Evolution, child development and the thyroid: a phylogenetic and ontogenetic introduction to normal thyroid function.

Congenital thyroid diseases can be explained in the context of the individual ontogenetic development; however, they can also be mirrored in the perspective of the phylogenetic evolution of the thyroid hormone system. The unique feature of the system, e.g., the generation of iodinated tyrosine derivatives by specialized enzymes that are frequently disrupted by mutations in congenital hypothyroidism, occurred very early in plant evolution and can still be demonstrated in algae today. All other components like the thyroid hormone receptors (TRs), the transporter molecules, the regulation by thyroid-stimulating hormone and thyrotropin-releasing hormone--and their respective receptors - as well as the structures that produce thyroid hormone with the human thyroid as the most recent development evolved in the animal kingdom. Already in the earliest animal species like Ciona intestinalis, specialized cells in the so-called endostyle not only iodinate tyrosine residues, but also secrete thyroid hormone itself, which activates TRs in target cells. During the following process of growing complexity of the thyroid system in higher species, pre-existing molecules and functions accumulated new variations, which enabled their assembly in new functional frames of the system and its central regulation. A deeper view into the range of evolutional variabilities and also flexibilities within the thyroid axis will most likely increase our understanding of the molecular defects and their potential treatment in the current human thyroid system.