Minimally Invasive Follicular Thyroid Carcinoma Developed in Dyshormonogenetic Multinodular Goiter Due to Thyroid Peroxidase Gene Mutation
ABSTRACT The occurrence of thyroid carcinoma in patients with congenital hypothyroidism (CH) caused by dyshormonogenesis is very rare, and has only been reported in one patient harboring mutations in the thyroid peroxidase (TPO) gene.
We report on a 29-year follow-up of two consanguineous siblings with CH due to total iodide organification defect who also had sensorineural hearing loss. Molecular analysis revealed a novel biallelic mutation of the TPO gene in which phenylalanine substitutes serine at codon 292 (c.875C>T, p.S292F) in exon 8. Despite early initiation, adequate doses of levothyroxine treatment and consequently normal thyrotropin (TSH) levels, the proposita developed a huge multinodular goiter (MNG) and underwent total thyroidectomy due to tracheal compression. Pathological examination revealed a unifocal follicular thyroid carcinoma without vascular invasion in the left lobe of the thyroid gland.
Our finding of follicular thyroid carcinoma arising from dyshormonogenetic MNG in a patient without elevated serum TSH levels indicates that genetic and environmental factors other than TSH level might be involved in the development of thyroid carcinoma in dyshormonogenetic MNG.
Despite the rare occurrence of thyroid carcinoma in dyshormonogenetic MNG, we recommend long-term follow-up and regular neck ultrasound imaging to prevent delayed diagnosis of thyroid carcinoma.
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ABSTRACT: Short title: Genetic variants at TPO and thyroid cancer risk Thyroid cancer risk involves the interaction of genetic and environmental factors. The thyroperoxidase (TPO) has a key role in the iodine metabolism, being essential for the thyroid function. Mutations in the TPO gene are common in congenital hypothyroidism, and there are also signs of the implication of TPO in thyroid cancer. We performed a case-control association study of genetic variants in TPO and differentiated thyroid carcinoma (DTC) in 1586 DTC patients and 1769 controls including two European populations (Italy: 1190 DTC and 1290 controls; Spain: 396 DTC and 479 controls). Multivariate logistic regression analyses were performed separately for each population and each SNP. From the three studied polymorphisms significant associations were detected between DTC and rs2048722 and rs732609 in both populations (P<0.05). In the Italian population both SNPs showed a negative association (rs2048722, OR=0.79, 95% CI=0.63-1.00, P=0.045; rs732609, OR=0.72, 95% CI=0.55-0.94, P=0.016), while in the Spanish population these SNPs showed a positive association (rs2048722, OR=1.39, 95% CI=1.03-1.89, P=0.033; rs732609, OR=1.41, 95% CI=1.06-1.87, P=0.018). The corresponding associations for papillary or follicular thyroid cancer were similar to those for all DTC, within population. No association was detected for the third TPO polymorphism in the Italian and the Spanish populations. Our results, for the first time, point to TPO as a gene involved in the risk of DTC, and suggest the importance of interactions between TPO variants and other unidentified population-specific factors in determining thyroid cancer risk. © 2013 Wiley Periodicals, Inc.International Journal of Cancer 06/2013; DOI:10.1002/ijc.28317
Article: Thyroid nodules.[Show abstract] [Hide abstract]
ABSTRACT: According to the literature, thyroid nodules (TNs) are quite rare in the first two decades of life and are predominantly non-cancerous, although cancerous TNs are more common in the first two decades of life than in adults. Therefore, it is important for clinicians to distinguish benign from malignant lesions preoperatively because the latter require a total thyroidectomy with or without neck lymph node dissection. A careful work-up and a fine-needle aspiration biopsy (FNAB) are mandatory to improve the preoperative diagnosis. High-resolution thyroid ultrasound and real-time elastosonography are adjuvant presurgical tools in selecting patients for surgery, particularly those with indeterminate or non-diagnostic cytology. Elevated thyroid-stimulating hormone (TSH) level in a patient with a thyroid nodule is a new laboratory predictor of thyroid cancer risk. The majority of thyroid carcinomas derive from the follicular cell, whereas medullary thyroid carcinoma (MTC) derives from calcitonin-producing cells. Patients with MTC are screened for germ-line RET mutations to detect carriers and identify family members for prophylactic or therapeutic thyroidectomy.03/2014; 28(2):245-277. DOI:10.1016/j.beem.2013.08.007
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ABSTRACT: Background: Defects in the thyroid peroxidase (TPO) gene have been associated with goitrous congenital hypothyroidism (CH). Case Report: In this study, we report 3 siblings possessing a homozygous mutation, c.1159G>A, but exhibiting different clinical phenotypes in a Malaysian-Malay family. The index patient was diagnosed with CH during a routine neonatal screening but the other 2 siblings appeared to be asymptomatic until the ages of 19 and 12.5, respectively, when they started to develop goiter. Results and Conclusion: The mutation was predicted to interrupt the correct splicing of pre-mRNA and also lead to structural alterations in the functional sites of the mutant TPO. The current results suggest the association of goiter development with a homozygous c.1159G>A mutation, but the CH in the index patient could be triggered by other genetic and epigenetic factors distinct from the c.1159G>A mutation. © 2014 S. Karger AG, Basel.Hormone Research in Paediatrics 04/2014; 81(5). DOI:10.1159/000359922