Thyroid development and its disorders: genetics and molecular mechanisms.

Stazione Zoologica Anton Dohrn, University of Naples Federico II, 80121 Naples, Italy.
Endocrine Reviews (Impact Factor: 19.36). 11/2004; 25(5):722-46. DOI: 10.1210/er.2003-0028
Source: PubMed

ABSTRACT Thyroid gland organogenesis results in an organ the shape, size, and position of which are largely conserved among adult individuals of the same species, thus suggesting that genetic factors must be involved in controlling these parameters. In humans, the organogenesis of the thyroid gland is often disturbed, leading to a variety of conditions, such as agenesis, ectopy, and hypoplasia, which are collectively called thyroid dysgenesis (TD). The molecular mechanisms leading to TD are largely unknown. Studies in murine models and in a few patients with dysgenesis revealed that mutations in regulatory genes expressed in the developing thyroid are responsible for this condition, thus showing that TD can be a genetic and inheritable disease. These studies open the way to a novel working hypothesis on the molecular and genetic basis of this frequent human condition and render the thyroid an important model in the understanding of molecular mechanisms regulating the size, shape, and position of organs.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting the generalization of these findings to individuals of non-European ethnicities. The Electronic Medical Records and Genomics (eMERGE) Network is a collaboration across institutions with biobanks linked to electronic medical records (EMRs). The eMERGE Network uses EMR-derived phenotypes to perform GWAS in diverse populations for a variety of phenotypes. In this report, we identified serum TSH levels from 4,501 European American and 351 African American euthyroid individuals in the eMERGE Network with existing GWAS data. Tests of association were performed using linear regression and adjusted for age, sex, body mass index (BMI), and principal components, assuming an additive genetic model. Our results replicate the known association of PDE8B with serum TSH levels in European Americans (rs2046045 p = 1.85×10-17, β = 0.09). FOXE1 variants, associated with hypothyroidism, were not genome-wide significant (rs10759944: p = 1.08×10-6, β = -0.05). No SNPs reached genome-wide significance in African Americans. However, multiple known associations with TSH levels in European ancestry were nominally significant in African Americans, including PDE8B (rs2046045 p = 0.03, β = -0.09), VEGFA (rs11755845 p = 0.01, β = -0.13), and NFIA (rs334699 p = 1.50×10-3, β = -0.17). We found little evidence that SNPs previously associated with other thyroid-related disorders were associated with serum TSH levels in this study. These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic studies in more diverse populations.
    PLoS ONE 12/2014; 9(12):e111301. DOI:10.1371/journal.pone.0111301 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Thyroid carcinoma arising in an extrathyroid area is a rare entity. We report a case of anaplastic carcinoma in the submandibular region occurring in a 70-year-old woman. The location of the mass along with no evidence of primary tumor at the orthotopic thyroid gland posed a diagnostic dilemma: was this an ectopic thyroid carcinoma or rather a case of occult differentiated thyroid carcinoma metastasis that transformed to anaplastic carcinoma? Based on the histopathological findings we concluded that the tumor arised in ectopic thyroid tissue. Although the mass was completely resected, the patient died 10 months after diagnosis due to pulmonary metastases. Conclusively, the possibility of ectopic thyroid tissue, with or without disease, should be considered in cases of a mass in the submandibular region. Copyright © 2015. Published by Elsevier Ltd.
    02/2015; 8. DOI:10.1016/j.ijscr.2015.02.015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Thyroglossal duct cyst (TDC) is a developmental anomaly that usually appears in early childhood. The common presentation is midline swelling of the neck, which moves with both tongue protrusion and deglutition. Diagnosis is usually clinical and radiological. Fine needle aspiration cytology (FNAC) can be used as a tool for the exclusion of malignancy in adult patients. In some cases thyroid scan is done to rule out the presence or absence of the normal thyroid gland. A complete work-up is mandatory before cyst removal given that it contains only thyroid tissue. We report the case of a 32-year-old woman with only thyroid tissue in thyroglossal duct cyst.
    Malaysian Family Physician 11/2014; 9(2):61-63.