patients was 41.96 ± 0.60 (41.15 ± 0.66 for the women and 45.25 ± 0.60 for the men; р=0.01). All patients had received thyroid-suppressing agents for 12-18 months. After discontinuation of these agents, patients were followed up every six months for five years. Stepwise regression analysis was performed to create a mathematical model for assessing the probability of TDG remission in patients receiving conventional thyroid suppression therapy. Based on the results of this analysis, a discriminant function (D) was developed to divide the patients into two groups. Group 1 included patients with a D value below 3.26, and Group 2 was made up of patients with a D value of 3.26 or higher.
Two hundred patients (108 [54%] women and 92 [46%] men) with newly diagnosed TDG were enrolled in the prospective study and followed up for four years. Their mean age at diagnosis was 42.96 ± 0.60 (44.17 ± 0.66 for the women and 46.25 ± 0.71 for the men). All patients received conventional thyroid suppression therapy for 12-18 months. Based on the proposed prognostic criteria, the patients were divided into groups, depending on their D values: Group 1 consisted of patients with a D value below 3.26 (low risk of recurrence of hyperthyroidism), and Group 2 was made up of patients with a D value of 3.26 or higher (high risk of recurrence of hyperthyroidism).
Study Results: Six significant discriminant variables were identified that influence the probability of TDG remission: initial volume of the thyroid gland (cm3), ophthalmopathy, age of disease onset (years), ratio of free triiodothyronine to free thyroxine, initial levels of anti-thyroid-stimulating hormone receptor antibodies, and tobacco smoking. The most informative parameters were selected to create a discriminant function D (equation). If the D value is below 3.26, the probability of remission is high, while D≥3.26 corresponds to a low probability of remission. The prospective study showed that this predictive model for assessing the probability of TDG remission is highly sensitive (86%) and specific (84%).
Conclusion: The proposed assessment scale for predicting the probability of TDG remission helps forecast disease course at diagnosis and optimize treatment approaches.
Contribution: Abramova, I.M. — study design, review of relevant publications, and writing the final manuscript; Allamova, G.G. — data processing analysis and interpretation; Panchoyan, S.M. — assistance with patient selection and statistical analysis of the study data; Dora, S.V. — review of critically important material, thematic publications reviewing. Volkova, A.R. — review of critically important material, approval of the manuscript for publication.
Conflict of interest: The authors declare that they do not have any conflict of interests.
A.R. Volkova — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. eLIBRARY.RU SPIN: 4007-1288. E-mail: email@example.com
S.V. Dora (Corresponding author) — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. eLIBRARY.RU SPIN: 9845-0065. E-mail: firstname.lastname@example.org
G.G. Allamova — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. E-mail: email@example.com
I.M. Abramova — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. E-mail: firstname.lastname@example.org
S.M. Panchoyan — Academician I.P. Pavlov First St. Petersburg State Medical University (a Federal Government-funded Educational Institution of Higher Education), Russian Ministry of Health; 6-8 Lev Tolstoy St., St. Petersburg, Russian Federation 197022. E-mail: email@example.com
Fig. 1. Design of a prospective observational study in a group of patients with toxic diffuse goiter
Significant variables influencing the prognosis for patients receiving treatment for toxic diffuse goiter
Fig. 2. ROC curve for sensitivity/specificity of the prognostic model for remission probability in patients with toxic diffuse goiter
Fig. 3. Assessment of toxic diffuse goiter remission using the D value: Group 1 – D value below 3.26, Group 2 – D value 3.26 or higher
- Dedov I.I., Melnichenko G.A., Fadeev V.V. Endocrinology. M.; 2008. 432 p. (in Russian)
- Braverman L.I., ed. Thyroid diseases. M.: Medicine; 2000: 194–220. (in Russian)
- Masiello E., Veronesi G., Gallo D., Premoli P., Bianconi E., Rosetti S. et al. Antithyroid drug treatment for Graves' disease: baseline predictive models of relapse after treatment for a patient-tailored management. J. Endocrinol. Invest. 2018; 41(12): 1425–32. DOI: 10.1007/s40618-018-0918-9
- Smith T.J., Hegedus L. Graves' disease. N. Engl. J. Med. 2016; 375(16): 1552–65. DOI: 10.1056/NEJMra1510030
- Troshina E.A., Sviridenko N.Yu., Vanushko V.E., Rumyantsev P.O., Fadeev V.V., Petunina N.A. Federal clinical recommendations for the diagnosis and treatment of thyrotoxicosis with diffuse goiter (diffuse toxic goiter, Graves — Bazedov's disease), node/multi-node goiter. M.; 2014. 25 р. (in Russian)
- Wiersinga W.M. Graves' disease: can it be cured? Endocrinol. Metab. (Seoul). 2019; 34(1): 29–38. DOI: 10.3803/EnM.2019.34.1.29
- Melnichenko G.A., Petrova N.D. Modern approaches to the treatment of thyrotoxicosis. Clin. Pharmacology and Therapy. 1997; 6: 60–5. (in Russian)
- Ross D.S., Burch H.B., Cooper D.S., Greenlee M.C., Laurberg P., Maia A.L. et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016; 26(10): 1343–421. DOI: 10.1089/thy.2016.0229
- Kahaly G.J., Bartalena L., Hegedüs L., Leenhardt L., Poppe K., Pearce S.H. 2018 European Thyroid Association guideline for the management of Graves' hyperthyroidism. Eur. Thyroid J. 2018; 7(4): 167–86. DOI: 10.1159/000490384
- Struja T., Fehlberg H., Kutz A., Guebelin L., Degen C., Mueller B. et al. Can we predict relapse in Graves' disease? Results from a systematic review and meta-analysis. Eur. J. Endocrinol. 2017; 176(1): 87–97. DOI: 10.1530/EJE-16-0725
- García-Mayor R.V., Álvarez-Vázquez P., Fluiters E., Valverde D., Andrade A. Long-term remission following antithyroid drug withdrawal in patients with Graves' hyperthyroidism: parameters with prognostic value. Endocrine. 2019; 63(2): 316–22. DOI: 10.1007/s12020-018-1785-z
- Vos X.G., Endert E., Zwinderman A.H., Tijssen J.G., Wiersinga W.M. Predicting the risk of recurrence before the start of antithyroid drug therapy in patients with Graves’ hyperthyroidism. J. Clin. Endocrinol. Metab. 2016; 101(4): 1381–89. DOI: 10.1210/jc.2015-3644
- Mohlin E., Filipsson Nystrom H., Eliasson M. Long-term prognosis after medical treatment of Graves' disease in a northern Swedish population 2000–2010. Eur. J. Endocrinol. 2014; 170(3): 419–27. DOI: 10.1530/EJE-13-0811
- Abraham P., Avenell A., Park C.M., Watson W.A., Bevan J.S. A systematic review of drug therapy for Graves' hyperthyroidism. Eur. J. Endocrinol. 2005; 153(4): 489–98. DOI: 10.1530/eje.1.01993
- Laurberg P. Remission of Graves’ disease during anti-thyroid drug therapy. Time to reconsider the mechanism? Eur. J. Endocrinol. 2006; 155(6): 783–6. DOI: 10.1530/eje.1.02295
- Takaichi Y., Tamai H., Honda K., Nagai K., Kuma K., Nakagawa T. The significance of antithyroglobulin and antithyroidal microsomal antibodies in patients with hyperthyroidism due to Graves' disease treated with antithyroidal drugs. J. Clin. Endocrinol. Metab. 1989; 68(6): 1097–100. DOI: 10.1210/jcem-68-6-1097
- World Health Organization, International Council for Control of Iodine Deficiency Disorders and United Nations Children's Fund (UNICEF). Indicators for assessing iodine deficiency disorders and their control through salt iodization. WHO/NUT/94.6. Geneva: WHO; 1994. 66 p.