There is strong evidence that the patched (PTCH) gene is a gene for susceptibility to the nevoid basal cell carcinoma syndrome. PTCH has also been shown to mutate in both familial and sporadic basal cell carcinomas. However, mutations of the gene seem to be rare in squamous cell carcinomas. In order to characterize the role of the gene in the broader spectrum of sporadic skin malignant and pre-malignant lesions, we performed a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis of genomic DNA extracted from 105 adult patients (46 females and 59 males). There were 66 patients with basal cell carcinomas, 30 with squamous cell carcinomas, 2 with malignant melanomas and 7 patients with precancerous lesions. Two tissue samples were collected from each patient, one from the central portion of the tumor and another from normal skin. Using primers that encompass the entire exon 1, exon 8 and exon 18, where most of the mutations have been detected, we were unable to demonstrate any band shift. Three samples suspected to present aberrant migrating bands were excised from the gel and sequenced directly. In addition, we sequenced 12 other cases, including tumors and corresponding normal samples. A wild-type sequence was found in all 15 cases. Although our results do not exclude the presence of clonal alterations of the PTCH gene in skin cancers or mutations in other exons that were not screened, the present data do not support the presence of frequent mutations reported for non-melanoma skin cancer of other populations.

In addition to the mutations that underlie most cases of the multiple endocrine neoplasia type 1 (MEN1) syndrome, somatic mutations of the MEN1 gene have also been described in sporadic tumors like gastrinomas, insulinomas and bronchial carcinoid neoplasm. We examined exon 2 of this gene, where most of the mutations have been described, in 148 endocrine and nonendocrine sporadic tumors. DNA was obtained by phenol/chloroform extraction and ethanol precipitation from 92 formalin-fixed, paraffin-embedded samples, and from 40 fresh tumor tissue samples. We used 5 pairs of primers to encompass the complete coding sequence of exon 2 of the MEN1 gene that was screened by the polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) technique in 78 sporadic thyroid cancers: 28 follicular adenomas, 35 papillary carcinomas, 14 follicular carcinomas, and 1 anaplastic thyroid carcinoma. We also examined 46 adrenal lesions (3 hyperplasias, 3 adenomas and 35 adrenocortical carcinomas, 2 pheochromocytomas, 2 ganglioneuroblastomas, and 1 lymphoma) and 24 breast cancers (6 noninvasive, 16 infiltrating ductal, and 2 invasive lobular tumors). The PCR product of 5 tumors suspected to present band shifts by SSCP was cloned. Direct sense and antisense sequencing did not identify mutations. These results suggest that the MEN1 gene is not important in breast, thyroid or adrenal sporadic tumorigenesis. Because the frequency of mutations varies significantly among tumor subgroups and allelic deletions are frequently observed at 11q13 in thyroid and adrenal cancers, another tumor suppressor gene residing in this region is likely to be involved in the tumorigenesis of these neoplasms.

Although the role of interleukin-2 (IL-2) and interferon gamma (<FONT FACE="Symbol">g</FONT>IFN) is still poorly understood in hyperthyroid diseases, it is reasonable to assume that these cytokines may be present at higher levels in Graves' disease (GD) than in other primarily non-autoimmune thyroid diseases. In order to look for an easy method to distinguish GD from primarily non-autoimmune causes of hyperthyroidism, we compared 13 healthy individuals with 21 treated and untreated hyperthyroid GD patients and with 19 patients with hyperthyroidism due to other etiologies: 7 cases of multinodular goiter, 5 cases of excessive hormone replacement and 7 cases of amiodarone-associated hyperthyroidism. All patients presented low TSH levels and a dubious clinical thyroid state. We found a good correlation between TSH and serum IL-2 levels (r = 0.56; P<0.01). Serum IL-2 (P<0.01) and <FONT FACE="Symbol">g</FONT>IFN (P<0.01) levels were lower in the hyperthyroid group of patients than in control subjects, suggesting a depressed TH1 pattern in the T-cell subset of hyperthyroid patients. GD had normal IL-2 levels, while patients with other forms of thyrotoxicosis presented decreased IL-2 levels (P<0.05). There was no difference between treated and untreated GD patients. We suggest that the direct measurement of serum IL-2 level may help to confirm hyperthyroidism caused by GD.

OBJETIVO: Comparar em recém-nascidos (RN) duas estratégias diferentes para o rastreamento do hipotiroidismo congênito (HC), a dosagem primária de TSH no sangue colhido do cordão umbilical (método 1) e a dosagem primária de T4 no sangue colhido por punção de calcanhar no 2º dia de internação (método 2). MÉTODOS: Os autores compararam as duas estratégias em 10.000 RN. Dosaram o TSH por método imunofluorimétrico sensível em papel de filtro e o T4 por radioimunoensaio em papel de filtro. A coleta de sangue do calcanhar foi realizada no 2º dia de vida RESULTADOS: Os dois programas diagnosticaram todos os casos de HC nos RN (4 casos, 1/2.500 RN). O índice de rechamada por coleta inadequada foi nulo no método 1 e de 8,5% (850 RN) no método 2. O índice de reconvocação para confirmação de resultados foi de 0,06% (6 RN) no método 1 e de 2,25% (225 RN) no método 2; quando este método incluía também a dosagem suplementar de TSH, o índice baixou para 1,63% (163 RN). CONCLUSÃO: Os dados dos autores evidenciam a superioridade técnica da coleta de sangue a partir do cordão umbilical em relação à punção de calcanhar, assim como da dosagem primária de TSH em relação à de T4, uma vez que apresentam índices muito menores de reconvocação.

OBJECTIVE: Compare two different strategies in newborn screening for congenital hypothyroidism, primary TSH in the umbilical cord blood (method 1) and primary T4 in blood collected from the heel in the 2nd day of life (method 2). METHODS: We compared both strategies in 10,000 newborns, measuring TSH by a sensitive immunofluorimetric assay and T4 by a radioimmunoassay. RESULTS: Both strategies detected all cases of hypothyroidism (4 cases, 1/2,500 newborns). The recalling index owing to insufficient amount of blood to perform the assays was zero in method 1 and 8.5% (850 newborns) in method 2. The recalling index for confirmation of the results was 0.06% (6 newborns) in method 1 and 2.25% (225 newborns) in method 2; when method 2 included supplementary TSH, the recalling index was reduced to 1.63% (163 newborns). CONCLUSION: Our data indicate the technical superiority of the umbilical cord blood compared to heel and primary TSH compared to primary T4 in the neonatal thyroid screening for congenital hypothyroidism.

Os valores das dosagens de T3 e de T4 diferenciaram os pacientes com boa e má evolução durante a internação em unidade de terapia intensiva. OBJETIVO. Procurar indicadores para o prognóstico de doentes graves por meio do estudo seqüencial dos níveis séricos dos hormônios tiroidianos. MÉTODOS. Os autores mediram as iodotironinas (T3, T4 e rT3) por ocasião da entrada e da alta de 42 pacientes internados em unidade de terapia intensiva. Verificaram, também, os dados referentes à última coleta de outros 17 doentes, transferidos para a UTI após o início do quadro clínico. RESULTADOS. Comparando pacientes que evoluíram bem com aqueles que foram a óbito, observaram, nos primeiros, níveis iniciais normais de T4 em 76% dos casos, valores que se mantiveram estáveis ou se elevaram em 65% dos pacientes durante a internação, de tal forma que níveis normais de T4 estavam presentes em 70% dos casos por ocasião de sua alta. Ao contrário, 56% dos pacientes que evoluíram mal já apresentavam T4 inicial baixo, que diminuiu ainda mais em 95% dos pacientes durante a internação, notando-se valores baixos em 81% dos casos por ocasião da última amostra. Os valores de T3 e de T4 em conjunto também diferenciaram os pacientes com boa e má evolução. CONCLUSÃO. Os autores sugerem que a observação dos níveis séricos das iodotironinas pode oferecer importante subsídio na avaliação prognóstica de doentes em estado grave.

In order to find prognostic parameters in patients with severe diseases, we analyzed sequentially the levels of thyroid hormones. METHODS. We measured iodothyronines (T3, T4 and rT3) in 42 patients before the admission and after the discharge in an intensive care unit. In addition, we also measured the iodothyronines in other 17 patients after the discharge. RESULTS. Comparing the group of good outcome with the patients who died, we observed in the former group initial normal T4 levels in 76% of the patients, which were maintained in 65% of them during hospitalization and in 70% of them at the time of delivery from the intensive care unit. Patients who died, however, presented initial low T4 levels in 56% of them, decreasing values in 95% of them during hospitalization and low levels in 81% of patients at the last dosage. The combined profile of T3 and T4 also differentiated good and bad outcome. CONCLUSION. We suggest that serial analysis of serum levels of thyroid hormones may help the evaluation of critical care patients.