Etiopathology, clinical features, and treatment of diffuse and multinodular nontoxic goiters.

Goiter, an enlargement of the thyroid gland, is a common problem in clinical practice associated with iodine deficiency, increase in serum thyroid-stimulating hormone (TSH) level, natural goitrogens, smoking, and lack of selenium and iron. Evidence suggests that heredity also has an important role in the etiology of goiter. The current classification divides goiter into diffuse and nodular, which may be further subdivided into toxic (associated with symptoms of hyperthyroidism, suppressed TSH or both), or nontoxic (associated with a normal TSH level). Nodular thyroid disease with the presence of single or multiple nodules requires evaluation due to the risk of malignancy, toxicity, and local compressive symptoms. Measurement of TSH, accurate imaging with high-resolution ultrasonography or computed tomography, and fine-needle aspiration biopsy are the appropriate methods for evaluation and management of goiter. This review discusses the clinical presentation, diagnostic evaluation, and treatment considerations of nontoxic diffuse and nodular goiters.

Approach to and treatment of goiters.

The main causes of simple diffuse goiter (SDG) and multinodular goiter (MNG) are iodine deficiency, increase in serum thyroid-stimulating hormone (TSH) level, natural goitrogens, smoking, chronic malnutrition, and lack of selenium, iron, and zinc. Increasing evidence suggests that heredity is equally important. Treatment of SDG and MNG still focuses on L-thyroxine-suppressive therapy surgery. Radioiodine alone or preceded by recombinant human TSH stimulation is widely used in Europe and other countries. Each of these therapeutic options has advantages and disadvantages, with acute and long-term side effects.

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.

Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter.

Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of 131I for treating MNG. Euthyroid patients with MNG (69.3 +/- 62.0 mL, 20 females, 2 males, 64 +/- 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq 131I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 +/- 17.6%) and II (21.6 +/- 17.8%), but not in group III (2.7 +/- 15.3%). After 12 months, TV decreased significantly in groups I (36.7 +/- 18.1%) and II (37.4 +/- 27.1%), but not in group III (19.0 +/- 24.3%). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N = 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed 131I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus 131I.

Radioiodine plus recombinant human thyrotropin do not cause acute airway compression and are effective in reducing multinodular goiter

Recombinant human thyrotropin (rhTSH) reduces the activity of radioiodine required to treat multinodular goiter (MNG), but acute airway compression can be a life-threatening complication. In this prospective, randomized, double-blind, placebo-controlled study, we assessed the efficacy and safety (including airway compression) of different doses of rhTSH associated with a fixed activity of 131I for treating MNG. Euthyroid patients with MNG (69.3 ± 62.0 mL, 20 females, 2 males, 64 ± 7 years) received 0.1 mg (group I, N = 8) or 0.01 mg (group II, N = 6) rhTSH or placebo (group III, N = 8), 24 h before 1.11 GBq 131I. Radioactive iodine uptake was determined at baseline and 24 h after rhTSH and thyroid volume (TV, baseline and 6 and 12 months after treatment) and tracheal cross-sectional area (TCA, baseline and 2, 7, 180, and 360 days after rhTSH) were determined by magnetic resonance; antithyroid antibodies and thyroid hormones were determined at frequent intervals. After 6 months, TV decreased significantly in groups I (28.5 ± 17.6 percent) and II (21.6 ± 17.8 percent), but not in group III (2.7 ± 15.3 percent). After 12 months, TV decreased significantly in groups I (36.7 ± 18.1 percent) and II (37.4 ± 27.1 percent), but not in group III (19.0 ± 24.3 percent). No significant changes in TCA were observed. T3 and free T4 increased transiently during the first month. After 12 months, 7 patients were hypothyroid (N = 3 in group I and N = 2 in groups II and III). rhTSH plus a 1.11-GBq fixed 131I activity did not cause acute or chronic changes in TCA. After 6 and 12 months, TV reduction was more pronounced among patients treated with rhTSH plus 131I.

Recombinant human TSH increases the efficacy of a fixed activity of radioiodine for treatment of multinodular goitre.

CONTEXT: High doses of (131)I are usually needed in the treatment of multinodular goitre (MNG) for effective thyroid volume (TV) reduction. Recombinant human thyroid-stimulating hormone (rhTSH) is an adjuvant to enhance (131)I uptake, allowing a decrease in radiation activity and enhancing (131)I efficacy. OBJECTIVE: To evaluate whether rhTSH increases the efficacy of a fixed activity of (131)I for the treatment of MNG. DESIGN: Two-year, observational, placebo-controlled study. SETTING: Patients received 0.1 mg rhTSH (A), 0.005 mg rhTSH (B) or placebo (C). A fixed activity of 1.11 GBq of (131)I was administered 24 h after rhTSH or placebo. PATIENTS: A total of 28 outpatients (26 females and two males) with MNG. MEASUREMENTS: TSH, free T4, T3, thyroglobulin (Tg) and TV. RESULTS: Basal radioactive iodine uptake and TV values were comparable among all groups. After rhTSH or placebo, peak levels of TSH, free T4, T3 and Tg were higher in A than in B or in C (p < 0.05). Hyperthyroidism was observed in A (n = 2), B (n = 6) and C (n = 4). Thyroid enlargement was reported in A (n = 3) and B (n = 6). After 24 months, 10 patients developed hypothyroidism (four in A, three in B and three in C). TV reduction was similar between A and B (37.2 +/- 25.5% vs. 39.3 +/- 27.9%, p = 0.88), but different from the non-significant reduction in C (15.3 +/- 28.3%, p = 0.08). CONCLUSIONS: Followed by 1.11 GBq, a very low dose of 0.005 mg rhTSH was equally safe and effective as 0.1 mg rhTSH. Both doses increased the efficacy of radioiodine. Adverse events were mild, transient and readily treatable.

[Acute hepatic failure in a patient with hyperthyroidism and virus B hepatitis: recovery after plasmapheresis and thyroidectomy--a case report]. / Disfunção hepática aguda em paciente com hipertireoidismo e hepatite por vírus B: recuperação após plasmaférese e tireoidectomia--relato de caso.

A 31-year-old man admitted with abdominal pain, nauseas, vomiting, jaundice and fever that had began 2 weeks before. He had a history of hyperthyroidism and an irregular treatment with propylthiouracil (PTU) for 2 years. He had stopped PTU when the current symptoms started. The patient presented diffuse goiter, about 120g, FT4 22.7 ng/dL (N: 0.8 - 1.9 ng/dL); THS < 0.002 microUI/mL (N 0.4-5 microUI/mL). Transaminases, serum total and direct bilirubins were increased. He was kept without PTU and propranolol was started and increased until the dose of 480 mg/day. Abdominal ultrasonography was normal and serologic markers for hepatitis A, B and C pointed to acute virus B hepatitis. The patient presented a worse of hepatic function and elevated thyroid hormones levels. To avoid the future need of antithyroid drugs, to get a fast normalization of thyroid hormones levels and because of the goiter size thyroidectomy was recommended. The patient underwent one therapeutic plasmapheresis session just before the surgery. A total thyroidectomy was performed without complications. At the 5th day after surgery the patient presented improvement of hepatic function and low FT4 serum levels. We concluded that preexisting hyperthyroidism may aggravate or perpetuate a hepatic failure caused for acute viral hepatitis and plasmapheresis is a rapid, reliable and effective way to lower thyroid hormones serum levels, allowing a successful thyroidectomy in patients with severe thyrotoxicosis.

Disfunção hepática aguda em paciente com hipertireoidismo e hepatite por vírus B: recuperação após plasmaférese e tireoidectomia - relato de caso / Acute hepatic failure in a patient with hyperthyroidism and virus B hepatitis: recovery after plasmapheresis and thyroidectomy - a case report

Paciente masculino, 31 anos, internado com quadro de dor abdominal, náuseas, vômitos, icterícia e febre, iniciado há duas semanas. História de hipertireoidismo e tratamento irregular com propiltiuracil há dois anos, interrompeu a medicação quando iniciou o quadro atual. Apresentava bócio difuso, cerca de 120 g, T4L 22,7 ng/dL (VN 0,8-1,9 ng/dL); TSH < 0,002 µUI/mL (VN 0,4-5 µUI/mL). Transaminases, bilirrubinas total e direta séricas elevadas. Foi mantido sem antitireoidiano e iniciado propranolol até a dose de 480 mg/dia. Ultra-sonografia de abdome foi normal e sorologias para hepatites A, B e C indicaram infecção aguda por vírus B. Ocorreu piora da função hepática e manutenção de níveis elevados de hormônios tireoidianos. Visando evitar necessidade futura de antitireoidiano, obter rápida normalização dos níveis de hormônios tireoidianos e em virtude do tamanho do bócio foi indicado tireoidectomia. O paciente foi submetido a uma sessão de plasmaférese terapêutica, imediatamente antes da cirurgia, e tireoidectomia subtotal sem intercorrências. No quinto dia após a cirurgia, o paciente apresentava melhora da função hepática e baixos níveis séricos de T4 livre. Concluímos que o hipertireoidismo prévio pode exacerbar e perpetuar a disfunção hepática causada por hepatite viral aguda e que a plasmaférese é um meio rápido, seguro e eficaz de reduzir os níveis de hormônio tireoidiano, permitindo uma tireoidectomia bem-sucedida em pacientes com tireotoxicose grave.

A 31-year-old man admitted with abdominal pain, nauseas, vomiting, jaundice and fever that had began 2 weeks before. He had a history of hyperthyroidism and an irregular treatment with propylthiouracil (PTU) for 2 years. He had stopped PTU when the current symptoms started. The patient presented diffuse goiter, about 120g, FT4 22.7 ng/dL (N: 0.8 - 1.9 ng/dL); THS < 0.002 µUI/mL (N 0.4-5 µUI/mL). Transaminases, serum total and direct bilirubins were increased. He was kept without PTU and propranolol was started and increased until the dose of 480 mg/day. Abdominal ultrassonography was normal and serologic markers for hepatitis A, B and C pointed to acute virus B hepatitis. The patient presented a worse of hepatic function and elevated thyroid hormones levels. To avoid the future need of antithyroid drugs, to get a fast normalization of thyroid hormones levels and because of the goiter size thyroidectomy was recommended. The patient underwent one therapeutic plasmapheresis session just before the surgery. A total thyroidectomy was performed without complications. At the 5th day after surgery the patient presented improvement of hepatic function and low FT4 serum levels. We concluded that preexisting hyperthyroidism may aggravate or perpetuate a hepatic failure caused for acute viral hepatitis and plasmapheresis is a rapid, reliable and effective way to lower thyroid hormones serum levels, allowing a successful thyroidectomy in patients with severe thyrotoxicosis.

Esclerose: uma opção de tratamento para os nódulos tireoidianos císticos / Sclerosis: an option for treatment of cystic thyroid nodules

OBJETIVO: Verificar o efeito da injeção percutânea de etanol guiada por ultra-sonografia no tratamento dos nódulos tireoidianos císticos. MATERIAIS E MÉTODOS: Comparou-se o volume de 34 nódulos benignos císticos, em 30 pacientes (26 do sexo feminino e quatro do sexo masculino), antes e uma média de 3,9 meses depois da alcoolização. O volume inicial dos nódulos foi avaliado por dois observadores, que realizaram a ultra-sonografia em momentos diferentes, sem qualquer informação prévia a respeito do tamanho dos nódulos, cuja finalidade foi conhecer a variação interobservador das medidas ecográficas. RESULTADOS: A média de volume dos nódulos antes do tratamento foi de 12,3 ± 18,0 ml. A média de redução de volume foi de 74,0 ± 26,1 por cento (p = 0,0001), e 20,6 por cento (7/34) deles desapareceram. Não houve correlação entre o volume inicial e o percentual de redução dos nódulos. A média de variação das medidas interobservadores foi de 0,5 ml para um alfa de 5 por cento. Dor moderada, no momento da aplicação, foi a complicação mais freqüente. CONCLUSÃO: A injeção percutânea de etanol é uma opção segura e eficaz no tratamento dos nódulos tireoidianos císticos.

OBJECTIVE: To check the effect of ultrasound-guided percutaneous ethanol injection for treatment of cystic thyroid nodules. MATERIALS AND METHODS: A comparison was made of the volume of 34 benign cystic nodules in 30 patients (26 female, four male), before and 3.9 months (on average) after alcoholization. For the purpose of finding out interobserver variations in echographic measurements, the initial volume of the nodules was assessed by means of ultrasound at different moments, by two observers, without any previous knowledge on the nodules size. RESULTS: Mean volume of nodules before treatment was 12.3 ± 18.0 ml. Mean reduction rate in nodules after alcoholization was 74.0 ± 26.1 percent (p < 0.0001) and 7/34 (20.6 percent) of the nodules disappeared. There was no correlation between nodules size and reduction rate. The average interobserver nodule measurement variation was 0.5 ml, for an alpha of 5 percent. Moderate pain at the time of injection was the most frequent complication. CONCLUSION: Ultrasound-guided percutaneous ethanol injection is a safe and effective option for treatment of cystic thyroid nodules.

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.

Bocio multinodular / Multinodular goiter

Reportamos el caso de una paciente de sexo femenino de 80 años con bocio multinodular. Este agrandamiento de la glándula tiroidea (normalmente pesa 15-25g) puede ser generalizada o focalizada o estar asociada con una secreción hormonal normal, aumentada o disminuida. Comúnmente, la etiología no puede ser determinada. En el caso de bocio multinodular no tóxico (eutiroideo) la manifestación clínica es solamente el agrandamiento de la glándula. Secuelas mecánicas incluyen compresión y desplazamiento de la tráquea o esófago y síntomas obstructivos. Los agrandamientos de tamaño pequeño a moderado de la glándula tiroidea administrada por vía oral. Esto, a menudo no logra disminuir el tamaño de la glándula, pero usualmente mantiene su crecimiento...

[Diffuse hyperthyroid goiter associated with occult papillary carcinoma of the thyroid. Report of 2 cases]. / Bocio difuso hipertiroideo asociado a carcinoma papilar oculto de tiroides. A proposito de 2 casos.

The association of diffuse hyperthyroid goiter and thyroid cancer is rare and interesting, considering that both diseases affect the same organ but have different pathogenesis and prognosis. We report two patients that consulted for diffuse hyperthyroid goiter and were subjected to a subtotal bilateral thyroidectomy due to antithyroid drug failure. Pathological study revealed the coexistence of diffuse gland hyperplasia and a papillary thyroid carcinoma of less than 7 mm phi. In both cases, the thyroid remanent was ablated with radioactive iodine during the postoperative period and thyroid substitution was started.

Bócio uninodular autônomo atóxico: estudo retrospectivo de 31 casos / Solitary nontoxic autonomously functioning nodules: retrospective study of 31 cases

Estudamos retrospectivamente o quadro clínico e laboratorial, assim como a evoluçäo, de 31 pacientes com diagnóstico de bócio uninodular autônomo atóxico (BUAA), acompanhados na Disciplina de Endocrinologia da Escola Paulista de Medicina de 1983 a 1989. Eram 29 mulheres e 2 homens, com idades variando de 18 a 68 anos, eutiroidianos clínica e laboratorialmente à apresentaçäo; 18 mostravam tecido extra-nodular parcialmente captante e 13 näo evidenciavam tecido extra-nodular captante; no teste TRH 8 tinham resposta abolida, 8 resposta parcial e 4 resposta normal; todos os 13 casos que se submeteram à supressäo com T3 tiveram a resposta abolida; todos os 12 casos que realizaram o teste de estímulo com TSH exógeno apresentaram resposta positiva. Näo houve correlaçäo entre o aspecto do nódulo ao mapeamento e a resposta do TSH ao TRH, nem entre o teste do TRH e o teste de supressäo com T3. Quanto ao seguimento, 4 pacientes evoluiram para o hipertiroidismo no espaço de 1 a 3 anos, enquanto que um apresnetou hipotiroidismo por tiroidite de Hashimoto; além disso, indicamos ciruriga ou radioterapia profiláticas em outros 7 casos por possuirem nódulos grandes ou doenças associadas

Bocio y embarazo. Comunicación preliminar / Goiter and pregnancy. Preliminary report

Se exponen los resultados clínicos, obstétricos y pediátricos de 14 gestantes portadoras de distintos tipos de bocio (3 nodulares y 11 difusos) estudiados por los métodos que pueden ser realizados durante el embarazo. Se analizan los riesgos a que están sometidos tanto la madre como su hijo cuando no están tratados; así como se detallan los resultados obtenidos con la terapia tiroidea y se discuten las razones de este tratamiento (AU)