Endocrine Abstracts

Thyroid hemiagenesis (TH) is a rare inborn anomaly presenting as failure of the development of one thyroid lobe. Recent research on the molecular background underlying thyroid dysgenesis have mainly focused on patients with congenital hypothyroidism; in contrast, subjects presenting TH were only sporadically involved. Changes in transcription factor genes, including TTF1, TTF2 and PAX8, which play an important role in thyroid embryogenesis, have been postulated. However, causative mutations that correlate with the phenotype of TH were found in only a few cases. The mechanism which governs the process of symmetric bilobation of the thyroid is still unknown. In addition, whether the same factors are responsible for development of TH and other forms of thyroid dysgenesis is still to be elucidated.

Recent experimental study has identified a novel role of Sonic Hedgehog protein (SHH) in indirect control of thyroid development. In shh knock-out mice, the thyroid develops as unilobate structure, while the process of differentiation in thyrocytes is undisturbed. We assume that dysfunction of human ortholog SHH could have similar phenotypical consequences and determine TH. To date, screening of SHH gene in patients with TH has not yet been performed. The aim of this study is to search for SHH gene mutations in a large cohort of subjects diagnosed with TH.

The studied group consists of 40 patients presenting TH, including 4 familial cases. The condition was diagnosed during medically indicated or performed as screening examination, thyroid ultrasonography. Complete unilateral absence of functional thyroid tissue was confirmed by thyroid scintiscan. Three exons of SHH gene were amplified using standard PCR conditions and were subsequently subjected to bidirectional sequencing. The preliminary results of the SHH analysis in 5 out of 40 patients did not reveal any abnormalities in coding sequence. Therefore a screening of the entire, representative cohort of patients needs to be conducted to provide more comprehensive knowledge in regards to the key factors in pathogenesis of TH in humans.