The molecular basis of hereditary non-autoimmune hyperthyroidism was elucidated by detecting activating germline mutations in the TSH receptor in the family reported by Thomas et al. (51). Gain-of-function mutations are by definition dominant, and alteration of one allele is thus sufficient for generating the phenotype. Interestingly, the onset of hyperthyroidism may vary in carriers of the same mutation in a given kindred. Hence, other factors, for example genetic background and/or iodine intake, appear to modulate the phenotypic expression (97, 99, 100).