BACKGROUND

What causes thyroid ophthalmopathy (TO)?

T-cell lymphocytic infiltration of orbital and periorbital tissues (secondary to autoimmune antibody–mediated reaction against the TSH receptor)

Name 2 conditions associated with TO.

Graves Dz and Hashimoto thyroiditis are both associated with TO.

What is the end result of untreated TO?

Untreated TO will lead to fibrosis, which develops over the course of 2–5 yrs.

What are the signs/Sx of TO?

Exophthalmos, impaired extraocular movements/diplopia, periorbital edema, and lid retraction. In severe cases, compression of the optic nerves and decreased visual acuity can occur.

WORKUP/STAGING

What does the general workup of TO include?

TO workup: H&P (Hertel exophthalmometer to measure proptosis), CBC, CMP, TFTs, and CT/MRI orbit

What is the staging/risk stratification?

There is no formal staging/risk stratification. Studies have grouped pts into mild, moderately severe, and severe TO, though the exact definition of these terms varies between studies.

TREATMENT/PROGNOSIS

What is the general Tx paradigm for TO?

TO Tx paradigm: Treat underlying disorder. For mild Dz, consider observation vs. RT; for moderately severe Dz, consider high-dose steroids (generally 1^st-line treatment with response in up to 60% of pts) vs. RT; and for severe Dz unresponsive to steroids, perform orbital decompression surgery (e.g., for acute visual acuity or color perception changes as these are symptoms of optic nerve compression).

RT should be initiated within how many mos from onset of TO?

RT should be initiated within 7 mos of TO onset for pts who fail or have contraindications to high-dose steroids. Delayed RT is not as effective based on retrospective data.

What are 2 common contraindications to high-dose steroids in pts with TO?

Optic neuropathy and corneal ulceration are 2 contraindications to steroids in pts with TO.

What are the typical RT dose/fractionations for TO? What evidence supports these doses?

Typical RT dose/fractionations for TO:

1. 20 Gy in 2 Gy/fx (most common)

2. 10 Gy in 1 Gy/fx

3. 20 Gy in 1 Gy/fx/wk ×20 wks

Kahaly et al. prospectively compared the 3 regimens above and found that all were equally effective (the latter 2 were better tolerated). (J Clin Endocrinol Metab 2000)

What beam arrangement is used for TO?

Opposed lats, half-beam block anteriorly to minimize divergence into contralateral lens.

What RT technique is used to minimize the dose to the contralat lens?

Place the isocenter posterior to lenses and the half-beam block anteriorly (limits divergence to contralat lens).

What structures define the post, sup, and ant borders of the RT fields?

Posterior: ant clinoids

Sup/Ant: bony orbit

In pts with moderately severe TO, what drug should be used concurrently with RT?

Continue or start steroids with RT, as pts can develop edema and worsening Sx.

What evidence is there to support RT for mild TO?

Prummel MF et al.: A double-blind RCT of 88 pts with Graves: 44 rcvd RT vs. 44 sham RT. RT improved clinical Sx (response rate 52% for RT vs. 27% for sham RT). There was no improvement in the QOL survey and no reduction in overall Tx costs. (J Clin Endocrinol Metab 2004)

What evidence is there against RT for mild TO?

Gorman CA et al.: In an RCT with crossover, RT was administered to 1 orbit and then the opposite orbit after 6 mos. At 6 mos, there was no difference in results for either eye. At 12 mos, there was minor improvement in the 1^st treated eye. The authors concluded that RT was not justified. (Ophthalmology 2001)

What evidence is there to support RT for moderately severe TO?

Premmel MF et al.: In an RCT, all pts with Graves rcvd RT vs. 3 mos of prednisone. RT and prednisone were equally effective, but RT was better tolerated. (Lancet 1993)

Mourits MP et al.: In an RCT, all pts with Graves rcvd RT vs. sham RT. RT improved diplopia and elevation but not proptosis or eyelid swelling. It was concluded that RT should be used to treat motility impairment only. (Lancet 2000)

Would a pt with diplopia or proptosis be more likely to see an improvement in Sx after RT?

Diplopia (Mourits MP et al., Lancet 2000); also supported by recent meta-analysis (Stiebel-Kalish H et al., J Clin Endocrinol Metab 2009)

Estimate the response rate of TO pts to RT.

Response rates to RT are 50%–70% in pts with TO. (Prummel MF et al., J Clin Endocrinol Metab 2004; Kahaly GJ et al., J Clin Endocrinol Metab 2000)

What % of TO pts will require further therapy after RT?

50%–75% of TO pts will require further therapy. (Mourits MP et al., Lancet 2000; Gorman CA et al., Ophthalmology 2001)