TSHR and goiter: In some patients, the initial manifestation of the constitutively active TSHR mutation is hyperthyroidism without any increase in the gland mass (4, 6, 8, 11, 12, 13, 14, 15), whereas in others (7, 10, 16, 17, 18, 19), goiter development may precede the onset of the clinical findings of hyperthyroidism.