Unilateral proptosis: the role of medical history

The most common cause of bilateral and unilateral exophthalmus among adults is Graves’ disease. Unilateral exophthalmus, although frequently seen in connection with thyroid diseases, has a much larger differential diagnosis than bilateral exophthalmus. With unilateral presentation one should think of orbital pseudotumour, orbital cellulitis, cavernous sinus thrombosis, or intraorbital neoplasms.¹

Graves’ ophthalmopathy (GO) usually is associated with Graves’ hyperthyroidism (GH) although the temporal relation to thyroid disease is not consistent. It has been estimated that 77% of GO patients are hyperthyroid, 21% euthyroid, and 2% hypothyroid.² The mean absolute interval between GH and GO is 3.3 years in men and 3.6 years in women. Two thirds of patients present with orbital symptoms within 18 months of diagnosis of thyroid disease.³

The following cases of Graves’ ophthalmopathy are described because of their unusual presentation: a long interval between thyroid disease and the development of predominantly unilateral Graves’ ophthalmopathy. Both cases were seen at the department of ophthalmology of the University Hospital Groningen, Netherlands.

Case 1

A female patient born in 1922 became hyperthyroid with minimal eye signs with possibly some lid retraction in 1948. She was treated by thyroidectomy and became clinically euthyroid. In 1980 her thyroid function and antibodies were tested because of complaints of dizziness. Thyroid hormones were within normal ranges and thyroperoxidase (TPO) colloid and antiparietal cell antibodies (APCA) were negative.

In January 1983 she presented with complaints of sharp pains in both eyes, a feeling of pressure, and an exophthalmus of her right eye. On ocular examination there were no abnormalities except for exophthalmus of the right eye. Hertel exophthalmometer values were 24 mm right eye and 19 mm left eye. In December 1983 signs and symptoms worsened. Examination at that time showed an obvious retraction of the upper eyelid of the right eye. The exophthalmus was stable. There was diplopia caused by a right hypotropia in primary position of 1.5 degrees with restriction of elevation. A computed tomograph (CT) scan showed enlargement of all external eye muscles of the right eye without involvement of the tendons. During this exacerbation laboratory testing showed thyroid hormone levels within normal ranges and again TPO and colloid antibodies tests were negative. The diplopia resolved without treatment.

Case 2

A male patient born in 1944 was diagnosed with hypothyroidism in 1979. Thyroid hormones were abnormal. FT4 was decreased, TSH was increased, antibodies against colloid were positive, and APCA and TPO antibodies were negative. Because of this primary hypothyroidism levothyroxine therapy was started and he gradually became euthyroid. His ocular history mentioned a disorder of the central retinal pigment epithelium and glaucoma which was treated with timolol.

In August 2000 he presented with unilateral proptosis and progressive loss of vision. Ocular examination showed chemosis and oedema of the eyelids in both eyes. Visual acuity was 20/60 right eye and 20/30 left eye. Pupillary reflexes were normal and symmetrical. Clinically and biochemically he presented as euthyroid. A CT scan showed bilateral enlargement of the eye muscles, more marked on the right side. He was treated with 60 mg prednisone daily.

One month later visual acuity of the right eye dropped further and he was referred to our hospital. Ocular examination showed marked soft tissue signs, worse in the right eye, bilateral chemosis, and unilateral exophthalmus of 26 mm in the right eye. Visual acuity was reduced to counting fingers in the right eye. Colour vision was diminished and there was a relative afferent pupillary defect in the right eye. He had restrictions of the eye movements of the right eye when looking upwards, downwards, and in adduction. Thyroid hormone levels were again within normal ranges. He was admitted and methylprednisone 250 mg four times a day intravenously and radiotherapy (10 × 2 Gy) were started. Antibody testing showed borderline thyroglobulin and TPO antibody titres. Results of TSH receptor antibody testing could not be traced.

As visual function was not restored within a reasonable time another CT scan was performed which showed enlargement of all recti muscles of right eye and in lesser extent of the left eye with signs of compression of the right optic nerve. An orbital decompression through a Caldwell-Luc approach was performed on the right side. Postoperatively, visual acuity of the right eye improved to 20/30 and proptosis in the right eye was reduced by 8 mm. A strabismus convergens of the right eye was the main side effect.

In April 2001 a bilateral medial recession and a recession of the inferior rectus of the right eye were performed to treat the strabismus convergens. Binocular single vision was achieved in the primary position with some diplopia at extremes of gaze.

Comment

Unilateral proptosis as a result of Graves’ disease cannot be rejected as a diagnosis, even 20 or 30 years after the onset of thyroid disease. Only one retrospective study among 557 patients mentioned intervals up to 25 years without giving exact numbers and underlying thyroid disease.³ For hypothyroidism and GO one study suggests intervals exceeding 15 years.⁴

Thyroid hormone testing should be performed to rule out abnormalities in thyroid hormone levels although thyroid status does not seem important as the active phase of ophthalmopathy can occur during hyperthyroidism, hypothyroidism, and euthyroidism.⁴ Thyroid antibody testing may be supportive for the diagnosis. A CT scan can be essential in further analysis showing enlargement of extraocular muscles with sparing of the tendons.⁵ It is also known that a CT scan can demonstrate contralateral eye muscle involvement in 50–90% of patients with clinically unilateral eye involvement.⁶

Our two patients illustrate that the medical history is important in evaluating proptosis. One should always think of Graves’ disease as a possible cause of unilateral exophthalmos even though a patient may have had thyroid disease more than 20 years earlier.