Nishiyama 09-19-07

Front 1

Antibodies in patients with Graves Disease

Back 1

Thyroid stimulating antibodies (TSAb)
Thyroid stimulating blocking antibodies (TSBAb)
Anti-thyroid peroxidase (TPOAb)
Anti-TGAb (anti-thyroglobulin antibodies)
Anti-iodide symporter
Anti-components of eye muscle and/ or fibroblasts
Antibodies to DNA
Antibodies to parietal cells (infrequent)
Antibodies binding to platelets

Front 2

Three diseases share same immunological changes, histology & genetic predisposition:
1) graves
2) ?
3) ?

Back 2

Graves dis, AITD, idiopathic failure

(AITD, characterized by goiter and various degrees of hypothyroidism
Idiopathic “atrophic” hypothyroidism is a result of AITD, and myxedema is most advanced form of disease)

Front 3

In the three diseases, antibodies & cell-mediated immunity are directed against:

Back 3

TSH receptor (megalin), thyroid peroxidase& thyroglobulin

Front 4

In pts with ophthalmopathy, antibodies against components of _____ _____ and fibroblasts are formed

Back 4

orbital muscles

Front 5

Pathogenesis of Graves Disease:

Three sets of antibodies are produced:

Back 5

TSAb: thyroid-stimulating & acts similar to TSH

TSBAb: thyroid stimulating blocking antibody – blocks binding of TSH, but not stimulatory by itself

Third set neither blocks nor stimulates thyroid function (TBII: thyrotropin binding inhibitory immunoglobulins

TSAb mediates the thyroid activity and hypersecretion seen in Graves Dis

Front 6

B cells produce what antibodies to cause Graves disease?

Back 6

anti-TSH receptor IgG

Front 7

What is the thyroid hormone feedback circuit?

Back 7

thyroid hormone tells pituitary to stop production of TSH.

Front 8

Describe the onycholysis of thyrotoxicosis

Back 8

Distal separation of the nail plate from the nail bed (Plummner's nails)

Front 9

Thyroid gland, acropachy (clubbing of fingers)

Back 9

?

Front 10

Pretibial myxedema

Back 10

?

Front 11

Thyroid gland, Localized myxedema (pretibial)

Back 11

?

Front 12

Other Causes of Hyperthyroidism

Back 12

Toxic nodular goiter
Follicular adenoma
Solitary “hot” nodule
TSH-mediated thyrotoxicosis
Pituitary tumor
Pituitary resistance to thyroid hormone
HCG-mediated hyperthyroidism
Hydatidiform mole
Choriocarcinoma
Other HCG-related tumors
Thyroid carcinoma (rare)

Front 13

Thyroid gland, nodular goiter, hyperthyroidism

Back 13

?

Front 14

Heart problem assoc with Graves

Back 14

pericardial effusion

acute necrosis of myocardium

Front 15

Autoimmune thyroiditis. Note: Clusters of Hurthle cells
in sea of lymphocytes

Back 15

?

Front 16

Bands of fibrous tissue in autoimmune thyroiditis.

Back 16

?

Front 17

Autoimmune thyroiditis in nodular goiter

Back 17

?

Front 18

What causes collections of lymphocytes in the gland and is responsible for epithelial cell damage?

Back 18

thyroid autoimmunity

Front 19

Progression of disease can change picture from “goitrous” hypothyroidism to “_______” thyroiditis (known as primary hypothyroidism)

Back 19

atrophic

Front 20

Alternative cause of “atrophic” hypothyroidism is development of ________ Abs

Back 20

thyroid stimulation blocking antibodies (TSBAb)

Front 21

thyroid stimulation blocking antibodies (TSBAb) Prevents TSH binding to TSH-R, but do not stimulate thyroid cells to produce _____

Back 21

hyperthyroidism

Front 22

Proposed that TSBAb binds to one end of TSH-R, while thyroid stimulating antibodies (TSAb) bind to ______

Back 22

opposite end of TSH-R

Front 23

A predominant TSAb response results in ______

Back 23

hyperthyroidism

Front 24

A predominant TSBAB response results in _______

Back 24

hypothyroidism

Front 25

HLA antigens of hypothyroid pts with TSAb were different from pts with Hashimoto thyroiditis & idiopathic myxedema and more similar to pts with ______ disease

Back 25

Graves

Front 26

Thyroid dysfunction may be induced by ______-mediated apoptosis of thyroid epithelial cells

Back 26

cytokine

Front 27

___ lymphocytes may not be directly involved in thyrocyte cell death

Back 27

T

Front 28

______ DNA, a feature of apoptosis, was found frequently in autoimmune thyroiditis

Back 28

Fragmented

Front 29

Ligand for Fas (Fas L), expressed on thyrocytes, induced by IL-1alpha, which is abundantly produced in thyroid gland of Hashimoto thyroiditis, induces ___ expression on thyrocytes

Back 29

Fas

Front 30

_______ interaction on thyrocytes may induce apoptosis & destruction of thyroid cells

Back 30

Fas-FasL

Front 31

Fas & FasL strongly stained in follicular cells which suggests that cytokines induce up-regulation of ______-

Back 31

apoptosis

Front 32

Increased serum TSH may inhibit ____-mediated apoptosis of thyrocytes

Back 32

Fas

Front 33

In contrast, _____ blocks inhibitory action of Fas-mediated apoptosis and induces thyroid atrophy

Back 33

TSBAb

Front 34

In relation to Fas-FasL system, mutations of Fas, which induce loss of function, found in thyroid lymphocytes of 38% of pts with ______ thyroiditis

Back 34

Hashimoto


(Additionally, in 64% of pts with malignant lymphoma)

Front 35

There is a relationship of AIT to malignant ______

Back 35

lymphoma

Front 36

Antithyroglobulin autoantibody stains colloid

Back 36

?

Front 37

Antimicrosomal antibody stains follicular epithelium

Back 37

?

Front 38

Most common cause of hypothyroidism in American women

Back 38

Autoimmune Thyroiditis (AIT)

Front 39

Etiology of AIT?

Back 39

Etiology unknown

Front 40

Who is affected by AIT?

Back 40

Affects older women (45-65 yrs), usually asymptomatic, with goiters (diffuse, non-nodular)

Front 41

Lab findings in early AIT?

Back 41

Early laboratory changes: decreased T4, increased TSH

Front 42

Treatment of AIT?

Back 42

Lifetime replacement with thyroid hormone

Front 43

Cancer risk after AIT?

Back 43

Slightly increased risk for malignant lymphoma of thyroid gland

Front 44

95% of malignant ______ arise within autoimmune thyroiditis

Back 44

lymphomas

Front 45

However, only 5% of patients with AIT are at risk for malignant _____

Back 45

lymphomas

Front 46

Radiogram of thyroid of pt
Thyroid is not taking up iodine

Back 46

?

Front 47

Thyroid gland, granulomatous thyroiditis. Note: partial involvement of gland

Back 47

?

Front 48

Thyroid gland, granulomatous thyroiditis.
Note: giant cells & smaller stromal cells

Back 48

?

Front 49

Thyroid gland, granulomatous thyroiditis, giant cell engulfing colloid

Back 49

?

Front 50

Thyroid gland, granulomatous thyroiditis. Inflammatory reaction
against colloid

Back 50

?

Front 51

Thyroid gland, granulomatous thyroiditis, giant cell reaction to colloid

Back 51

?

Front 52

Thyroid gland, FNA, granulomatous thyroiditis, giant cell

Back 52

?

Front 53

Clinical findings to thyroiditis

Back 53

Severe pain, extreme tenderness in region of thyroid gland.
Malaise, fatigue, myalgia & arthralgia, common
Mild to moderate fever
Disease may peak in 3-4 days & subside within a week
More typical. Onset over 1-2 weeks & continues for 3-6 wks
Symptoms may also extend over many months
Thyroid gland enlarged 2-3 times normal

Tender to palpation

About ½ of pts present with symptoms of thyrotoxicosis: nervousness, heat intolerance, tremors, increased sweating

Thyroid function returns to normal

<10% of pts develop permanent hypothyroidism

Front 54

Lab findings of thyroiditis

Back 54

Laboratory findings: striking elevation of ESR

Elevated C-reactive protein

High serum T3, T4, thyroglobulin, low radionuclide uptake, absent or low TG antibodies

Front 55

Thyroid gland, radionuclide scan, granulomatous thyroiditis

Back 55

?