ABSTRACT
Introducción: El gen FOXE1 (Forkhead box E1) codifica para un factor de transcripción involucrado en la morfogénesis tiroidea. El cáncer papilar de tiroides (CPT) se ha asociado con polimorfismos (SNP) de FOXE1 rs1867277 y rs965513 en población asiática y europea. Nuestro objetivo fue investigar la frecuencia y asociación de SNP rs1867277 y rs965513 con CPT y el riesgo de recurrencia de CPT en sujetos chilenos. Métodos: Se reclutaron sujetos con y sin CPT, se describieron sus características epidemiológicas y la forma de presentación clínica (AJCC VIII y MINSAL 2013). Se aisló ADN de leucocitos periféricos y evaluó ambos SNP mediante PCR-HRM y secuencia. Se compararon las frecuencias alélicas y genotípicas entre casos CPT y controles, y entre pacientes CPT de distintos riesgos de recurrencia. Se compararon frecuencia y se estimó el riesgo con test de Fisher y cálculo de odds-ratio (OR). Resultados: De los 184 sujetos, 156 (85%) eran mujeres, edad 39,3±12,3 años; 90 con CPT y 94 sin CPT 26 (28,9%) pacientes eran de riesgo muy bajo, 45 (50%) bajo, 16 (17,8%) intermedio y 3 (3,3%) alto según MINSAL 2013. En relación a la frecuencia de alelo menor (MAF) calculada en sujetos control y CPT, fue 31,7% y 24,5% (SNP rs965513), y 36,7% y 30,1% 8 (rs1867277), respectivamente (p NS). Tampoco fueron diferentes las MAF calculados y comparados entre pacientes con CPT de riesgo bajo e intermedio/alto. Sin embargo, la combinación de los genotipos rs1867277GG y rs965513AA se asoció a mayor riesgo de CPT. Conclusiones: En pacientes chilenos, se describe una frecuencia MAF de los SNP rs1867277 y rs965513 cercana a un 30%, las cuales no se asocian a CPT ni riesgo de recurrencia, sin embargo, sujetos con una combinación genotípica particular podrían tener mayor riesgo de CPT.
FOXE1 gene (Forkhead E1 box) codes for a transcription factor involved in thyroid morphogenesis. Papillary thyroid cancer (PTC) has been associated with FOXE1 polymorphisms (SNPs) rs1867277 and rs965513 in Asian and European population. Our aim was to investigate the frequency and the association of SNPs rs1867277 and rs965513 with PTC and the risk of recurrence of PTC in Chilean subjects. Methods: We recruited subjects with and without PTC. In those with PTC, their epidemiological characteristics and clinical features presentation are described according to AJCC VIII and MINSAL 2013 scales. Peripheral leukocyte DNA was isolated and both SNPs were evaluated using PCR-HRM and sequencing. Allelic and genotypic frequencies were compared between PTC cases and controls, and between PTC patients with different recurrence risks. Results: Of the 184 subjects, 156 (85%) were women, age 39.3 ± 12.3 years; 94 (51%) without PTC and 90 with PTC (49%): 26 (28.9%) patients had very low, 45 (50%) low, 16 (17.8%) intermediate and 3 (3.3%) high risk of recurence according to MINSAL 2013. Regarding the minor allele frequency (MAF) calculated on control and PTC subjects, was 31.7% and 24.5% (SNP rs965513), and 36.7% and 30.1% (rs1867277), respectively (p NS). In patients with PTC, MAFs were not different between patients with low and intermediate/high risk PTC. However, the combination of rs1867277GG and rs965513AA genotypes were associated with an increased risk of PTC. Conclusions: In Chilean patients, the MAF frequency of SNPs rs1867277 and rs965513 is near 30%, and they are are not associated with PTC or its risk of recurrence. However, subjects with a particular genotypic combination may have an increased risk of PTC.
Subject(s)
Humans , Male , Female , Adult , Thyroid Neoplasms/epidemiology , Polymorphism, Single Nucleotide , Thyroid Cancer, Papillary/epidemiology , Polymorphism, Genetic , Thyroid Neoplasms/genetics , Biomarkers, Tumor/genetics , Chile/epidemiology , Polymerase Chain Reaction , Risk Assessment , Genetic Predisposition to Disease , Forkhead Transcription Factors/genetics , Thyroid Cancer, Papillary/genetics , Gene Frequency , Genotype , Neoplasm Recurrence, Local/epidemiologyABSTRACT
Fine needle thyroid biopsy is a safe and cost effective diagnostic method for thyroid nodules. Its use has reduced the number of unnecessary thyroidectomies, performed to excise thyroid nodules. Since it is an invasive diagnostic method, its indications should be specified according to ultrasonographic criteria. The massive use of fine needle biopsies increase the number of unsatisfactory samples and indeterminate results. Although it is possible to obtain biopsies from exceedingly small nodules, the clinical significance of these small carcinomas is not yet defined. Ultrasonography, mmunohistochemical markers such as citokeratin, 19, HBME-1, galectin 3) and genetic determinants such as oncogene RET/PTC, 1, 2, 3, RAS oncogene and BRAF V600E mutation along with clinical follow up, will readily identify those patients that are benefited with fine needle biopsies.
Subject(s)
Humans , Biopsy, Fine-Needle/methods , Thyroid Nodule/pathology , Thyroid Gland/pathology , Thyroid Gland , Biomarkers , Thyroid Nodule/blood , Thyroid Nodule , Ultrasonography, InterventionalABSTRACT
Cushing´s disease results from overproduction of glucocorticoids due to excessive corticotropin secretion by a tumor of the pituitary gland´s corticotroph cells and is the cause of 80 percent of all forms of ACTH dependent hypercortisolism. Both its diagnosis and treatment represent a challenge and transsphenoidal surgical resection is currently the treatment of choice.The success of the surgery depends on the tumor size and on the experience of the center which performs the intervention, achieving remission of the disease in around 70 percent of microadenomas and 15 percent of tumors larger than 1 cm. Among patients who achieved control of hypercortisolism, there is a relapse rate that fluctuates between 5 and 25 percent. The clash of these cases represents an even greater challenge than the previous one, especially with regard to the treatment. We report the case of a 30 years old woman with Cushing's disease, operated on and cured through a transsphenoidal resection, who relapsed 10 years after surgery.
Subject(s)
Humans , Female , Adult , ACTH-Secreting Pituitary Adenoma/surgery , Adenoma/surgery , Pituitary Neoplasms/surgery , Adrenalectomy , Sphenoid Bone/surgery , Recurrence , Reoperation , Nelson SyndromeABSTRACT
Thyroid hormone resistance syndrome is a genetic disease determined by a mutation that modifies the configuration of the beta thyroid hormone receptor, affecting its T3 binding capacity. Increased T3 and T4, determined by a compensatory TSH elevation secondary to pituitary resistance, allows an euthyroid functional state in most of the cases. The coexistence of pregnancy and thyroid hormone resistance is uncommon. Therefore, the optimal diagnosis and treatment strategy has not been determined. We report a 32 years old woman with thyroid hormone resistance, that became pregnant. During her pregnancy, she wassupplemented with levothyroxine in doses of 50 to 60 ug/day and remained euthyroid. Fetal development and growth were normal.