Article

October 15, 2016

Simultaneous ocular myasthenia gravis and thyroid eye disease: beware

Thyroid eye disease (TED) is an autoimmune disease that is usually seen in patients with Graves’ thyrotoxicosis although it can also be seen in hypothyroid as well as euthyroid patients. Myasthenia gravis (MG) is also an autoimmune antibody mediated disorder characterized by fluctuating weakness of the skeletal muscles that can occur with TED.

MG is due to impaired neuromuscular transmission due to circulating anti-acetylcholine receptor antibodies (AchRAb). MG has a high incidence of association with other autoimmune diseases including Graves’ disease and autoimmune thyroiditis. It has been found that about 40% of people with ocular myasthenia gravis have anti-thyroid antibodies.^{1, 2}

The most common lid feature of TED is lid retraction while that of ocular MG is ptosis.³

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Thus, patients with ocular MG who present with lid retraction or TED who present with ptosis should be considered to have both disorders until proven otherwise.

Case report

A 67-year-old white female presented with a 2 year history of binocular horizontal diplopia, bilateral ptosis, Cogan’s lid twitch and orbicularis weakness. She was diagnosed with ocular MG and had positive acetylcholine receptor antibodies.

She started oral pyridostigmine which modestly helped with her symptoms. She never developed any systemic weakness or generalized MG. A CT scan of the chest was negative for thymoma. She returned to the neuro-ophthalmology clinic with a new complaint of eyelid retraction of her left eye (OS). At the time of her prior evaluation she had bilateral ptosis.

Can MD and TED coexist?

In addition to the lid retraction OS she had persistent residual ptosis of the right eye (OD) and variable diplopia. Motility exam showed a 30 prism diopter left exotropia (XT). When her right (ptotic) eye was occluded, the lid retraction on the left side decreased slightly but did not completely resolve consistent with the presence of both pseudo-retraction and true lid retraction.

When the ptotic eyelid OD was manually lifted, the retraction on the left eye was reduced but did not resolve consistent with the diagnosis of pseudoptosis and real ptosis OD. Orbital ultrasound confirmed extraocular muscle enlargement.Thyroid peroxidase and antiacetylcholine receptor antibodies were both positive.

Can MG and TED co-exist?

Both disease are autoimmune, antibody mediated disorders and thus can co-exist.

Although MG is only seen in 0.2% of patients with thyroid disease (commonly thyrotoxicosis), autoimmune thyroid disorders (ATD) are present in 3% to 8% of MG patients.⁴

It is also thought that MG associated with ATD has preferential ocular involvement, specifically restricted to eye muscles, and lower frequency of thymic disease and AchRAb.²In addition, generalized MG was found to be more frequent in patients without thyroid disease²and it was found that two-thirds of the patients with both disorders show improvement in myasthenia gravis after treatment of their thyroid disease. ⁵

How to approach patients with possible MG and TED

The presence of variable, intermittent diplopia or ptosis should prompt further questioning looking for symptoms of systemic MG.

Likewise, the symptom of diplopia with lid retraction and proptosis should prompt evaluation for TED. In patients with ptosis suspected of having MG, the presence of orbicularis weakness, Cogan’s lid twitch, variability and fatigability should suggest the diagnosis MG. In contrast, the presence of lid retraction with lateral flare, proptosis, lid lag and restrictive strabismus should raise suspicion for TED.

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Although MG can present with any pattern of painless, pupil spared, non-proptotic ophthalmoplegia the presence of concomitant TED can cause pain (either inflammatory or exposure keratopathy related), proptosis, and visual loss due to compressive optic neuropathy. In addition the pattern of extraocular muscle involvement in TED preferentially involves restriction of the inferior rectus and medial rectus first then the superior rectus and the lateral rectus last (consider the mnemonic for the order of IMSL: “I’M So Lucky”).

Thus, the typical pattern of ophthalmoplegia in TED is esotropia (tight medial rectus) or hypotropia (tight inferior rectus) and not exotropia (lateral rectus). The presence of exotropia in TED should suggest concomitant MG.

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Table 1 summarizes the combination of findings that should suggest both disorders.

Table 1

Table 1: Combinations of findings that should suggest both myasthenia gravis (MG) and thyroid eye disease (TED)

· Simultaneous or sequential true ptosis and true lid retraction

· Exotropia rather than esotropia in a patient with TED

· Proptosis in a patient with MG

· Optic neuropathy (compressive TED) in a patient with MG

· Eye pain in a patient with MG (MG is a neuromuscular and not sensory disease)

· Exposure keratopathy in a patient with MG not due to weak lid closure

· Variability and fatigue of findings in TED

· Orbicularis weakness in TED

Typically, if suspected clinically of having both conditions (MG and TED) undergo laboratory tests first (thyroid function studies and thyroid and acetylcholine receptor antibodies).

Additional tests

Additional tests to confirm the diagnosis of MG include electrophysiologic testing (e.g., repetitive nerve stimulation, single-fiber electromyography), CT scan of the chest (for thymic lesions), and neurologic consultation. Antibody tests are usually less sensitive in ocular MG than generalized MG with only about 50% of patients with disease restricted to ocular muscles having detectable antiAChR antibodies in serum (versus 80% to 99% in generalized MG).⁶

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Additional imaging studies for TED might include orbital ultrasound or CT scan of the orbits to evaluate for extraocular muscle involvement or apical compression in patients with TED related visual loss.

In our patient with MG, she had an ultrasound that showed enlarged extraocular muscles and tested positive for thyroid peroxidase antibody after being negative 2 years prior.

We hypothesize that her lid findings of true ptosis and pseudoptosis on the right, combined with true lid retraction and pseudo-retraction on the left can be explained by the combination of both autoimmune disorders, TED and concomitant ocular MG.

Thus, clinicians should consider both conditions (MG and TED) in every patient but especially when confronted with combinations of findings that cannot be explained by one or the other disease alone.

References

1. Garlepp MJ, Dawkins RL, Christiansen FT, et al. Autoimmunity in ocular and generalised myasthenia gravis. J Neuroimmunol. 1981;1:325-32.

2. Marino M, Ricciardi R, Pinchera A, et al. Mild clinical expression of myasthenia gravis associated with autoimmune thyroid diseases. J Clin Endocrinol Metab. 1997;82:438-43.

3. Bartley GB. The epidemiologic characteristics and clinical course of ophthalmopathy associated with autoimmune thyroid disease in Olmsted County, Minnesota. Trans Am Ophthalmol Soc. 1994;92:477-588.

4. Ratanakorn D, Vejjajiva A. Long-term follow-up of myasthenia gravis patients with hyperthyroidism. Acta Neurol Scand. 2002;106:93-8.

5. Ali AS, Akavaram NR. Neuromuscular disorders in thyrotoxicosis. Am Fam Physician. 1980;22:97-102.

6. Nair AG, Patil-Chhablani P, Venkatramani DV, Gandhi RA. Ocular myasthenia gravis: a review. Indian J Ophthalmol. 2014;62:985-91.

Andrew G. Lee, MD

P: 713/441-8843

E: aglee@houstonmethodist.org

Dr. Lee is associated with Blanton Eye Institute, Houston Methodist Hospital. None of the authors indicated any proprietary interest in the subject matter.

Ama Sadaka MD, and Shauna Berry, MD, are fellows affiliated with the Blanton Eye Institute of Houston Methodist Hospital (AS, SB, AGL) and the Department of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medical College; Department of Ophthalmology, University of Texas Medical Branch, Galveston; Department of Ophthalmology, University of Texas MD Anderson Cancer Center; Department of Ophthalmology, Baylor College of Medicine; Department of Ophthalmology, The University of Iowa Hospitals and Clinics, Iowa City, Iowa (AGL).