Thyroid Gland - Applied Pathology

The thyroid gland in an adult weighs 15-40 gm and is composed of 2 lateral lobes connected in the midline by a broad isthmus. Thyroid gland is composed of lobules of colloid- filled spherical follicles or acini. The follicles are the main functional units of the thyroid gland.

The major function of thyroid gland is to maintain a high rate of metabolism which is done by means of iodine containing thyroid hormones, thyroxine (T4) and Triiodothyronine (T3). T3 and T4 are formed by sequential reactions occurring in the thyroglobulin molecule under the control of TSH. Total plasma level of T4 is 4-8µ g/ dl. And T3 is 150-250 n g/ dl. Normal range of TSH is up to 5 µ units per ml.

Diffuse enlargement of the thyroid gland is described as goiter (goiter or bronchocele). It is derived from the Latin word, Gutter- the throat. Goitre is merely a symptom of a more serious thyroid condition, such as:

Hyperthyroidism

Hypothyroidism etc

Classification of Goitre

Simple goiter

a. Physiological goiter

b. Parenchymatous goitre

c. Colloid goiter

d. Multinodular goiter

Toxic goiter

a. Grave’s disease

b. Secondary thryotoxicosis in M N G

c. Solitary nodule

Neoplastic goiter

a. Benign adenoma (follicular adenoma)

b. Malignant tumours

i. Primary

ii. Metastatic (Secondary)

Thyroiditis

i. Autoimmune thyroiditis

ii. Infectious thyroiditis

iii. Granulomatous thyroiditis

iv. Riedel’s thyroiditis

SIMPLE GOITRE

This may be endemic or sporadic. Puberty goiter, colloid goiter, and parenchymatous goiter are included in this group. The thyroid gland is diffusely enlarged, painless and non-tender. It may be soft or firm in consistency.

Etiology

Simple goiter is the result of iodine deficiency.

Endemic goiter:

Prevalence of goiter in a geographic area in more than 10% of the population is termed endemic goiter. Such endemic areas are high mountainous regions far from the sea where iodine content of drinking water and food is low. Some cases occur due to goitrogens and genetic factors. Goitrogens are substances which interfere with the synthesis of thyroid hormones. These substances are drugs used in the treatment of hyperthyroidism and certain items of food such as cabbage, cauliflower, turnips and cassava (tapioca) roots. Cabbage contains thiocyanates which inhibit iodine uptake. Cassava contains cyanogenic glycosides which are converted to thiocyanate.

Sporadic goiter:

Sporadic goiter is less common than the endemic variety. In most cases the etiology of sporadic goitre is unknown. A number of causal influences have been attributed. These include:

Suboptimal iodine intake in conditions of increased demand as in puberty and pregnancy.

Genetic factors.

Dietary goitrogens.

Hereditary defect in thyroid hormone synthesis and transport (dyshormonogenesis).

Inborn errors of iodine metabolism

Pathologic Changes

Grossly, the enlargement of in simple goiter is moderate (weighing up to 100-150 gm), symmetric and diffuse. Cut surface is gelatinous and translucent brown.

Histologically two stages are distinguished:

Ø Hyper plastic stage: It is the early stage and characterized by tall columnar epithelium showing papillary infoldings and formation of small new follicles.

Ø Involution stage: This stage generally follows hyper plastic stage. This stage is characterized by large follicles distended by colloid and lined by flattened follicular epithelium.

The cells may undergo hyper involution. In this case the acini become filled with colloid and diffuse colloid goiter may develop. With repeated episodes of iodine depletion and repletion, multi nodular goiter may develop.

Preventive measures

Fortification of common salt with iodide (1 part to 100000 parts) and distribution in endemic areas has been partially successful in many regions.

Treatment

Administration of thyroxine up to .3mg/ day brings about a favorable response in 60% of subjects. The gland shrinks within 3 months of starting treatment.

TOXIC GOITRE- THYROTOXICOSIS

It is a complex of disorder which occurs due to increased levels of thyroid hormones (Hyperthyroidism) and manifests clinically with various signs and symptoms. The causes of thyrotoxicosis are:

Primary thyrotoxicosis (Grave’s disease, exophthalmic goiter)

Secondary thyrotoxicosis secondary to multi nodular goiter (Plummer’s disease).

Solitary toxic nodule: Autonomous nodule which is not under the influence of TSH, but occurs due to hypertrophy and hyperplasia of gland (tertiary thyrotoxicosis).There is an increase in T3 and T4 level. Iodine 131 scan can demonstrate a hot nodule. Histological diagnosis can be made by FNAC.

Other causes of thyrotoxicosis

I. Thyrotoxicosis facticia: False thyrotoxicosis occurs due to over dosage of thyroxine, given for puberty goiter.

II. Jod Basedow’s thyrotoxicosis: Jod means iodine in German language, Basedow means toxic goiter.Iodine induced thyrotoxicosis (iodine given for hyperplastic endemic goiters).

III. Initial stage of thyroiditis.

IV. Very rarely, malignant goiters can be toxic.

V. Neonatal thyrotoxicosis occurs in babies born to thyrotoxic mothers.

GRAVE’S DISEASE (Diffuse toxic goiter, Parry’s disease, Base Dow’s disease).

Etiology

Exact etiology is unknown. Possible etiological factors are:

Autoimmune disorder is the first possible cause due to the demonstration of auto antibodies in the circulation.

Familial: The disease can run in families.

Thyroid Stimulating Immunoglobulins (TSI) and long acting thyroid stimulator (LATS) are responsible for pathological changes in the thyroid gland in Grave’s disease.

Exophthalmos producing substance (EPS) is responsible for ophthalmopathy which is seen in Grave’s disease.

Female sex, emotions, stress, young age also have been considered as the other factors responsible for the disease.

Pathology

Thyroid is diffusely enlarged due to hyperplasia of acinar cells and increased vascularity. Histologically the acinar cells are hyper plastic, with absorption of colloid. Varying degrees of lymphocytic infiltration is also seen.

Thyroid associated eye disease is a frequent manifestation of thyroid disorders, particularly hyper thyroidism. Extra ocular muscles are the target of auto immune response. The interstitium shows diffused mono nuclear infiltration, primarily by activated T-cells with some B-cells and occasional macrophages. The retro bulbar fibroblasts and skin fibroblasts are affected by the auto immune process. Grave’s ophthalmopathy and dermopathy are strongly associated.

Clinical features

Grave’s disease is more frequent in young women. The general symptoms attributable to hyper metabolic state includes:-

Rarely mental changes like sever agitations and frank psychosis may be the presenting features.

Examination of the neck shows the thyroid to be diffusely enlarged, but some times it may be asymmetrical. It is soft, warm, pulsatile and tender. Arterial thrills and bruit may be detectable. These phenomena indicate increased vascularity.

Thyroid associated eye disease may present in several ways, 90% have overt hyperthyroidism. 10% have no obvious thyroid dysfunction. Those with no signs of thyrotoxicosis are known as ophthalmic Grave’s disease. Main clinical features include diplopia with vertical separation of visual images, asymmetry of palpebral fissures, movement disorders of eye balls and lids and compression of the optic nerve. Sympathetic over activity leads to lid lag, stare, increased watering and infrequent blinking. These subside with correction of thyroid function. There is abnormal protrusion of eye ball (exophthalmos) and partial or complete ophthalmoplegia. In severe cases there is chemosis of the conjunctiva, prolapse of the eye ball, failure of closure of the eye lids, corneal ulsarations and blindness can occur. These constitute malignant exophthalmos.

The skin is soft and moist. The hair is soft, sweating is excessive and the nails show thinning (Onycholysis). Sometimes localized myxoedematous deposits may occur. The common site is in front of the leg (hence called pretibial myxoedema). Over this site the skin is raised. The lesions may be pruritic. Examination reveals ‘peau de orange’ appearance. Pretibial myxoedema is attributed to local non-responsiveness of tissues to the thyroid hormones. Some cases show clubbing of fingers and toes and hypertrophic oesteoartropathy (thyroid acropachy).

There is excessive weakness and fatigue. The proximal muscles of pelvic and pectoral girdles may show myopathy. Myasthenia gravis may coexist with Grave’s disease.

Cardiac out put increases out of proportion to the rise in basal metabolic rate. Atrial fibrillation occurs in up to 25% of the cases. Other arrythmias such as paroxysmal tachycardia and atrial flutter are also common. Some patients develop effort angina.

Menses may be scanty and fertility is reduced. In men libido and potency may be altered variably. Gynecomastia may develop, oligospermia may occur.

The general clinical picture produced by toxic diffused goiter and toxic nodular goiter is similar in many respects. However eye changes and pretibial myxoedema are more common in toxic diffuse goiter. Grave’s disease is more frequent in younger age group. Toxic adenomas occur usually in later age groups. In them cardiovascular manifestations are more prominent. In toxic adenoma local examination of thyroid may not reveal generalized hypervascularity and bruit, but the condition can be easily diagnosed by palpating nodules.

In florid cases clinical diagnosis is easy. In all cases it is advisable to confirm diagnosis and establish its severity by investigations.

I 131 uptakes by the thyroid gland, levels of T4 and T3 are all increased. TSH is low.

Follicular adenoma: is the most common benign thyroid tumor occurring more frequently in adult women.

It is characterized by four features so as to distinguish from a nodule of nodular goiter

Histologically the tumor cells are benign follicular epithelial cells forming follicles of various sizes or may show trabecular, solid and cord patterns with little follicle formation. Accordingly the following six types of growth patterns are distinguished.

5) Hurthle cell (oxyphilic) adenoma: composed of large cells having abundant granular or oxyphilic cytoplasm

6) Atypical adenoma: follicular adenoma which has more pronounced cellular proliferation so that features may be indicative of malignancy.

It is the most common type of thyroid carcinoma. It is typically a slow growing tumor, most often presenting as an asymptomatic solitary nodule. Involvement of the regional lymph node is common but distant metastases to organs are rare.

Sometimes the tumor is transformed into a cyst, into which numerous papillae project and is termed papillary cystadenocarcinoma. Histologically the following features are present:

2) Tumor cells have overlapping pale nuclei (ground glass appearance) and clear or oxyphilic cytoplasm.

4) Half of the papillary carcinomas show typical small, concentric, calcified spherules called psammoma bodies.

It may be either in the form of a solitary adenoma- like circumscribed nodule or as an obvious cancerous irregular thyroid enlargement. Microscopically it is composed of follicles of various sizes and may show trabecular or solid pattern. However, variance like clear cell type and hurthle cell type may occur. Vascular invasion is common but lymphatic invasion is rare.

It is a less frequent type derived from parafollicular or C- cells present in the thyroid. It has genetic association with genetic defect in chromosome-10. They secrete calcitonin, the hypocalcaemic hormone. These hormones elaborations are responsible for a number of clinical syndromes such as carcinoid syndrome, Cushing’s syndrome and diarrheoa and they have amyloid deposits in the trauma. The tumour may either appear as a unilateral solitary nodule (sporadic form) or have bilateral and multi centric involvement (familial form).

Undifferentiated or anaplastic carcinoma comprises less than 5% of all thyroid cancers. The prognosis is poor. The tumour is generally large and irregular. There are three histological variants.

This is a group of thyroiditis having, in common, infiltration of the thyroid by lymphocytes and plasma cells and occurrence of thyroid specific auto antibodies in the serum. Autoimmune thyroiditis includes:

a. Hashimoto’s Thyroiditis: Also called diffuse lymphocytic thyroiditis, struma lymphomatosa or Goitrous auto immune thyroiditis.