Abstract
Gravesʼ orbitopathy is an autoimmune disease of the orbit that most frequently occurs
with Gravesʼ hyperthyroidism. The occurrence of autoantibodies directed against the
TSH receptor (TRAb) is of central importance for the diagnosis and pathogenesis. These
autoantibodies are mostly stimulating, and induce uncontrolled hyperthyroidism and
tissue remodelling in the orbit and more or less pronounced inflammation. Consequently,
patients suffer to a variable extent from periocular swelling, exophthalmos, and fibrosis
of the eye muscles and thus restrictive motility impairment with double vision. In
recent decades, therapeutic approaches have mainly comprised immunosuppressive treatments
and antithyroid drug therapy for hyperthyroidism to inhibit thyroid hormone production.
With the recognition that TRAb also activates an important growth factor receptor,
IGF1R (insulin-like growth factor 1 receptor), biological agents have been developed.
Teprotumumab (an inhibitory IGF1R
antibody) has already been approved in the USA and the therapeutic effects are enormous,
especially with regard to the reduction of exophthalmos. Side effects are to be considered,
especially hyperglycaemia and hearing loss. It is not yet clear whether the autoimmune
reaction (development of the TRAb/attraction of immunocompetent cells) is also influenced
by anti-IGF1R inhibiting agents. Recurrences after therapy show that the inhibition
of antibody development must be included in the therapeutic concept, especially in
severe cases.
Key words
Gravesʼ orbitopathy - pathogenesis - risk factors - guidelines - targeted therapies
- clinical classification
