Thyroid Diseases: Rodrigues F

Rodrigues F, Limbert E, Marques AP, Santos AP, Lopes C, Rodrigues E, Borges F, Carrilho F, Castro JJ, Neto J, Salgado L, Oliveira MJ, Anonymous00295. · No affiliation provided · Acta Med Port. · Pubmed #16202330 links to  free full text

Abstract: Differentiated thyroid carcinoma of follicular origin (DTCFO), although not very frequent, has registered a raising incidence in the last decades. In the majority of the cases, DTCFO is a curable disease when treated and monitored by experienced, multidisciplinary teams. These factors contribute to an increasing number of DTCFO survivors requiring life-long monitoring, due to the possibility of occurrence of recurrences many years after the initial treatment. Several aspects of the treatment and management of these patients are still controversial. The present protocol represents the consensus of the members of the Grupo de Estudo da Tiróide of the Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo. It aims to define guidelines, in agreement with the current state of the art and contemplating the necessary adaptations to local constrains, that ensure decreased mortality and protection of patients' quality of life, avoiding unnecessarily aggressive or ineffective treatments, optimizing the use of the available resources.

Araujo J, Segat L, Guimarães RL, Brandão LA, Souza PE, Santos S, Soares TS, Falcão EA, Rodrigues F, Carvalho R, de Lima-Filho JL, Arraes LC, Crovella S. · Pediatric Endocrinology Unit of Clinical Hospital, Federal University of Pernambuco, Pernambuco, Brazil. · Clin Immunol. · Pubmed #19185543 No free full text.

Abstract: In our study we investigated the possible role of MBL2 functional single nucleotide polymorphisms (SNPs) in the augmented susceptibility to develop other autoimmune diseases in presence of type 1 diabetes (T1D) in a group of Brazilian patients. Patients were stratified for the presence of autoimmune diseases known to be associated with T1D, such as autoimmune thyroid disease (AITD) and celiac disease (CD), and compared with healthy controls (HC). Our findings suggest that MBL2 functional SNPs are more closely related to AITD than to T1D, being MBL2 SNPs frequencies in T1D patients not affected by AITD comparable to the HC ones, while significantly different between AITD patients and patients not affected by the disease. Thus, the association between MBL2 polymorphisms and T1D that we previously reported, seems to result from the stronger association of MBL2 SNPs with another autoimmune disease, the AITD, frequently associated with T1D.

Lemos MC, Coutinho E, Gomes L, Carrilho F, Rodrigues F, Regateiro FJ, Carvalheiro M. · Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal. · J Endocrinol Invest. · Pubmed #18591888 No free full text.

Abstract: Individual susceptibility to cancer is influenced by polymorphisms of genes encoding drug-metabolizing enzymes such as the glutathione S-transferases (GST). The null polymorphisms of the GSTM1 and GSTT1 genes have been associated to a modified risk of several cancers but studies of thyroid cancer have produced conflicting results. The aim of this study was to investigate the relationship between these polymorphisms and the risk of papillary thyroid cancer (PTC). A total of 188 patients with PTC and 247 controls were genotyped using a PCR-based assay. Odds ratios (OR) and 95% confidence intervals (CI) for each homozygous null genotype were determined. The frequency of each of the GSTM1 and GSTT1 null genotypes did not differ significantly between patients and controls (OR=0.83, 95%CI: 0.56-1.21; p=0.328; and OR=0.66, 95%CI: 0.39-1.12; p=0.123, respectively), but the frequency of individuals that had the combined GSTM1 null/GSTT1 null genotypes was significantly lower in the patient group (OR=0.50, 95%CI: 0.26-0.97; p=0.040). The GSTM1 null genotype was associated with a lower risk of advanced cancer stages (III/IV) (OR=0.50, 95%CI: 0.26-0.96; p=0.036) and the GSTT1 null genotype was associated with a lower risk of the follicular variant of PTC (OR=0.31, 95%CI: 0.10-0.97; p=0.044). These results suggest that GSTM1 and GSTT1 null genotypes are weak, yet possible, modifiers of the risk of PTC. This protective effect may be due to a role of the GSTM1 and GSTT1 encoded enzymes in the metabolic activation of putative thyroid carcinogens or in other pathways involved in thyroid carcinogenesis.

Prazeres HJ, Rodrigues F, Soares P, Naidenov P, Figueiredo P, Campos B, Lacerda M, Martins TC. · Molecular Pathology Laboratory, Portuguese Institute of Oncology of Coimbra FG, EPE, Avenida Bissaya Barreto, 98, 3000-075, Coimbra, Portugal. · Fam Cancer. · Pubmed #17823852 No free full text.

Abstract: Linkage studies have identified susceptibility loci for familial nonmedullary thyroid cancer (FNMTC), with and without cell oxyphilia, at chromosomal regions 19p13.2 and 2q21. There are few genetic analyses of FNMTC tumours reported at the present time and the eventual gene involved was not identified yet. The aim of this study was to assess the occurrence of loss of heterozygosity (LOH) at these loci in the tumours from familial clusters of NMTC. We have analysed LOH in 14 tumours from 9 two-case familial clusters of NMTC. Using paired blood (normal) and tumour DNA samples, we have genotyped ten microsatellite and one SNP markers throughout 19p13.2 and fourteen microsatellite markers at 2q21. Overall, eight (57%) and two (14%) out of the fourteen tumours analysed exhibited LOH at 19p13.2 and 2q21, respectively. In two families (22%), LOH for the same markers was demonstrable in the tumours of the two members of the same family. In one family (11%) LOH was demonstrable at both loci analysed. In four two-case familial clusters (44%), LOH at the 19p13.2 locus was found in only one of the tumour cases analysed. Detailed haplotype analysis showed that, in two families (22%), the pattern of LOH in tumours was consistent with selective retention of the haplotype shared by affected members. In the remaining cases, it was consistent with random allelic losses. In conclusion, we report the finding of LOH at the 19p13.2 and 2q21 loci in tumours from familial clusters of NMTC, providing evidence that inactivation of putative genes in these regions, acting as tumour-suppressors, may be involved in the development of tumours in the context of FNMTC.

Cunha N, Rodrigues F, Curado F, Ilhéu O, Cruz C, Naidenov P, Rascão MJ, Ganho J, Gomes I, Pereira H, Real O, Figueiredo P, Campos B, Valido F. · Serviço de Patologia Clínica, Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE, Av. Bissaya Barreto, 98, 3000 Coimbra, Portugal. · Eur J Endocrinol. · Pubmed #17609408 links to  free full text

Abstract: BACKGROUND: Fine-needle aspiration cytology is frequently used for differential diagnosis of neck masses of unknown origin. Inconclusive and even false-negative results are not uncommon. AIM: To evaluate the utility of thyroglobulin (Tg) measurement in fine-needle aspirates (FNA-Tg) for detecting cervical lymph node (CLNs) metastases from differentiated thyroid carcinomas. METHODS: An ultrasound-guided fine-needle aspiration was done in 67 patients with 83 suspicious enlarged CLNs to obtain material for cytology and Tg measurement in the needle washout, using an immunometric chemiluminescent assay. Measurement of anti-Tg antibodies (FNA-TgAb) was also carried out in half of all the aspirates. Subjects were divided into two groups: one of 16 patients awaiting thyroidectomy and the other of 51 patients in follow-up after surgery. RESULTS: The first group of patients had positive FNA biopsy (FNAB-Tg) in 14 out of the 18 studied CLNs with a range of 3.2-43 352 ng/ml, while FNAB-cytology indicated metastasis in only 8 out of the 14 CLNs with positive histology. A total of 65 CLNs were studied in the follow-up group. Lymphadenectomy was performed in 23 patients and 28 aspirated CLNs were removed. Histology confirmed the diagnosis of metastasis suggested by FNAB-Tg in 20 CLNs and of reactive lymphadenitis in the remaining 8 CLNs. FNAB-cytology was positive in only 11 CLNs. Sensitivity of FNAB-Tg was not affected by the studied FNAB-TgAb. CONCLUSIONS: The FNAB-Tg achieved a sensitivity of 100% in both groups. FNAB-Tg is an easy and inexpensive technique which proved to increase the diagnostic of cytology in the early diagnosis of papillary carcinoma recurrence to CLN even in the presence of serum TgAb.

Lemos MC, Carrilho F, Rodrigues F, Coutinho E, Gomes L, Carvalheiro M, Regateiro FJ. · Centro de Investigação em Ciências da Saúde (CICS), Faculdade de Ciências da Saúde, Universidade da Beira Interior, 6200-506 Covilhã, Portugal. · Clin Endocrinol (Oxf). · Pubmed #17547692 No free full text.

Abstract: OBJECTIVE: Xenobiotic-metabolizing enzymes are widely polymorphic and confer interindividual variation in the ability to detoxify carcinogens or to activate pro-carcinogens. A common polymorphism of cytochrome P450 2D6 (CYP2D6) results in lack of enzyme activity and has been associated with an altered susceptibility to several cancers. The aim of this study was to investigate the association between the CYP2D6 poor metaboliser genotype and the risk of papillary thyroid cancer (PTC). DESIGN: Retrospective case-control study. PATIENTS: One hundred and eighty-seven patients with PTC and 256 controls. MEASUREMENTS: Genotyping was performed by PCR and restriction enzyme analysis to detect the presence of the common CYP2D6*4 poor metaboliser allele. RESULTS: The frequency of individuals with the homozygous poor metaboliser genotype was lower in the patient group [1.6 vs. 5.5%, P = 0.037, OR = 0.28 (95% CI 0.09-0.93)]. The CYP2D6*4 allele frequency was also lower in the patient group [13.4 vs. 21.7%, P = 0.002, OR = 0.56 (95% CI 0.39-0.80)]. CONCLUSIONS: The results suggest that the poor metaboliser genotype is associated with a protective effect against PTC. This could be explained by a possible role of CYP2D6 on the metabolic activation of putative environmental chemical thyroid carcinogens or by linkage to another cancer-causing gene. Further research may allow the identification of metabolic risk factors and contribute towards understanding the molecular mechanisms involved in thyroid carcinogenesis.

Prazeres HJ, Rodrigues F, Figueiredo P, Naidenov P, Soares P, Bugalho MJ, Lacerda M, Campos B, Martins TC. · Molecular Pathology Laboratory, Regional Centre of Oncology of Coimbra, Portuguese Institute of Oncology, Coimbra, Portugal. · Clin Endocrinol (Oxf). · Pubmed #16712668 No free full text.

Abstract: OBJECTIVE: Medullary thyroid carcinoma (MTC) occurs both sporadically and in the context of autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN2) syndromes: MEN2A, MEN2B, and familial medullary thyroid carcinoma (FMTC), which are caused by activating germline mutations in the RET proto-oncogene. The aim of this study was to characterize the RET mutational spectrum in MEN2 families and apparently sporadic MTC (AS-MTC) cases originating from the central region of Portugal. SUBJECTS AND METHODS: We studied a total of 82 individuals (64 affected and 18 family members), comprising five MEN2 families (four MEN2A and one MEN2B), as well as 53 AS-MTC cases. RET germline mutations were screened using PCR-DNA sequencing, SSCP and RFLP. The haplotypes associated with recurrent mutations were determined by fragment analysis of microsatellite markers, and by RFLP, in the case of intragenic polymorphisms. RESULTS: Frequency of the Cys611Tyr (TGC-TAC) mutation was significantly increased in this region of Portugal, due to the fact that three apparently unrelated MEN2A/FMTC families, out of the five in which mutations were identified, harboured this specific mutation. Haplotype analysis revealed that a common haplotype was shared between two of these three families. We have also characterized a novel RET mutation, Arg886Trp, located in the tyrosine kinase domain, which was found in an AS-MTC case. CONCLUSIONS: There are regional specificities in the relative frequency of RET mutations, which are consistent with a cluster-like distribution of specific disease-causing mutations, as a result of the inheritance of a shared haplotype. These data, along with the finding of a novel RET mutation (Arg886Trp), have important implications towards facilitating and improving the molecular diagnosis of hereditary MTC on a regional basis.

Vilar H, Carrilho F, Borges F, Limbert E, Rodrigues F, Oliveira MJ, Castro JJ, Anonymous00115. · Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo. · Acta Med Port. · Pubmed #16684479 links to  free full text

Abstract: INTRODUCTION: The best diagnostic and treatment strategy for an approach to the nodular thyroid disease continues to be a controversial issue. OBJECTIVES: The aim of this study was to characterise medical practice in the diagnosis and treatment of nodular thyroid disease by endocrinologists and surgeons in Portugal in 2002. METHODS: A questionnaire based on that used by the European Thyroid Association and the American Thyroid Association was drawn up. The questionnaire, based on a well-defined index case, was circulated by the Portuguese Endocrinology Society to endocrinologists and surgeons: 42 year-old woman with solitary thyroid nodule measuring 2 x 3 cm, with no history of malfunction or painful symptoms. Each doctor was asked to reply as to the adopted diagnosis and therapy procedures for the index case. Eleven variations to the original case were proposed in order to evaluate the alterations for each variation. RESULTS: 1492 questionnaires were sent out, 163 to endocrinologists and 1329 to surgeons. A total of 104 were returned. The global response rate was 7%. The response rate for endocrinologists was 27% and 4.5% for surgeons. Of the 104 questionnaires returned, 42% were from endocrinologists and 58% from surgeons. Concerning tests prescribed, surgeons would use more tests than endocrinologists for the index case. The main differences in laboratory terms were the higher number of prescriptions for total T4 and T3 and thyroglobulin by surgeons and more prescriptions for AATPO by endocrinologists. The average number of tests was 4.6, 4.1 for endocrinologists and 5.1 for surgeons. Relative to imaging and cytology, 32% of doctors advocated a scintigraphy to diagnose the index case, with no significant differences between endocrinologists and surgeons. Ultrasonography was used by over 85% of respondents. 90% prescribed a cytology, 83% guided by palpation and 18% ultrasonography-guided. Concerning treatment, 33% of doctors advocated levothyroxin treatment; surgery was advocated by 16.3% of endocrinologists and 36.6% of surgeons. Meanwhile, the majority of doctors (68%) would opt for no treatment and simply maintain the patient under surveillance. CONCLUSIONS: There are important differences in the approach to nodular thyroid disease among the various doctors and specialists, which highlight the difficulty in achieving a diagnostic and therapeutic consensus.

Rodrigues F. · Serviço de Endocrinologia, Diabetes e Metabolismo, Instituto Português de Oncologia, Coimbra. · Acta Med Port. · Pubmed #14750284 No free full text.

Abstract: The author refers to the main clinical symptoms, diagnosis, treatment and evaluation of the post-partum thyroiditis. Researches can reveal different post-partum thyroiditis, considering the diagnosis and screening. Normally the classical presentation of post-partum thyroiditis includes a period of thyrotoxicosis, followed by hypothyroidism and finally thyroid functions in its normal levels. According to some statistic investigation, authors mention that after a period of normal and stable status, hypothyroidism can prevail as a long-term disease.

Paiva S, Bastos M, Gomes L, Durão A, Moreira A, Barros L, Rodrigues D, Ruas L, Ribeiro C, Rodrigues F, Paiva I, Fagulha A, Carrilho F, Geraldes E, Carvalheiro M, Ruas MM. · Serviço de Endocrinologia, Diabetes e Metabolismo, Hospitais da Universidade de Coimbra, Coimbra. · Acta Med Port. · Pubmed #12525025 No free full text.

Abstract: We review the pathophysiology, clinical features and therapy of acute thyroiditis. Four cases are reported stressing the role of fine needle aspiration for the diagnosis of this clinical entity.