Disorders of thyroid morphogenesis.

Developmental anomalies of the thyroid gland, defined as thyroid dysgenesis, underlie the majority of cases of congenital hypothyroidism. Thyroid dysgenesis is predominantly a sporadic disorder although a reported familial enrichment, variation of incidence by ethnicity and the monogenic defects associated mainly with athyreosis or orthotopic thyroid hypoplasia, suggest a genetic contribution. Of note, the most common developmental anomaly, thyroid ectopy, remains unexplained. Ectopy may result from multiple genetic or epigenetic variants in the germline and/or at the somatic level. This review provides a brief overview of the monogenic defects in candidate genes that have been identified so far and of the syndromes which are known to be associated with thyroid dysgenesis.

Thyroid cancer in lingual thyroid and thyroglossal duct cyst / Cáncer de tiroides en tiroides lingual y quiste del conducto tirogloso

Ectopy is the most common embryogenetic defect of the thyroid gland, representing between 48 and 61% of all thyroid dysgeneses. Persistence of thyroid tissue in the context of a thyroglossal duct remnant and lingual thyroid tissue are the most common defects. Although most cases of ectopic thyroid are asymptomatic, any disease affecting the thyroid may potentially involve the ectopic tissue, including malignancies. The prevalence of differentiated thyroid carcinoma in lingual thyroid and thyroglossal duct cyst is around 1% of patients affected with the above thyroid ectopies. We here review the current literature concerning primary thyroid carcinomas originating from thyroid tissue on thyroglossal duct cysts and lingual thyroid (AU)

La ectopia es el defecto embriogenético más frecuente de la glándula tiroides, responsable de entre el 48 y el 61% de todas las disgenesias tiroideas. La persistencia de tejido tiroideo en el contexto de un resto de conducto tirogloso y el tejido tiroideo lingual son los defectos más comunes. Aunque la mayoría de los casos de tiroides ectópico son asintomáticos, cualquier proceso que afecte al tiroides puede afectar potencialmente al tejido ectópico, incluidos los tumores malignos. La prevalencia de carcinoma tiroideo diferenciado en tiroides lingual y quiste del conducto tirogloso es de alrededor del 1% en los pacientes con las ectopias tiroideas antes citadas. Revisamos aquí la bibliografía actual sobre los carcinomas tiroideos primarios originados a partir de tejido tiroideo de quistes del conducto tirogloso y tiroides lingual (AU)

Mechanisms of thyroid development and dysgenesis: an analysis based on developmental stages and concurrent embryonic anatomy.

Thyroid dysgenesis is the most common cause of congenital hypothyroidism that affects 1 in 3000 newborns. Although a number of pathogenetic mutations in thyroid developmental genes have been identified, the molecular mechanism of disease is unknown in most cases. This chapter summarizes the current knowledge of normal thyroid development and puts the different developmental stages in perspective, from the time of foregut endoderm patterning to the final shaping of pharyngeal anatomy, for understanding how specific malformations may arise. At the cellular level, we will also discuss fate determination of follicular and C-cell progenitors and their subsequent embryonic growth, migration, and differentiation as the different thyroid primordia evolve and merge to establish the final size and shape of the gland.

Surgical anatomy of the thyroid and parathyroid glands.

This article describes the anatomy and embryology of the thyroid and parathyroid glands and the recurrent laryngeal nerve, discussing how the anatomy affects function and dysfunction of the glands.

Agenesis of isthmus of thyroid gland, its embryological basis and clinical significance--a case report.

A wide range of morphological varieties and developmental anomalies of the thyroid gland have been reported in literature such as hypoplasia, ectopy, hemi agenesis, and agenesis. Out of these the incidence of agenesis of the isthmus of thyroid gland is rare and very few cases have been reported. In the present case report a male cadaver was found with agenesis of isthmus of thyroid gland with pyramidal lobe and levator glandulae thyroidae arising from right lobe.

Clinical evaluation of isolated nonvisualized fetal gallbladder.

OBJECTIVE: Isolated nonvisualized fetal gallbladder (INVFGB) is relatively rare. In most cases, the gallbladder will eventually be detected. In some cases however, INVFGB may be associated with serious abnormalities, cystic fibrosis (CF), aneuploidy, and agenesis of the gall bladder. We describe a clinical evaluation of prenatally diagnosed INVFGB. METHODS: Cases of nonvisualized gallbladder were first evaluated by serial scans. Cases with no additional malformations were designated as INVFGB, and were further evaluated by mutation analysis for CF, and amniocentesis for karyotype and microvillar membrane enzymes (MME). RESULTS: A total of 22 cases of nonvisualized gallbladder were detected. Of these, 2 had additional malformations, and 3 were excluded because of incomplete evaluation. Of the remaining 17 cases, 3 (17.6%) had adverse outcomes: 1 case of CF, 1 case of 47,XXX, and 1 case of multiple congenital anomalies detected only postnatally. Abnormal levels of MMEs were detected in 3 cases, 1 of which was diagnosed with CF. In 2 cases, the gallbladder was not detected even after birth, but development is normal. CONCLUSION: Evaluation of INVFGB should include genetic counselling, amniocentesis for karyotype and MME analysis, CFTR mutation analysis and repeated ultrasound scans.

The 22q11 deletion syndrome candidate gene Tbx1 determines thyroid size and positioning.

Thyroid dysgenesis is the major cause of congenital hypothyroidism in humans. The underlying molecular mechanism is in most cases unknown, but the frequent co-incidence of cardiac anomalies suggests that the thyroid morphogenetic process may depend on proper cardiovascular development. The T-box transcription factor TBX1, which is the most probable gene for the 22q11 deletion syndrome (22q11DS/DiGeorge syndrome/velo-cardio-facial syndrome), has emerged as a central player in the coordinated formation of organs and tissues derived from the pharyngeal apparatus and the adjacent secondary heart field from which the cardiac outflow tract derives. Here, we show that Tbx1 impacts greatly on the developing thyroid gland, although it cannot be detected in the thyroid primordium at any embryonic stage. Specifically, in Tbx1-/- mice, the downward translocation of Titf1/Nkx2.1-expressing thyroid progenitor cells is much delayed. In late mutant embryos, the thyroid fails to form symmetric lobes but persists as a single mass approximately one-fourth of the normal size. The hypoplastic gland mostly attains a unilateral position resembling thyroid hemiagenesis. The data further suggest that failure of the thyroid primordium to re-establish contact with the aortic sac is a key abnormality preventing normal growth of the midline anlage along the third pharyngeal arch arteries. In normal development, this interaction may be facilitated by Tbx1-expressing mesenchyme filling the gap between the pharyngeal endoderm and the detached thyroid primordium. The findings indicate that Tbx1 regulates intermediate steps of thyroid development by a non-cell-autonomous mechanism. Thyroid dysgenesis related to Tbx1 inactivation may explain an overrepresentation of hypothyroidism occurring in patients with the 22q11DS.