Current Knowledge on Graves' Orbitopathy

Abstract

(1) Background: Graves' orbitopathy (GO) is an autoimmune inflammation of the orbital tissues and the most common extra-thyroid symptom of Graves' disease (GD). Mild cases of GO are often misdiagnosed, which prolongs the diagnostic and therapeutic process, leading to exacerbation of the disease. A severe course of GO may cause permanent vision loss. (2) Methods: The article presents an analysis of GO-its etiopathogenesis, diagnostics, current treatment and potential future therapeutic options based on a review of the currently available literature of the subject. (3) Results: Current treatment of the active GO consists predominantly in intravenous glucocorticoids (GCs) administration in combination with orbital radiotherapy. The growing knowledge on the pathogenesis of the disease has contributed to multiple trials of the use of immunosuppressive drugs and monoclonal antibodies which may be potentially effective in the treatment of GO. Immunosuppressive treatment is not effective in patients in whom a chronic inflammatory process has caused fibrous changes in the orbits. In such cases surgical treatment is performed-including orbital decompression, adipose tissue removal, oculomotor muscle surgery, eyelid alignment and blepharoplasty. (4) Conclusions: Management of GO is difficult and requires interdisciplinary cooperation in endocrinology; ophthalmology, radiation oncology and surgery. The possibilities of undertaking a reliable assessment and comparison of the efficacy and safety of the therapeutic strategies are limited due to the heterogeneity of the available studies conducted mostly on small group of patients, with no comparison with classic systemic steroid therapy. The registration by FDA of Teprotumumab, an IGF1-R antagonist, in January 2020 may be a milestone in future management of active GO. However, many clinical questions require to be investigated first.

Keywords: Graves’ disease; Graves’ orbitopathy; clinical activity score; glucocorticoids; immunosuppressive treatment; radiotherapy.

Figure 1

Signaling cascade involved in Graves’ orbitopathy (GO) pathogenesis.IGF1-R: insulin-like growth factor 1 receptor, TSH-R: thyrotropin receptor, TRAb: Thyrotropin receptor antibodies, HA: Hyaluronic Acid, GAG: glycosaminoglycans, IL-1β: interleukin-1β, IL-2: interleukin-2, IL-6: interleukin-6, TNF-α: tumour necrosis factor alpha, IFN-y: interferon gamma.

Figure 2

Presents a clinical picture of a 55 years old female admitted to our clinic with active GO (Graves’ Orbitopathy). Medical history of 131-I treatment of hyperthyroidism in the course of GD (Graves’ Disease) two years before.

Figure 3

Orbital magnetic resonance imaging (MRI) of a female patient, whose clinical picture was shown on Figure 2. The examination was performed without intravenous administration of paramagnetic. We can observe significantly widened outlines of the straight muscles, the outlines of the extraocular muscles with increased signal intensity in T2-dependent images, ocular adipose tissue with features of edema. Also, edema present in the tissues of both eyelids.

Figure 4

Transverse magnetic resonance imaging (MRI) image of the orbits of a 60 years old female patient with active GO, in whom the orbital changes were asymmetrical—the left orbit was more involved. The examination was performed in T1 and T2 sequences. The left inferior rectus muscle is significantly edematous, the left medial and lateral rectus muscle and the right inferior rectus muscle are also slightly edematous— the picture indicates active inflammatory orbital changes in the course of the underlying disease. Moreover, there is exophthalmos of the left eyeball and a slightly increased amount of the fluid in the left optic nerve sheath compared to the right side. There are no deviations of the lacrimal glands or the extra-conial adipose tissue.

Figure 5

The management of GO (Graves’ Orbitopathy) depending on the disease severity and activity according to EUGOGO (The European Group on Graves’ Orbitopathy) guidelines [53]. MRI: magnetic resonance imaging, GCS: Glucocorticoids.