Thyroid-associated orbitopathy

Last revised by Rohit Sharma on 12 May 2024

Thyroid-associated orbitopathy, also known as thyroid-associated ophthalmopathy or thyroid eye disease, is the most common cause of proptosis in adults and is most frequently associated with Graves disease. On imaging, it is characterized by bilateral and symmetrical enlargement of the extraocular muscle bellies. The typical distribution is inferior rectus muscle most commonly affected, followed by medial rectus, then superior rectus, with sparing of their tendinous insertions.

The demographics of thyroid-associated orbitopathy reflects that of patients with thyroid disease and is, therefore, more frequently seen in women. Although Graves disease is the most common cause, Hashimoto thyroiditis has also been implicated 16. It may precede the onset of abnormal thyroid function, occur concurrently, or commence following its onset.

Clinical features include:

  • lid retraction and lagophthalmos

  • proptosis/exophthalmos, with resultant periorbital edema, chemosis and corneal dryness/ulceration

  • ophthalmoplegia with diplopia 1

  • optic nerve compression, potentially leading to blindness

  • hypoglobus: uncommon

While the aforementioned clinical features are usually bilateral and symmetric, approximately 10% of cases may be unilateral, and approximately 30% of bilateral cases may be markedly asymmetric 17.

Thyroid-associated orbitopathy is characterized by enlargement of the extraocular muscles as well as an increase in the orbital fat volume 1. While the exact mechanism is unknown, antibodies to thyroid-stimulating hormone (TSH) receptor appear to cross-react with antigens in the orbit resulting in infiltration by activated T lymphocytes 3, with subsequent release of inflammatory mediators.

The muscles are infiltrated with inflammatory cells (lymphocytes, macrophages, plasma cells, and eosinophils), and increased mucopolysaccharide deposition. In long-standing cases, increased collagen deposition leads to fibrosis 1.

Involvement of the extraocular muscles in decreasing order of frequency:

The order is captured by the mnemonic I'M SLOw, with the exception of the levator palpebrae superioris muscle 11.

An increase in orbital fat volume is a result of venous congestion from the compression of the superior ophthalmic vein by the enlarged muscles and/or intrinsic adipose inflammation.

Due to its widespread availability and rapid image acquisition, the diagnosis is often first made on CT. Intravenous contrast, although ideal, is not necessary, as the differing densities of orbital fat and muscle allow for adequate delineation of the orbital contents.

Findings include:

  • exophthalmos

    • the reference line for measurement of proptosis is the interzygomatic line (a line that connects the anterior edges of the zygomatic bones):

      • the distance from this line to the posterior sclera is normally 9.9 +/- 1.7 mm 9

      • the distance from this line to the anterior surface of the globe should be <23 mm 10

      • a greater distance indicates exophthalmos

  • extraocular muscle enlargement and fatty attenuation

    • characteristic order of muscle involvement can be remembered by the mnemonic I'M SLOw

    • bilateral (~90%) and symmetric (~70%) involvement is typical 17

    • the anterior tendon is typically spared (although it can be involved in acute cases), with the swelling largely confined to the muscle belly

    • reference normal size range:

      • inferior rectus: 3.2-6.5 mm

      • medial rectus: 3.3-5.0 mm

      • superior group: 3.2-6.1 mm

      • lateral rectus: 1.7-4.8 mm

    • the size of the muscles correlates with both the severity of disease and the risk of optic nerve compression 7

  • increase in retro-ocular orbital fat

The greater the extraocular muscle bulk (especially medial rectus bulk nearer to the apex) and the longer and narrower the bony orbit, the more crowded the orbital apex will become. Apical crowding could result in optic neuropathy due to optic nerve compression 1,2. A Barrett's index of ≥60% is highly suggestive of optic neuropathy 12.

Other rarer signs include 7:

  • enlargement of the lacrimal glands (lymphocytic infiltration)

  • chemosis

  • anterior displacement of the orbital septum

Evaluation with MRI may be useful due to improved soft-tissue contrast and multiplanar capabilities. MRI avoids ionizing radiation to the lens and corresponding increased risk of radiation-induced cataracts. Location and involvement of the ocular muscles generally follow the described CT appearances. Specific MRI sequences findings may include:

  • T1: isointense to the other facial muscles, or fatty infiltration

  • T2: increased signal intensity may be seen due to the inflammatory process

  • T1 C+ (Gd): enhancement may be present

Although in many instances the disease is self-limiting, spontaneously improving within 2-5 years 3, treatment is often required if there is discomfort, any cosmetic issues, risk of corneal ulceration, and/or optic nerve compression. Options include:

  • smoking cessation

  • medical: supportive, selenium, glucocorticoids, rituximab, tocilizumab, teprotumumab 13-15

  • radiotherapy 3

  • surgical decompression

General imaging differential considerations include:

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