Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

The published studies confirming the safety and efficacy of rhTSH for diagnostic purposes have ledto an increased interest in its use for preparation for radioiodine (RI) dose administration in patientswith recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RItherapy after rhTSH, we have reviewed 39 rhTSH-aided radioiodine treatment in a series of 28 DTC patients.Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin(Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease.Median follow-up after the first rhTSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months).Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease.In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, infour in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels wereundetectable after rhTSH. In the follow-up, two patients with lateral neck uptake were rendered disease free,four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. Inconclusion, rhTSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients(GI). rhTSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rhTSHis a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing thequality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patientsonly with stimulated Tg levels.

Los estudios publicados que confirman la seguridad yeficacia de la TSH recombinante (rhTSH) llevaron a un incremento en el interés para su uso como adyuvanteterapéutico en el CDT (ablación o tratamiento de enfermedad metastática). Para evaluar la efectividad de laadministración de dosis terapéuticas de RI luego de la administración de rhTSH, realizamos un análisisretrospectivo en 28 pacientes con CDT que recibieron 39 dosis de RI. Los pacientes se dividieron en 2 grupos:GI (n=17) pacientes con captación en el lecho tiroideo y niveles indetectables de tiroglobulina (Tg) bajo tratamientosupresivo con levotiroxina y GII (n=11), pacientes con enfermedad metastática local o a distancia, previamentecomprobada. El seguimiento promedio luego de la primera dosis de RI fue de 32 ± 13 meses (rango 8 a 54meses). Dieciseis pacientes (94%) del GI fueron considerados libres de enfermedad y un paciente presentó unapersistencia local. En el GII, las captaciones patológicas fueron: en 4 pacientes en pulmones; en 4 en mediastinoy en 3 a nivel lateral cervical. Dos pacientes con captaciones mediastinales presentaron niveles indetectablesde Tg. En el seguimiento, dos pacientes con captaciones latero-cervicales se consideraron libres de enfermedad,cuatro pacientes murieron (tres debido al CDT avanzado) y cinco de los restantes tienen enfermedad persistente.En conclusión, la terapia con RI luego de rhTSH fue útil para ablacionar remanentes normales en el GI. Losniveles de Tg estimulados con rhTSH fueron indetectables en dos pacientes con metástasis mediastinales. Eluso de rhTSH parece ser una alternativa válida frente a la suspensión de la terapia hormonal en el tratamientode pacientes con CDT, incrementando la calidad de vida de estos pacientes.

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.

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.

Normal Gallbladder Visualization during Post-Ablative Iodine-131 Scan of Thyroid Cancer

Whole body iodine-131 scan is a well-established imaging method for the detection of metastatic or residual tumor sites in patients with well-differentiated thyroid cancer. Many false-positive iodine-131 scan findings mimicking metastatic thyroid cancer have long been reported. The authors describe a false positive uptake in normal gallbladder on post-ablative iodine-131 scan in a patient with papillary thyroid cancer. This finding should be considered to be another possible false-positive finding on iodine-131 whole body scan.

Molecular technology and the recombinant TSH have changed diagnostics of thyroid carcinoma with positive I-131 whole body scan but low serum thyroglobulin

The early detection of recurrent differentiated thyroid carcinoma (DTC) cells in the post surgery DTC patients relies on the sensitivity of measuring both the level of thyroglobulin (Tg) and 131-Iodine distribution by Whole Body Scan (WBS). Undetectable level of Tg associated with negative WBS or elevated levels of Tg associated with positive WBS ("concordant") is ordinarily indicative of either absence or presence of disease. At times, elevated level of Tg with negative WBS or low levels of Tg with positive WBS ("discordant") could also occur. In the present study, we retrospectively reviewed series of 573 patients with DTC followed in the Diagnostic Imaging and Radiotherapy of the University "Federico II" of Naples between 1993 and 1997. We focused on 9 out of 573 patients (1.56%) who had a discordant pattern with low level of Tg/positive WBS in the post-surgical follow-up. Four patients were metastatic at presentation while 5 patients with metastasis during follow-up still remained in persistently low levels of Tg (<5 ng/mL). This result does point to some flaw in the evaluation of "discordant" cases. Reviewing data previously described series by resetting cut-off values of Tg <1 ng/ml as undetectable changed the apparent "discordant" subgroup of patients into "concordant". Recent introduction of recombinant human TSH (rhTSH) to enhance the expression level of Tg brought significant increase in the sensitivity of diagnostic evaluation of thyroid cancer patients. The role of burdensome WBS in the follow up evaluation of DTC patients is significantly reduced over time especially in low-risk patients while the relevance of Tg assay is steadily increased. Sensitive Tg assays, significantly improved our ability to assess disease status in follow-up of DTC. Given the possibility of late disease relapses, the need for long-term follow-up, and reduced delay in treatment of persistent disease, there is still need for greater sensitive diagnostic tools for DTC.

Absorption of unlabeled reduced iron of small particle size from a commercial source. A method to predict absorption of unlabeled iron compounds in humans

The absorption of a commercial brand of small-particle reduced iron was evaluated in 10 normal subjects. For each subject, the hemoglobin incorporation method was used to measure the true absorption of 60 mg of iron from either ferrous sulfate or ferric ammonium citrate. The iron tolerance test (ITT) was also studied for these two compounds and for reduced iron. This procedure consisted of measuring the area under the curve of plasma iron elevations at specified times for 6 hours, or the peak plasma iron, corrected by the plasma iron disappearance rate obtained from measuring plasma iron at specified times for 4 hours after the slow intravenous injection of 0.4 mg of iron as ferric citrate. Only the ITT was used to measure the absorption of 60 mg of reduced iron. Reference dose iron ascorbate absorption was measured in each subject. The absorption of ferric ammonium citrate and reduced iron was expressed as percent of dose and also as absorption percent of that of ferrous sulfate. Mean geometric "true absorptions" were 39.0 for reference dose, 10.4 for FeSO4 and 2.4 for ferric ammonium citrate. The later was 23 that of FeSO4. By ITT the mean geometric absorptions were 7.9, 3.7 and 3.2 for FeSO4, ferric ammonium citrate and reduced iron respectively, or 47 and 41 of that of FeSO4. We propose that the true absorption of the commercial brand of reduced iron tested was 20 that of FeSO4 based on the relation between the ITT results of reduced iron and the ITT and true absorption values of ferric ammonium citrate in relation to FeSO4. The use of this method for measuring absorption of unlabeled iron compounds is discussed.

Discordant findings of Iodine-131 scintiscan and chest radiogram in carcinoma of thyroid patients.

Since 1987, 560 patients have been treated in our department for carcinoma of thyroid with radioactive Iodine-131. Recently, we have come across a patient with bilateral pulmonary concentration of Iodine-131, that is visualised on Iodine-131 whole body scintiscan, whereas chest radiogram was negative. Respectively, the files of 560 patients of carcinoma of thyroid were analysed. It is found, out of 560 patients treated, 16 patients, had pulmonary concentration of Iodine-131. The chest radiogram was normal in six out of these 16 patients. Details of both chest radiogram and scintiscans are presented in this study.

Diagnóstico de metástase do carcinoma diferenciado de tireóide: pesquisa de corpo inteiro versus tireoglubulina sérica / Diagnosis of metastasis of differentiated thyroid carcinoma: total body scans versus serum thyroglobulin

Noventa e seis pacientes portadores de carcinoma diferenciado de tireóide foram avaliados através da pesquisa de corpo inteiro (PCI), após administraçäo de I, e da dosagem sérica de tireoglobulina (Tg) por RIE, para identificaçäo de focos metastáticos. Os pacientes haviam sido submetidos entre 1973 e 1986 à tireoidectomia total e à radioiodoterapia ablativa (100mCi de I nos casos com resíduo tireoideano cuja captaçäo nas 24h fosse superior ou igual a 1%). Os pacientes eram mantidos com hormonioterapia supressiva da secreçäo de TSH (1-tiroxina, 3-4microng/Kg/dia); com comprovaçäo através do estudo da secreçäo de TSH pós-TRH. A monitorizaçäo da concentraçäo sérica de Tg foi realizada na vigência da hormonioterapia com T4 e imediatamente antes da realizaçäo da PCI. A PCI foi feita quatro semanas após a interrupçäo da terapia com T4, momento em que os pacientes apresenta-se em franco hipotireoidismo (TSH > ou igual 50 micronU/ml). O estudo foi realizado 48 h após a administraçäo de 2-5mCi de I. Em 81 pacientes (84%) observou-se PCI negativa e níveis séricos de Tg < 5 ng/ml, enquanto que em 11 pacientes (12%) encontrou-se PCI positiva e níveis de Tg elevados. Em três casos (3%) observou-se PCI negativa e níveis elevados de Tg. Em um caso (1%) observou-se PCI positiva e Tg em níveis indetectáveis. Devido à alta correlaçäo entre os dois métodos e a alguns inconvenientes da PCI, propöe-se a dosagem sérica de Tg como método de escolha para o acompanhamento de pacientes com carcinoma diferenciado de tireóide que já tenham sido submetidos à tireoidectomia total (cirurgia + radioiodoterapia)

Effects of some carbohydrates on iron absorption

Se llevaron a cabo dos experimentos, con el propósito de examinar el efecto de varios carbohidratos (fructosa, lactosa, almidón de maíz, almidón de papa y almidón de trigo) en la utilización del hierro, por ratas deficientes en este elemento. Las ratas recibieron una sola comida marcada con 59Fe que contenia el carbohidrato a ensayar a un nivel de 60%. En el resto del experimento las ratas fueron alimentadas ad libitum con una dieta que contenía glucosa como fuente de carbohidratos al nivel de 60%. En ambos ensayos las ratas no recibieron alimento durante la noche anterior, y la dosis se ofreción como una comida, en la mañana. Para determinar el hierro 59, las ratas se contaron en un "contador de cuerpo entero entre dos y cuatro horas después de la dosis, y cada día durante los 10 días siguientes. Se determinarón el porcentaje de retención y el porcentaje de absorción así como los valores de hemoglobina. En el primer experimento, el reemplaxo de glucosa por fructosa al nivel de 60% aumentó significativamente la retención y la absorción del hierro. Con la lactosa también se notó un aumento de estos parámetros, pero dicho incremento no fue estadísticamente significativo. La administración de 59Fe como un quelato 59Fe-fructosa no tuvo efecto significativo en la retención y absorción del hierro, comparada con el efecto resultante de dosificar con el 59Fe absorbido a la fructosa. Este hallazgo no descarta la posibilidad de que la quelación sea el mecanismo responsable del efecto promotor de la fructosa en la basroción del hierro. El complejo puede haberse formado en el estómago, dando como resultado una absorción similar para la comida marcada con 59Fe, y la marcada con el complejo 59Fe-fructosa...

Vitamin B12 absorption studies using radioactive vitamin B12: comparison of whole body retention and urinary excretion after flushing dose (Schilling's test).

Vitamin B-12 absorption of 12 healthy young male subjects was determined by using labelled vitamin B-12 by Schilling's test and whole body retention test. The whole body retention test was performed first using low energy Co57 isotope and a week later, Schilling's test was performed. Whole body retention showed a mean absorption of 56.5% while Schilling's test showed mean absorption of 16.9% in the same subjects. Data supports the whole body retention test being more accurate.