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Man presents with swollen red, painful eyes and subclinical hyperthyroidism
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A 49-year-old Brazilian male presented to the endocrine clinic for bulging red eyes and diplopia. He developed swollen eyes with a gritty sensation about 18 months before presentation but developed diplopia in the prior 2 to 3 months. He denied prior history of thyroid dysfunction or head and neck radiation.
His family history and personal history were negative for autoimmune disease. He had never smoked cigarettes. He denied tremor, perspiration, palpitations, frequent stools or weight loss. He had bilateral chemosis (conjunctival and scleral edema), conjunctival injection and periorbital edema and proptosis. He had bilateral proptosis by Hertel ophthalmometer with both eyes measuring 27 mm (normal <20 mm) with a span of 100 mm. On forward gaze he had strabismus with his left eye deflected downward, suggesting shortening of the left inferior rectus muscle. His extraocular motion, especially of the left eye, was restricted with superior and right lateral gaze.
Figure 1. Orbital CT scan without contrast. Coronal view of the normal orbit (A) and thyroid orbitopathy. The images show bilateral increase in all of the extraocular muscles, especially the inferior rectus muscle. The extraocular muscles seen on the CT scan are the inferior rectus (I), medial rectus (M), superior rectus (S), lateral rectus (L) and superior oblique (SO). Optic nerve (O).
Source: Stephanie L. Lee, MD, PhD
He did not have tachycardia, tremor or palmar erythema on exam. His thyroid was slightly enlarged (twofold; about 30 g) and slightly firm without nodules or auscultated bruit.
Diagnosis, treatment
Laboratory testing showed subclinical hyperthyroidism with a suppressed thyroid-stimulating hormone of <0.01 mIU/L (normal range: 0.35 mIU/L-4.50 mIU/L); free thyroxine of 1.4 ng/dL (normal range: 0.89 ng/dL-1.89 ng/dL); total triiodothyronine of 224 ng/dL (normal range: 90 ng/dL-180 ng/dL); and markedly elevated thyroperoxidase antibody of 7,580 IU/mL (normal range: <35 IU/mL).
His mild thyrotoxicosis was easily treated with methimazole, but his eye symptoms continued to worsen. An orbital CT scan showed severe proptosis with swelling of his extraocular muscles and increased retro-orbital fat (Figures 1-3). Because there was no improvement after high-dose oral glucocorticoid therapy and thyroidectomy, his eye disease was treated with external beam radiation. Both eyes were treated with 10 daily fractions of 2 Gy with a prednisone taper for an additional month after the radiation. By the end of the radiation, there was a significant regression of proptosis with improved symptoms. Evaluation by an ophthalmologist 4 weeks after the radiation confirmed marked resolution of exophthalmos and periorbital edema with complete resolution of his conjunctival injection but continued extraocular muscle dysfunction on exam.
Figure 2. Orbital CT scan without contrast. Axial view of view of thyroid orbitopathy (A) and normal orbit (B). This view shows the dramatic increase in retroorbital fat (F) and muscle thickness resulting in pushing the globe forward (proptosis).
Figure 3. Assessment of proptosis on CT scan: Two methods to assess proptosis. Proptosis is suggested when (A) more than two-thirds of the globe is anterior to a line drawn between the bilateral orbital ridges of the zygomatic bones (Z); or (B) more than one-half of the globe is anterior to the line drawn between the nasal bone (N) and the ipsilateral lateral orbital ridge of the zygomatic bone (Z). Eyeball globe (G).
Orbital change and thyroid disease
The orbital changes of autoimmune thyroid disease have had many names, including Graves’ orbitopathy, thyroid eye disease and thyroid associated ophthalmopathy. Orbitopathy usually occurs at the onset of hyperthyroidism but may present up to 1 year before, to as long as 5 years after, but about 10% to 15% of patients never become hyperthyroid, and a small number have autoimmune hypothyroidism. The incidence of ophthalmopathy has decreased in the past 2 decades, with the only known risk factors of cigarette smoking and radioiodine therapy. It is also suspected that prolonged hypothyroidism may worsen the eye disease. The clinical course (Figure 4) of thyroid orbitopathy was observed by Francis Rundle, who described an initial worsening and then partial resolution of the changes over time.
Figure 4. Rundle’s curve showing the natural history of thyroid orbitopathy with an initial worsening and then partial resolution over time.
Graves’ ophthalmopathy appears to result from inflammatory cell infiltration and glycosamine glycan deposition in the extraocular muscles and retro-orbital adipose and connective tissues, causing increased volume in the orbit and pushing the eye globe anteriorly. Fluid also accumulates in the orbit due to the hydrophilic ability of the glucosamine glycan to hold onto water and venous congestion caused by compression of the superior ophthalmic vein by orbital contents. Clinically, these changes can result in proptosis with corneal dryness and reactive tearing, optic nerve compression with risk for blindness and, with time, muscle fibrosis leading to diplopia. CT imaging provides excellent visualization of the retro-orbital space and bony architecture, which allows screening for optic nerve compression and assessment of disease progression. A CT scan will show enlarged extraocular muscle bellies, usually >4 mm in diameter, and increased fat content of the orbit with variable degrees of proptosis (forward protrusion of the globe out of the orbit).
Proptosis on an axial CT scan is defined as protrusion of more than two-thirds of the globe anterior to a line drawn between the bilateral lateral orbital ridges of the zygomatic bones or one-half of the globe protruding anterior to a line between the anterior nasal bone and the ipsilateral lateral orbital ridge (Figure 3). It has been observed clinically that the order of severity for the extraocular muscles involvement is indicated by the mnemonic IMSLO (“I’m slow”; inferior, medial, superior, lateral recti, oblique extraocular muscle). Notably, the tendons of the extraocular muscles are characteristically spared.
Disadvantages of CT imaging are primarily the associated inconvenience, cost and radiation exposure. An effective but underutilized imaging methodology is orbital ultrasonography, which is inexpensive and efficient by allowing in-office tracking of ophthalmopathy. Ultrasound exams will show enlarged extraocular muscles with moderate to high internal echogenicity. Disadvantages of ultrasonography are the inability to assess bony anatomy and optic nerve compression. MRI scan can accurately assess the fat content of the orbit, enlargement of the extraocular muscles and is particularly excellent at imaging the orbital apex where the optic nerve is damaged from compression.
References:
- Bartley G. Arch Ophthalmol. 2011;129:356-357.
- Lazarus JH. Best Pract Res Clin Endocrinol Metab. 2012;26:273-279.
- Yen MT. Imaging in thyroid ophthalmopathy. Available at: emedicine.medscape.com/article/383412-overview. Accessed Nov. 26. 2012.
For more information:
- Stephanie L. Lee, MD, PhD, is associate professor of medicine and associate chief in the Section of Endocrinology, Diabetes and Nutrition at Boston Medical Center. Gregory L. Peterfreund is a student in the Medical Scientist Training Program at the Perelman School of Medicine at the University of Pennsylvania. Lee can be reached at Boston Medical Center, 88 E. Newton St., Endocrinology Evans 201, Boston, MA 02118; email: stephanie.lee@bmc.org. Lee reports no relevant financial disclosures.