Ultrasonographic Thyroid Volume as a Reliable Prognostic Index of Radioiodine-131 Treatment Outcome in Graves’ Disease Hyperthyroidism

Abstract

Objective: We studied the relationship between thyroid volume, thyroid function and immunological markers of Graves’ disease (GD) to determine prognostic factors of treatment response to low-dose radioiodine-131 (¹³¹I). Material and methods: A prospective study of 40 patients with GD hyperthyroidism treated with ¹³¹I (141 ± 85MBq) and 10 GD patients who went spontaneously into remission (controls). Free T₄, total T₃ and basal TSH levels, TSH-receptor antibodies (TRAb) and anti-thyroid peroxidase antibodies (TPOAb) were studied. Thyroid volume was determined by ultrasonography. Logistic regression models were used to predict the probability of final thyroid status. Receiver-operating characteristics (ROC) curves and Hosmer Lemeshow tests were used to evaluate the final statistical models. Results: Of 40 patients treated with ¹³¹I, 16 became euthyroid, 12 hyperthyroid and 12 hypothyroid at 12 months. Median thyroid volume was reduced from 24.8 ml before to 8.5 ml at 12 months (p < 0.001). In 10 control patients, the median reduction was from 16.6 ml to 11.3 ml (p = 0.029). Thyroid volume reduction was lower in the hyperthyroid than in the euthyroid group, but higher in the hypothyroid group. Thyroid volume at baseline and at 3 months predicted hyperthyroidism outcome with a cut-off of 45 ml and 24.4 ml, respectively (odds ratio 1.074, p = 0.003, ROC curve 0.78 and odds ratio 1.182, p = 0.012, ROC curve 0.86 respectively). Thyroid volume at 6 months differentiated the hyperthyroid group with a cut-off of 17 ml. Thyroid volume at 3 and 6 months with a cut-off of 8.5 ml and 9.3 ml respectively, predicts permanent hypothyroidism outcome (odds ratio 0.768 and 0.685, p = 0.012 and p = 0.008, ROC curve 0.89 and 0.88, respectively). Changes in thyroid echogenicity and TRAb and TPOAb levels did not show any predictive value in the follow-up after ¹³¹I therapeutic outcome. Conclusion: The study shows that the ultrasonographic thyroid volume at 3 and 6 months after low-dose ¹³¹I treatment for GD hyperthyroidism could be a reliable prognostic factor of thyroid function outcome in the first year after treatment, and also reveals that the changes in the thyroid echogenicity and in the immunological markers of GD have no prognostic value.

Graves’ hyperthyroidism - Radioiodine-131 therapy - Thyroid volume - Thyroid echogenicity - Treatment outcome - TSH-receptor antibodies - Anti-thyroid peroxidase antibodies - Prognostic factors

References

• 1 Kendall-Taylor P, Keir M J, Ross W M. Ablative radioiodine therapy for hyperthyroidism. Long-term follow-up study.  Br Med J. 1984;  289 361-363
• 2 Sridama V, McCornlck M, Kaplan E L, Fauchet R, DeGroot L J. Long-term follow-up study of compensate low dose 131I therapy for Graves’ disease.  N Engl J Med. 1984;  16 426-432
• 3 Goolden A WG, Stewart J SW. Long-term results from graded low-dose radioactive iodine therapy for thyrotoxicosis.  Clin Endocrinol (Oxf). 1986;  24 217-222
• 4 Franklyn J A, Daykin J, Drolc Z, Farmer M, Sheppard M C. Long-term follow-up of treatment of thyrotoxicosis by three different methods.  Clin Endocrinol (Oxf). 1991;  34 71-76
• 5 Nordike R A, Gilbert F I. Optimal iodine-131 dose for eliminating hyperthyroidism in Graves’ disease.  J Nucl Med. 1991;  32 487-496
• 6 Leisner B. Ultrasound evaluation of thyroid diseases.  Horm Res. 1987;  26 33-41
• 7 Berghout A, Wiersinga W M, Smits N J, Touber J L. The value of thyroid volume measured by ultrasonography in the diagnosis of goitre.  Clin Endocrinol (Oxf). 1998;  28 409-414
• 8 Aizawa Y, Yoshida K, Kaise N, Kaise K, Fukazawa H, Kiso Y. Long-term effects of radioiodine on thyrotropin receptor antibodies in Graves’ disease.  Clin Endocrinol (Oxf). 1995;  42 517-522
• 9 Rieu M, Raynaud A, Richard A, Laplanche S, Sambor B, Berrod J L. Evidence for the effect of antibodies to TSH receptors on the thyroid ultrasonographic volume in patients with Graves’ disease.  Clin Endocrinol (Oxf). 1994;  41 667-671
• 10 Murakami Y, Takamatsu J, Sakane S, Kurna K, Ohsawa N. Changes in thyroid volume in response to radioactive iodine for Graves’ hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome.  J Clin Endocrinol Metab. 1996;  81 3257-3260
• 11 Leslie W D, Peterdy A E, Dupont J O. Radioiodine treatment outcomes in thyroid glands previously irradiated for Graves’ hyperthyroidism.  J Nucl Med. 1988;  39 712-716
• 12 Gómez N, Gómez J M, Orti A. et al . Transient hypothyroidism after iodine-131 therapy for Graves’ disease.  J Nucl Med. 1995;  36 1539-1542
• 13 Brunn J, Block U, Ruf G, Bos L, Kunze W, Scriba P C. Volumetrie der Schilddrüsenlappen mittels realtime Sonographie.  Dtsch Med Wochenschr. 1981;  106 1338-1340
• 14 Gómez J M, Maravall F J, Gómez N, Gumà A, Soler J. Determinants of thyroid volume as measured bu ultrasonography in healthy adults randomly selected.  Clin Endocrinol (Oxf). 2000;  53 629-634
• 15 Gómez-Arnaiz N, Gómez Sáez J M, Orti Llaveria A, Gavaldà Mestre L, Mairal Pairó L. Resultados del tratamiento de la enfermedad de Graves Basedow con 131I a dosis bajas calculadas.  Rev Clin Esp. 1998;  198 57-60
• 16 Gómez J M, Gómez N, Amat M, Biondo S, Rafecas A, Jaurrieta E, Soler J. Hypothyroidism after iodine-131 or surgical therapy for Graves’ disease hyperthyroidism.  Ann Endocrinol. 2000;  61 184-191
• 17 Virgili N, Gómez J M, Montaña E, Soler J, Castells M, Roca M. Short-term follow-up of patients with Graves’ disease treated with I131. The prevalence of transient hypothyroidism.  Rev Clin Esp. 1988;  183 300 - 303
• 18 Müller-Gartner H W, Schneider C, Schroeder S. Autoimmune-resistance in Graves’ disease tissues: indication of a structural and functional heterogenicity.  Acta Endocrinol (Copenh). 1986;  113 233-241
• 19 Chiovato L, Fiore E, Vittl P. et al . Outcome of thyroid function in Graves’ patients with radioiodine: role of thyroid-stimulating and thyrotropin-blocking antibodies and of radioiodine- induced thyroid damage.  J Clin Endocrinol Metab. 1998;  83 40-46
• 20 Tsuruta M, Nagayama Y, Yokoyama N, Izumi M, Nagataki S. Long-term follow-up studies on iodine-131 treatment of hyperthyroid Graves’ disease based on the measurement of thyroid volume by ultrasonography.  Ann Nucl Med. 1993;  7 193-197
• 21 Marcocci C, Gianchecchi O, Masini I. et al . A reappraisal of the role of methimazole and other factors on the efficacy and outcome of radioiodine therapy of Graves’ hyperthyroidism.  J Endocrinol lnves. 1990;  13 513-520
• 22 Ralls P W, Mayekawa O S, Lee K P. et al . Color-flow doppler sonography in Graves’ disease: ”Thyroid inferno”.  Am J Roentg. 1988;  150 781-784
• 23 Vitti P, Raga T, Mancusi F. et al . Thyroid hypoechogenic pattern at ultrasanography as a tool for predicting recurrence of hyperthyroidism after medical treatment in patients with Graves’ disease.  Acta Endocrinol (Copenh). 1992;  126 128-131
• 24 Zingrillo M, D’Aloiso L, Ghíggi M R. et al . Thyroid hypoechogenicity after methimazole withdrawal in Graves’ disease: a useful index for predicting recurrence?.  Clin Endocrinol (Oxf). 1996;  45 201-206
• 25 Macchia E, Concetti R, Borgoni F, Cetani F, Fenzi C F, Pinchera A. Assays of TSH-receptor antibodies in 576 patients with various thyroid disorders: their influence, significance and clinical usefulness.  Autoimmunity. 1989;  3 103-112
• 26 Ludgate M E, Vassart G. The thyrotropin receptor.  Ball Clin Endocrinol Metab. 1995;  9 95-113
• 27 Okamoto Y, Hamada N, Fujisawa T. et al . Why no simple relationship between thyroid peroxidase activity-inhibiting immunoglobulins and the thyroid function in autoimmune thyroid disease?.  Acta Endocrinol (Copenh). 1991;  124 442-448
• 28 Vassart G, Dumont J E. The thyrotropin receptor and the regulation of thyrocyte function and growth.  Endocrin Rev. 1992;  13 569-611