Antithyroglobulin antibodies (TgAb) were measured using a chemiluminescent immunoassay (ICMA) and an agglutination test. TgAb laboratory and clinical interference with Tg measurements were assessed. The course of TgAb concentration and disease status were compared during 3 years after initial treatment. The agglutination test failed to detect all titers < 10IU/mL (ICMA). Interference from TgAb was common at high titers, but even low antibody titers (< 5IU/mL) were able to interfere with Tg measurement. Cases of distant metastases with undetectable Tg (by IRMA) and those apparently free of disease and without thyroid remnants with Tg> 2ng/ml (by RIA) were identified among patients with TgAb. The exogenous Tg recovery test was normal (> 80%) by the two methods in 22% of patients with TgAb and confirmed laboratory interference. Absence of reduction in TgAb levels was a marker of persistent disease. In conclusion, TgAb should be determined by immunoassays; interference with Tg measurements occurred mainly but not always at high concentrations, with a normal Tg recovery test not excluding this interference. The behavior of TgAb is related to disease persistence or cure. Anticorpos anti-tireoglobulina (TgAb) foram medidos por um imunoensaio de quimioluminescência (ICMA) e um teste de aglutinação. Avaliamos a interferência clínica e laboratorial dos TgAb com as medidas de Tg. A evolução da concentração dos TgAb e o estado da doença foram comparados durante 3 anos após o início do tratamento. O teste de aglutinação falhou em detectar todos o títulos <10UI/mL (ICMA). Interferência dos TgAb foi comum com títulos altos, mas mesmo títulos baixos dos anticorpos (<5UI/mL) interferiram na medida de Tg. Casos com metástases à distância e Tg indetectável (por IRMA) e aqueles aparentemente livres da doença e sem remanescentes tireoidenos com Tg >2ng/ml (por RIA) foram identificados entre pacientes com TgAb. O teste de recuperação da Tg exógena foi normal (>80%) por ambos os métodos em 22% dos pacientes com TgAb, confirmando a interferência laboratorial. Ausência de redução dos níveis de TgAb foi um marcador de persistência da doença. Em conclusão, TgAb deve ser determinada por imunoensaios; interferência com as medidas de Tg ocorreram principalmente mas não somente em altas concentrações, com um teste normal de recuperação de Tg não excluindo esta interferência. O comportamento dos TgAb está relacionado à persistência ou à cura da doença.
Postoperative measurement of cervical I-131 uptake could be a reasonable predictor of the success of the remnant ablation, and perhaps a guide in deciding the ablative dose of I-131, based on the inverse correlation between the uptake and ablation efficacy.
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.
Twenty-three patients submitted to thyroidectomy and before ablative therapy and with cervical uptake >10% were compared to 48 patients with uptake <2%. All but 3 patients with large remnants reached TSH levels >30 mIU/l after thyroxin withdrawal. Cervical pain requiring anti-inflammatory treatment after radioiodine was more frequent in patients with larger remnants (34.7% vs. 10.4%). Remnant ablation was successful in 56% of the individuals with uptake >10% and in 93.3% of those with uptake <2%. The sensitivity of diagnostic scanning for pulmonary metastases was similar (71.4% vs. 77.7%). The specificity of stimulated thyroglobulin at a cut-off of 5 ng/ml was 100% for patients with discrete remnants but only 37.5% for the others. We conclude that significant thyroid remnants (cervical uptake >10%) result in a lower efficacy of ablation, cause more local symptoms after radioiodine, and compromise the specificity of thyroglobulin measurements.
RESUMOEste estudo avaliou a tireoglobulina (Tg) sérica dosada em hipotireoidismo em 207 pacientes com carcinoma diferenciado de tireóide tratados com tireoidectomia total e ablação com radioiodo e anticorpos anti-Tg indetectáveis. O estadiamento da doença foi definido pelo exame clínico, Tg estimulada, varredura com radioiodo pré e/ou pós-terapia ablativa e outros métodos de imagem (RX, US, TC e varredura com sestamibi). O intervalo médio desde a terapia inicial foi de 2,3 anos. Dos pacientes, 153 (74%) não apresentavam doença evidente, 34 (16,4%) tinham metástases (Mt) cervicais ou mediastinais e 20 (9,6%) Mt distantes. O valor de 1ng/ml da Tg foi o que melhor discriminou pacientes com e sem doença aparente, com 100% de sensibilidade para Mt distantes, 88,2% para doença em leito tireoidiano ou linfonodos e especificidade de 88,8% para Mt de qualquer natureza, e 74,8% considerando apenas Mt distantes. Dos pacientes com Tg 1ng/ml, 2,8% apresentavam Mt cervicais. Doença cervical ou mediastinal representou 26% dos casos com valores de Tg entre 1 e 5ng/ml. Tg entre 5 e 10ng/ml foi associada a Mt distantes em 14,2% dos casos, os demais apresentavam Mt linfonodais. Mt distantes foram diagnosticadas em 51,3% dos pacientes com Tg >10ng/ml. Sugerimos a necessidade de US cervical mesmo em pacientes com Tg 1ng/ml; que pacientes com Tg <5ng/ml sejam investigados apenas com US cervical e TC de mediastino; e que a terapia empírica fique reservada aos casos com Tg no mínimo >5ng/ml. This study analyzed serum thyroglobulin (Tg) during hypothyroidism in 207 patients with differentiated thyroid carcinoma treated with total thyroidectomy and radioiodine ablation and undetectable anti-Tg antibodies. Disease staging was defined by clinical examination, stimulated Tg, pre-and post-ablative radioiodine scanning, and other imaging methods (X-Ray, US, CT and MIBI-scan). The average interval from initial therapy was 2.3 years. 153 patients (74%) had no evident disease, 34 (16.4%) presented neck/mediastinal disease, and 20 (9.6%) had distant metastases (Mt). The best cut-off for Tg was 1ng/ml, showing 100% sensitivity for distant Mt and 88.2% for local recurrence or lymph node Mt, and 88.8% specificity for any Mt and 74.8% for distant Mt. In patients with Tg <1ng/ml, 2.8% showed cervical lymph nodes Mt. Cervical or mediastinal disease were 26% of cases with Tg between 1 and 5ng/ml. Tg from 5 to 10ng/ml was associated to distant Mt in 14.2% of the cases and others showed lymph nodes Mt. In patients with Tg >10ng/ml, 51.3% presented distant Mt. We suggest the need for neck US even in cases with Tg <1ng/ml. In addition, patients with Tg levels <5ng/ml should be investigated by neck US and medi-
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.
We studied 58 patients with distant metastases of differentiated thyroid carcinoma diagnosed after initial therapy. Lymph node metastases were observed in 65% of the patients on initial presentation. All lymph node metastases, ninety percent of the lung metastases and only 25% of the bone metastases were asymptomatic. Radiography revealed lytic metastases in cases of bone involvement, was normal in 39.6% of the patients, and showed micrometastases in 34.5% and macrometastases in 25.8% of the patients with lung disease. Thyroglobulin (Tg) under thyroxine use was detectable in all patients without antibodies at a cut-off > 1 ng/ml, in 90% at > 5 ng/ml and in 80% at > 10 ng/ml, and after thyroxine withdrawal in 100% at a cut-off > 5 ng/ml and in 94% at > 10 ng/ml. In the case of patients with antibodies (13.8%), Tg was undetectable in half of them. Diagnostic scanning was positive in 83 and 77.6% of the patients with bone and lung metastases, respectively. After ablative therapy, the sensitivity was 100 and 93%, respectively. Eighty-five percent of patients with a negative diagnostic scan had lung metastases visible on radiographs. The determination of serum Tg is the best method in the follow-up of patients with differentiated thyroid cancer. Elevated Tg levels suggest the presence of metastases, indicating the need for ablative therapy with posttreatment scanning, which might reveal non-apparent metastases.
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