Use of a dosimetry-based RAI protocol for treatment of benign hyperthyroidism optimises response while minimising exposure to ionising radiation.

BACKGROUND: The optimal treatment strategy for radioiodine (RAI) treatment protocols for benign hyperthyroidism remains elusive. Although individualised activities are recommended in European Law, many centres continue to provide fixed activities. Our institution implemented a dosimetry protocol in 2016 following years of fixed dosing which facilitates the calculation of individualised activities based on thyroid volume and radioiodine uptake. METHODS: This was a retrospective study comparing success rates using a dosimetry protocol targeting an absorbed dose of 150 Gy for Graves' disease (GD) and 125 Gy for Toxic Multinodular Goiter (TMNG) with fixed dosing (200MBq for GD and 400MBq for TMNG) among 204 patients with hyperthyroidism. Success was defined as a non-hyperthyroid state at 1 year for both disease states. Results were analysed for disease specific or patient specific modulators of response. RESULTS: This study included 204 patients; 74% (n = 151) received fixed activities and 26% (n = 53) of activities administered were calculated using dosimetry. A dosimetry-based protocol was successful in 80.5% of patients with GD and 100% of patients with TMNG. Differences in success rates and median activity administered between the fixed (204Mbq) and dosimetry (246MBq) cohort were not statistically significant (p = .64) however 44% of patients with GD and 70% of patients with TMNG received lower activities following treatment with dosimetry as opposed to fixed activities. Use of dosimetry resulted in successful treatment and reduced RAI exposure for 36% of patients with GD, 70% of patients with TMNG, and 44% of patients overall. CONCLUSION: This retrospective clinical study demonstrated that treatment with a dosimetry-based protocol for TMNG and GD achieved comparable success rates to fixed protocols while reducing RAI exposure for over a third of patients with GD and most patients with TMNG. This study also highlighted that RAI can successfully treat hyperthyroidism for some patients with activities lower than commonplace in clinical practise. No patient or disease specific modulators of treatment response were established in this study; however, the data supports a future prospective trial which further scrutinises the individual patient factors governing treatment response to RAI.

Long-term effects of radioiodine treatment on thyroid functions and ultrasonographic features in patients with toxic adenoma and toxic multinodular goitre.

OBJECTIVE: This study aimed to investigate the long-term effect of radioiodine (RAI) treatment on thyroid functions and ultrasonographic changes in the thyroid gland and toxic nodules. METHODS: Thyroid function tests and ultrasonography reports of patients diagnosed with toxic adenoma (TA) or toxic multinodular goitre (TMNG) between 2000 and 2021 were retrospectively analysed. RESULTS: We included 100 patients whom thyroid function and ultrasonography results were obtained from our outpatient clinic before and at least 36 months post-RAI. At the end of the follow-up period, the mean thyroid volume reduction in patients with TA and TMNG was 56.6% ± 3.1% and 51.1% ± 6.7%, respectively; the mean volume decrease of all toxic nodules was 80.5% ± 1.9%. The volume of the thyroid and toxic nodules was significantly reduced up to 12 years (p < 0.01). Between 3 and 10 years after RAI therapy, the annual incidence of hypothyroidism was 2.0% and 1.5% in the TA and TMNG groups, respectively. Toxic nodules were more frequently solid and hypoechoic in post-RAI ultrasounds (p < 0.01). CONCLUSIONS: The volume of thyroid gland and toxic nodules continuously decreases, as the risk of hypothyroidism increases up to 10 years after RAI treatment. After RAI treatment, patients should be followed up to check their thyroid functions. In post-RAI examinations, toxic nodules may show ultrasonographic features suspicious for malignancy. History taking should include previous RAI therapies and old scintigraphy scans should be evaluated to avoid unnecessary procedures and non-diagnostic biopsy results.

Efficacy and Safety of Long-Term Methimazole versus Radioactive Iodine in the Treatment of Toxic Multinodular Goiter.

BACKGRUOUND: This study compared the degree of sustained control of hyperthyroidism in patients with toxic multinodular goiter (TMNG) treated with long-term methimazole (LT-MMI) or radioactive iodine (RAI). METHODS: In this clinical trial, 130 untreated patients with TMNG were randomized to either LT-MMI or RAI treatment. Both groups were followed for 108 to 148 months, with median follow-up durations of 120 and 132 months in the LT-MMI and RAI groups, respectively. Both groups of patients were followed every 1 to 3 months in the first year and every 6 months thereafter. RESULTS: After excluding patients in whom the treatment modality was changed and those who were lost to follow-up, 53 patients in the LT-MMI group and 54 in the RAI group completed the study. At the end of the study period, 50 (96%) and 25 (46%) patients were euthyroid, and two (4%) and 25 (46%) were hypothyroid in LT-MMI and RAI groups, respectively. In the RAI group, four (8%) patients had subclinical hyperthyroidism. The mean time to euthyroidism was 4.3±1.3 months in LT-MMI patients and 16.3± 15.0 months in RAI recipients (P<0.001). Patients treated with LT-MMI spent 95.8%±5.9% of the 12-year study period in a euthyroid state, whereas this proportion was 72.4%±14.8% in the RAI-treated patients (P<0.001). No major treatment-related adverse events were observed in either group. CONCLUSION: In patients with TMNG, LT-MMI therapy is superior to RAI treatment, as shown by the earlier achievement of euthyroidism and the longer duration of sustained normal serum thyrotropin.

Predictors of Hypothyroidism Following Empirical Dose Radioiodine in Toxic Thyroid Nodules: Real-Life Experience.

OBJECTIVE: We aimed to determine the factors predicting hypothyroidism after radioactive iodine (RAI) treatment in patients with toxic adenoma and toxic multinodular goiter. METHODS: We retrospectively collected the data of 237 patients with toxic multinodular goiter or toxic adenoma who had consecutively received RAI treatment between 2014 and 2020 at 2 medical centers. Patients who received the second RAI treatment and whose medical records could not be accessed were excluded from the study. Finally, 133 patients were included in the study. RAI was administered at an empirical dose of 15 or 20 mCi. RESULTS: The median age of the 133 participants was 69 years (interquartile range, 62-75 years), and 64.7% of the participants were women. A total of 42.1% of the patients had toxic adenoma, whereas 57.9% of patients had toxic multinodular goiter. The median follow-up was 24 months (interquartile range, 11-38 months). During the follow-up, 61.7% of patients became euthyroid, 30.8% developed hypothyroidism, and 7.5% remained hyperthyroid. The median month of hypothyroidism onset was 4 months (interquartile range, 2-9 months). Regression analysis revealed 2 factors that could predict hypothyroidism: thyroid-stimulating hormone (odds ratio, 2.548; 95% CI, 1.042-6.231; P = .04) and thyroid volume (odds ratio, 0.930; 95% CI, 0.885-0.978; P = .005). CONCLUSION: Overall, 30.8% of the cases developed hypothyroidism after the RAI treatment. Approximately 78% of hypothyroidism developed within the first 10 months. The risk of hypothyroidism was higher in patients with higher thyroid-stimulating hormone and smaller thyroid volume.

Fixed 30 mCi 131I-iodine therapy without recombinant human thyroid-stimulating hormone stimulation as an attractive therapeutic alternative in nontoxic nodular goiter.

OBJECTIVE: To analyze outcomes of patients with compressive nontoxic multinodular goiter after 131I-iodine 30 mCi treatment without previous use of recombinant human thyroid-stimulating hormone or methimazole. METHODS: We evaluated fixed-dose radioiodine therapy outcomes in patients with nontoxic multinodular goiter who did not accept thyroidectomy as a therapeutic option. Laboratory thyroid function and thyroid volume estimated by ultrasound were assessed before and one year after radioiodine therapy. RESULTS: Twenty euthyroid female patients received 30 mCi of 131I-iodine without recombinant human thyroid-stimulating hormone or methimazole pretreatment. Median thyroid volume and Tc-99m sodium pertechnetate thyroid uptake before radioiodine therapy were 68.05 cm (31.3-295.3) and 0.5% (0.1%-1.2%), respectively. One year after radioiodine therapy, thyroid volume decreased to 55.4 cm (19.8-149.9), and merely 4 patients (20%) developed hypothyroidism. Thyroid volume decreased significantly after radioiodine therapy, presenting a variation of -21.1 cm (-161.3 to -0.8) and -30.61% (-73.88 to -1.02), both with P < 0.0001. Thyroid volume variation was positively correlated with thyroid uptake in Spearman's correlation (r = 0.4730; P = 0.0352). The group satisfied with radioiodine therapy (85%, n = 17) showed a significant reduction in thyroid volume, -25.8 cm (-161.3 to -6.2) and -36.74% (-73.88 to -9.95). The dissatisfied group (15%, n = 3) showed -1.0 cm (-2.0 to -0.8) and -1.67% (-3.38 to -1.02) in thyroid volume, P = 0.0081. Patients that complained about dysphagia presented a lower percentage of thyroid volume decrease after radioiodine therapy, -21.97% (-70.12 to -1.02, P = 0.0430). CONCLUSIONS: A substantial reduction in thyroid volume associated with a low incidence of hypothyroidism and a high satisfaction rate support the use of conventional radioiodine therapy with a fixed dose of 30 mCi. This therapy is an attractive and cheaper therapeutic alternative in selected patients with nontoxic multinodular goiter.

Long-term Effects of Radioiodine in Toxic Multinodular Goiter: Thyroid Volume, Function, and Autoimmunity.

CONTEXT: Long-term studies evaluating the treatment of toxic multinodular goiter (TMNG) with fixed activities of radioiodine (RAI) are lacking. OBJECTIVE: The objective of this work is to describe the effects of 15 mCi on thyroid volume, function, and autoimmunity in the long term. DESIGN AND SETTING: A population-based, retrospective analysis with up to 12 years of follow-up was conducted in Siena, Italy. PARTICIPANTS: Adult patients (n = 153) with TMNG, naive to RAI, were included. METHODS: Evaluation was performed of thyroid function, antithyroid antibodies, and ultrasound scans before and yearly after RAI. MAIN OUTCOME MEASURES: Evaluations included hyperthyroidism cure, hypothyroidism, volume reduction, nadir and regain, and antibody titer change. RESULTS: The study revealed mean volume reductions greater than or equal to 50% at 3 years after RAI; the greatest annual reduction was observed during the first year (30 ± 17.8%; P < .001). Most patients (60%) achieved their volume nadir 3 to 6 years after RAI. Although 22% patients showed volume regain, the net reduction was statistically significant as late as 9 years after RAI (P = .005). The mean time to hypothyroidism was 2.7 ± 2.4 years, and it was associated with greater reductions in volume (P = .01). During the first 3 years after treatment, hyperthyroid patients decreased approximately by 50% per year without additional RAI. There was no statistically significant association of antibody titers with thyroid function except for antithyrotropin receptor antibodies and hyperthyroidism (P = .004). At the end of follow-up there were 61.6% euthyroid patients, 11% hyperthyroid (4.8% overt), and 27.4% hypothyroid patients (2.7% overt). Hyperthyroidism was cured in 89%. CONCLUSIONS: The treatment of TMNG with 15 mCi of RAI induced low hypothyroidism rates while providing high cure rates and significant volume reduction, which was maintained in the long term.

The significance of serum thyroglobulin measurement before and after the treatment of toxic nodular goiter with 131I.

OBJECTIVES: Thyroglobulin is routinely used as a tumor marker in follow up of patients with thyroid carcinoma, but is also elevated in patients with toxic nodular goiter. The aim of this study was to evaluate the role of thyroglobulin measurement prior to and after the radioiodine therapy (RIT) in patients with toxic nodular goiter and to compare the results with the therapy outcome. PATIENTS AND METHODS: In 109 patients with toxic nodular goiter (102 females, 7 males, aged 45-85 years), 61 with multinodular toxic goiter and 48 with toxic adenoma, thyroglobulin level was measured before RIT and during the first 12 months after the treatment and compared to therapy outcome, defined as euthyroid, hypothyroid and persistent hyperthyroidism. RESULTS: In patients with euthyroid and hypothyroid outcome, a significant fall of thyroglobulin level was noted during the first 12 months after RIT, more prominent in the latter group. In patients with persistent hyperthyroidism, the initial thyroglobulin level was higher than in other two groups and no significant decrease was noted by the end of the first year after therapy, especially in patients with multinodular toxic goiter. CONCLUSIONS: The significant fall of thyroglobulin after RIT observed in patients in whom euthyroidism and hypothyroidism was achieved indicates that thyroglobulin values can be related to the treatment outcome. In patients with high initial thyroglobulin levels (above 400 ng/l), and possible unfavorable RIT outcome, higher radioiodine activities or other treatment options might be considered.Video abstract: http:/links.lww.com/NMC/A163.

Enhancing the efficacy of 131I therapy in non-toxic multinodular goitre with appropriate use of methimazole: an analysis of randomized controlled study.

PURPOSE: It is possible to raise the rate of the uptake of 131I in the thyroid gland (RAIU) by increasing the endogenous TSH level through appropriate use of methimazole (MMI) prior to 131I therapy. The purpose of this paper is to assess the impact of pre treatment with MMI on the efficacy of 131I therapy in non-toxic multinodular goitre (NMG). METHODS: Thirty-one patients with NMG received 131I treatment in order to reduce the volume of the thyroid (TVR). Those in group 1 (n = 16) were administered 10 mg of methimazole for 6 weeks. Four days after its discontinuation, they received 131I. Patients in group 2 (n = 15) were given a placebo instead of MMI. The therapeutic activity of 131I was constant (800 MBq) and was repeated every 6 months. Treatment was discontinued when TVR reached <40 ml. RESULTS: In group 1, RAIU increased approximately twofold. Ten patients from group 2 and four patients from group 1 received further doses of 131I. The median of time until TVR decreased below 40 ml was 9 months [6-12 months] and 18 months [14-22 months] in group 2. At 2 years after the 131I therapy, the occurrence of hypothyroidism did not differ significantly (36% in group 1 and 33% in group2, p = 0.074). CONCLUSIONS: Radioiodine treatment of NMG preceded with appropriate application of MMI is efficient thanks to increased RAIU, shorter period of treatment, and lower frequency of 131I administration, without an increase in the incidence of post-treatment hypothyroidism.

Resultados a corto plazo del tratamiento con 131I en el bocio multinodular: valor adicional de la estimulación previa con rhTSH / Short-term results of treatment with 131I in multinodular goiter: additional value of previus stimulation with Recombinant human thyrotropin

OBJETIVO: El yodo radiactivo (131I) es una opción terapeútica segura y eficaz cuando se utiliza solo o con la estimulación previa de TSH recombinante humana (rhTSH) en el tratamiento del bocio multinodular (BMN). En espera de ensayos clínicos que determinen la dosis óptima, demuestren seguridad y confirmen la eficacia, diferentes protocolos se utilizan para aplicar la dosis de 131I. Analizamos la respuesta al tratamiento con una dosis calculada por protocolo mixto (dosis fijas y cálculo por porcentaje de captación) en pacientes con BMN toxico y no toxico en nuestro hospital, en el periodo 2010-2013. MATERIALES Y MÉTODOS: Estudio prospectivo en pacientes con BMN no quirúrgico (BMNNQ) que requerían reducción del volumen glandular y/o tratamiento del hipertiroidismo. Se evaluaron 134 pacientes, 14 cumplieron con los criterios de inclusión (13mujeres) de edad media 71.08 años. Un grupo con BMN toxico, otro grupo con BMN no toxico, un tercer grupo con BMN no toxico estimulado con 0,1 mg de rhTSH previo a la dosis. Se evaluó, función tiroidea, captación tiroidea de 99ᵐTc, volumen tiroideo y síntomas compresivos. Se siguió a los pacientes durante 12 meses. RESULTADOS: Se aplicaron dosis entre 15 y 30 mCi de 131I. Remitió el hipertiroidismo en 6 de 7 pacientes. Hubo una reducción del volumen glandular (p<0.01).Los pacientes con estímulo de 0,1 mg rhTSH, aumentaron el porcentaje de captación de 99ᵐTc a las 24 h en un 32.43±10.61 permitiendo aplicar menor dosis de 131I. La tasa de aparición de hipotiroidismo fue de 7.41 por cada 100 pacientes.mes, mayor en pacientes con BMN toxico tratados con dosis bajas (p-=0.03). Hubo una mejoría subjetiva de la clínica compresiva en todos los pacientes. No hubo eventos adversos. CONCLUSIONES: Una dosis de 131I calculada por protocolo mixto es efectiva y segura para la reducción del volumen glandular y control del hipertiroidismo asociado. La estimulación con rhTSH logra el mismo efecto con una menor dosis administrada.

OBJECTIVE: Radioactive iodine (131I) is a safe and effective therapeutic option when used alone or with prior stimulation of recombinant human Thyrotropin (rhTSH) in the treatment of multinodular goiter (MNG). In absence of clinical trials that determine the optimal dose, demonstrate safety and confirm efficacy, different protocols are used to apply the dose of 131I. We analyze the response to treatment with a dose calculated by mixed protocol (fixed doses and calculation by percentage of uptake) in patients with toxic and non-toxic MNG in our hospital, in the period 2010-2013. MATERIALS AND METHODS: Prospective study in patients with non-surgical MNG that required glandular volume reduction and / or treatment of hyperthyroidism. 134 patients were evaluated, 14 met the inclusion criteria (13 women) of average age 71.08 years. One group with toxic MNG, another group with non-toxic MNG and a third with non-toxic multinodular goiter stimulated with 0.1 mg of rhTSH prior to the dose. Patients were followed for 12 months. Upon following, we assessed Thyroid function, 99ᵐTc thyroid uptake, thyroid volume and compressive symptoms. RESULTS: Doses between 15 and 30 mCi of 131I were applied. We observed hyperthyroidism remission in 6 of 7 patients. There was a reduction in glandular volume (p <0.01) considering all patients. Patients with a stimulus of 0.1 mg rhTSH, increased the percentage of uptake of 99ᵐTc at 24 h by 32.43 ± 10.61, allowing a lower dose of 131I to be applied. The rate of onset of hypothyroidism was 7.41 per 100 patients-month, and was higher in patients with toxic MNG treated with low doses (p = 0.03). There was a subjective improvement of the compression clinic in all patients. No adverse events were observed. CONCLUSIONS: A dose of 131I calculated by a mixed protocol is effective and safe for achieving glandular volume reduction and associated hyperthyroidism control. Stimulation with rhTSH produces the same effect with a lower administered dose.

Incidence of Hypothyreoidism after Radioactive Iodine-I131 Treatment in Dependance of Hyperthyreoidism Etiology and Therapy Dose.

INTRODUCTION: Consensus hasn't been yet achieved about optimal dose quantity that could prevent post therapy hypothyroidism, thus dosing approach varies among different centers. I131 doses can be fixed or calculated, although treatment outcomes don't differ significantly according to recent acknowledgments. AIM: Determination of the incidence of hypothyroidism after radioiodine treatment (I131) in dependence of hyperthyroidism etiology and quantity of applied doses. MATERIALS AND METHODS: The study included 100 patients which have had radioiodine treatment, with a three year post-treatment follow up. The study was conducted at the Nuclear Medicine Department, University Clinical Center of Sarajevo. Data were provided from the patient medical histories. Research is designed as a retrospective, descriptive study. All data were analyzed using Microsoft Excel and the statistical program SPSS 13.0. RESULTS: After the three year follow up, incidence of hypothyroidism within patients with Graves' disease was 89.5%, with diffuse goiter 50%, with toxic adenoma (TA) 26.8%, and with multinodulare goitre (MNG) 57.1%. Hypothyreoidism in patients with diffuse goiter, Graves' disease and TA was mostly developed after I131 therapy with a dose quantity of 10.1-15 mCi and in MNG patients after RAI therapy with applied doses of 15.1-20 mCi. CONCLUSION: The hypothyroidism incidence rate is the highest among patients with Graves' diseases and the lowest among the TA patients. It's mostly developed after dose quantity of 10.1-15mCi and it is rare at dose quantity less than 5mCi. 50% of hypothyroidism were developed among patients with diffuse goiter, Graves'disease.

Clinical outcomes 1 year after empiric 131I therapy for hyperthyroid disorders: real life experience and predictive factors of functional response.

Radioiodine is a therapeutic option in Europe for Graves' disease (GD) and toxic multinodular goiter (MNG). PURPOSE: To compare empiric and calculated I activities using 2013 EANM recommendations. To look for predictive factors of therapeutic response to an empiric activity of I. To assess clinical situations favoring calculated treatment modalities. PATIENTS AND METHODS: Prospective monocentric study of clinical outcomes at 1 year follow-up in 86 patients with GD and MNG who received empiric I therapeutic activities (348-939 MBq). Differences between empiric and calculated activities were confronted to clinical outcomes. Physicians were not aware of the calculated activity at the time of prescription. RESULTS: One year after treatment, 9% (5/57) of GD patients and 7% (2/29) of MNG patients were still in a hyperthyroid state. Thyroid volume was reduced by 67% for GD and by 50% for MNG. In GD, empiric I activities were higher than calculated ones (564±131 vs. 316±319 MBq, P<0.001) in 93% (53/57) of patients. Pretherapeutic thyroid volume (>26 ml for GD; >40 ml for MNG) was associated with persistent hyperthyroidism. CONCLUSION: Empirically administered I for GD and MNG was associated with very high efficacy in thyroid function control and no side effects. Thyroid volume reduction did not preclude treatment efficacy. Activity calculation could be a useful method for treating patients with GD and thyroid volumes higher than 26 ml or patients with MNG and thyroid volumes higher than 40 ml. A selective approach based on pretherapeutic thyroid volume and radioiodine biokinetics might improve treatment success.

Increased Cardiovascular Mortality and Morbidity in Patients Treated for Toxic Nodular Goiter Compared to Graves' Disease and Nontoxic Goiter.

BACKGROUND: Previous research has suggested an increased risk of death and cardiovascular disease in patients treated for hyperthyroidism. However, studies on this subject are heterogeneous, often based on old data, or have not considered the impact that treatment for hyperthyroidism might have on cardiovascular risk. It is also unclear whether long-term prognosis differs between Graves' disease and toxic nodular goiter. The aim of this study was to use a very large cohort built on recent data to assess whether improvements in cardiovascular care might have changed the prognosis over time. The study also investigated the impact of different etiologies of hyperthyroidism. METHODS: This was an observational register study for the period 1976-2012, with subjects followed for a median period of 18.4 years. Study patients were Stockholm residents treated for Graves' disease or toxic nodular goiter with either radioactive iodine or surgery (N = 12,239). This group was compared to Stockholm residents treated for nontoxic goiter (N = 3685), with adjustments made for age, sex, comorbidities, and time of treatment. Comparisons were also made to the general population of Stockholm. Outcomes were assessed in terms of all-cause and cardiovascular mortality as well as cardiovascular morbidity. RESULTS: The hazard ratios (HR) for all-cause mortality and for cardiovascular mortality were 1.27 [confidence interval (CI) 1.20-1.35] and 1.29 [CI 1.17-1.42], respectively, for hyperthyroid patients compared to those with nontoxic goiter. For cardiovascular morbidity, the HR was 1.12 [CI 1.06-1.18]. Patients aged ≥45 years who were treated for toxic nodular goiter were generally at greater risk than others, and those included from the year 1990 and onwards were at greater risk than those included earlier. Increased all-cause mortality, as well as cardiovascular mortality and morbidity, were also seen in comparisons with the general population. CONCLUSIONS: This is the first large study to indicate that the long-term risk of death and cardiovascular disease in hyperthyroid subjects is due to the hyperthyroidism itself and not an effect of confounding introduced by its treatment. Much of the excess risk is confined to individuals treated for toxic nodular goiter. Despite advances in cardiovascular care during recent decades, hyperthyroidism is still a diagnosis associated with increased cardiovascular morbidity and mortality.

Recombinant human thyrotropin stimulation prior to 131I therapy in toxic multinodular goitre with low radioactive iodine uptake. / La estimulación previa con rhTSH mejora la respuesta al tratamiento con radioyodo en pacientes con bocio multinodular tóxico de baja captación.

AIM: Stimulation with recombinant human thyrotropin (rhTSH) increases thyroid radioiodine uptake, and is an aid to 131I therapy in non-toxic multinodular goitre (MNG). However, there are not many studies using rhTSH prior to 131I in toxic multinodular goitre to improve hyperthyroidism and compressive symptoms. MATERIAL AND METHOD: A prospective study was conducted on patients with MNG and hyperthyroidism. Patients were recruited consecutively and divided into group I, stimulated with 0.3mg of rhTSH before radioiodine therapy, and a control group or group II, without stimulation. Thyroid function, radioiodine thyroid uptake, thyroid weight, and compressive symptoms were measured, and patients were followed-up for 9 months. RESULTS: Group I consisted of 16 patients (14 women), with a mean age 69.7 years, and group II with 16 patients (12 women), with a mean age 70.7 years. After stimulation with 0.3mg rhTSH in group I, 131I uptake (RAIU) at 24h increased by 78.4%, and the estimated absorbed dose by 89.3%. In group II, the estimated absorbed dose was lower than group I after stimulation with rhTSH (29.8Gy vs. 56.4Gy; P=0.001). At 9 months of follow-up, hyperthyroidism was controlled in 87.5% of patients in group I, and 56.2% in group II (P=0.049). The mean reduction in thyroid weight was higher in group I than in group II (39.3% vs. 26.9%; P=0.017), with a tendency towards subjective improvement of compressive symptoms in group I, although non-significant. Only 2 patients described tachycardias after rhTSH administration, which were resolved with beta-blockers. CONCLUSION: Stimulation with 0.3mg of recombinant human thyrotropin prior to radioiodine therapy achieves a reduction in thyroid weight and functional improvement in patients with hyperthyroidism and multinodular goitre with low uptake, and with no need for hospital admission.

Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter.

BACKGROUND: Radioiodine therapy (RIT) in patients with large nontoxic multinodular goiter (MNG) recently becomes more common method in comparison to surgery (especially in elderly patients and with contraindications because of severe chronic diseases other systems). Repeatedly low thyroid radioactive iodine uptake (RAIU) decreases effectiveness of RIT or makes it impossible. The recombinant human thyrotropin can increase RAIU and improve the results of RIT. THE AIM OF THE STUDY: was to assess the influence of a single very low dose (0.03 mg) of rhTSH on RAIU and thyroid function in euthyroid (MNG-EU) and subclinical hyperthyroid (MNG-SC) patients with a large multinodular goiter. MATERIAL AND METHODS: 40 patients (14 male, 26 female, age 57-80 yr) with large non-toxic MNG over 80 grams and with baseline RAIU < 40% were included into the double-blind randomized study and divided into two groups: rhTSH-group and control group. First group received the single intramuscular injection of 0.03 mg rhTSH and the second received placebo. The RAIU were measured 24 and 48 hours after the rhTSH and then all the patients were administered therapeutic doses of I-131. TSH and free thyroxine levels were measured at 1st and 2nd day after the injection of rhTSH and later, at 4 and 8 weeks after the RIT. RESULTS: The mean RAIU increased significantly from 30.44 ± 7.4% to 77.22 ± 8.7% (p < 0.001). There were no statistically significant differences in RAIU between euthyroid (MNG-EU) and subclinically hyperthyroid (MNG-SC) patients. The peak of serum TSH was noticed 24 hours after rhTSH injection and in MNG-EU patients it has remained within normal range, similarly as fT4. In the MNG-SC group the administration of rhTSH resulted in a significant increase in the TSH values after 24 hours, whose mean level slightly exceeded the upper limit of the normal range with normalization at 48 hours. 8 weeks after the RIT, the TSH and fT4 levels did not exceed the normal range and did not differ in a statistically significant way. CONCLUSIONS: Even the single very low dose of rhTSH increases the values of RAIU in significant way, in euthyroid and subclinically hyperthyroid patients. The administration of rhTSH is well-tolerated. Neoadjuvant administration of a low dose (0.03 mg) of rhTSH before I-131 seems to be an optimal method of management which may increase the effectiveness of RIT and decrease the exposure of the patients to absorbed doses of ionizing radiation.

[Changes in radioiodine therapy for thyroid disorders]. / Változások a pajzsmirigybetegségek radiojódkezelésében.

Radioiodine therapy for benign and malignant thyroid diseases was introduced about 70 years ago, however, there is still a lack of consensus regarding indications, doses and procedure. This review covers treatment results in immunogenic hyperthyroidism including the problem of orbitopathy. Radioiodine therapy for toxic and non-toxic multinodular goiter is also discussed with striking possibility of enhanching the radioiodine uptake. In this respect the recombinant human thyrotropin should be mentioned. Thyroid cancer treatment protocol has changed, too, due to ineffectivity in low-risk patients. More attention is needed to the carcinogenecity of radioiodine. The numerous problems mentioned above require large and well-designed prospective trials to resolve the fundamental questions. The author emphasizes that radioiodine dose should be administered in doses as low as reasonably achievable.

TREATMENT OF SUBCLINICAL HYPERTHYROIDISM: EFFECT ON BODY COMPOSITION.

BACKGROUND: subclinical hyperthyroidism (SHT) is associated with harmful effects on cardiovascular system, bone metabolism and progression to clinical hyperthyroidism. Loss of weight is a common fact in patients with clinical hyperthyroidism and of particular relevance in elderly patients. OBJECTIVE: to assess changes in body composition after radioiodine therapy for SHT due to toxic nodular goiter. SUBJECTS AND METHODS: prospective controlled cohort study. Patients with persistent SHT due to toxic nodular goiter were purposed to receive treatment with radioiodine (treatment group) or to delay treatment until the study was over (control group). All treated patients received 555 MBq of ¹³¹I. Body composition (lean mass, fat mass and bone mineral content) was determined by dual-energy X-ray absorptiometry (DEXA) at baseline and 12 months after. RESULTS: twenty-nine patients were studied (age 69.5 ± 11.5; 75.9% women; BMI 27.1 ± 5.7 kg/m²; serum thyrotropin (TSH) 0.20 ± 0.21 µUI/mL; serum free thyroxine (T4) 1.01 ± 0.19 ng/dL), 17 belonging to the treatment group and 12 to the control group. Study groups were comparable, although there was a trend for the treatment group to have more fat mass. No longitudinal changes in body composition were noted in either group, except for a trend to gain fat mass. However, when individuals with age > 65 years were selected, only patients who received radioiodine therapy showed a significant increase in body weight (from 64.1 ± 10.0 to 66.9 ± 9.2 kg), BMI (from 27.3 ± 4.8 to 28.7 ± 4.5 kg/m²), fat mass (from 26.1 ± 8.5 to 27.8 ± 7.9 kg), lean mass (from 36.3 ± 0.4 to 37.4 ± 0.4 kg) and skeletal muscle mass index (SMI) (from 6.0 ± 0.6 to 6.3 ± 0.6 kg/m²). CONCLUSIONS: treatment of SHT has impact on body composition in subjects older than 65 years. Weight gain reflects increases in fat and, more interestingly, in lean mass.

Introducción: el hipertiroidismo subclínico (HS) se asocia a efectos deletéreos sobre el sistema cardiovascular, el metabolismo óseo y puede progresar a hipertiroidismo clínico. La pérdida de peso es habitual en los pacientes con hipertiroidismo clínico y adquiere especial relevancia en los sujetos añosos. Objetivo: evaluar los cambios en la composición corporal después del tratamiento del HS por bocio nodular con radioyodo. Sujetos y métodos: estudio de cohortes prospectivo controlado. A los pacientes con HS persistente debido a bocio nodular tóxico se les ofreció la opción de recibir tratamiento con radioyodo (grupo tratamiento) o retrasar dicho tratamiento hasta que el estudio hubiera acabado (grupo control). Al final, todos los pacientes recibieron 555 MBq de 131I. La composición corporal (masa magra, masa grasa y contenido mineral óseo) se determinó por absorciometría con rayos X de doble energía (DEXA) al inicio y a los 12 meses. Resultados: se estudiaron 29 pacientes (edad 69,5 ± 11,5; 75,9% mujeres; BMI 27,1 ± 5,7 kg/m²; tirotropina sérica (TSH) 0,20 ± 0,21 µUI/mL; tiroxina libre sérica(T4) 1,01 ± 0,19 ng/dL), 17 pertenecientes al grupo tratamiento y 12 al grupo control. Los grupos de estudio fueron comparables, aunque existía una tendencia del grupo tratamiento a presentar más masa grasa. No se detectaron cambios en la composición corporal en ningún grupo, salvo una tendencia general a ganar masa grasa. Sin embargo, cuando se seleccionaron los individuos con edad > 65 años, sólo los pacientes que recibieron tratamiento con radioyodo mostraron un significativo incremento de peso (de 64,1 ± 10,0 a 66,9 ± 9,2 kg), IMC (de 27,3 ± 4,8 a 28,7 ± 4,5 kg/m²), masa grasa (de 26,1 ± 8,5 a 27,8 ± 7,9 kg), masa magra (de 36,3 ± 0,4 a 37,4 ± 0,4 kg) e índice de masa muscular esquelética (de 6,0 ± 0,6 a 6,3 ± 0,6 kg/m²). Conclusiones: el tratamiento del HS tiene impacto sobre la composición corporal en sujetos mayores de 65 años. La ganancia de peso refleja incrementos en la masa grasa y, lo que es más interesante, en la masa magra.

Radioiodine therapy increases the risk of cerebrovascular events in hyperthyroid and euthyroid patients.

BACKGROUND AND OBJECTIVE: Hyperthyroid patients treated with radioiodine have increased morbidity and mortality from cerebrovascular events. This risk has until now has been attributed to the hyperthyroidism. However, radioiodine therapy of benign thyroid diseases exposes the carotid arteries to radiation and is capable of inducing atherosclerosis. The objective of the study was to elucidate whether ionizing radiation from radioiodine might contribute to cerebrovascular morbidity. METHODS: In a retrospective register cohort study, 4000 hyperthyroid and 1022 euthyroid goitre patients treated with radioiodine between 1975 and 2008 were matched 1:4 on age and sex with random controls. The cohort was followed from the date of treatment until hospitalization due to cerebrovascular event, death, 20 years of follow-up or March 2013. Data were analyzed in competing risk models adjusting for age, sex, Charlson's comorbidity score, atrial fibrillation and previous cerebrovascular events. RESULTS: Mean follow-up time was 11.5 years, mean age 61 years, with a total number of 3228 events. Comparing all radioiodine-treated patients with controls, the fully adjusted model showed increased risk of cerebrovascular events among all treated patients, hazard ratio (HR) 1.18 (95% CI 1.09-1.29). The risk was increased among hyperthyroid (HR 1.17; 95% CI 1.07-1.28) as well as euthyroid patients (HR 1.21; 95% CI 1.02-1.44). CONCLUSIONS: We report an increased risk of cerebrovascular events in hyperthyroid as well as euthyroid patients treated with radioiodine for benign thyroid disorders. That these patient groups have similar risks suggests the possibility that radiation from radioiodine contributes to cerebrovascular morbidity via acceleration or initiation of atherosclerosis.

Thiamazole Pretreatment Lowers the (131)I Activity Needed to Cure Hyperthyroidism in Patients With Nodular Goiter.

CONTEXT: Relatively low radioiodine uptake (RAIU) represents a common obstacle for radioiodine ((131)I) therapy in patients with multinodular goiter complicated by hyperthyroidism. OBJECTIVE: To evaluate whether thiamazole (MTZ) pretreatment can increase (131)I therapeutic efficacy. DESIGN AND SETTING: Twenty-two patients with multinodular goiter, subclinical hyperthyroidism, and RAIU < 50% were randomized to receive either a low-iodine diet (LID; n = 10) or MTZ 30 mg/d (n = 12) for 42 days. Thyroid function and 24-hour RAIU were measured before and after treatment. Thyroid volume was evaluated by either magnetic resonance imaging or single photon emission computed tomography. RESULTS: Mean 24-hour RAIU increased significantly from 32 ± 10% to 63 ± 18% in the MTZ group (P < .001). Consequently, there was a 31% decrease in the calculated median therapeutic (131)I activity after MTZ (P < .05). No significant changes in 24-hour RAIU were observed after diet. In the MTZ group, median serum TSH levels increased significantly by 9% and mean serum free T4 and free T3 concentrations decreased by 22% and 15%, respectively, whereas no changes in thyroid function were observed in the LID group. Thyroid volume did not significantly change in either of the two groups. At 12 months after radioiodine treatment, median serum TSH was within the normal range in both groups. CONCLUSIONS: MTZ treatment before (131)I therapy resulted in an average 2-fold increase in thyroid RAIU and enhanced the efficiency of radioiodine therapy assessed at 12 months. MTZ pretreatment is therefore a safe, easily accessible alternative to recombinant human TSH stimulation and a more effective option than LID.

Clinical efficacy of radioiodine therapy in multinodular toxic goiter, applying an implemented dose calculation algorithm.

Radioiodine is a common therapeutic option for Multinodular Toxic Goiter (MTG). We evaluated an algorithm for personalized radioiodine activity calculation. Ninety-three (28 male, 65 female; 43-84 years) patients with MTG eligible for radioiodine treatment (131I-iodide) were studied. The quantity of 131I-iodide to be administered was estimated by Thyroid Volume Reduction (TVR) algorithm, developed for Graves' disease. It takes into account 131I uptake, its effective half-life (T1/2eff), thyroid volume, and its expected reduction during treatment. A comparison with the activity calculated by other dosimetric protocols and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid volume by ultrasonography (US), thyroid stimulating hormone (TSH), and thyroid hormones by standard immunometric methods. In a follow-up of 6-120 months, remission of hyperthyroidism after a single 131I-iodide treatment was observed in 76 patients (64 euthyroid, 12 hypothyroid). The thyroid volume reduction observed by US after the treatment fairly correlated with what predicted by our model; T1/2eff was highly variable and critically affected dose calculation. The administered activities (median 526 MBq, range 156-625 MBq) were slightly lower than the "fixed" activities (600 MBq) and with respect to the other protocols' prescriptions (-15/38%); the median 131I activity administered to relapsed patients (605 MBq) was significantly greater (P=0.01) with respect to the dose administered to cured patients (471 MBq). Our study shows that an effective cure of MTG can be obtained with relatively low 131I activities and probably with a relatively low incidence of hypothyroidism, using TVR method.

Recombinant human TSH and radioactive iodine therapy in the management of benign multinodular goiter.

Multinodular goiter (MNG) is a very common thyroid disorder determined by diverse goitrogenic factors, the most important one being iodine deficiency. The clinical presentation of a patient with MNG varies from a completely asymptomatic goiter to a life-threatening disease due to upper airway compression. Patients can develop underlying subclinical or overt hyperthyroidism due to autonomously hyperfunctioning nodules. In the absence of clinical, ultrasonographic, or cytological findings suggestive of malignancy, the best therapeutic approach for a patient with MNG will depend on the size and location of the goiter, the presence and severity of compressive symptoms, and the presence or absence of thyrotoxicosis. There is still no consensus regarding the treatment of atoxic MNGs. Hence, its optimal management remains controversial; possible therapies include levothyroxine (lT4), surgery, and radioactive iodine ((131)I). Suppressive treatment with lT4 is discouraged due to the development of sub-clinical or overt hyperthyroidism and to its low efficacy when compared with surgery or (131)I. Total thyroidectomy is effective; however, it is associated with the risk of surgical complications and is often refused by the patient. (131)I therapy is an alternative to thyroid surgery to reduce the size of benign MNGs. Based on the ability of recombinant human TSH (rhTSH) to more than double thyroid (131)I uptake, this compound has been evaluated as an adjuvant to (131)I in the treatment of MNG. Very small doses of rhTSH have been used in patients with MNG and few safety concerns have been observed, but the ideal dose, both effective and safe, is yet to be defined.