■Graves orbitopathy (GO) is part of an autoimmune systemic disease, which is composed of hyperthyroidism, orbitopathy, dermopathy, and acropachy.

■Stimulating antibodies against the TSH receptor are directly involved in the pathogenesis of hyperthyroidism; their role is less clear with regard to the other manifestations. However, high TSH receptor antibody concentrations are associated with a higher prevalence and more severe course of extra-thyroidal symptoms.

■Main symptoms of GO are orbital soft tissue inflammation, proptosis due to increase (mainly through adipogenesis) of orbital volume and impairment of ocular and lid motility due to inflammation, and scarring of chiefly the levator, inferior, and medial rectus muscles. In severe cases, vision-threatening compression of the optic nerve can occur.

■Inflammatory phase is self-limiting but may relapse, in most cases, owing to insu ciently controlled thyroid disease, but also indepen-

dently. To restrict damage, anti-inflammatory therapy (e.g., systemic steroids or orbital radiotherapy) is indicated in moderate to severe active disease stages.

■Patients with sight-threatening GO should be treated with i.v. steroids as first-line treatment; if the response is poor after 1 to 2 weeks, they should be immediately referred for surgical decompression.

■In patients with mild GO, local measures and an expectant strategy are usually su cient, but treat-

ment may be justified if quality of life is reduced significantly.

■ In the inactive disease stages, proptosis can be alleviated through orbital decompression; restricted ocular and lid motility can be improved by muscle recession and appearance can be improved by blepharoplasty of lower and upper lids.

■Important for the successful treatment of GO is continuous and stable sustenance of euthyroidism and smoking cessation.

16.1Graves Orbitopathy (GO): Pathogenesis and Clinical Signs

16.1.1Graves Orbitopathy is Part of a Systemic Disease: Graves Disease (GD)

Graves orbitopathy is a part of a systemic autoimmune disease. The full clinical picture is composed of hyperthyroidism, orbitopathy, pretibial myxedema, and acropachy. The full symptom complex is very rare – Myxedema and acropachy occur only in 3–5%. With a prevalence of 0.5–2%, GD is a relatively common autoimmune disease [1]. In nearly all patients, antibodies against the TSH

receptor (TSHR) can be measured in the serum as indicators of the failed immune system. Those antibodies stimulate the TSHR in an uncontrolled manner and are directly responsible for the development of hyperthyroidism. Whether the TSHR alone or in combination with other antigens is responsible for the extra-thyroidal aspects of GD is of considerable research interest. Symptoms of GO are caused by inflammation in the connective tissue of the orbit, an increase of intraorbital volume due to enhanced adipogenesis, overproduction of glycosaminoglycanes (GAG), and fibrosis of the extraocular muscles [2]. Orbital fibroblasts are pivotal to these pathologic processes. Cultured orbital fibroblasts can be