Thyroid Hemiagenesis in a Euthyroid man

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.

While performing a systematic ultrasound study of the thyroid gland volume for the evaluation of iodine deficiency in 2845 normal Belgian school children, we found an absence of the left lobe in 6 children (4 girls and 2 boys). There was no association with other thyroid malformations or dysfunction. This first systematic ultrasound evaluation of thyroid hemiagenesis in normal children established a prevalence of thyroid hemiagenesis of 0.2% and confirmed the female predominance and higher incidence of agenesis of the left lobe.

Congenital hypothyroidism (CH) is most frequently caused by thyroid developmental abnormalities and it has recently been seen to have a familial component. The aim of this study was to investigate whether thyroid developmental abnormalities exist in first degree relatives of CH children with thyroid dysgenesis, an anomaly which, when present, is sometimes asymptomatic. Thyroid ultrasonography and function were evaluated among first degree relatives (n = 241) of 84 isolated CH children with thyroid dysgenesis. The results were compared with those of an unselected control population (n = 217). In 19 individuals (7.9% of cases) belonging to 18 families (21.4%), 21 cases of thyroid developmental abnormalities were detected, whereas only 2 subjects (0.9%) were affected in controls (P < 0.001). These 21 thyroid developmental abnormalities included thyroglossal duct cysts (n = 14), additional thyroid tissue with presence of a pyramidal lobe (n = 3), thyroid hemiagenesis (n = 3), and ectopic thyroid tissue (n = 1). All of these subjects showed normal thyroid function and belonged to nuclear families of CH children with athyreosis (n = 8), ectopic thyroid tissue (n = 9), or hemiagenesis (n = 1). A segregation analysis led to the conclusion that thyroid developmental abnormalities are compatible with an autosomal dominant mode of inheritance with a low penetrance estimated at 21% for asymptomatic thyroid developmental abnormalities and a probability of less than 7% of developing CH for a carrier of the susceptibility allele. In conclusion, these observations support the hypothesis of a common genetic component of the disorder with heterogeneous phenotypes.