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.

Evaluation of percutaneous ethanol injections in benign thyroid nodules / Avaliação do tratamento com injeção percutânea com etanol em nódulos benignos de tireoide

Objective The objective of this study was to evaluate the efficacy and safety of percutaneous ethanol injection (PEI) in the treatment of benign thyroid nodules. Subjects and methods We evaluated 120 patients with benign thyroid nodules. Patients underwent evaluation of serum TSH and free T4, cervical ultrasound, and thyroid scintigraphy (in those with suppressed TSH levels). The application of sterile ethanol 99% was guided by ultrasound, with the injected volume amounting to one-third of the nodule volume. Response was considered complete (reduction of 90%); partial (reduction between 50 and 90%); or none (reduction of < 50%). Autonomous nodules were evaluated for normalization of TSH levels. Results Among the nodules studied, 30.8% were solid, 56.7% were mixed, 12.5% were cystic, and 21.6% were hyperfunctioning. The initial volume of the treated nodules ranged from 0.9 to 74.8 mL (mean 13.1 ± 12.4 mL). We performed 1-8 sessions of PEI, applying an average of 6.2 mL of ethanol for patient. After 2 years of follow-up, 17% of patients achieved a complete response (94% reduction); 53%, a partial response (70% reduction); and 30%, no response. A reduction in the volume of autonomous nodules was noted in 70% of cases, and 54% had a normalized value of TSH. The main side effect is local pain, lasting less than 24 hours in most cases. Conclusion This study showed that PEI is a safe and effective procedure for treatment of benign, solid or mixed thyroid nodules. Most cases resulted in significant reduction in nodule volume, with normalization of thyroid function. Arq Bras Endocrinol Metab. 2014;58(9):912-7 .

Objetivo O objetivo deste estudo foi avaliar a eficácia e segurança da injeção percutânea de etanol (IPE) no tratamento de nódulos tireoidianos benignos. Sujeitos e métodos Foram avaliados 120 pacientes com nódulos benignos de tireoide. Todos realizaram dosagens de TSH, T4 livre, ecografia cervical (US) e cintilografia de tireoide (em pacientes com TSH suprimido). A aplicação de etanol estéril a 99% foi guiada por US e o volume de etanol injetado correspondeu a um terço do volume nodular calculado. A resposta foi considerada completa (redução de 90%); parcial (redução entre 50 e 90%) ou ausência de resposta (redução menor que 50%). Nos nódulos autônomos, foi avaliada a normalização do TSH. Resultados Entre os nódulos estudados, 30,8% eram sólidos, 56,7% eram mistos, 12,5% eram císticos e 21,6%, nódulos hiperfuncionantes. O volume inicial dos nódulos tratados variou de 0,9 a 74,8 mL (média 13,1 ± 12,4 mL). Foram realizadas de 1 a 8 sessões de IPE (média 2,8), com aplicação média de 6,2 mL de etanol por paciente. Após dois anos de seguimento, 17% dos pacientes obtiveram resposta completa (redução de 94%), 53% obtiveram resposta parcial (redução de 70%) e 30% não responderam. Houve redução de volume nos nódulos autônomos em 70% dos casos, e 54% normalizaram o valor do TSH. Os efeitos colaterais registrados foram decorrentes apenas do desconforto no local de aplicação. Conclusão Este trabalho mostrou que a IPE é um procedimento seguro e eficaz para tratamento de nódulos benignos, sólidos ou mistos de tireoide. ...

Evaluation of percutaneous ethanol injections in benign thyroid nodules.

OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of percutaneous ethanol injection (PEI) in the treatment of benign thyroid nodules. SUBJECTS AND METHODS: We evaluated 120 patients with benign thyroid nodules. Patients underwent evaluation of serum TSH and free T4, cervical ultrasound, and thyroid scintigraphy (in those with suppressed TSH levels). The application of sterile ethanol 99% was guided by ultrasound, with the injected volume amounting to one-third of the nodule volume. Response was considered complete (reduction of 90%); partial (reduction between 50 and 90%); or none (reduction of < 50%). Autonomous nodules were evaluated for normalization of TSH levels. RESULTS: Among the nodules studied, 30.8% were solid, 56.7% were mixed, 12.5% were cystic, and 21.6% were hyperfunctioning. The initial volume of the treated nodules ranged from 0.9 to 74.8 mL (mean 13.1 ± 12.4 mL). We performed 1-8 sessions of PEI, applying an average of 6.2 mL of ethanol for patient. After 2 years of follow-up, 17% of patients achieved a complete response (94% reduction); 53%, a partial response (70% reduction); and 30%, no response. A reduction in the volume of autonomous nodules was noted in 70% of cases, and 54% had a normalized value of TSH. The main side effect is local pain, lasting less than 24 hours in most cases. CONCLUSION: This study showed that PEI is a safe and effective procedure for treatment of benign, solid or mixed thyroid nodules. Most cases resulted in significant reduction in nodule volume, with normalization of thyroid function.

Changes associated with percutaneous ethanol injection in the treatment of thyroid nodules.

Percutaneous ethanol injection (PEI) is an alternative therapy for thyroid nodules (TN). However, some concern is raised on its carcinogenic effects. To evaluate the cytological and clinical changes caused by PEI in patients with benign TN. Thirty-nine patients with TN (23.1% hyperfunctioning) were submitted to a median of three PEI sessions. After a median of 17 months, patients were reassessed. A new ultrasound-guided fine needle biopsy (US-FNB) was performed, and the smears were analyzed after May-Grünwald-Giemsa staining. The diagnostic findings and the cellular characteristics were compared before and after treatment. There was an increase in the proportion of nondiagnostic/unsatisfactory results (from 2.5% to 18.9%). No malignant cases were observed. The proportion of moderate/intense macrophage infiltration decreased from 60% to 15%. Before treatment, 23.1% patients had hyperthyroidism, which was completely or partially resolved in 66.7%. By ultrasound, the percentage of homogeneous nodules decreased from 64.0% to 38.4% (p=0.0235), and the mean nodule volume decreased from 13.4 ± 12.2 to 5.3 ± 5.1 cm(3). We demonstrate that PEI increases the proportion of nondiagnostic/unsatisfactory results from US-FNB. Therefore, cytological findings after PEI must be evaluated with caution. Our results also suggest that PEI is an efficacious and safe therapeutic option, with no carcinogenic effects observed on cytological evaluations. Safety and efficacy must be evaluated in larger studies with longer follow-up periods.

Modified-release recombinant human TSH (MRrhTSH) augments the effect of (131)I therapy in benign multinodular goiter: results from a multicenter international, randomized, placebo-controlled study.

BACKGROUND: Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). OBJECTIVE, DESIGN, AND SETTING: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. PATIENTS AND INTERVENTION: Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. MAIN OUTCOME MEASURES: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. RESULTS: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. CONCLUSION: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.

High prevalence of side effects after recombinant human thyrotropin-stimulated radioiodine treatment with 30 mCi in patients with multinodular goiter and subclinical/clinical hyperthyroidism.

BACKGROUND: Treatment of multinodular goiters (MNGs) is highly controversial. Radioiodine (RAI) therapy is a nonsurgical alternative for the elderly who decline surgery. Recently, recombinant human thyrotropin (rhTSH) has been used to augment RAI uptake and distribution. In this study, we determined the outcome of 30 mCi RAI preceded by rhTSH (0.1 mg) in euthyroid (EU) and hyperthyroid (subclinical/clinical) patients with large MNGs. METHODS: This was a prospective cohort study. Forty-two patients (age, 43-80 years) with MNGs were treated with 30 mCi RAI after stimulation with 0.1 mg of rhTSH. Patients were divided into three groups, according to thyroid function: EU (n = 18), subclinically hyperthyroid (SC-H, n = 18), and clinically hyperthyroid (C-H, n = 6). All patients underwent a 90-day low-iodine diet before treatment, and those with clinical hyperthyroidism received methimazole 10 mg daily for 30 days. Serum TSH, free thyroxine (FT4), total triiodothyronine (TT3), and thyroglobulin were measured at baseline and at 24, 48, 72, 168 hours, and 1, 3, 6, 9, 12, 18, 24, and 36 months after therapy. Thyroid volume was assessed by computed tomography at baseline and every 6 months. RESULTS: Patients had high iodine urinary excretion (308 +/- 108 microg I/L) at baseline. TSH levels at baseline were within the normal range (1.5 +/- 0.7 microU/mL) in the EU group and suppressed (<0.3 microU/mL) in the SC-H and C-H groups. After rhTSH, serum TSH peaked at 24 hours reaching 12.4 +/- 5.85 microU/mL. After RAI administration, patients in both hyperthyroid groups had a higher increase in FT4 and TT3 compared with those in the EU group (p < 0.001). Thyroglobulin levels increased equally in all three groups until day 7. Thyroid volume decreased significantly in all patients. Side effects were more common in the SC-H and C-H groups (31.4% and 60.4%, respectively) compared with EU patients (17.8%). Permanent hypothyroidism was more prevalent in the EU group (50%) compared with the SC-H (11%) and C-H (16.6%) groups. CONCLUSIONS: Patients with MNG may have subclinical and clinical nonautoimmune iodine-induced hyperthyroidism. Despite a low-iodine diet and therapy with methimazole, hyperthyroid patients have a significantly higher increase in FT4 and TT3 levels after RAI ablation. This can lead to important side effects related mostly to the cardiac system. We strongly advise that patients with SC-H and C-H be adequately treated with methimazole and low-iodine diet aiming to normalize their hyperthyroid condition before rhTSH-stimulated treatment with RAI.

Thiamazole as an adjuvant to radioiodine for volume reduction of multinodular goiter.

BACKGROUND: Radioiodine ((131)I) is an alternative to surgery for the treatment of multinodular goiter (MNG). Frequently, high activities of (131)I are required for effective thyroid volume reduction (TV), due to the low and heterogeneous radioactive iodine uptake (RAIU). Thiamazole (MTZ) may be used as an adjuvant to (131)I, by increasing RAIU. OBJECTIVE: To evaluate the effects of MTZ in the treatment of MNG with (131)I, in terms of TV reduction. DESIGN/METHODS: Nine female patients (aged 73.8 +/- 7.4 years) with MNG (eight with subclinical hyperthyroidism) were treated with MTZ. Doses started at 10 - 20 mg, and were adjusted monthly based on thyroid hormone levels. RAIU and TV were measured at baseline, and repeated when TSH levels > 6 mU/l were achieved. At that time, 1.11 GBq of (131)I were administered. RESULTS: Patients were treated with MTZ for 2.8 +/- 0.8 months. When a tracer activity of (131)I was administered, the mean serum TSH was elevated to 11.7 +/- 5.4 mU/l. MTZ led to significant increases in 24-h RAIU, from 21.3 +/- 8.1% to 78.3 +/- 15.3% (p < 0.001). One year after (131)I, median TV decreased from 97 ml (range 47 - 555 ml) to 56 ml (range 13 - 350 ml), a mean reduction of 46.2 +/- 17.8% (p = 0.012). Eight patients (89%) had subclinical hyperthyroidism, which was reversed in all patients after 1 year. Five patients (56%) developed overt hypothyroidism, and no clinical adverse events were observed. CONCLUSION: Pretreatment with MTZ targeting against an increased serum TSH did not impair the effects of (131)I. In our patients with MNG, MTZ increased RAIU and possibly enhanced (131)I efficacy, leading to significant TV reduction and reversion of hyperthyroidism in all patients.

Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

Recombinant human thyroid-stimulating hormone (rhTSH) enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 ± 13.1 years), who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 ± 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 ± 9.7 to 49.6 ± 13.4 percent (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 ± 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 ± 0.48 ng/dL for free-T4, 204.61 ± 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6 percent), painful thyroiditis (29.4 percent) and hypothyroidism (52.9 percent). Thyroid volume was reduced by 34.3 ± 14.3 percent after 6 months (P < 0.001) and by 46.0 ± 14.6 percent after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

Cardiovascular assessment of hyperthyroid patients with multinodular goiter before and after radioiodine treatment preceded by stimulation with recombinant human TSH.

Treatment of large multinodular goiter (MNG) with radioiodine preceded by recombinant human thyrotropin (0.1 mg rhTSH) has been shown to be a safe alternative for patients with comorbidities that preclude surgery. However, the increase in serum thyroid hormones that follows both treatments may be harmful for some patients, particularly those with underlying cardiovascular disease. In this study, we evaluated cardiac parameters (clinical, ECG, 24-h Holter, Doppler echocardiogram, treadmill stress test) in 27 of 42 patients (ages 42-80 years) with large MNGs who were treated with rhTSH before receiving 30 mCi radioiodine therapy. At baseline, 18 patients had subclinical and six patients had overt iodine-induced hyperthyroidism. All patients had a transient surge in serum levels of free T4 and total T3 into the hyperthyroid range after therapy. However, repeated cardiac evaluation did not show significant changes as compared with baseline evaluation. In conclusion, rhTSH stimulated RAI treatment of MNG did not affect structural and functional parameters of the heart, despite transient high-serum levels of thyroid hormones.

Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone.

Recombinant human thyroid-stimulating hormone (rhTSH) enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 +/- 13.1 years), who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 +/- 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 +/- 9.7 to 49.6 +/- 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 +/- 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 +/- 0.48 ng/dL for free-T4, 204.61 +/- 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 +/- 14.3% after 6 months (P < 0.001) and by 46.0 +/- 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

[Alcoholization in the treatment of thyroid nodule in colloid goiter endemic region]. / Alcoolização de nódulo tiroidiano em região endêmica de bócio colóide.

Thyroid nodular disease is a common clinical disorder mainly in iodine lacking regions. This study has evaluated the effectiveness of percutaneous ethanol injection (PEI) in the treatment of single, multiple, solid, and cystic thyroid nodules of different sizes with or without glandular dysfunction, in goiter endemic region. Forty-two patients with diagnosis of colloid goiter or colloid nodular hyperplasia in fine-needle aspiration (FNA) were selected for analysis, after having been submitted to at least two PEI. Thyroid nodules were multiple (solid and or cystic) in 52.4% of the patients, single and solid or mixed in 35.7%, and single and cystic in 11.9%. The mean reduction of nodules after ethanol injection was of 58.2% in the single and of 60.8% in the cystic ones. The reduction of the whole thyroid lobe was evaluated in the multiple nodules and it reached 52.4%. The side-effects were registered only as a consequence of the application discomfort. This study points out that the percutaneous ethanol injection reaching volume mean reductions, varying from 49% to 60%, is a safe, effective, and simple method for the treatment of benign thyroid nodules.

Peripheral blood levels of thyroglobulin mRNA and serum thyroglobulin concentrations after radioiodine ablation of multinodular goiter with or without pre-treatment with recombinant human thyrotropin.

We investigated the effect of therapeutic doses of radioiodine (RAI) on peripheral serum messenger thyroglobulin RNA (Tg mRNA) and serum thyroglobulin (sTg) in patients with multinodular goiter (MNG) preceded or not by treatment with recombinant human TSH (rhTSH). Fourteen patients with large MNG (91-542 ml) received RAI (550-2960 MBq). Half of the patients received 0.45 mg of rhTSH prior to the treatment (RAI+rhTSH group) and half did not (RAI group). Patients' blood samples were collected before and 24, 48, and 72 h; 7 and 30 days; and 6, 9, and 12 months after RAI treatment. Serum Tg was measured by immunoradiometric assay, serum anti-Tg by radioimmunoassay, and quantification of circulating Tg mRNA was performed by real-time PCR. The shrinkage of MNG volume was documented by serial computed tomography (CT) scans before, 6 and 12 months after RAI. Peak Tg mRNA and sTg were reached earlier in the RAI+rhTSH group (24 h and 48 h) than in the RAI group (7 days). Both declined after the peak and the lowest levels were observed at 12 months. The mean reduction of the thyroid volume was 19.8% (RAI group) and 30.3% (RAI+rhTSH group) at 6 months (ns) and 32.8% RAI and 52.5% (RAI+rhTSH group) at 12 months (p<0.05). After RAI treatment there was a significant and positive correlation between goiter volume and sTg only in the RAI group (r=0.7; p=0.032). Serum anti-Tg had a transitory and relatively small elevation in 3 and 2 patients, respectively, in the RAI and RAI+rhTSH groups. We concluded that after RAI ablation of MNG there is a rapid release of Tg into the serum possibly from the colloid, which is followed by an elevation of serum Tg mRNA that may be due to an increased release of follicular cells into the blood stream. Both phenomena are enhanced by the use of rhTSH before RAI treatment as a consequence of a more effective and prolonged radiation exposure of the thyroid follicles.

Alcoolização de nódulo tiroidiano em região endêmica de bócio colóide / Alcoholization in the treatment of thyroid nodule in colloid goiter endemic region

A doença nodular tiroidiana é problema clínico comum, principalmente em regiões com carência de iodo. Esse estudo avaliou a eficácia da injeção percutânea de etanol (IPE) no tratamento de nódulos tiroidianos únicos, múltiplos, sólidos, císticos, de diferentes tamanhos com ou sem disfunção glandular, em região endêmica de bócio. Quarenta e dois pacientes com diagnóstico de bócio colóide ou hiperplasia nodular colóide, na punção biópsia aspirativa por agulha fina (PBAAF), foram selecionados para análise após terem sido submetidos a pelo menos duas IPEs. Os nódulos tiroidianos eram múltiplos (sólidos e ou císticos) em 52,4 por cento dos pacientes, únicos e sólidos ou mistos em 35,7 por cento e únicos e císticos em 11,9 por cento. A redução média dos nódulos após injeção de etanol foi de 58,2 por cento para os únicos e 60,8 por cento nos císticos. Nos nódulos múltiplos, avaliou-se a redução de todo o lobo tiroidiano, alcançando 52,4 por cento de redução. Os efeitos colaterais registrados foram decorrentes apenas do desconforto na aplicação. Este estudo indica que a injeção percutânea de etanol (IPE), alcançando reduções médias de volume que variam de 49 a 60 por cento, é método seguro, eficaz e simples para o tratamento de nódulos tiroidianos benignos.

Thyroid nodular disease is a common clinical disorder mainly in iodine lacking regions. This study has evaluated the effectiveness of percutaneous ethanol injection (PEI) in the treatment of single, multiple, solid, and cystic thyroid nodules of different sizes with or without glandular dysfunction, in goiter endemic region. Forty-two patients with diagnosis of colloid goiter or colloid nodular hyperplasia in fine-needle aspiration (FNA) were selected for analysis, after having been submitted to at least two PEI. Thyroid nodules were multiple (solid and or cystic) in 52.4 percent of the patients, single and solid or mixed in 35.7 percent, and single and cystic in 11.9 percent. The mean reduction of nodules after ethanol injection was of 58.2 percent in the single and of 60.8 percent in the cystic ones. The reduction of the whole thyroid lobe was evaluated in the multiple nodules and it reached 52.4 percent. The side-effects were registered only as a consequence of the application discomfort. This study points out that the percutaneous ethanol injection reaching volume mean reductions, varying from 49 percent to 60 percent, is a safe, effective, and simple method for the treatment of benign thyroid nodules.

Human recombinant TSH preceding a therapeutic dose of radioiodine for multinodular goiters has no significant effect in the surge of TSH-receptor and TPO antibodies.

Radioiodine (RAI) treatment has increasingly been used mostly in elderly patients with multinodular goiter (MNG) as an alternative for surgery. Recombinant human thyrotropin (rhTSH) has been demonstrated to increase the uptake of RAI and also to promote a more even distribution of radionuclide among the various nodules. We have compared the surge of autoantibodies to thyroid peroxidase (anti-TPO) and to the TSH receptor (TRAb) in two groups of patients with MNG. Group RAI (n = 15) received only RAI, and Group RAI+rhTSH (n = 15) received RAI 24 h after 0.45 mg of rhTSH intramuscularly. At baseline, all 30 patients had negative anti-TPO antibodies. After RAI, 16 patients (eight in each group) exhibited a positive anti-TPO test (range, 70-2359 U/mL). In the rhTSH-treated group, anti-TPO values were significantly higher (as compared to basal levels; p < 0.02) after 3 months of RAI treatment. After 12 months, the anti-TPO values decreased to lower but still positive concentrations in nine patients (Group RAI: three patients; Group RAI+rhTSH: five patients). Only one patient had a positive TRAb test at baseline (67.5% inhibition of the TSH binding). After RAI, positive TRAb values were present in 21/30 patients. After 6 months of RAI treatment, there was a significant increase of the TRAb values in Group RAI+rhTSH patients. After 12 months, only four patients had positive TRAb (Group RAI: three patients; Group RAI+rhTSH: one patient). Two patients, one of each group, had an elevation of free T4 levels and suppressed serum TSH values, indicating hyperthyroidism (Graves' disease). Bioassay of TSH receptor (TSHR) indicated absence of a significant elevation of cAMP in the medium before and after RAI treatment in all patients. Moreover, predominantly blocking TSHR autoantibodies were detected in six of the 30 patients (three of each group). Sera from these patients were able to reduce the TSH-stimulated cAMP generation by CHO cells. We conclude that the autoantibodies to the TSHR and to TPO may occur after RAI treatment of patients, either with or without previous stimulation by rhTSH. The antibodies to the TSH comprised a combination of agonist (stimulating) and antagonist (blocking) antibodies, which in most patients did not induce clinical and laboratory evidence of active Graves' disease.

Administration of a single dose of recombinant human thyrotrophin enhances the efficacy of radioiodine treatment of large compressive multinodular goitres.

OBJECTIVE: Patients with very large multinodular goitres, frequently found among elderly people, often suffering from cardiovascular or other disabling disorders, may be considered as unsuitable for surgery. We have evaluated the feasibility of relatively high-dose 131I therapy in such patients. As subclinical or clinical hyperthyroidism is commonly found in these patients, associated with a low radioiodine (RAI) uptake at 24 h, we pretreated a group of patients with a single intramuscular injection of recombinant human TSH (rhTSH 0.45 mg) in order to increase the uptake of the therapeutic dose of RAI. DESIGN AND PATIENTS: Forty-one patients with large, long-standing multinodular goitres, were recruited for this study. After a careful and detailed clinical and laboratory evaluation, 34 patients (28 women, six men) were included and randomly assigned to group 1 (control, n = 17, 15 women, two men, age 63.1 +/- 11.2 years) receiving only RAI. Patients in group 2 (n = 17, 13 women, four men, age 63.6 +/- 12.3 years) received the therapeutic dose of RAI, having been pretreated (24 h) with 0.45 mg of rhTSH. Both groups of patients were submitted to a low iodine diet, 4-6 months before RAI treatment, while seven thyrotoxic patients also received methimazole (40 mg/day) until they reached euthyroidism. Ultrasonographic studies were performed for all patients and fine-needle aspiration biopsy (FNAB) were performed on one or two nodules before RAI treatment. RAI was given as a single oral dose to the hospitalized isolated patients. Blood samples for thyroid function tests and serum thyroglobulin (Tg) were collected daily during the first week following RAI treatment, and at 1, 3, 6, 9 and 12 months thereafter. MEASUREMENTS: Goitre volume was estimated by computed tomography scan. Thyroid function tests (total T3, free T4, TSH and serum Tg) were assayed with commercial kits. Urinary excretion of iodine was assayed by the Sandell-Kolthoff method. RESULTS: After the RAI therapeutic dose, serum thyroid function tests were carried out daily for the first week and then on a monthly basis (1, 3, 6, 9 and 12 months). Serum TSH levels rose to a peak level of 45.9 +/- 19.1 mU/l (24 h) in group 2 returning to normal at 72 h. Free T4 serum concentrations rose significantly to 59.35 +/- 21.61 pmol/l at 48 h (in group 2) returning to normal at 7 days. Similarly, serum TT3 also peaked above normal levels only in group 2 (6.12 +/- 1.89 nmol/l) at 24 h. Serum Tg increased in both groups (significantly higher in group 2) and remained elevated during the following 12 months. Both groups had a significant reduction in goitre volume at 12 months (group 2: 57.8%vs. group 1: 39.7%, P < 0.05). Hypothyroidism was detected after RAI treatment, respectively, in 21.4% (group 1) and 64.7% (group 2), of the patients at 12 months. CONCLUSIONS: Our results indicate that the use of hTSH increased the efficacy of the RAI therapeutic dose. This was basically due to an increased uptake of the radionuclide (as a consequence of the higher serum TSH levels) and a more extensive distribution of 131I within the nodules of the multinodular goitre. A more intense radiation effect was reflected in there being a higher output of serum Tg and thyroid hormones (group 2). As a consequence this group had a significantly higher reduction of the goitre volume. Also incidence of hypothyroidism post-RAI was significantly higher in group 2. We concluded that pretreatment with rhTSH in elderly patients with large multinodular goitres increases the uptake of the RAI therapeutic dose, thereby significantly reducing the multinodular goitre volume and relieving the compressive symptoms with relatively few side-effects.

Bócio nodular benigno. Acurácia da PAAF no diagnóstico e eficácia do tratamento com tiroxina / Benign nodular goiter. Accuracy of (FNBB) in diagnosis and efficacy of treatment with thyroxine

Com o objetivo de avaliar a acurácia da punçäo aspirativa por agulha fina (PAAF), comparando-a com a histopatologia, e o comportamento do nódulo tireoidiano submetido ou näo ao tratamento hormonal supressivo com tiroxina exógena, analisamos retrospectivamente 97 pacientes acompanhados no Serviço de Endocrinologia do HUCFF/UFRJ no período de 1986 a 1994. Trinta e cinco pacientes foram submetidos a tireoidectomia por motivos diversos, 25 foram tratados com doses supressivas de tiroxina por um período de 8 a 24 meses, com o hormônio estimulador da tireóide (TSH) basal mantido abaixo de 0,3 UI/L (V.N.: 0,47 a 5,0), 26 foram mantidos em observaçäo apenas e 11 se evadiram. Dos 35 pacientes operados, quatro tinham câncer da tireóide, o que demonstra uma acurácia da PAAF de 88,6 por cento e uma taxa de resultados falso-negativos de 11,4 por cento. No grupo tratado com tiroxina (n=25), seis (24 por cento) evoluíram com diminuiçäo do tamanho do nódulo, dois (8 por cento) com aumento, e 17 (68 por cento) näo demonstraram qualquer alteraçäo no tamanho do nódulo na reavaliaçao clínica e ultrassonográfica. No grupo näo tratado (n=26), dois (7,6 por cento) apresentaram diminuiçäo do tamanho do nódulo, cinco (19 por cento) mostraram aumento, enquanto 19 (73 por cento) permaneceram estáveis. A análise estatística (teste t de Student) mostrou que os valores médios "pré-tratamento" näo diferem significativamente (p=0,26) entre os dois grupos e que a variaçäo média do "pré" para o "pós-tratamento" par ambas as diferenças relativa e absoluta (p=0,08 e p=0,09 rspectivamente), também näo difere significativamente entre os dois grupos. Conclusöes: 1) a PAAF foi altamente concordante com os achados histopatológicos; 2) a terapia supressiva com tiroxina näo revelou maior eficácia do que a simples observaçäo dos nódulos.

Levothyroxine suppressive therapy is partially effective in treating patients with benign, solid thyroid nodules and multinodular goiters.

We prospectively evaluated the effect of thyrotropin (TSH)-suppressive therapy with levothyroxine (LT4) on the size of a benign, solitary, solid nodule and multinodular goiter in a relatively low iodine intake area. In this study, 101 euthyroid subjects with a benign, solitary, predominantly solid nodule (n = 54) confirmed by biopsy or multinodular goiter (n = 47) received 200 microg of levothyroxine daily as a single morning tablet for 12 months. Thirty-five receiving no therapy were considered as controls (solitary nodules, n = 20, multinodular, n = 15). Patients were admitted to the study after evaluation of thyroid biochemical parameters (thyroxine [T4], free thyroxine [FT4], triiodothyronine [T3], thyrotropin [TSH], and thyroglobulin [Tg]), thyroid scanning, ultrasound examination, and fine-needle aspiration biopsy. Every 3 months, thyroid function tests and every 6 months ultrasound examinations were repeated. Twelve months later 20 of 54 (37.1%) patients with single, solid nodules had 50% or more regression of the nodular volume (responders). Eleven of 54 (20.3%) patients had more than 20%, but less than 49.9% reduction of nodular volume (partial responders). Nonresponders were 23 of 54 (42.5%). One-third of subjects with multinodular goiter had 50% or more regression of the glandular volume, whereas 46.8% were considered as nonresponsive. The mean serum Tg levels decreased significantly only in responders with solitary nodular disease or multinodular goiter. In the control group only 1 patient (5% of total) with a solitary nodule had a 50% reduction in the nodular volume. Five others had a partial response (<49%, >20% reduction). None of the patients with multinodular goiter had a significant reduction (>50%) of the combined nodular volumes. We concluded that LT4 may be effective, among other factors, in arresting the growth or in reducing the volume of relatively small, benign, solitary, solid thyroid nodules or the combined nodular volume of multinodular goiter.

Terapêutica descontínua como fator precipitante de reaçöes adversas ao propiltiouracil / Discontinuous treatment as a precipitant factor of adverse reaction to propylthiouracil

As drogas antitiroidianas sao amplamente prescritas para controle dos estados hipertiroidianos desde 1940. Existem evidências de que as reaçoes adversas ao propiltiouracil (PTU) sao imunologicamente mediadas. A sua utilizaçao é, em geral prolongada e a descontinuidade da terapêutica nao é infrequente. Esta exposiçao repetida ao PTU poderia estar associada a um maior risco de desencadeamento das reaçoes adversas por induzir mecanismo de hipersensibilidade. Estudamos, retrospectivamente 56 pacientes (média de idade = 38,7+ 14,6 anos; 43 femininos e 13 masculinos) com hipertiroidismo tratados com PTU e que tiveram necessidade de internaçao, sendo que 46,4 por cento tiveram o tratamento descontinuado por pelo menos 15 dias. Efeitos adversos ao PTU foram observados em 23,2 por cento dos pacientes estudados. Daqueles com uso descontínuo, 34 por cento apresentaram efeitos adversos, sendo 56 por cento dos casos potencialmente graves (agranulocitose e hepatite), enquanto somente 13,3 por cento daqueles que usaram continuamente a medicaçao (p=OO3) presentaram reaçoes - um caso de anemia aplástica e 3 casos de reaçoes consideradas de menor importância clínica(leucopeniae e "rash" cutâneo). Sugerimos que as reaçoes imunes adversas ao PTU podem ser desencadeadas mais frequentemente em pacientes que fazem uso descontínuo desta medicaçao.