Examine this patient's face.
Perform a general examination of this patient.
· Obtain a history of thyrotoxicosis
· History of smoking (ophthalmopathy is more common in cigarette smokers, Lancet
1991; 338: 25-7).
· Prominent eyeballs.
· Look at the patient's eyes from behind and above for proptosis.
· Comment on lid retraction (the sclera above the upper limbus of the cornea will be
seen); this is Dalrymple's sign.
· Comment on the sclera visible between the lower eyelid and the lower limbus of
the cornea (i.e. comment on the exophthalmos). Most patients have bilateral
exophthalmos with unilateral prominence.
· Check for lid lag (ask the patient to follow your finger and then move it along the
arc of a circle from a point above her head to a point below the nose - the
move-ment of the lid lags behind that of the globe); this is von Graefe's sign.
Voluntary staring can result in a false lid lag, and the patient must be suitably
relaxed before eliciting this sign.
· Check for extraocular movements and comment on the cornea.
· Look for the following:
- Signs of thyrotoxicosis (fast pulse rate, tremor and sweating). - Goitre (listen for a
bruit). - Post-thyroidectomy scar.
This patient has marked exophthalmos with ophthalmoplegia (lesions) with signs of
thyrotoxicosis (functional status) due to Graves' disease (aetiology).
What eye signs of thyroid disease do you know?
Werner's mnemonic, NO SPECS (J C/in Endocrinol Metab 1977; 44: 2034):
No signs or symptoms.
Only signs of upper lid retraction and stare, with or without lid lag and exophthalmos.
Soft tissue involvement.
Extraocular muscle involvement.
Sight loss due to optic nerve involvement.
How would you investigate this patient?
· History and clinical examination for signs of thyrotoxicosis and thyroid
enlarge-ment and bruit.
· Serum T4, triiodothyronine (T3), TSH.
· Thyroid antibodies.
Mention the factors implicated in the phenomenon of lid lag.
· Sympathetic overstimulation, causing overaction of Mtiller's muscle.
· Myopathy of the inferior rectus causing overaction of superior rectus and levator
· Restrictive myopathy of the levator muscle.
What is euthyroid Graves' disease?
The patient will be clinically and biochemically euthyroid but will have mani-festations
of Graves' ophthalmopathy. A thyrotrophin-releasing hormone (TRH) stimulation
test will show a flat response curve.
What would you recommend if a patient with unilateral exophthalmos is
clinically and biochemically euthyroid?
· Ophthalmological referral.
· Ultrasonography of the orbit.
· CT scan of the orbit.
How is proptosis quantified?
It is assessed using a Hertel's exophthalmometer. The upper limit of normal is subject
to ethnic variation: usually, more than 20 mm is considered as proptosis.
How would you manage a patient with Graves' ophthalmopathy?
The single most important aspect is a close liaison between the physician and the
Severe Graves' disease and visual loss should be treated immediately with high
doses of corticosteroids, orbital irradiation and plasma exchange as an adjunct
and, if there is no improvement within 72-96 hours, orbital nerve decompression by
surgical removal of the floor and medial wall of the orbit is necessary.
Moderate ophthalmopathy improves substantially in 2-3 years in most patients. In the
interim the patient is treated symptomatically:
· Pain and grittiness is treated with methylcellulose eye drops by day and a
lubricating eye ointment at night.
· Exposure keratitis may be relieved by lateral tarsorrhaphy, surgery of the lower
· Diplopia may be relieved by prisms or surgery of the extraocular muscles.
· Static or worsening ophthalmopathy is an indication for steroids, orbital
decom-pression or orbital irradiation.
· Patients should be advised to stop smoking.
Mild ophthalmopathy should be rectified by cosmetic eyelid surgery. It is important to
remember that patients can be distressed by their appearance. During the early
acute phase patients will have considerable symptomatic relief from the following
· Elevating the head at night.
· Diuretics to reduce oedema.
· Tinted glasses for protection from the sun, wind and foreign bodies.
What is the role of radioiodine in thyroid eye disease?
· Firstly, since radioiodine treatment carries a substantial risk of exacerbating
pre-existing thyroid eye disease, it should be avoided as far as possible in patients
with active or severe ophthalmopathy, in whom medical therapy with a thionamide
drug such as carbimazole is preferable. Radioiodine may be used in patients with
mild eye disease but adjuvant oral corticosteriods should be prescribed (N Engl J
Med 1998; 338: 73-8).
· Secondly, patients without clinical evidence of thyroid disease have a small risk of
developing ophthalmopathy and a very low risk of developing severe eye disease.
It is prudent to warn all patients of this complication, but the risks do not justify
denying most patients the benefits of definitive treatment with radioiodine when
indicated. In addition, the risks do not justify the routine use of corti-costeroids in
patients without ophthalmopathy (BMJ 1999; 319: 68-9).
· Thirdly, smoking, a raised serum triiodothyronine concentration, and uncorrected
hypothyroidism are also factors which can exacerbate thyroid eye disease.
There-fore, to reduce the risk of thyroid eye disease, patients should be
encouraged to stop smoking, be rendered euthyroid with a thionamide before
radioiodine, and be monitored closely to detect and treat early hypothyroidism or
Mention the less important eponyms related to thyroid eye disease
· Infrequent blinking - Stellwag's sign.
· Tremor of closed eyelids - Rosenbach's sign.
· Difficulty in everting upper eyelid - Gifford's sign.
· Absence of wrinkling of forehead on sudden upward gaze - Joffroy's sign.
· Impaired convergence of the eyes - M6bius' sign.
· Weakness of at least one of the extraocular muscles - Ballet's sign.
· Paralysis of extraocular muscles - Jendrassik's sign.
· Poor fixation on lateral gaze - Suker's sign.
· Dilatation of pupil with weak adrenaline solution - Loewi's sign.
· Jerky pupillary contraction to consensual light - Cowen's sign.
· Increased pigmentation of the margins of eyelids - Jellinek's sign.
· Upper lid resistance on downward traction - Grove's sign.
· Abnormal fullness of the eyelid - Enroth's sign.
· Unequal pupillary dilatation - Knie's sign.
· When the eyeball is turned downwards, there is arrest of the descent of the lid,
spasm and continued descent - Boston's sign.
· When the clinician places his or her hand on a level with the patient's eyes and
then lifts it higher, the patient's upper lids spring up more quickly than the eyeball -
J. Dalrymple (1804-1852), an English ophthalmologist.
Exophthalmos associated with goitre and non-organic heart disease was first
described by English physician Caleb Hillard Parry (1775-1822) in a paper
published posthumously in 1825. He graduated in medicine from Edinburgh and
practised in Bath. He described hyperthyroidism before Graves' disease.
In 1977, Solomon et al presented the evidence that three independent autoimmune
diseases tended to occur concomitantly in the same euthyroid Graves'
ophthalmopathy: idiopathic hyperthyroidism, Hashimoto's thyroiditis and Graves'
Anthony Tort, an endocrinologist at Edinburgh Royal Infirmary, is past President of
the Royal College of Physicians of Edinburgh.