**4. Goiter**

In GD, goiter is characteristically diffuse. May have asymmetric or lobular character, with variable volume. In some patients, there is thrill and murmur over the gland, produced by increased flow of blood, this finding being exclusive to the disease. Any patient with diffuse goiter and hyperthyroidism has GD until they prove the opposite [4, 12]. In the elderly, when present, the goiter tends to be small [1].

#### **5. Ophthalmopathy**

The clinical manifestations of hyperthyroidism are due to the stimulatory effect of thyroid hormones on metabolism and tissues. Nervousness, eye complaints, insomnia, weight loss, tachycardia, palpitations, heat intolerance, damp and hot skin with excessive sweating, tremors, hyperdefecation and muscle weakness are the main characteristics [13, 14].

In GD, goiter is singularly diffuse, being present in 97% of cases. Asymmetric or lobular, with variable volume. In some patients, an exclusive finding of the disease is that the increase in blood flow brings the presence of thrill and murmur over the gland. Any patient with diffuse goiter and hyperthyroidism has GD until proven otherwise. In the elderly, when present, the goiter tends to be small [15, 16].

Ophthalmopathy or orbitopathy has an equivalent autoimmune pathogenesis as GD hyperthyroidism and may exacerbate both hypo and thyroid hyperfunction. Antibodies react by causing intraorbital auto-aggression, as in tissue thyroid. Ophthalmopathy can precede hyperthyroidism (20% of the time), succeed it (40%) or appear concomitantly with it (40%) [1, 15].

The cases during which ophthalmopathy, transiently or permanently, isn't in the course of hyperthyroidism are called Graves' euthyroid disease. Clinically evident ophthalmopathy occurs in up to 50% of patients with GD. It stems from the thickening of the muscles extraocular and increased retrobulbar fat, which results in a rise in intraorbital pressure. Consequently, protrusion of the eyeball (proptosis or exophthalmos) and decreased venous drainage may occur, leading to periorbital edema, conjunctival edema and conjunctival hyperemia [16, 17].

The most common ocular manifestations in the GD are the eyelid retraction, the stare or frightened look and the sign of lid-lag (delay in lowering the upper eyelid when the eyeball is moved down). Nevertheless, they occur in any sort of thyrotoxicosis, as they're consequent to adrenergic hyperactivity. On the opposite hand, the finding of periorbital edema and exophthalmos practically confirms the diagnosis of GD. Additionally, diplopia can occur in 5 to 10% of patients, because of the functional impairment of the musculature extrinsic ocular. Ophthalmoplegia and eyelid ptosis also can occasionally be seen. Finally, severe cases, there could also be dysfunction of the nervus opticus, defects in the visual fields, disturbance of vision in color or loss of vision [1, 15–18].

GD exophthalmos is typically bilateral, but it can be unilateral. During this situation, it must be differentiated from a tumor retrobulbar or arteriovenous malformation using computerized tomography or resonance imaging. The most effective way to verify the existence of the property and establish its magnitude is by using Hertel's exophthalmometer. A measurement greater than 20 mm in Caucasians is taken into account abnormal, 18 mm between Orientals and 22 mm in blacks. However, caution is required in borderline interpretations of up to

2 mm. Proposals are often selected as mild (increase of 3 to 4 mm), moderate (5 to 7 mm) and severe (>7 mm) [1, 16, 18].
