Thyroid disorder

Thyroid disorder

• Hyperthyroidism (increased levels of free T3 and T4)

• Hypothyoridism (decreased thyroid hormone)

Hyperthyroidism

Cause:Primary:• Diffuse toxic hyperplasia (Graves disease)• Hyperfunctioning multinodular goiter• Hyperfunctioning adenomaSecondary:• TSH secreting pituitary adenoma

Clinical featuresIncreased sympathetic activity:

Skin: soft, warm, flushedWeight loss despite increase appetiteCardiac:

Tachycardia,palpitationNeuromuscular system: tremor,anxietyOccular changes: staring gaze, lid lagGIT: malabsorption,diarrhoeaSkeletal system: osteoporosis, increased risk fracture

Lab diagnosis

TSH (thyroid stimulating hormones): DecreasedT4 and T3: increased.

Hypothyroidism

Structural or functional derrangement that interfer with production thyroid hormones (decreased T3 and T4)

Cause:Primary:• Developmental: thyroid dysgenesis,thyroid

agenesis• Defect in thyroid hormone receptor• Autoimmune hypothyroidism: Hashimoto

thyroiditis• Iodine deficiencySecondary: • Pituitary failure: pituitary adenoma

CRETINISM

• Cretinism refers to hypothyroidism that develops in infancy or early childhood.

Clinical features • impaired development of the skeletal system

and central nervous system: manifested by• severe mental retardation• short stature • protruding tongue • umbilical hernia

MYXEDEMA

• hypothyroidism developing in the older child or adult.

• Also called Gull disease• Clinical features of myxedema are

characterized by a slowing of physical and mental activity.

Graves Disease

Graves disease

• Graves disease is characterized by a triad of clinical findings

1. Hyperthyroidism: due to diffuse, hyperfunctional enlargement of the thyroid

2. Infiltrative ophthalmopathy: with resultant exophthalmos

3. Localized, infiltrative dermopathy, sometimes called pretibial myxedema, (which is present in a minority of patients)

Syn: Basedow’s disease/ diffuse toxic goiter

• Age: between 20 and 40 years of age• Women are affected as much as 10 times

more frequently than men.

Pathogenesis

• breakdown in self-tolerance to thyroid auto-antigens, most importantly the TSH receptor. The result is the production of multiple autoantibodies, including

1.Thyroid-stimulating immunoglobulinThis IgG

bindsTSH recptor

Mimic the action of TSH

Adenyl cyclase

Increase release of thyroid hormones

2. Thyroid growth-stimulating immunoglobulins• directed against the TSH receptor• proliferation of thyroid follicular epithelium3. TSH-binding inhibitor immunoglobulinanti–TSH receptor antibodies prevent TSH from

binding normally to its receptor on thyroid epithelial cells

• Autoimmunity also plays a role in the development of the infiltrative ophthalmopathy

• The volume of the retro-orbital connective tissues and extraocular muscles is increased for several reasons

1.marked infiltration of the retro-orbital space by mononuclear cells, predominantly T cells

2. inflammatory edema and swelling of extraocular muscles;

3. accumulation of extracellular matrix components

4. increased numbers of adipocytes (fatty infiltration)

These changes displace the eyeball forward

Morphology

• Gross: symmetrically enlarged because of diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells

• On cut section- soft, meaty appearance (Red fleshy) resembling normal muscle

• Microscopic:• Papillae formation: The follicular cells are tall

and more crowded and thrown into papillae with lack of fibrovascular core.

• The colloid is thin and pale with scalloped margins

Changes in extra thyroid tissue

• lymphoid hyperplasia• Heart: hypertrophied and ischemic changes• Opthalmopathy: • orbit are edematous• Infiltration by lymphocytes and fibrosis• Dermatopathy: thickening of the dermis due

to deposition of glycosaminoglycans and lymphocyte infiltration.

FIGURE 24-13 Graves disease. A, There is diffuse symmetric enlargement of the gland and a beefy deep red parenchyma.

The follicles are lined by tall, columnar epithelium. The crowded, enlarged epithelial cells project into the lumens of the follicles. These cells actively resorb the colloid in the centers of the follicles, resulting in the scalloped appearance of the edges of the colloid

Clinical features

• Diffuse hyperplasia of the thyroid,• Ophthalmopathy : abnormal protusion of eye

ball (exophthalmos)• Dermopathy: most common in the skin

overlying the shiny scaly thickening and induration

Lab findings…

• Free T4 and T3: Increased• TSH levels: Decreased

Thyroiditis

Thyroiditis

• inflammation of the thyroid gland

Types• Acute thyroiditis: Caused by bacteria/fungus• Hashimoto thyroiditis • Granulomatous (de Quervain) thyroiditis• Subacute lymphocytic thyroiditis.• Reidel (Fibrous) Thyroiditis

Hashimoto Thyroiditis

• Characterized by gradual thyroid failure because of autoimmune destruction of the thyroid gland

• Most common cause of hypothyroidism• Age: 45 and 65 years of age• Sex:

Female:Male -10 : 1 to 20 : 1

Pathogenesis

• Multiple immunologic mechanisms may contribute to thyroid cell death:

• The main defect in Hashimotos thyroiditis is a T cell defect

• The T cell recognises the thyroid antigen and causes proliferation of T cells

• CD8+ cytotoxic T cell–mediated cell death: CD8+ cytotoxic T cells may cause thyrocyte destruction.

• .

• Cytokine-mediated cell death: Excessive T-cell activation leads to the production of TH1 inflammatory cytokines such as interferon-γ in the thyroid gland: recruitment and activation of macrophages and damage to follicles

• Binding of anti-thyroid antibodies (anti-thyroglobulin, and anti-thyroid peroxidase antibodies

Pathogenesis

FIG:athogenesis of Hashimoto thyroiditis. Breakdown of peripheral tolerance to thyroid auto-antigens, results in progressive autoimmune destruction of thyrocytes by infiltrating cytotoxic T cells, locally released cytokines, or by antibody-dependent cytotoxicity.

Morphology

• Gross: -The thyroid diffusely enlarged-The capsule is intact, and the gland is well

demarcated from adjacent structures.

Microscopic:• Extensive infiltration of parenchyma by a

mononuclear inflammatory infiltrate containing small lymphocytes and plasma cells

• Lymphoid follicle formation with well developed germinal centers

• Thyroid follicles are atrophic and are lined by Hurthles cells

• Hurthle cells: epithelial cells with abundant eosinophilic granulkar

Fig.Hashimoto thyroiditis showing lymphoid follicles with prominent germinal centers and oncocytic follicular epithelium

Fig.Hashimoto thyroiditis with extensive fibrosis, atrophy of follicular epithelium

Clinical features

• painless enlargement of the thyroid• Hypothyroidism…

THANK YOU