Childhood hypothyroidism causes delayed endochondral ossification, impaired bone mineralization and growth retardation. In contrast, thyrotoxicosis induces accelerated growth, advanced bone age and increased mineralization, but leads to premature closure of the epiphyseal growth plates and short stature. In severe cases accelerated intramembranous ossification results in early closure of the skull sutures and craniosynostosis. In adults, thyrotoxicosis causes increased bone turnover, accelerated bone loss and a greater than 3-fold increase in osteoporotic fracture. Thyroid hormone (T3) binds to nuclear T3 receptors (TRα and TRβ), which act as hormone-dependent transcription factors that regulate target gene expression in response to T3. Concentrations of circulating thyroid hormones are maintained in a narrow physiological range by the hypothalamic-pituitary-thyroid (HPT) axis, in which TRβ controls activity of a negative feedback loop. The TRα and TRβ receptors are expressed in temporo-spatial specific patterns during development and in different ratios in individual tissues.