[Diabetes mellitus associated with atypical antipsychotic medications: case report and review of the literature]. / Diabetes mellitus associado com drogas antipsicóticas atípicas: relato de caso e revisão da literatura.

Since the introduction of atypical antipsychotic medications, starting with clozapine in 1990, many studies have associated these drugs with the development of diabetes among other metabolic disorders, as well as with the onset of the disease as ketoacidosis. We report the case of a 28-year-old patient with schizophrenia who was admitted with diabetic acidosis 1 month after the beginning of clozapine therapy. No weight gain was reported and the patient maintains satisfactory glycemia levels with no treatment required after discontinuation of the drug. The literature on this subject and cases reported so far are reviewed, including the association of other atypical antipsychotic drugs also involved in endocrine disorders. The objective of this report is to raise the awareness of physicians treating psychiatric patients to the possibility of new-onset diabetes during therapy with atypical antipsychotic drugs and to emphasize the necessity for increased vigilance and close metabolic follow-up of these patients.

Latent autoimmune diabetes in adults (LADA): usefulness of anti-GAD antibody titers and benefit of early insulinization.

OBJECTIVE: To determine the clinical and laboratory parameters and the progression to insulin requirement in two groups of LADA patients separated according to GADA titers, and to evaluate the benefit of early insulinization in patients at high risk of premature beta-cell failure (high GADA titers). METHODS: Among the diabetic adults seen at our service and screened for GADA at diagnosis, 54 were diagnosed with LADA and classified as having low (> 1 U/ml and < 17.2 U/ml) or high (> 17.2 U/ml) GADA titers. Fifty-four patients with type 2 diabetes (GADA-) were selected for comparison. In addition, 24 patients who had GADA titers > 20 U/ml and who were not initially insulinized were compared to 16 patients who were insulinized at diagnosis. RESULTS: Insulin resistance was higher in the GADA- group, followed by patients with low GADA titers. BMI and the frequency of arterial hypertension, elevated triglycerides and reduced HDL cholesterol were lower in the high GADA+ group, with no difference between the GADA- or low GADA+ groups. The high GADA+ group showed a greater reduction and lower levels of C-peptide and required insulin earlier during follow-up. Patients with GADA titers > 20 U/ml and insulinized early presented no significant variation in C-peptide levels, had better glycemic control and required a lower insulin dose than patients who were insulinized later. CONCLUSION: We agree that patients with LADA should be differentiated on the basis of GADA titers and that patients with GADA titers > 20 U/ml benefit from early insulinization.

Diabetes mellitus associado com drogas antipsicóticas atípicas: relato de caso e revisão da literatura / Diabetes mellitus associated with atypical antipsychotic medications: case report and review of the literature

Desde a introdução das medicações antipsicóticas atípicas, iniciando com a clozapina, em 1990, muitos relatos associam essas drogas ao desenvolvimento de diabetes mellitus, entre outros distúrbios metabólicos, assim como abertura da doença como cetoacidose. Relatamos o caso de um paciente de 28 anos, com esquizofrenia, admitido em cetoacidose diabética 1 mês após início da terapia com clozapina, sem relação com ganho de peso, mantendo-se com níveis satisfatórios de glicemia, sem tratamento, após suspensão da droga. Revisamos o assunto, com outros casos relatados até o momento, incluindo a associação de outros antipsicóticos atípicos igualmente envolvidos em distúrbios endócrinos. Objetivamos, com o relato deste caso, aumentar a atenção dos clínicos envolvidos no tratamento dos pacientes portadores de distúrbios psiquiátricos para a possibilidade do surgimento de diabetes durante a terapia, e enfatizar a necessidade de aumento da vigilância e do acompanhamento metabólico desses pacientes.

Since the introduction of atypical antipsychotic medications, starting with clozapine in 1990, many studies have associated these drugs with the development of diabetes among other metabolic disorders, as well as with the onset of the disease as ketoacidosis. We report the case of a 28-year-old patient with schizophrenia who was admitted with diabetic acidosis 1 month after the beginning of clozapine therapy. No weight gain was reported and the patient maintains satisfactory glycemia levels with no treatment required after discontinuation of the drug. The literature on this subject and cases reported so far are reviewed, including the association of other atypical antipsychotic drugs also involved in endocrine disorders. The objective of this report is to raise the awareness of physicians treating psychiatric patients to the possibility of new-onset diabetes during therapy with atypical antipsychotic drugs and to emphasize the necessity for increased vigilance and close metabolic follow-up of these patients.

Latent autoimmune diabetes in adults (LADA): usefulness of anti-GAD antibody titers and benefit of early insulinization

OBJECTIVE: To determine the clinical and laboratory parameters and the progression to insulin requirement in two groups of LADA patients separated according to GADA titers, and to evaluate the benefit of early insulinization in patients at high risk of premature beta-cell failure (high GADA titers). METHODS: Among the diabetic adults seen at our service and screened for GADA at diagnosis, 54 were diagnosed with LADA and classified as having low (> 1 U/ml and < 17.2 U/ml) or high (> 17.2 U/ml) GADA titers. Fifty-four patients with type 2 diabetes (GADA-) were selected for comparison. In addition, 24 patients who had GADA titers > 20 U/ml and who were not initially insulinized were compared to 16 patients who were insulinized at diagnosis. RESULTS: Insulin resistance was higher in the GADA- group, followed by patients with low GADA titers. BMI and the frequency of arterial hypertension, elevated triglycerides and reduced HDL cholesterol were lower in the high GADA+ group, with no difference between the GADA- or low GADA+ groups. The high GADA+ group showed a greater reduction and lower levels of C-peptide and required insulin earlier during follow-up. Patients with GADA titers > 20 U/ml and insulinized early presented no significant variation in C-peptide levels, had better glycemic control and required a lower insulin dose than patients who were insulinized later. CONCLUSION: We agree that patients with LADA should be differentiated on the basis of GADA titers and that patients with GADA titers > 20 U/ml benefit from early insulinization.

OBJETIVO: Determinar os parametros clínicos e laboratoriais e a progressão para a necessidade de insulina em dois grupos de pacientes com LADA, divididos de acordo com os títulos de GADA, e avaliar o benefício da insulinização precoce naqueles com risco elevado de falência prematura das células beta (títulos altos de GADA). MÉTODOS: Dentre os pacientes adultos com diabetes (DM) seguidos em nosso serviço e rastreados para GADA no diagnóstico, 54 foram diagnosticados com LADA e classificados como tendo títulos de GADA baixos (> 1 U/ml e < 17,2 U/ml) ou altos (> 17,2 U/ml). A comparação foi feita com 54 pacientes selecionados com DM tipo 2 (GADA-). Além disso, 24 pacientes com títulos de GADA > 20 U/ml, mas que não foram insulinizados no início, foram comparados com 16 outros que foram insulinizados desde o diagnóstico. RESULTADOS: A resistência à insulina foi maior no grupo GADA-, seguidos por aqueles com títulos baixos de GADA. O IMC, a frequência de hipertensão arterial, os triglicérides elevados e o HDL-colesterol reduzido foram menores no grupo com títulos elevados de GADA, sem diferença entre os GADA- ou com baixos títulos de GADA. O grupo com títulos elevados de GADA mostrou uma redução maior e menores níveis de peptídeo C, tendo requerido insulina mais precocemente durante o seguimento. Pacientes com títulos de GADA > 20 U/ml e precocemente insulinizados não apresentaram variações significantes nos níveis de peptídeo C, tiveram melhor controle glicêmico e requereram doses mais baixas de insulina do que aqueles que foram insulinizados mais tardiamente. CONCLUSÃO: Nós concordamos que pacientes com LADA devem ser diferenciados com base nos títulos de GADA e que aqueles com títulos > 20 U/ml beneficiam-se de insulinização precoce.

[Follow-up of high-risk patients with differentiated thyroid cancer without persistent disease after initial therapy]. / Seguimento de pacientes de alto risco com carcinoma diferenciado de tireóide sem doença persistente após a terapia inicial.

This study evaluated the follow-up of high-risk patients with thyroid cancer after initial therapy. A total of 125 high-risk patients (tumor >4 cm and/or extrathyroid invasion and/or lymph node metastases, and age >45 years), with complete resection of the tumor, were selected. All patients underwent total thyroidectomy and ablation with (131)I[3.7-5.5 GBq (100-150 mCi)]. Eighteen patients (14.8%) presenting metastases on post-dose whole-body scan (RxWBS) were excluded. The negative predictive value of stimulated Tg < or =1 ng/ml in combination with neck US during first assessment (612 mo. after ablative therapy) was 96.2% for the absence of recurrence up to 5 years. This value increased to 98.7% when adding WBS performed with 185 MBq (5 mCi) (131)I (DxWBS). The positive predictive value (PPV) of stimulated Tg >1 ng/ml was 52% for the detection of the presence of metastases up to 5 years; however, considering only patients with initially negative DxWBS and US, the PPV was 19% (9% if Tg of 110 ng/ml vs. 40% if Tg >10 ng/ml). Tg levels decreased spontaneously in patients with stimulated Tg >1 ng/ml during first assessment, negative US and DxWBS, and no recurrence during follow-up, with Tg being undetectable in half these patients at the end of 5 years. Twenty patients presented uptake in the thyroid bed upon DxWBS during the first year after ablative therapy, with stimulated Tg and US being negative, and were not treated with 131I; these patients did not relapse and no uptake on DxWBS was observed in 60% after 5 years. Recurrence after 5 years was only 1.3% in patients without apparent disease (negative US and DxWBS) and stimulated Tg <1 ng/ml. An algorithm for the follow-up of high-risk patients after initial therapy is presented in this study.

Malformations in the offspring of women with thyroid cancer treated with radioiodine for the ablation of thyroid remnants.

RATIONALE: Since ovarian function is only temporarily compromised by radioiodine therapy, many women with thyroid cancer treated with radioiodine can become pregnant. The present study evaluated the evolution of these pregnancies and the consequences for the offspring. PATIENTS AND METHODS: We retrospectively analyzed 78 pregnancies of 66 women submitted to total thyroidectomy, followed by radioiodine therapy 3.75-5.5 GBq (131)I, mean 4.64 GBq). In all patients, conception occurred one year after ablative therapy (mean of 30 months). Age ranged form 19 to 36 years (mean of 30.6 years) at the time of radioiodine treatment and from 23 to 39 years (mean of 32.8 years) at the time of conception. RESULTS: Four (5.1%) of the 78 pregnancies resulted in spontaneous abortions. Three (4%) of the 74 deliveries were preterm and there was no case of stillbirth. The birthweight was > 2500 g in 94.6% of the children (+/- SD: 3350 +/- 450 g) and only one infant (1.3%) presented an apparent malformation at birth (intraventricular communication). No difference in the age at the time of radioiodine therapy or conception or in radioiodine dose was observed between pregnancies with an unfavorable outcome and those with a favorable outcome. CONCLUSION: We conclude that pregnancies that occur 12 months after ablative therapy are safe.

Seguimento de pacientes de alto risco com carcinoma diferenciado de tireóide sem doença persistente após a terapia inicial / Follow-up of high-risk patients with differentiated thyroid cancer without persistent disease after initial therapy / Follow-up of high-risk patients with differentiated thyroid cancer without persistent disease after initial therapy

Este estudo avaliou o seguimento de pacientes com câncer de tireóide de alto risco, após a terapia inicial. Foram selecionados 125 pacientes de alto risco (tumor >4 cm e/ou invasão extra-tireoidiana e/ou metástases linfonodais e idade >45 anos), com ressecção tumoral completa. Todos foram tratados com tireoidectomia total e ablação com 131I [3,7­5,5 GBq (100­150 mCi)] e foram excluídos 18 casos (14,8 por cento) com metástases na PCI pós-dose (t-PCI). O valor preditivo negativo da Tg estimulada <1 ng/ml combinada ao US cervical na primeira avaliação (6­12 meses após a terapia ablativa) foi de 96,2 por cento para ausência de recidivas em até 5 anos. Este valor aumentou para 98,7 por cento quando acrescentamos a PCI com 185 MBq (5 mCi) 131I (d-PCI). O valor preditivo positivo (VPP) da Tg estimulada >1 ng/ml foi de 52 por cento para presença de metástases detectadas até 5 anos depois, mas considerando apenas pacientes que apresentaram d-PCI e US negativos inicialmente, o VPP foi 19 por cento (9 por cento se Tg 1­10 ng/ml vs. 40 por cento se Tg >10 ng/ml). Tg reduziu espontaneamente nos pacientes com Tg estimulada >1 ng/ml na primeira avaliação, US e d-PCI negativos e sem recidiva no seguimento, sendo indetectável em metade destes ao final de 5 anos. No primeiro ano após a terapia ablativa, 20 pacientes tiveram captação em leito tireoidiano na d-PCI com Tg estimulada e US negativos e não foram tratados com 131I; estes evoluíram sem recidiva e 60 por cento apresentavam uma d-PCI sem nenhuma captação após 5 anos. Em pacientes sem doença aparente (no US e d-PCI) e Tg estimulada <1 ng/ml, a recidiva em 5 anos foi de apenas 1,3 por cento. Um algoritmo para o seguimento de pacientes de alto risco após a terapia inicial é apresentado por este estudo.

This study evaluated the follow-up of high-risk patients with thyroid cancer after initial therapy. A total of 125 high-risk patients (tumor >4 cm and/or extrathyroid invasion and/or lymph node metastases, and age >45 years), with complete resection of the tumor, were selected. All patients underwent total thyroidectomy and ablation with 131I [3.7­5.5 GBq (100-150 mCi)]. Eighteen patients (14.8 percent) presenting metastases on post-dose whole-body scan (RxWBS) were excluded. The negative predictive value of stimulated Tg <1 ng/ml in combination with neck US during first assessment (6­12 mo. after ablative therapy) was 96.2 percent for the absence of recurrence up to 5 years. This value increased to 98.7 percent when adding WBS performed with 185 MBq (5 mCi) 131I (DxWBS). The positive predictive value (PPV) of stimulated Tg >1 ng/ml was 52 percent for the detection of the presence of metastases up to 5 years; however, considering only patients with initially negative DxWBS and US, the PPV was 19 percent (9 percent if Tg of 1­10 ng/ml vs. 40 percent if Tg >10 ng/ml). Tg levels decreased spontaneously in patients with stimulated Tg >1 ng/ml during first assessment, negative US and DxWBS, and no recurrence during follow-up, with Tg being undetectable in half these patients at the end of 5 years. Twenty patients presented uptake in the thyroid bed upon DxWBS during the first year after ablative therapy, with stimulated Tg and US being negative, and were not treated with 131I; these patients did not relapse and no uptake on DxWBS was observed in 60 percent after 5 years. Recurrence after 5 years was only 1.3 percent in patients without apparent disease (negative US and DxWBS) and stimulated Tg <1 ng/ml. An algorithm for the follow-up of high-risk patients after initial therapy is presented in this study.

Malformations in the offspring of women with thyroid cancer treated with radioiodine for the ablation of thyroid remnants / Malformações na prole de mulheres com câncer de tireóide tratadas com radioiodo para ablação de remanescentes tireoideanos

RATIONALE: Since ovarian function is only temporarily compromised by radioiodine therapy, many women with thyroid cancer treated with radioiodine can become pregnant. The present study evaluated the evolution of these pregnancies and the consequences for the offspring. PATIENTS AND METHODS: We retrospectively analyzed 78 pregnancies of 66 women submitted to total thyroidectomy, followed by radioiodine therapy (3.7­5.5 GBq 131I, mean 4.64 GBq). In all patients, conception occurred one year after ablative therapy (mean of 30 months). Age ranged form 19 to 36 years (mean of 30.6 years) at the time of radioiodine treatment and from 23 to 39 years (mean of 32.8 years) at the time of conception. RESULTS: Four (5.1 percent) of the 78 pregnancies resulted in spontaneous abortions. Three (4 percent) of the 74 deliveries were preterm and there was no case of stillbirth. The birthweight was > 2500 g in 94.6 percent of the children (mean ± SD: 3350 ± 450 g) and only one infant (1.3 percent) presented an apparent malformation at birth (intraventricular communication). No difference in the age at the time of radioiodine therapy or conception or in radioiodine dose was observed between pregnancies with an unfavorable outcome and those with a favorable outcome. CONCLUSION: We conclude that pregnancies that occur 12 months after ablative therapy are safe.

ARRAZOADO: Uma vez que a função ovariana está apenas temporariamente comprometida pela terapia com radioiodo, muitas mulheres com câncer de tireóide tratadas com radioiodo podem engravidar. O presente estudo avaliou a evolução dessas gravidezes e suas conseqüências para a prole. PACIENTES E MÉTODOS: Analisamos retrospectivamente 78 gravidezes de 66 mulheres submetidas a tiroidectomia total seguida de radioiodoterapia (3,7­5,5 GBq 131I, média 4,64 GBq). Em todas, a concepção ocorreu um ano após a terapia ablativa (média de 30 meses). A idade variou de 19 a 36 anos (media de 30,6) à época do tratamento com radioiodo e de 23 a 39 anos (média de 32,8) na época da concepção. RESULTADOS: Quatro (5,1 por cento) das 78 gravidezes resultaram em abortamento espontâneo. Três (4 por cento) dos 74 partos foram pré-termo, mas não houve nenhum natimorto. O peso ao nascer foi >2.500 g em 94,6 por cento das crianças (média ± DP: 3.350 ± 450 g) e somente uma delas (1,3 por cento) apresentou uma malformação aparente ao nascimento (comunicação intraventricular). Nenhuma diferença quanto à idade na época da radioiodoterapia ou na concepção ou na dose de radioiodo foi observada entre as gravidezes com ou sem um desfecho favorável. CONCLUSÃO: Gravidezes que ocorrem 12 meses após terapia ablativa com radioiodo são seguras.

Managing thyroid cancer without thyroxine withdrawal.

Thyroxine (T4) withdrawal or recombinant TSH is used for the stimulation of thyroglobulin (Tg), whole-body scanning (WBS) and iodine-131 treatment in patients with thyroid carcinoma. This study evaluated the T4 dose reduction protocol as an alternative for patients' preparation. Fifty-one patients were submitted to total T4 withdrawal for WBS and Tg measurement. T4 treatment was then resumed and maintained until TSH reached levels < 0.3 mIU/l. The T4 dose was then decreased to 0.8 microg/kg/day and TSH was measured weekly. Tg was assayed when TSH was > 30 mIU/l. Patients diagnosed with the disease upon initial evaluation were treated. We also evaluated the clinical and laboratory changes observed for both preparations. Using the reduced dose protocol, TSH levels > 30 mIU/l were reached within 6 and 8 weeks in 84.6 and 100% of the patients, respectively. T4 withdrawal was associated with more common symptoms of hypothyroidism and elevation of creatine kinase (CK) and LDL cholesterol. The T4 dose reduction protocol proved to be useful for Tg stimulation and ablative therapy, without the complication of severe hypothyroidism or the cost of recombinant TSH.

Managing thyroid cancer without thyroxine withdrawal

A suspensão da tiroxina (T4) ou o TSH recombinante são usados para a estimulação da tireoglobulina (Tg), para o mapeamento de corpo inteiro (MCI) e para o tratamento com 131Iodo em pacientes com carcinoma tireoideano. Esse estudo avaliou um protocolo de redução de dose do T4 como alternativa para o preparo desses pacientes. Cinquenta e um pacientes submeteram-se à suspensão total de T4 para o MCI e a medida de Tg. Tratamento com T4 foi então reinstituído e mantido até que o TSH atingisse níveis < 0.3 mUI/l. A dose de T4 foi então dominuída para 0,8 µg/kg/dia e o TSH medido semanalmente. A Tg foi analisada quando o TSH estava > 30 mUI/l. Pacientes diagnosticados com a doença na fase inicial da avaliação foram tratados. Nós também avaliamos as alterações clínicas e laboratoriais observadas para ambos os preparos. Usando o protocolo de redução de dose, níveis de TSH > 30 mUI/l foram atingidos em 6 e 8 semanas em 84,6 and 100% dos pacientes, respectivamente. A suspensão do T4 esteve associada com sintomas mais comuns de hipotireoidismo e com elevação da creatino- quinase (CK) e LDL-colesterol. O protocolo de redução da dose de T4 mostrou-se útil para a estimulação da Tg e terapia ablativa, sem apresentar as complicações do hipotireoidismo severo ou chegar ao custo do TSH recombinante.

[Safety of radioiodine therapy in patients with thyroid carcinoma younger than 21 years]. / Segurança da radioiodoterapia em pacientes com carcinoma de tireóide com menos de 21 anos.

We studied 20 patients with differentiated thyroid carcinoma undergoing radioiodine therapy (> or = 100 mCi dose) before the age of 21: 10 patients without distant metastases received a mean dose of 145 mCi and 10 with lung involvement received 270 mCi. One or more years after ablative therapy, xerostomia was present in two patients but was not accompanied by more severe complications such as oral ulcers or fissures, and 99mTcO4- scintigraphy confirmed salivary dysfunction. One patient showed keratoconjunctivitis sicca. Blood counts did not reveal abnormalities caused by radioiodine therapy. FSH was normal in 18 patients. Patients with elevated levels had received radioiodine just over a year ago and repetition of the exam after 6 months showed that FSH had returned to normal. The 6 male patients had normal LH and testosterone levels. Analysis did not reveal signs of pulmonary fibrosis secondary to treatment in the 10 cases with iodine-accumulating metastases in this organ. Our data suggest that ablative therapy employing a dose of 100 to 300 mCi is safe in young individuals, but persistent complications such as salivary dysfunction and conjunctivitis may occur.

[Investigating patients with differentiated thyroid carcinoma and elevated serum thyroglobulin but negative whole-body scan]. / Abordagem dos pacientes com carcinoma diferenciado de tireóide com tireoglobulina sérica elevada e pesquisa de corpo inteiro negativa.

Findings of elevated thyroglobulin (Tg) and a negative whole-body scan (WBS) are not uncommon during the follow-up of differentiated thyroid carcinoma. In 12% of our patients submitted to thyroidectomy and radioiodine with Tg >10 ng/ml during hypothyroidism had a negative diagnostic WBS. This finding generally corresponds to a false-negative WBS. Inadequate preparation in terms of iodine exposure and insufficient elevation of TSH should be excluded. Micrometastases which do not accumulate sufficient iodine to be detected by low radioiodine activity and the loss of the capacity to express the sodium/iodine symporter explain many cases. In patients with elevated Tg, metastases can be identified after the administration of a therapeutic radioiodine dose, with this procedure being indicated in cases with Tg >10 ng/ml during hypothyroidism or >5 ng/ml after recombinant TSH, after exclusion of lung and cervical macrometastases. In the present study, 5 of 7 patients with these criteria showed ectopic uptake on post-therapy WBS. If the post-therapy scan is negative or reveals discrete uptake in the thyroid bed, other methods (e.g. FDG PET) can be performed, and the physician should not insist on radioiodine therapy. If WBS detect lymph node metastases, surgery is indicated, while in cases of diffuse lung metastases radioiodine is indicated until the occurrence of a negative WBS or normalization of stimulated Tg levels. Patients with a positive post-therapy scan may show a significant reduction in Tg, with even complete remission in some cases after radioiodine, but the impact of this treatment on mortality remains controversial.

TSH recombinante no tratamento e seguimento de pacientes com carcinoma diferenciado de tireóide: uso na prática clínica / Recombinant TSH in ablative therapy and follow-up of patients with differentiated thyroid carcinoma

Os estudos que avaliaram a eficácia e segurança do TSH recombinante no preparo dos pacientes com carcinoma diferenciado de tireóide (CDT) para o tratamento ablativo e no seguimento com tireoglobulina sérica (Tg) e varredura de corpo inteiro com iodo-131 foram revisados neste artigo. No acompanhamento após a terapia inicial, o TSH recombinante é eficaz na geração da Tg e para realização da varredura de corpo inteiro com radioiodo e apresenta vantagens sobre o hipotireoidismo iatrogênico, poupando os pacientes dos sintomas de hipotireoidismo e da piora da qualidade de vida induzida pela suspensão da levotiroxina, resultando em menor exposição a um TSH elevado, e reduzindo o período de afastamento das atividades. TSH recombinante é a forma de preparo indicada para o diagnóstico de metástases, tanto em pacientes de baixo (Tg após TSH recombinante), quanto de moderado ou alto risco (Tg e varredura com iodo-131 após TSH recombinante). Para terapia ablativa, os resultados são promissores com a dose de 100mCi na ablação de remanescentes, mas o hipotireoidismo ainda é preferível, exceto em pacientes que não alcançam a elevação desejada do TSH após a retirada da levotiroxina, com doenças de base que são agravadas pelo hipotireoidismo agudo e severo (cardiopatia e doença pulmonar graves, coronariopatia, função renal comprometida, passado de psicose por mixedema), indivíduos debilitados por doença avançada e idosos. Os estudos também mostram que a administração do TSH recombinante é segura, com poucos efeitos adversos leves ou moderados.

5mCi pretreatment scanning does not cause stunning when the ablative dose is administered within 72 hours

OBJETIVO: Determinar a interferência de uma dose traçadora de 5mCi de 131I. PACIENTES E MÉTODO: Nós analisamos retrospectivamente 145 pacientes que receberam o primeiro tratamento ablativo em nosso serviço. Eles foram divididos de acordo com o estadio da doença determinado pelo rastreamento pós-terapêutico (101 pacientes com remanescentes tireoidianos e 44 com metástases pulmonares) e scanning de corpo inteiro antes da ablação (realizada em 69 indivíduos). Todos os pacientes com remanescentes tireoidianos foram tratados com uma dose ablativa de 100mCi e aqueles com metástases receberam 200mCi. RESULTADOS: Nos pacientes com remanescentes apenas (n= 41) ou metastases (n= 28) submetidos ao scanning diagnóstico, a captação encontrava-se aparentemente aumentada na maioria dos patientscasos (71 e 73%, respectivamente) 7 dias após a terapia, enquanto captação reduzida (visual) não foi observada em nenhum paciente. A eficácia da ablação foi similar nos grupos submetidos ou não ao rastreamento diagnóstico: 71 e 80% em pacientes sem metástases (p= 0,28), respectivamente, e 43 e 50% naqueles com envolvimento pulmonar (p= 0,64). CONCLUSAO: Esses resultados indicam que o rastreamento diagnóstico usando uma dose de 5mCi de 131I não interefere com a captação da dose ablativa ou com a eficácia do tratamento quando a ablação é realizada dentro de 72h.

Seguranca da radioiodoterapia em pacientes com carcinoma de tireóide com menos de 21 anos / Safety of radioiodine therapy in patients with thyroid carcinoma younger than 21 years

Avaliamos 20 pacientes com carcinoma diferenciado de tireóide que receberam radioiodoterapia (dose > 100mCi) antes dos 21 anos: 10 sem metástases distantes receberam uma dose média de 145mCi e 10 com acometimento pulmonar difuso, 270mCi. Após um ano ou mais da terapia ablativa, xerostomia estava presente em dois pacientes sem complicacões mais sérias, como úlceras orais ou fissuras, e a cintilografia com 99mTcO4- confirmou a disfuncão salivar. Um deles apresentava ceratoconjutivite seca. O hemograma não revelou anormalidades atribuíveis à radioiodoterapia. FSH foi normal em 18 deles, e os pacientes com valores elevados haviam recebido radioiodo há pouco mais de um ano e, na repeticão do exame em 6 meses, houve normalizacão. Os seis pacientes masculinos tinham LH e testosterona normais. Nossa avaliacão não revelou sinais de fibrose pulmonar secundária ao tratamento nos 10 casos com metástases captantes neste órgão. Nossos dados sugerem que a terapia ablativa com dose de 100 a 300mCi é segura em jovens, mas complicacões persistentes como disfuncão salivar e conjuntivite podem ocorrer.

Abordagem dos pacientes com carcinoma diferenciado de tireóide com tireoglobulina sérica elevada e pesquisa de corpo inteiro negativa / Investigating patients with differentiated thyroid carcinoma and elevated serum thyroglobulin but negative whole-body scan

No seguimento do carcinoma diferenciado de tireóide (CDT), o achado de tireoglobulina (Tg) elevada e pesquisa de corpo inteiro (PCI) diagnóstica negativa não é incomum. Em 12 por cento dos nossos pacientes tratados com tireoidectomia e radioiodo com Tg >10ng/ml em hipotireoidismo apresentou PCI diagnóstica negativa. Este achado geralmente indica resultado falso-negativo da PCI. Devem ser excluídos exposicão inadequada ao excesso de iodo e elevacão insuficiente do TSH. Micrometástases que não captam o suficiente para serem detectadas com baixa atividade de radioiodo e perda da capacidade de expressar o simportador sódio/iodeto (NIS) também explicam alguns casos. Em pacientes com Tg elevada, metástases podem ser reveladas após uma dose terapêutica de radioiodo (100mCi ou mais), estando esta indicada nos casos com Tg maior que 10ng/ml em hipotireoidismo ou 5ng/ml com TSH recombinante, após exclusão de macrometástases pulmonares e cervicais. Cinco de 7 pacientes com estes critérios apresentaram captacão ectópica na PCI pós-dose em nossa série. Se a PCI pós-dose for negativa ou revelar captacão discreta em leito tireoidiano, outros métodos, por exemplo FDG-PET, podem ser utilizados, não se insisitindo na radioiodoterapia. Para estes casos, outras modalidades terapêuticas (cirurgia, radioterapia, quimioterapia, ácido retinóico) podem ser utilizadas. Se a PCI revelar metástases linfonodais, cirurgia é a terapia mais adequada; enquanto para metástases pulmonares difusas indica-se a radioiodoterapia até a negativacão da PCI pós-dose ou normalizacão da Tg com TSH elevado. Pacientes com PCI pós-dose positiva podem apresentar reducão significativa da Tg e até remissão completa com radioidodoterapia em alguns casos, mas o impacto deste tratamento na mortalidade permanece indefinido.

[Recombinant TSH in ablative therapy and follow-up of patients with differentiated thyroid carcinoma]. / TSH recombinante no tratamento e seguimento de pacientes com carcinoma diferenciado de tireóide: uso na prática clínica.

The studies evaluating the efficacy and safety of recombinant TSH in the ablative therapy and follow-up of patients with differentiated thyroid carcinoma by serum thyroglobulin (Tg) measurement and iodine scanning were reviewed in this article. Recombinant TSH is comparable to hypothyroidism in the generation of Tg and in the execution of iodine-131 whole-body scanning, with the advantage of sparing patients from the symptoms of hypothyroidism and from impaired quality of life induced by levothyroxine withdrawal, in addition to a reduced exposure to elevated TSH and shorter absence from work, with recombinant TSH being the preparation indicated for the diagnosis of metastases in both low risk (Tg after recombinant TSH) and moderate or high risk patients (Tg and iodine-131 scanning after recombinant TSH). In the case of ablative therapy, the results are promising when using a dose of 100 mCi for remnant ablation, but hypothyroidism is still preferred, except for patients in whom the desired TSH elevation after levothyroxine withdrawal is not achieved, patients with base diseases that are aggravated by acute and severe hypothyroidism (severe heart and lung disease, coronary disease, compromised renal function, history of psychosis due to myxedema), patients debilitated by advanced disease, and elderly individuals. The studies also show that the administration of recombinant TSH is safe, with few mild or moderate adverse effects.

5 mCi pretreatment scanning does not cause stunning when the ablative dose is administered within 72 hours.

OBJECTIVE: To determine the stunning effect of a tracer dose of 5 mCi iodine-131. PATIENTS AND METHODS: We retrospectively analyzed 145 patients who received the first ablative treatment at our service. Patients were divided according to disease status determined upon post-treatment scanning (101 patients with thyroid remnants and 44 with pulmonary metastases) and whole-body scanning before ablation (performed on 69 individuals). All patients with thyroid remnants were treated with an ablative dose of 100 mCi and those with metastases received 200 mCi. RESULTS: In patients with remnants only (n= 41) or metastases (n= 28) submitted to diagnostic scanning, uptake was found to be apparently increased in most patients cases (71 and 73%, respectively) 7 days after therapy, while reduced uptake (visual) was not observed in any patient. The efficacy of ablation was similar in the groups submitted or not to diagnostic scanning: 71 and 80% in patients without metastases (p= 0.28), respectively, and 43 and 50% in those with pulmonary involvement (p= 0.64). CONCLUSION: The present results indicate that diagnostic scanning using a 5 mCi iodine-131 dose does not interfere with uptake of the ablative dose or with treatment efficacy when ablation is performed within 72 h.

Tratamento do microcarcinoma de tireóide / Treatment of papillary microcarcinoma of the thyroid

Avaliamos, retrospectivamente, a recorrência, presença de metástases distantes e mortalidade em 78 pacientes com microcarcinoma papilífero seguidos durante 6,8 anos, em média. Dos 56 pacientes com tumor unifocal sem metástases, nenhum apresentou recorrência, independente do tratamento (22 loboistmectomia, 11 tireoidectomia total sem ablação e 23 com ablação). O mesmo ocorreu nos 15 casos de tumor multicêntrico restrito à tireóide e tratados com tireoidectomia total e radioiodo. Dos 7 casos com metástases na apresentação inicial e submetidos a cirurgia extensa e terapia ablativa, recorrência cervical ocorreu em apenas 1 paciente. A presença de anticorpos anti-tireoglobulina foi mais comum após a lobectomia (22,7 por cento vs. 9 por cento) e a especificidade da tireoglobulina (Tg) ficou comprometida com este procedimento, mas não nos pacientes com tireoidectomia total sem ablação. Observou-se dois casos de hipoparatireoidismo definitivo no gruposubmetido à tireoidectomia total (3,5 por cento) e nenhum com lobectomia. O presente estudo concorda que a loboistmectomia pode ser suficiente para o tratamento do microcarcinoma papilífero único restrito à tireóide. No entanto, a especificidade da Tg no seguimento fica comprometida. Para tumores multicêntricos ou com linfonodos acometidos, recomenda-se a tireoidectomia total, mas o uso rotineiro da radioiodoterapia é controvertido.