In mild disease, patients present with eyelid retraction. In fact, upper eyelid retraction is the most common ocular sign of Graves' orbitopathy. This finding is associated with lid lag on infraduction (Von Graefe's sign), eye globe lag on supraduction (Kocher's sign), a widened palpebral fissure during fixation (Dalrymple's sign) and an incapacity of closing the eyelids completely (lagophthalmos). Due to the proptosis, eyelid retraction and lagophthalmos, the cornea is more prone to dryness and may present with chemosis, punctate epithelial erosions and superior limbic keratoconjunctivitis. The patients also have a dysfunction of the lacrimal gland with a decrease of the quantity and composition of tears produced. Non-specific symptoms with these pathologies include irritation, grittiness, photophobia, tearing, and blurred vision. Pain is not typical, but patients often complain of pressure in the orbit. Periorbital swelling due to inflammation can also be observed.

- Eye signs in TED

In moderate active disease, the signs and symptoms are persistent and increasing and include myopathy. The inflammation and edema of the extraocular muscles lead to gaze abnormalities. The inferior rectus muscle is the most commonly affected muscle and patient may experience vertical diplopia on upgaze and limitation of elevation of the eyes due to fibrosis of the muscle. This may also increase the intraocular pressure of the eyes. The double vision is initially intermittent but can gradually become chronic. The medial rectus is the second-most-commonly-affected muscle, but multiple muscles may be affected, in an asymmetric fashion.

In more severe and active disease, mass effects and cicatricial changes occur within the orbit. This is manifested by a progressive exophthalmos, a restrictive myopathy that restricts eye movements and an optic neuropathy. With enlargement of the extraocular muscle at the orbital apex, the optic nerve is at risk of compression. The orbital fat or the stretching of the nerve due to increased orbital volume may also lead to optic nerve damage. The patient experiences a loss of visual acuity, visual field defect, afferent pupillary defect, and loss of color vision. This is an emergency and requires immediate surgery to prevent permanent blindness.

Graves ophthalmopathy (also known as thyroid eye disease (TED), dysthyroid/thyroid-associated orbitopathy (TAO), Graves' orbitopathy (GO)) is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and bulging eyes (exopthalmos). It occurs most commonly in individuals with Graves' disease, and less commonly in individuals with Hashimoto's thyroiditis, or in those who are euthyroid.

It is part of a systemic process with variable expression in the eyes, thyroid, and skin, caused by autoantibodies that bind to tissues in those organs. The autoantibodies target the fibroblasts in the eye muscles, and those fibroblasts can differentiate into fat cells (adipocytes). Fat cells and muscles expand and become inflamed. Veins become compressed, and are unable to drain fluid, causing edema.

Annual incidence is 16/100,000 in women, 3/100,000 in men.

About 3–5% have severe disease with intense pain, and sight-threatening corneal ulceration or compression of the optic nerve. Cigarette smoking, which is associated with many autoimmune diseases, raises the incidence 7.7-fold.

Mild disease will often resolve and merely requires measures to reduce discomfort and dryness, such as artificial tears and smoking cessation if possible. Severe cases are a medical emergency, and are treated with glucocorticoids (steroids), and sometimes ciclosporin. Many anti-inflammatory biological mediators, such as infliximab, etanercept, and anakinra are being tried, but there are no randomized controlled trials demonstrating effectiveness.

Measurement of the degree of exophthalmos is performed using an exophthalmometer.

Most sources define exophthalmos/proptosis as a protrusion of the globe greater than 18 mm.

The term exophthalmos is often used when describing proptosis associated with Graves' disease.

Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in an orbital tumor). Complete or partial dislocation from the orbit is also possible from trauma or swelling of surrounding tissue resulting from trauma.

In the case of Graves' disease, the displacement of the eye is due to abnormal connective tissue deposition in the orbit and extraocular muscles which can be visualized by CT or MRI.

If left untreated, exophthalmos can cause the eyelids to fail to close during sleep leading to corneal dryness and damage. Another possible complication would be a form of redness or irritation called "Superior limbic keratoconjunctivitis", where the area above the cornea becomes inflamed as a result of increased friction when blinking. The process that is causing the displacement of the eye may also compress the optic nerve or ophthalmic artery, leading to blindness.

Infiltrative ophthalmopathy is found in 5-10% of patients with Graves disease and resembles exophthalmos, except that the blurry or double vision is acquired because of weakness in the ocular muscles of the eye. In addition, there is no known correlation with the patient's thyroid levels. Exophthalmos associated with Grave's disease disappears when the thyrotoxicosis is corrected. Infiltrative ophthalmopathy at times may not be cured. Treatments consist of high dose glucocorticoids and low dose radiotherapy. The current hypothesis is that infiltrative ophthalmopathy may be autoimmune in nature targeting retrobulbar tissue. Smoking may also have a causative effect.

Thyroid storm is a severe form of thyrotoxicosis characterized by rapid and often irregular heart beat, high temperature, vomiting, diarrhea, and mental agitation. Symptoms may be unusual in the young, old, or pregnant. It is a medical emergency and requires hospital care to control the symptoms rapidly. Even with treatment, death occurs in 20% to 50%.

Hyperthyroidism may be asymptomatic or present with significant symptoms. Some of the symptoms of hyperthyroidism include nervousness, irritability, increased perspiration, heart racing, hand tremors, anxiety, difficulty sleeping, thinning of the skin, fine brittle hair, and muscular weakness—especially in the upper arms and thighs. More frequent bowel movements may occur, and diarrhea is common. Weight loss, sometimes significant, may occur despite a good appetite (though 10% of people with a hyperactive thyroid experience weight gain), vomiting may occur, and, for women, menstrual flow may lighten and menstrual periods may occur less often, or with longer cycles than usual.

Thyroid hormone is critical to normal function of cells. In excess, it both overstimulates metabolism and exacerbates the effect of the sympathetic nervous system, causing "speeding up" of various body systems and symptoms resembling an overdose of epinephrine (adrenaline). These include fast heart beat and symptoms of palpitations, nervous system tremor such as of the hands and anxiety symptoms, digestive system hypermotility, unintended weight loss, and (in "lipid panel" blood tests) a lower and sometimes unusually low serum cholesterol.

Major clinical signs include weight loss (often accompanied by an increased appetite), anxiety, heat intolerance, hair loss (especially of the outer third of the eyebrows), muscle aches, weakness, fatigue, hyperactivity, irritability, high blood sugar, excessive urination, excessive thirst, delirium, tremor, pretibial myxedema (in Graves' disease), emotional lability, and sweating. Panic attacks, inability to concentrate, and memory problems may also occur. Psychosis and paranoia, common during thyroid storm, are rare with milder hyperthyroidism. Many persons will experience complete remission of symptoms 1 to 2 months after a euthyroid state is obtained, with a marked reduction in anxiety, sense of exhaustion, irritability, and depression. Some individuals may have an increased rate of anxiety or persistence of affective and cognitive symptoms for several months to up to 10 years after a euthyroid state is established. In addition, those with hyperthyroidism may present with a variety of physical symptoms such as palpitations and abnormal heart rhythms (the notable ones being atrial fibrillation), shortness of breath (dyspnea), loss of libido, amenorrhea, nausea, vomiting, diarrhea, gynecomastia and feminization. Long term untreated hyperthyroidism can lead to osteoporosis. These classical symptoms may not be present often in the elderly.

Neurological manifestations can include tremors, chorea, myopathy, and in some susceptible individuals (in particular of Asian descent) periodic paralysis. An association between thyroid disease and myasthenia gravis has been recognized. The thyroid disease, in this condition, is autoimmune in nature and approximately 5% of patients with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is not well understood.

In Graves' disease, ophthalmopathy may cause the eyes to look enlarged because the eye muscles swell and push the eye forward. Sometimes, one or both eyes may bulge. Some have swelling of the front of the neck from an enlarged thyroid gland (a goiter).

Minor ocular (eye) signs, which may be present in any type of hyperthyroidism, are eyelid retraction ("stare"), extraocular muscle weakness, and lid-lag. In hyperthyroid "stare" (Dalrymple sign) the eyelids are retracted upward more than normal (the normal position is at the superior corneoscleral limbus, where the "white" of the eye begins at the upper border of the iris). Extraocular muscle weakness may present with double vision. In lid-lag (von Graefe's sign), when the patient tracks an object downward with their eyes, the eyelid fails to follow the downward moving iris, and the same type of upper globe exposure which is seen with lid retraction occurs, temporarily. These signs disappear with treatment of the hyperthyroidism.

Neither of these ocular signs should be confused with exophthalmos (protrusion of the eyeball), which occurs specifically and uniquely in hyperthyroidism caused by Graves' disease (note that not all exophthalmos is caused by Graves' disease, but when present with hyperthyroidism is diagnostic of Graves' disease). This forward protrusion of the eyes is due to immune-mediated inflammation in the retro-orbital (eye socket) fat. Exophthalmos, when present, may exacerbate hyperthyroid lid-lag and stare.

A goitre, associated with hypothyroidism or hyperthyroidism, may be present with symptoms of the underlying disorder. For hyperthyroidism, the most common symptoms are associated with adrenergic stimulation: tachycardia, palpitations, nervousness, tremor, increased blood pressure and heat intolerance. Clinical manifestations are often related to hypermetabolism, (increased metabolism), excessive thyroid hormone, an increase in oxygen consumption, metabolic changes in protein metabolism, immunologic stimulation of diffuse goitre, and ocular changes (exophthalmos). Hypothyroid individuals may have weight gain despite poor appetite, cold intolerance, constipation and lethargy. However, these symptoms are often non-specific and make diagnosis difficult.

Regarding morphology, goitres may be classified either as the growth pattern or as the size of the growth :

- Growth pattern:

- Uninodular goitre: one thyroid nodule; can be either an inactive or a toxic nodule.

- Multinodular goitre: multiple nodules; can likewise be inactive or toxic, the latter is called toxic multinodular goitre and associated with hyperthyroidism; thyroid cancer is identified in 13.7% of the patients operated for multinodular goitre. These nodules grow up at varying rates and secrete thyroid hormone autonomously, thereby suppressing TSH-dependent growth and function in the rest of gland.

- Diffuse goitre: the whole thyroid appearing to be enlarged due to hyperplasia.

- Size:

- Class I (palpation goitre): in normal posture of the head, it cannot be seen; it is only found by palpation.

- Class II: the goitre is palpable and can be easily seen.

- Class III: the goitre is very large and is retrosternal; pressure results in compression marks.

Thyroid-associated ophthalmopathy (TAO), or thyroid eye disease (TED), is the most common extrathyroidal manifestation of Grave's disease. It is a form of idiopathic lymphocytic orbital inflammation, and although its pathogenesis is not completely understood, autoimmune activation of orbital fibroblasts, which in TAO express the TSH receptor, is thought to play a central role.

Hypertrophy of the extraocular muscles, adipogenesis, and deposition of nonsulfated glycoaminoglycans and hyaluronate, causes expansion of the orbital fat and muscle compartments, which within the confines of the bony orbit may lead to dysthyroid optic neuropathy, increased intraocular pressures, proptosis, venous congestion leading to chemosis and periorbital edema, and progressive remodeling of the orbital walls. Other distinctive features of TAO include lid retraction, restrictive myopathy, superior limbic keratoconjunctivitis, and exposure keratopathy.

Severity of eye disease may be classified by the mnemonic: "NO SPECS":

- Class 0: No signs or symptoms

- Class 1: Only signs (limited to upper lid retraction and stare, with or without lid lag)

- Class 2: Soft tissue involvement (oedema of conjunctivae and lids, conjunctival injection, etc.)

- Class 3: Proptosis

- Class 4: Extraocular muscle involvement (usually with diplopia)

- Class 5: Corneal involvement (primarily due to lagophthalmos)

- Class 6: Sight loss (due to optic nerve involvement)

Typically the natural history of TAO follows Rundle's curve, which describes a rapid worsening during an initial phase, up to a peak of maximum severity, and then improvement to a static plateau without, however, resolving back to a normal condition.

The signs and symptoms of Graves' disease virtually all result from the direct and indirect effects of hyperthyroidism, with main exceptions being Graves' ophthalmopathy, goiter, and pretibial myxedema (which are caused by the autoimmune processes of the disease). Symptoms of the resultant hyperthyroidism are mainly insomnia, hand tremor, hyperactivity, hair loss, excessive sweating, shaking hands, itching, heat intolerance, weight loss despite increased appetite, diarrhea, frequent defecation, palpitations, muscle weakness, and skin warmth and moistness. Further signs that may be seen on physical examination are most commonly a diffusely enlarged (usually symmetric), nontender thyroid, lid lag, excessive lacrimation due to Graves' ophthalmopathy, arrhythmias of the heart, such as sinus tachycardia, atrial fibrillation, and premature ventricular contractions, and hypertension. People with hyperthyroidism may experience behavioral and personality changes, including: psychosis, mania, anxiety, agitation, and depression.

Myxedema can occur in the lower leg (pretibial myxedema) and behind the eyes (exophthalmos).

Myxedema is known to occur in various forms of hypothyroidism, and also in Graves' disease. One of the hallmarks of Grave's disease is pretibial myxedema, myxedema of the lower limb.

Myxedema is more common in women than in men.

Myxedema can occur in:

- "Hyperthyroidism", associated with pretibial myxedema and exophthalmos. Pretibial myxedema can occur in 1–4% of patients with Graves' disease, a cause of hyperthyroidism.

- "Hypothyroidism", including Hashimoto's thyroiditis.

Enophthalmos is the posterior displacement of the eyeball within the orbit due to changes in the volume of the orbit (bone) relative to its contents (the eyeball and orbital fat), or loss of function of the orbitalis muscle. It should not be confused with its opposite, exophthalmos, which is the anterior displacement of the eye.

It may be a congenital anomaly, or be acquired as a result of trauma (such as in a blowout fracture of the orbit), Horner's syndrome (apparent enophthalmos due to ptosis), Marfan syndrome, Duane's syndrome, silent sinus syndrome or phthisis bulbi.

Lagophthalmos can arise from a malfunction of the facial nerve. Lagopthalmos can also occur in comatose patients having a decrease in orbicularis tone, in patients having palsy of the facial nerve (7th cranial nerve), in people with severe exophthalmos, and in people with severe skin disorders such as ichthyosis.

Today, lagophthalmos may arise after an overenthusiastic upper blepharoplasty. Blepharoplasty is an operation performed to remove excessive skin overlying the upper eyelid (suprapalpebral hooding) that often occurs with aging. This can appreciably improve the patient's appearance, and make the patient look younger. If, however, excessive skin is removed, the appearance is unnatural and "lagophthalmos" is one of the signs of such excessive skin removal.

Lagophthalmos is the inability to close the eyelids completely.

Blinking covers the eye with a thin layer of tear fluid, thereby promoting a moist environment necessary for the cells of the exterior part of the eye. The tears also flush out foreign bodies and wash them away. This is crucial to maintain lubrication and proper eye health. If this process is impaired, as in lagophthalmos, the eye can suffer abrasions and infections. Lagopthalmos leads to corneal drying and ulceration.

Broadly speaking, endocrine disorders may be subdivided into three groups:

1. Endocrine gland hyposecretion (leading to hormone deficiency)

2. Endocrine gland hypersecretion (leading to hormone excess)

3. Tumours (benign or malignant) of endocrine glands

Endocrine disorders are often quite complex, involving a mixed picture of hyposecretion and hypersecretion because of the feedback mechanisms involved in the endocrine system. For example, most forms of hyperthyroidism are associated with an excess of thyroid hormone and a low level of thyroid stimulating hormone.

Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.

Hormone secreting pituitary adenomas cause one of several forms of hyperpituitarism. The specifics depend on the type of hormone. Some tumors secrete more than one hormone, the most common combination being GH and prolactin, which present as unexpected bone growth and unexpected lactation (in both men and women).

A patient with pituitary adenoma may present with visual field defects, classically bitemporal hemianopsia. It arises from the compression of the optic nerve by the tumor. The specific area of the visual pathway at which compression by these tumours occurs is at the optic chiasma.

The anatomy of this structure causes pressure on it to produce a defect in the temporal visual field on both sides, a condition called bitemporal hemianopsia. If originating superior to the optic chiasm, more commonly in a craniopharyngioma of the pituitary stalk, the visual field defect will first appear as bitemporal inferior quadrantanopia, if originating inferior to the optic chiasm the visual field defect will first appear as bitemporal superior quadrantanopia. Lateral expansion of a pituitary adenoma can also compress the abducens nerve, causing a lateral rectus palsy.

Also, a pituitary adenoma can cause symptoms of increased intracranial pressure.

Prolactinomas often start to give symptoms especially during pregnancy, when the hormone progesterone increases the tumor's growth rate.

Various types of headaches are common in patients with pituitary adenomas. The adenoma may be the prime causative factor behind the headache or may serve to exacerbate a headache caused by other factors. Amongst the types of headaches experienced are both chronic and episodic migraine, and more uncommonly various unilateral headaches; primary stabbing headache, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) - another type of stabbing headache characterized by short stabs of pain -, cluster headache, and hemicrania continua (HS).

Non-secreting adenomas can go undetected for an extended time because no obvious abnormalities are seen; the gradual reduction in normal activities due to decreased production of hormones is rather less evident. For example, insufficient adrenocorticotropic hormone means that the adrenal glands will not produce sufficient cortisol, resulting in slow recovery from illness, inflammation and chronic fatigue; insufficient growth hormone in children and adolescents leads to diminished stature but which can have many other explanations.

Various psychiatric manifestations have been associated with pituitary disorders including pituitary adenomas. Psychiatric symptoms such as depression, anxiety apathy, emotional instability, easy irritability and hostility have been noted.

Chemosis is the swelling (or edema) of the conjunctiva. It is due to the oozing of exudate from abnormally permeable capillaries. In general, chemosis is a nonspecific sign of eye irritation. The outer surface covering appears to have fluid in it. The conjunctiva becomes swollen and gelatinous in appearance. Often, the eye area swells so much that the eyes become difficult or impossible to close fully. Sometimes, it may also appear as if the eyeball has moved slightly backwards from the white part of the eye due to the fluid filled in the conjunctiva all over the eyes except the iris. The iris is not covered by this fluid and so it appears to be moved slightly inwards.

Patients who have malignant gliomas of the optic nerve have rapidly progressive, painful visual loss accompanied by signs of an optic neuropathy. Initial visual loss may be unilateral or bilateral (chiasmal involvement), but rapid progression to bilateral blindness and death are constant features. Depending on the initial location of the tumor, visual loss may be accompanied by exophthalmos, extraocular motility

Optic nerve melanocytoma does not usually produce symptoms or grow. If they slowly grow, optic nerve melanocytoma can produce afferent pupillary defects (30%), subretinal fluid (10%), and an enlarged blind spot (75%).

On fundoscopic exam, the optic disc may be swollen, atrophic, or even normal. Central retinal vein occlusion may occur.

If the tumor is next to the optic nerve, growth can compress the nerve and cause gradual loss of vision and unilateral proptosis. Dyschromatopsia may occur. Growth can also cause compressive vascular problems like central retinal vein occlusion. Lastly, growth also causes the tumor to exceed its blood supply. In these cases, necrotic areas form inside the tumor. Necrosis can (in turn) cause intraocular and rarely orbital inflammation.

It is usually caused by allergies or viral infections, often inciting excessive eye rubbing. Chemosis is also included in the Chandler Classification system of orbital infections.

If chemosis has occurred due to excessive rubbing of the eye, the first aid to be given is a cold water wash for eyes.

Other causes of chemosis include:

- Superior vena cava obstruction, accompanied by facial oedema

- Hyperthyroidism, associated with exophthalmos, periorbital puffiness, lid retraction, and lid lag

- Cavernous sinus thrombosis, associated with infection of the paranasal sinuses, proptosis, periorbital oedema, retinal haemorrhages, papilledema, extraocular movement abnormalities, and trigeminal nerve sensory loss

- Carotid-cavernous fistula - classic triad of chemosis, pulsatile proptosis, and ocular bruit

- Cluster headache

- Trichinellosis

- Systemic lupus erythematosus (SLE)

- Angioedema

- Acute glaucoma

- Panophthalmitis

- Orbital cellulitis

- Gonorrheal conjunctivitis

- Dacryocystitis

- Spitting cobra venom to the eye

- High concentrations of phenacyl chloride in chemical mace spray

- Urticaria

- Trauma

- Post surgical

- Rhabdomyosarcoma of the orbit

An optic nerve melanocytoma is a tumor made up of melanocytes and melanin. These tumors are typically a benign; they can grow, but rarely transform into a malignancy. Even so, local growth can affect adjacent tissues.

Symptoms are usually limited to one side of the head, and in most cases the individual affected will experience intense, sharp pain and paralysis of muscles around the eye. Symptoms may subside without medical intervention, yet recur without a noticeable pattern.

In addition, affected individuals may experience paralysis of various facial nerves and drooping of the upper eyelid (ptosis). Other signs include double vision, fever, chronic fatigue, vertigo or arthralgia. Occasionally the patient may present with a feeling of protrusion of one or both eyeballs (exophthalmos).