Thyroid

Dr. Mohanned Abulihya

• Normal appearance of the
thyroid gland on the anterior
trachea of the neck.

• The thyroid gland has a right

lobe and a left lobe connected by
a narrow isthmus.

• The normal weight of the thyroid

is 10-30 g.
• It cannot easily be palpated on
physical examination. 2
• Normal thyroid seen microscopically consists of spherical follicles, lined by low
cuboidal-to-columnar epithelium, and filled with thyroglobulin-rich colloid
• Hypothalamus-pituitary-thyroid axis

Negative-feedback loop 5
 Pathology of the Thyroid

• Goiter

• Hyperthyroidism (Thyrotoxicosis)

• Hypothyroidism

• Thyroid Tumors
 Goiter
• Functional:
– Simple goiter
– Toxic goiter

• Morphology:
– Diffuse goiter
– Multinodular goiter

• Causes:
– Endemic goiter
– Sporadic goiter 7
 Goiter
Definition:
– Simple enlargement of the thyroid
– The most common thyroid disease
Nontoxic goiter:
– Euthyroid or hypothyroid
Toxic goiter:
– Hyperthyroid
 Goiter

1. Endemic goiter:
– In area with dietary iodine deficiency
– > 10% of the population
2. Sporadic goiter: F > M
– Peak incidence in puberty or young adult life
– Causes of sporadic goiter:
• Idiopathic
• Hereditary enzymatic defects
• Ingestion of substances that interfere with thyroid hormone synthesis
Goiter
1. Diffuse goiter:
– Hypertrophy and hyperplasia of thyroid follicular cells
– Symmetric enlargement of the gland
2. Multinodular goiter:
– Irregular asymmetric enlargement of the thyroid
– Unknown mechanisms
– Contains colloid-rich follicles
– Plummer disease: nodular goiter with hyperthyroidism but no exophthalmos (i.e. not Grave’s Disease)
• This is diffusely enlarged nodular thyroid gland. This patient was euthyroid.
This represents the most common cause for an enlarged thyroid gland and
the most common disease of the thyroid--a nodular goiter
Goiter: Clinical Features

• Large neck mass

– Airway obstruction
– Dysphagia
– Compression of large vessels in the neck and upper thorax

• In toxic goiter: hyperthyroidism

• In simple goiter: hypothyroidism
Thyroid Diseases: Diagnosis

• Serum TSH

• Free T4 and T3

• Radioactive iodine uptake

• Ultrasonography

• Fine-needle aspiration biopsy

• Histologic examination of the resected specimen

 Causes of Thyrotoxicosis
•Graves disease

•Hyperfunctioning ("toxic") multinodular goiter

•Hyperfunctioning ("toxic") adenoma

•TSH-secreting pituitary adenoma

•Subacute granulomatous thyroiditis (painful)

•Subacute lymphocytic thyroiditis (painless)

•Struma ovarii (ovarian teratoma with ectopic thyroid)

•Factitious thyrotoxicosis (exogenous thyroxine intake)

Hyperthyroidism: Clinical Features
General:
– Soft, warm, and flushed skin
– Heat intolerance and excessive sweating
– Weight loss despite increased appetite
Gastrointestinal:
– Hypermotility, malabsorption, and diarrhea
Cardiac:
– Palpitations, tachycardia, CHF in elderly
Neuromuscular:
– Nervousness, tremor, and irritability
– Proximal muscle weakness (thyroid myopathy)
Hyperthyroidism: Clinical Features
• Ocular:
– Wide, staring gaze and lid lag
– Proptosis (only in Graves disease)
• Thyroid storm:
– Severe hyperthyroidism
– Mostly in patients with Graves disease
– Acute elevation of catecholamine levels
– Complication: cardiac arrhythmias
• Apathetic hyperthyroidism:
– Thyrotoxicosis in the elderly
 Proptosis or exophthalmos

Lid retraction and staring gaze

Hyperthyroidism: Diagnosis
• Low serum TSH
• High free T4 and T3
• Radioactive iodine uptake:
– Increased uptake in whole gland (Graves disease)
– Increased uptake in solitary nodule (toxic adenoma)
– Decreased uptake (thyroiditis)
 Graves Disease

• The most common cause of endogenous hyperthyroidism

• Triad of:
• Thyrotoxicosis, diffuse enlargement (goiter) of the thyroid is present in all cases
• Exophthalmos: an infiltrative ophthalmopathy in ~ 40% of patients
• Pretibial myxedema: a localized, infiltrative dermopathy in a minority of cases
Pretibial myxedema
Graves dermopathy, with TSH receptor-bearing pretibial fibroblasts secreting
glycosaminoglycans in response to stimulatory autoantibodies and cytokines
Graves Disease
• Occurs in younger adults (20 – 40 yr)

• F:M ratio is 7:1

• Increased incidence among family members of affected patients

(associated with HLA)

• Autoimmune disorder with antibodies against:

– TSH receptor
– Thyroid peroxisomes
– Thyroglobulin
• Graves disease:
• The thyroid gland is diffusely enlarged because of the presence of diffuse
hypertrophy and hyperplasia of thyroid follicular epithelial cells.
• The crowded, enlarged epithelial cells project into the lumina of the follicles
Graves Disease: Clinical Features
• Clinical features of thyrotoxicosis
• Diffuse hyperplasia of the thyroid
– Usually smooth and symmetric
– Audible bruit
• Ophthalmopathy- Exophthalmos
• Dermopathy- Pretibial myxedema
– Localized thickening and hyperpigmentation of the skin
– Over the anterior aspect of the feet and lower legs
The globe protrudes out of the
orbital cavity (exophthalmos); the
lids are retracted .

There is conjunctival injection and

lateral edema of the eyelids .

The combination of findings

indicates Graves orbitopathy.
Graves Disease: Diagnosis

• Low TSH levels

• Elevated free T4 and T3 levels

• Increased radioactive iodine uptake

• Radioiodine scans: diffuse uptake of iodine

 Causes of hypothyroidism

Primary:
• Postablative (after surgery or radioiodine therapy)

• Primary idiopathic hypothyroidism

• Hashimoto thyroiditis*

• Iodine deficiency*

• Congenital biosynthetic defect (dys-hormonogenetic goiter)*

Secondary:
• Pituitary or hypothalamic failure (uncommon)
Associated with enlargement of thyroid
 Hypothyroidism: clinical features
Cretinism:
– Hypothyroidism in infancy or early childhood
• Causes:
– Dietary iodine deficiency
– Enzyme deficiencies
• Clinical features of cretinism:
– Severe mental retardation
– Short stature
– Protruding tongue
– Umbilical hernia
 Hypothyroidism: clinical features
• Myxedema:
– Hypothyroidism in older children and adults
• Clinical features of myxedema:
– Weight gain
– Cold intolerance
– Coarse facial features
– Enlarged tongue, deepen voice
– Decreased bowel motility and constipation
– Pericardial effusions, CHF later
– Lethargy
Hypothyroidism: Diagnosis
• TSH level:
– Increased in primary hypothyroidism
– Normal in hypothalamic or pituitary disease

• T4 levels are decreased

 Thyroiditis: Classifications
1) Duration of disease:
• Acute: acute thyroiditis
• Subacute: de-Quervain thyroiditis, subacute lymphocytic thyroiditis
• Chronic: Hashimoto thyroiditis

2) Predominant inflammatory response:

• Polymorphonuclear: acute thyroiditis
• Lymphocytic: Hashimoto thyroiditis
• Granulomatous: de Quervain thyroiditis
 Hashimoto’s thyroiditis

• Chronic Lymphocytic Thyroiditis

• Most common cause of hypothyroidism

• Autoimmune inflammatory disorder of the thyroid

• Initially leads to painless enlargement of the thyroid, followed by atrophy

years later
 Hashimoto thyroiditis
• The thyroid parenchyma contains a dense lymphocytic infiltrate with
germinal centers. Residual thyroid follicles lined by deeply eosinophilic
Hürthle cells are also seen.
• Hashimoto's thyroiditis demonstrates the pink Hurthle cells at the center and
right. The lymphoid follicle is at the left. Hashimoto's thyroiditis initially leads
to painless enlargement of the thyroid, followed by atrophy years later.
Hashimoto thyroiditis: Clinical Features
• Mostly between 45 - 65 years of age
• F > M ~ 10:1 ratio
• Painless enlargement of the thyroid
– symmetric and diffuse
• Intially, transient thyrotoxicosis
– High T4 and T3, low TSH
• Later, hypothyroidism
– Low T4 and T3, high TSH
• Increased risk for B-cell non-Hodgkin lymphomas
 Subacute Lymphocytic Thyroiditis

• Also known as "silent" or "painless" thyroiditis

• Painless neck mass
• Mostly affects middle-aged women
• Follows pregnancy (postpartum thyroiditis)
• Autoimmune in etiology
• Initial phase of thyrotoxicosis
• Return to a euthyroid state within a few months
• In minority- progress to hypothyroidism
• Risk of recurrence
• Unlike Hashimoto, follicular atrophy are not commonly seen
 Subacute granulomatous thyroiditis
• Also known as de quervain thyroiditis

• Common between the ages of 30 and 50

• F>M

• The cause is unknown

• Preceded by viral URTI

• Firm gland, unilaterally or bilaterally enlarged

• Histologically, granulomatous reaction

 Subacute Granulomatous Thyroiditis

Clinical Features:
• Pain in the neck (mainly when swallowing)

• Fever, leukocytosis

• Enlargement of the thyroid

• Intially: transient hyperthyroidism

• Later: transient hypothyroidism

• Self-limited within 6 to 8 weeks

• Subacute thyroiditis. The thyroid parenchyma contains a chronic
inflammatory infiltrate with a multinucleate giant cell (above left) and a
colloid follicle (bottom right)
 Other Forms of Thyroiditis
• Riedel thyroiditis:
– Rare disorder of unknown etiology

– Characterized by extensive fibrosis

– Hard and fixed thyroid mass

• Palpation thyroiditis:
– Caused by forceful clinical palpation of the thyroid gland

– Results in multifocal follicular disruption

 Neoplasms of the Thyroid
1. Benign- adenomas

2. Malignant- carcinomas

• Increase risk of neoplasia with:

– Solitary nodules > multiple nodules

– Solid nodules > cystic nodules

– Nodules in younger patients > older patients

– Nodules in males > females

– Nodules that do not take up radioactive iodine

(cold nodules)
 Adenomas of the thyroid
• Benign neoplasms

• derived from follicular epithelium

• Follicular adenomas are usually solitary

Two types:

– Nonfunctional adenoma

– Toxic adenomas
• A. Follicular adenoma of the thyroid. A solitary, well-circumscribed nodule
by a well-formed capsule is seen

• B. Well-differentiated follicles resemble normal thyroid parenchyma

A. B.

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 Adenomas: Clinical Features

• Painless nodules
• Cold nodules on radionuclide scanning
• In toxic adenomas:
– Features of thyrotoxicosis
– "Warm" or "hot" nodule in the scan
Diagnosis:
– US
– FNA biopsy
– Tissue biopsy: the definitive distinction of follicular adenomas from carcinomas
 Carcinomas of the thyroid

The major subtypes: F > M

1. Papillary carcinoma (75% to 85% of cases)

2. Follicular carcinoma (10% to 20% of cases)

3. Medullary carcinoma (5% of cases)

4. Anaplastic carcinomas (<5% of cases)

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 Thyroid Cancer: Pathogenesis

• Genetic Factors

• Ionizing Radiation

– Radiotherapy to neck

– Atomic bomb

• Preexisting Thyroid Disease

– multinodular goiter
 Papillary carcinoma
• The most common form
• Occur at any age
• Associated with ionizing radiation
• Nonfunctional tumors
• Present as a painless mass in the neck
• Metastasis mainly to cervical LN
• 10-year survival rates of up to 85%
 Follicular carcinomas

• Second most common form

• Peak incidence in the middle adult years
• Mostly in areas of dietary iodine deficiency
Microscopically:
– Composed of cells forming small follicles
– Invasion of adjacent thyroid parenchyma
Clinical features:
– Solitary "cold" nodules
– Metastasize to the lungs, bone, and liver
– Regional nodal metastases not found commonly
 Medullary carcinomas

• Derived from the parafollicular cells, or C cells

• Secrete calcitonin

• Tumors typically contain amyloid

• Presented as mass in the neck

• Familial in 20% of cases

– Part of multiple endocrine neoplasia (MEN) syndromes 2A or 2B

• A. Medullary carcinoma of thyroid. These tumors typically show a solid pattern of
growth and do not have connective tissue capsules
• B. Here the amyloid stroma of the medullary thyroid carcinoma has been stained
with Congo red.

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 Anaplastic carcinomas

• The most aggressive thyroid neoplasms

• Occur predominantly in elderly patients
• Bulky masses that typically grow rapidly
• Composed of highly anaplastic cells
• Metastases to distant sites are common
• Death occurs in < 1 year
• Compression on vital structures in the neck