THYROIDITIS 
The more common and clinically significant thyroidites are:  
1. Hashimoto thyroiditis 
2. Subacute granulomatous thyroiditis
3. Subacute lymphocytic thyroiditis 

Hashimoto thyroiditis 

Hashimoto thyroiditis (Chronic Lymphocytic Thyroiditis) is the most common cause of hypothyroidism. It results from gradual autoimmune destruction of the thyroid gland. There is striking female predominance (10: 1 to 20:1), and is most prevalent around a mean age of 50 years. 

Pathogenesis 
• The dominant feature is progressive destruction of thyroid follicular epithelial cells with gradual replacement by mononuclear cell infiltration and fibrosis. 
• Sensitization of CD4+ T-helper cells to thyroid antigens seems to be the initiating event.
• The reaction of CD4+ T cells with thyroid antigens produces interferon γ  which promote inflammation and activate macrophages. Injury to the thyroid results from the toxic products of these inflammatory cells. 
• CD8+ cytotoxic T cells also contribute to epithelial cells killing as are natural killer cells. 
• There is a significant genetic component to disease pathogenesis. This is supported by 
1.  The increased frequency of the disease in first-degree relatives, 
2.  Unaffected family members often have circulating thyroid autoantibodies.  

Gross features 
• The thyroid shows moderate, diffuse, and symmetric enlargement.
• The cut surface is pale, gray-tan, firm, nodular and somewhat friable. 
• Eventually there is thyroid atrophy 

Microscopic features

• There is widespread, diffuse infiltration of the parenchyma by small lymphocytes, plasma cells.  The lymphocytes are also form follicles some with well-developed germinal centers 
• The thyroid follicles are atrophic and lined by epithelial cells having abundant eosinophilic, granular cytoplasm (Hurthle cells). This is a metaplastic response to the ongoing injury; ultrastructurally the Hurthle cells are stuffed by numerous mitochondria. 
• Interstitial connective tissue is increased and may be abundant.

Hashimoto thyroiditis presents as painless symmetrical goiter, usually with some degree of hypothyroidism. In some cases there is an initial transient thyrotoxicosis caused by disruption of thyroid follicles, with secondary release of thyroid hormones ("hashitoxicosis"). As hypothyroidism supervenes T4 and T3 levels progressively fall & TSH levels are increased. Patients often have other autoimmune diseases and are at increased risk for the development of B-cell non-Hodgkin lymphomas. 

Subacute Granulomatous (de Quervain) Thyroiditis 

Subacute Granulomatous (de Quervain) Thyroiditis is much less common than Hashimoto disease.

- It is most common around the age of 40 years and occurs more frequently in women than in men.

- An upper respiratory infection just before the onset of thyroiditis. Thus, a viral infection is probably the cause.

- There is firm uni- or bilateral enlargement of the gland.

Microscopically, there is disruption of thyroid follicles, with extravasation of colloid. The extravasated colloid provokes a granulomatous reaction, with giant cells.
Thyroid function tests are those of thyrotoxicosis but with progression and gland destruction, a transient hypothyroid phase occurs. The condition is self-limited, with most patients returning to a euthyroid state within at most 2 months.

Subacute Lymphocytic Thyroiditis

Subacute Lymphocytic Thyroiditis may follow pregnancy (postpartum thyroiditis).

- It is most likely autoimmune in etiology, because circulating antithyroid antibodies are found in the majority of patients.

- It mostly affects middle-aged women and present as painless, mild, symmetric neck mass. Initially, there is thyrotoxicosis, followed by return to a euthyroid state within a few months. In a minority there is progression to hypothyroidism.

Microscopically, there is a lymphocytic infiltration and hyperplastic germinal center within the thyroid parenchyma; unlike Hashimoto thyroiditis, follicular atrophy or Hürthle cell metaplasia are not commonly seen.

Riedel thyroiditis 

Riedel thyroiditis is a rare disorder of unknown etiology, characterized by extensive fibrosis involving the thyroid and the surrounding neck structures. The presence of a hard and fixed thyroid mass may be confused clinically with thyroid cancer. It may be associated with idiopathic fibrosis in other sites, such as the retroperitoneum. The presence of circulating antithyroid antibodies in most patients suggests an autoimmune etiology. 

Acute pericarditis

1. Characterized by inflammation of the pericardium.
2. Causes include:
a. Viral infection.
b. Bacterial infection, including Staphylococcus, Pneumococcus.
c. Tuberculosis.
d. MI.
e. Systemic lupus erythematosus.
f. Rheumatic fever.

3. Signs and symptoms include:
a. Pericardial friction rub on cardiac auscultation.
b. Angina.
c. Fever.

4. Consequences include constrictive pericarditis,which results from fusion and scarring of the pericardium. This may lead to the restriction of ventricular expansion, preventing the heart chambers from filling normally.

Rheumatic fever

Before antibiotic therapy, this was the most common cause of valvular disease.
1. Usually preceded by a group A streptococci respiratory infection; for example, strep throat.
2. All three layers of the heart may be affected. The pathologic findings include Aschoff bodies, which are areas of focal necrosis surrounded by a dense inflammatory infiltration.

3. Most commonly affects the mitral valve, resulting in mitral valve stenosis, regurgitation, or both.

Actinic keratosis
1. Dry, scaly plaques with an erythematous base.
2. Similar to actinic cheilosis, which occurs along the vermilion border of the lower lip.
3. Caused by sun damage to the skin.
4. Dysplastic lesion, may be premalignant.

Acanthosis nigricans is a pigmented skin lesion commonly present in the axilla which is a phenotypic marker for an insulin-receptor abnormality as well as a marker for adenocarcinoma, most commonly of gastric origin.

Immunodeficiency

This may be :- 
- Congenital (Primary)
- Acquired (Secondary)

Features : Complete or near complete lack of T & B lymphoid tissue. Fatal early in life Even with marrow grafting, chances of graft versus host reaction is high.

T Cell Defects :

- Thymic dysplasia
- Digeorge’s syndrome
- Nazelof’s syndrome
- Ataxia teltngiectaisa
- Wiscott Aldrich’s syndrome

These  lessons show predominantly defective cell mediated immunity. But they may also show partial immunoglobulin defects cell mediated immunity. But they may also show partial immunoglobulin defects due to absence og T-B co-operation.

C. Humoral immunity defects.
Bruron type- aggammaglobulinaemia.
- Dysgammaglobulinaemias-variable immunodeficiency’s of one or more classes.

Acquired deficiency

A. Immuno suppression by :
- Irradiation.
- Corticoids.
- Anti metabolites.
- Anti lymphocyte serum.

B. Neaplasia  of lymphoid system :

- Hodgkin's and Non Hodgkin's lymphomas.
- Chronic lymphocytic leukaemia..
- Multime myeloma and other paraproteinaemias (normal immunoglobulins reduced in spite of hyperglobulinaemia).

c. excessive protein loss.
- Nephrotic Syndrome.
- Protein losing enteropathy.