Constitutive TSH receptor activation as a hallmark of thyroid autonomy

Since its cloning more than 30 years ago, the thyrotropin receptor (TSHR) has emerged as a pivotal player in thyroid physiology and pathophysiology. In particular, hyperthyroidism due to autoimmune disease or thyroid autonomy is linked with TSHR activation via autoantibodies or mutations respectively. This review summarises clinical aspects of constitutive TSH receptor activation by naturally occurring somatic or germline TSHR mutations resulting in TSH-independent thyroid function and cell proliferation.