by: Isra'a Amer

lec: Pathology of the thyroid gland

Green = book

Bold = slides

The thyroid gland consists of two bulky lateral lobes connected by a relatively thin isthmus.

The thyroid is divided into lobules, each composed of dispersed follicles. which is filled with

thyroglobulin . In response to TSH , Thyroid follicular epithelial cells convert thyroglobulin

into thyroxine (T4) and lesser amounts of triiodothyronine (T3). T4 and T3 are released

into the systemic circulation, where most of these peptides are bound to circulating plasma

proteins, such as T4-binding globulin, for transport to peripheral tissues. There is of curse Small

fraction of free hormone for regulation .

T4 is the predominant hormone .

In the periphery, the majority of free T4 is deiodinated toT3

T3 : binds to thyroid hormone nuclear receptors in target cells with 10-fold greater affinity

than T4 . (so the receptor is in the nucleus )

The interaction of thyroid hormone with its nuclear thyroid hormone receptor (TR) results

in the formation of a hormone-receptor complex that binds to thyroid hormone response

elements (TREs) in target genes, regulating their transcription

This produces diverse cellular effects, including increased carbohydrate and lipid catabolism and protein synthesis in a wide range of cell types. The net result of these processes is an increase in the basal metabolic

rate. ^^from the book

A hormone response element (HRE) is a short sequence of DNA within the promoter of a gene that is able to bind a specific hormone

receptor complex and therefore regulate transcription. "from Wikipedia" .

Slid 5

• Hyperthyroidism : excessive release of thyroid hormones

• Hypothyroidism: thyroid hormone deficiency

HYPERTHYROIDISM

• Thyrotoxicosis: Elevated circulating levels of free T3 and T4 ( often is referred to as

hyperthyroidism )

• Hyperthyroidism is m.c (Hyperthyroidism is the most common cause of Thyrotoxicosis)

primary means that the cause is from thyroid gland.

secondary ; from pituitary or hypothalamus .

The three most common causes of thyrotoxicosis are associated with hyperfunction of the gland:

• Diffuse hyperplasia of the thyroid associated with Graves disease, a form of autoimmune thyroid disease

(accounts for 85% of cases) • Hyperfunctioning (“toxic”) multinodular goiter

• Hyperfunctional (“toxic”) adenoma of the thyroid

-the doctor asks : what's Struma ovarii ?

Teratomas are germ cell tumors commonly composed of multiple cell types derived from one or more

of the 3 germ layers , most common in ovary , And the struma ovarii is a rare form of monodermal

teratoma that contains mostly thyroid tissue, which may cause hyperthyroidism (thyroid tissues give

thyroid hormone )

• Manifestations of thyrotoxicosis:

Hypermetabolic state –mainly protean -

heat intolerance

weight loss despite increased appetite = most common symptom

soft, warm, and flushed skin

malabsorption, and diarrhea

Palpitations and tachycardia= most common in ealderly people

congestive heart failure

nervousness, tremor, and irritability= most common in young people

50% develop proximal muscle weakness (thyroid myopathy)

These symptoms look-like the symptoms of sympathetic stimulation.

• staring gaze and lid lag (sympathetic overstimulation of the levator palpebrae superioris) Lid lag is the static situation in which the upper eyelid is higher than normal

• True thyroid ophthalmopathy associated with proptosis/exophthalmus is a feature seen

only in Graves disease ---- Bilateral, accumulation of loose connective tissue, fatty

infiltration, mononuclear cells infiltration, and edema behind the orbits---- corneal

damage Proptosis/exophthalmus ; protrusion of the eye orbit anteriorly .

Slid 10

• Thyroid storm: abrupt onset of severe hyperthyroidism, sudden increase in thyroid hormones in the serum.

Hyperthyroidism patient ---- stress (truama, surgery, emotional, infection,)

---- not receive Tx (no treatment )

medical emergency

Tachycardia (because of sympathetic over stimulation), cardiac arrhythmias (AF), fever, agitation,

confusion

Slid 11

• Apathetic hyperthyroidism--- elderly persons

No specific symptoms, so discovered by investigation.

We have to require thyroid test when the symptoms are not specific

Slide 12

* The measurement of serum TSH is the most useful single screening test for hyperthyroidism (first TSH test )

- TSH levels are decreased, increased levels of free T4 or occasionally free T3 (2nd T4,T3 test )

3rd RAIDIOACTIVE IODIN TEST

- TSH levels normal or raised ; pituitary- or hypothalamus-associated (secondary) hyperthyroidism

In primary hyperthyroidism :

TSH; low / T4 or T3 ; high

Slid 13

• measurement of radioactive iodine uptake by the thyroid gland often is valuable in determining the etiology.

-such scans may show diffusely increased (whole gland) uptake in Graves disease

-increased uptake in a solitary nodule in toxic adenoma(focus)

-decreased uptake in thyroiditis.

HYPOTHYROIDISM

• Worldwide, the most common cause of hypothyroidism is dietary deficiency of iodine ,

• while in most developed nations, autoimmune causes predominate.

• Hashimoto

• Manifestations:

Cretinism !!التخلف

Cretinism refers to hypothyroidism developing in infancy or early childhood. common in areas of the world where dietary iodine deficiency is endemic, including mountainous areas .

The severity of the mental impairment in cretinism seems to be influenced by the time of onset of the deficient state in utero. If maternal thyroid deficiency is present before the development of the fetal thyroid gland, mental retardation is severe. reduction in maternal thyroid hormones later in pregnancy, after the fetal thyroid has developed, allows normal brain development.

• Myxedema : Hypothyroidism in older children and adults

Gull disease (another name)

------------

hyper: االعراض :عكس ال

Generalized apathy

mental sluggishness

cold intolerant

Obese

Constipation

Extra loose c.t >> most important glycosaminoglycan: coarsening of facial features تخشن مالمح الوجه, enlargement of the

tongue, and deepening of the voice (accumulation of mucopolysaccharide-rich edematous fluid)

heart failure

umbilical hernia is the most important physical signs in baby with hypothyroidism.

Slide 20

• measurement of serum TSH is the most sensitive screening test

• T3,t4 + radioactive…..

serum TSH--increased--- primary hypothyroidism(due to lose of - feedback)

serum TSH—not increased--- secondary hypothy

Serum T4--- decreased

Thyroid function test = at 1st month after birth

THYROIDITIS

* inflammation of the thyroid

(1) Hashimoto thyroiditis

(2) granulomatous (de Quervain) thyroiditis;

(3) subacute lymphocytic thyroiditis

All of them give us transient phase thyrotoxicosis

Slid 22

• Hashimoto thyroiditis: net result is hypothyroidism

the m.c cause of hypothyroidism in areas of the world where iodine levels are sufficient.

it may be preceded by transient thyrotoxicosis

Chronic Lymphocytic Thyroiditis (another name )

(Medill age ) 45 and 65 years, Females(cause they are ovarian disease), painless enlargement of the

thyroid,

Autoimmune--- other autoimmune diseases

increased risk for the development of B cell non-Hodgkin lymphomas and papillary

carcinomas

• Circulating autoantibodies against thyroid antigens are present in the vast majority of patients. • CD8+ cytotoxic T-cell–mediated killing of thyroid epithelial cells.

• Cytokine-mediated cell death. T-cell activation leads to the production of inflammatory cytokines such as

interferon-γ in the thyroid gland, with resultant recruitment and activation of macrophages and damage to

follicles.

• antithyroid antibodies:

-antithyroglobulin,

-antithyroid peroxidase antibodies

The thyroid usually is diffusely and symmetrically enlarged (and so for graves)

Slide 26

• Subacute Lymphocytic Thyroiditis: المرحلة التي تسبقHashimoto

in a subset of patients the onset of disease follows pregnancy (postpartum thyroiditis)

Autoimmune, females

painless neck mass

Thyrotoxicosis --- euthyroid

--- hypothyroidism

Subacute lymphocytic thyroiditis also is known as silent or painless thyroiditis; in a subset of patients, the onset follows

pregnancy (postpartum thyroiditis). This disease is most likely autoimmune in etiology, as circulating antithyroid

antibodies are found in a majority of patients. It mostly affects middle-aged women, who present with a painless neck

mass or features of thyroid hormone excess. The initial phase of thyrotoxicosis (which is likely to be secondary to thyroid

tissue damage) is followed by return to a euthyroid state within a few months. In a minority of affected individuals, the

condition eventually progresses to hypothyroidism.

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• subacute Granulomatous (de Quervain) Thyroiditis:

ages of 30 and 50

Females

Viral infection—hx of an upper respiratory infection

pain in the neck, fever, malaise

Transient hyperthyroidism--- transient

Hypothyroidism

self-limited ---- euthyroid state within 6 to 8 weeks.

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• Riedel thyroiditis: mimic malignances

extensive fibrosis involving the thyroid and contiguous neck structures

fixed thyroid mass, simulating a thyroid neoplasm.

Autoimmune

• Hashimoto thyroiditis is an autoimmune disease characterized by progressive destruction of thyroid parenchyma, and mononuclear (lymphoplasmacytic) infiltrates, with or without extensive fibrosis.

• Multiple autoimmune mechanisms account for thyroid injury in Hashimoto disease, including cytotoxicity

mediated by CD8+ T cells, cytokines (IFN-γ), and anti-thyroid antibodies.

• Subacute granulomatous (de Quervain) thyroiditis is a selflimited disease, probably secondary to a viral infection, and ischaracterized by pain and the presence of a granulomatous inflammation in the thyroid.

• Subacute lymphocytic thyroiditis is a self-limited disease that often occurs after a pregnancy (postpartum thyroiditis), typically is painless, and is characterized by lymphocytic inflammation

in the thyroid.

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GRAVES DISEASE

• Graves disease is the most common cause of endogenous hyperthyroidism

• Triad of:

1- Thyrotoxicosis (diffusely enlarged thyroid) autoimmune desise

2- Ophthalmopathy---- exophthalmos

3- dermopathy / pretibial myxedema/ shins (glycosaminoglycans and lymphocyte

infiltration)

ages of 20 and 40, females, autoimmune

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• breakdown in self-tolerance to thyroid autoantigens, of which the most important is the

TSH receptor.

Most important autoantibodies

1-Thyroid-stimulating immunoglobulin

2-Thyroid growth-stimulating immunoglobulins

3-TSH-binding inhibitor immunoglobulins

T cell–mediated----- ophthalmopathy

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• the thyroid gland is enlarged, symmetrically

• diffuse

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DIFFUSE AND MULTINODULAR GOITER (enlargment)

Start with hypo. Because of iodine deficiency which lead to – feedback then we have hyper

• impaired synthesis of thyroid hormone (dietary iodine deficiency)

--------------

• compensatory rise in the serum TSH, which in turn causes hypertrophy and hyperplasia of thyroid follicular

cells

---------------

• Goiter : Enlargement of the thyroid ----- large neck mass---- airway obstruction, dysphagia, and

compression of large vessels in the neck and upper thorax (so-called superior vena cava syndrome).

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enough to overcome the hormone deficiency, ensuring a euthyroid metabolic state

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• Endemic goiter------- little iodine

• Sporadic goiter----- physiologic demand for T4, puberty, females ,

coal flower and cabbage الدرقية الغدة هرمونات وتصنيع اليود تخزين مع تتداخل مواد

Most goitre patient are suffered from euthyroid , also hypo and hyper BUT less than euthyroid , because it's a

compensatory process.

• Diffuse goiter ---- diffuse, symmetric enlargement of the gland

recurrent episodes of hyperplasia and involution

• Multinodular goiter ---- irregular enlargement

of the thyroid

toxic multinodular goiter ----- autonomous nodules ----Plummer syndrome

sorry for any mistake

good luck