*6.2.1. Risk factors for Graves' ophthalmopathy*

There is no specific genetic predisposition for graves' ophthalmopathy. Environmental factors are more important for ophthalmopathy.

#### *Smoking*

166 Thyroid Hormone

**4.6. Super antigens** 

**5. Pathology** 

lobe is often prominent.

**6. Clinical features**

other causes of thyrotoxicosis.

**6.1. Thyroid gland** 

Super antigens are endogenous or exogenous proteins such as microbial proteins, capable of stimulating a strong immune response through molecular interactions with non-variant

Grossly the thyroid gland is diffusely enlarged with smooth and hyperemic surface. Rarely the gland is grossly nodular. Consistency of the gland varies from soft to firm. Pyramidal

Microscopically both hypertrophy and hyperplasia are seen. Follicles are small with scanty colloid, and lined by hyperplasic columnar epithelium which can give a pseudopapillary appearance. Vascularity of the gland is increased. There is varying degree of infiltration by lymphocytes and plasma cells. T cells predominate in the interstitium, whereas B cells and

On electron microscopy there is increased golgi reticulum and mitochondria, and it is also

After treatment with antithyroid drugs and radioiodine, the vascularity of the gland decreases, follicles enlarges and filled with colloid, and papillary projection regresses.

Graves' disease is the most common cause of thyrotoxicosis. Most common age of onset is third to fourth decade of life but it can occur in children and elderly. The hallmark of Graves' disease is signs and symptoms of thyrotoxicosis along with diffuse goiter and typical Graves' orbitopathy. Most of the signs and symptoms are similar to other causes of thyrotoxicosis, but some of the signs and symptoms like orbitopathy, dermopathy or

Onset of Graves' disease is usually gradual. Signs and symptoms are presents months before the diagnosis, and usually patients do not remember the exact date of onset of symptoms. Onset can be abrupt in some cases. The signs and symptoms are usually more severe than

Thyroid gland is diffusely enlarged in Graves' disease, but it can be nodular especially in areas of iodine deficiency where nodular goiter preexists before the onset of Graves' disease. Goiter size is variable. It can range from normal size thyroid gland to massively enlarged thyroid. Usually size of goiter is two to three times that of normal. Normal size thyroid gland can the seen in as many as 20% of patients and most of them are elderly. The consistency of the goiter varies from soft to firm but softer than the goiter of Hashimoto's

pretibial myxedema and thyroid acropachy are unique to Graves' disease.

parts of the T- cell repertoire and the HLA class II proteins.

plasma cells predominate in lymphoid follicles.

characterized by presence of prominent microvilli.

Smoking is a major risk factor for ophthalmopathy. Smoking also increases the risk for worsening of ophthalmopathy after radioiodine treatment. Possible contributors are orbital hypoxia and free radical present is smoke. 32,33

#### *Gender*

Graves' disease is predominantly a disease of females (F: M= 8-10:1). In comparison to Graves' disease, ophthalmopathy is relatively more common in males (F: M= 1:1.8-2.8) than females. 34,35

#### *Radioiodine*

Graves' disease patients treated with radioiodine are at increased risk for onset and worsening of eye disease, as compared to antithyroid drugs alone. 36,37 This risk can be decreased by concurrent use of corticosterodis.38,39

#### *6.2.2. Pathogenesis*

Current evidence support an autoimmune pathogenesis with important environmental influences, particularly smoking. Orbital muscles, connective tissues, and adipose tissues are infiltrated by lymphocytes and macrophages. TH1 mediated immune response predominates in early stage of disease while TH2 response predominates in late stage. 40 In response to cytokines secreted by the infiltrating immune cells, orbital fibroblasts start synthesizing and secreting hydrophilic glycosaminoglycans, resulting in edema of orbital

tissues. Additionally adipocytes present in orbit become active and results in expansion of orbital adipose tissues. Both these factors are responsible for expansion of orbital tissues.

Thyroid Hormone Excess: Graves' Disease 169

**Classes Ocular symptoms and signs** 0 No signs and symptoms

3 Proptosis (>22 mm)

5 Corneal involvement

*6.2.6. Clinical activity of ophthalmopathy* 

active ophthalmopathy.

subcutaneous tissues.

acropachy.

**6.4. Thyroid acropachy** 

**6.3. Thyroid dermopathy** 

**Table 3.**

1 Only signs (lid retraction, lid lag, proptosis upto 22 mm)

To know the clinical activity of ophthalmopathy is important, because active disease is more likely to respond to immunosuppressive therapy. Clinical Activity Score (CAS) is used to know the clinical activity. Seven parameters are used in the clinical activity scoring which include spontaneous retrobulbar pain, pain on eye movement, eyelid erythema, conjuctival injection, swelling of the eyelids, inflammation of the caruncle and conjunctival edema or chemosis. Each parameter is assigned 1 point. CAS of more than or equal to 3/7 indicates

Thyroid dermopathy presents in less than 5% of patients with Graves' disease. It is almost always accompanied by moderate to severe ophthalmopathy. Most commonly it is present over anterior and lateral aspects of leg, hence it is also known as pretibial myxoedema. Less commonly it can present over dorsa of the feet, dorsa of the hands, forearm, face and elbows, particularly after trauma. The typical lesion is a noninflamed, indurated plaque with a deep pink or purple color and an orange skin appearance. Nodular form is the intermediate while elephantiasis is the most severe form of thyroid dermopathy. Thyroid dermopathy occurs due to accumulation of glycosaminoglycans in the dermis and

Thyroid acropachy is the least common manifestation of Graves' disease. It is a form of clubbing, and presents in less than 1 percent of patients of Graves' disease. It is almost always associated with the severe and long standing ophthalmopathy and dermopathy. An alternate diagnosis should be considered in the absence of ophthalmopathy and dermopathy. Deposition of glycosaminoglycans in skin is responsible for thyroid

2 Soft tissue involvement (periorbital edema)

4 Extraocular muscle involvement (diplopia)

6 Sight loss (optic nerve involvement)
