L1 Hypo, Hyperthyroidism and Hashimoto Thyroiditis

Lecture 1:
Hypo and Hyperthyroidism

& Hashimoto’s Thyroiditis
◘ Important ◘ Notes ◘ Explanation

Objectives
The student should :
 Know the ways in which thyroid disorders present.

 Know the major causes and manifestations of hypo,
hyperthyroidism and thyroiditis.
MIND MAB :
Pathology of the
Thyroid Gland
Hypothyroidism Thyrotoxicosis Thyroiditis
Subacute
Not associated
granulomatous
Cretinism Hyperthyroidism with
(de Quervain)
hyperthyroidism
thyroiditis
Hashimoto’s
Myxedema Graves’ Disease
Thyroiditis
Hypothyroidism
introduction:
• It is a Decrease in the levels of thyroid hormones in the circulation.
• Caused by any structural or functional derangement that interferes with the production of adequate
levels of thyroid hormone
• Prevalence of overt (documented) hypothyroidism is 0.3%, while subclinical (not diagnosed)
hypothyroidism can be found in greater than 4%.
• Increases with age, and more common in females than in males.
Causes classified into:

Primary (Majority) Secondary (Central)
(related to the thyroid itself) (related to hypothalamus & pituitary)
• Developmental (thyroid dysgenesis: PAX8, FOXE1, TSH receptor • Pituitary failure (deficiency of TSH)
mutations) • Hypothalamic failure (deficiency of TRH)
• Postablative (following radioactive ablation (destruction of
thyroid tissue) in treatment for hyperthyroidism). * Both are rare.
• Iodine deficiency
• Acquired
Surgery, radioiodine therapy (radiation-induced ablation), or
external irradiation
• Autoimmune hypothyroidism (Hashimoto’s thyroiditis)
The most common cause of hypothyroidism in iodine sufficient
area.
• Congenital biosynthetic defect by:
1. endemic iodine deficiency in the diet
2. inborn errors of thyroid metabolism (dyshormonogenetic
goiter) less common.
Clinical manifestation:
Cretinism • In infants or early childhood

• Sever mental retardation, short stature, coarse facial features, protruding tongue
and umbilical hernia.
Myxedema • In older child or adult.

• slowing of physical and mental activity, mental sluggishness-overweight.
• Histologically:
accumulation of matrix substances such as: Glycosaminoglycans and hyaluronic
acid, in skin, subcutaneous tissue, visceral sites, results in:
Non-pitting edema, a broadening and coarsening of facial features,
enlargement of the tongue, deepening of the voice.
Thyrotoxicosis
Hyperthyroidism
• Hypermetabolic state caused by elevated circulating levels of free T3 and T4
• Caused most commonly by hyperfunction of the thyroid gland
• Thyrotoxicosis is the increase the amount of thyroid hormone whatever the cause, and hyperthyroidism is the
major cause of it.
Thyrotoxicosis, Causes:
ASSOCIATED WITH HYPERTHYROIDISM:
Primary:
• Diffuse hyperplasia of the thyroid associated with Graves’ disease (accounts for 85% of cases)
• Hyperfunctional multinodular goiter (most of cases are associated with normal thyroid hormone).
• Hyperfunctional adenoma of the thyroid (most of cases the nodules are nonfunctional or cold nodules)
Secondary:
• TSH-secreting pituitary adenoma (rare)
NOT ASSOCIATED WITH HYPERTHYROIDISIM:

• Granulomatous (de Quervain) thyroiditis (painful)
• Sub-acute lymphocytic thyroiditis (painless)(sub acute: 1-2 weeks granuloma, fibrous thyroiditis: fibrosis in the neck
compressing the airway that’s why we need to remove it.)
• Struma ovarii (ovarian teratoma with ectopic thyroid) (presence of thyroid follicles in ovaries → secretion of thyroid
hormones. Shown in radioactive iodine uptake test.)
• Factitious thyrotoxicosis (exogenous thyroxine intake)
Graves’ Disease
• Graves: “violent and long continued palpitations in females" associated with enlargement of the thyroid
gland.
Pathogenesis:
• An autoimmune disorder: (autoantibodies to the TSH receptor):
• LATS* proved to be an IgG antibody that binds to the TSH receptor and mimics the action of TSH =
increase release of thyroid hormones.
• Coexistence of stimulating & inhibiting immunoglobulins in the serum of the same patient, a finding that
could explain why some patients with Graves’ disease spontaneously develop episodes of hypothyroidism.
*long-acting thyroid stimulator (LATS), so named because it stimulated thyroid function more slowly than TSH
Characterized by:
• Thyrotoxicosis, caused by a diffusely enlarged, hyperfunctional thyroid.
• Infiltrative ophthalmopathy (exophthalmos).
• A localized, infiltrative dermopathy (pretibial myxedema).
Microscopically:
- Diffusely hyperplastic thyroid
- The follicles are lined by tall columnar epithelial cells that project
into the lumina resulting in “scalloped” appearance of the edges
pretibial myxedema of the colloid.
- Pseudo-papillary like formation (due to hyper activity of the
gland). & vacuolated colloid.
Thyroiditis
inflammation of the thyroid gland, include diverse group of diseases characterized by some form of thyroid
inflammation.
These diseases include conditions that result in:

• Acute illness with severe thyroid pain (e.g., infectious thyroiditis, subacute granulomatous thyroiditis)
• Disorders with little inflammation, manifested by thyroid dysfunction (subacute lymphocytic thyroiditis and
fibrous [Reidel] thyroiditis).
Subacute granulomatous (de Quervain) thyroiditis:

• Viral infection (e.g., coxsackie virus, mumps)
• Occurs most often in women 40 to 50 years old
Clinical findings:
- Most common cause of painful thyroid gland
- Often preceded by an upper respiratory infection
- Cervical adenopathy is not prominent.
-Initial thyrotoxicosis from gland destruction:
Increased serum T4, decreased serum TSH
• Permanent hypothyroidism is uncommon.
• Self-limited; does not require treatment
Microscopically:
Granulomatous inflammation with giant cells.
Hashimoto’s Thyroiditis: (chronic lymphocytic thyroiditis)
• The most common cause of hypothyroidism in areas of the world where iodine levels are sufficient.
• The name Hashimoto thyroiditis report by Hashimoto, describing patients with goiter & intense lymphocytic
infiltration of the thyroid (struma lymphomatosa).
• Hashimoto thyroiditis and Graves disease are the two most common immunologically mediated disorders
of the thyroid.
• Female predominance of 10:1 to 20:1. Age 45-65 .
• Hashimoto thyroiditis is characterized by gradual thyroid failure because of autoimmune destruction of the
thyroid gland.
• It is a major cause of non-endemic goiter in the pediatric population.
• Strong genetic component, 40% of monozygotic twins, as well as the presence of circulating antithyroid
antibodies in approximately 50% of asymptomatic siblings.
Pathogenesis:
It is an autoimmune disease in which the immune system reacts against a variety of thyroid antigens
(thyroglobulin & thyroid peroxidase)
Features:
Progressive depletion of thyroid epithelial cells (thyrocytes), replaced by mononuclear cell infiltration and
fibrosis.
Clinically:
- Painless enlargement of the thyroid, usually associated with the degree of hypothyroidism develops
gradually. (Hyperthyroidism followed by Hypothyroidism episode)
- The enlargement is usually symmetric and diffuse.
Morphology:
• The thyroid is often diffusely enlarged.
• The cut surface is pale, yellow, tan, firm, and somewhat nodular.
• Microscopic examination reveals extensive infiltration of the parenchyma by a mononuclear inflammatory
infiltrate containing small lymphocytes, plasma cells, and well-developed germinal centers.
• The thyroid follicles are atrophic and are lined in many areas by epithelial cells distinguished by the
presence of abundant eosinophilic (pinkish), granular cytoplasm, termed Hürthle cells.
The thyroid parenchyma contains a dense

lymphocytic infiltrate with germinal centers.
Residual thyroid follicles lined by deeply
eosinophilic Hürthle cells are also seen.
Summary (from Robbin’s basic pathology)
Thank You!
We hope you found this helpful and informative.
Done by :
Awatif Al-enzi
Nada Bin dawood
Reviewed by : Team Leaders :

Mohammed Bin askar Ghaida Alawaji & Abdullah Alatar
Contact us :
@pathology433 [email protected]

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Lecture 1:

Hypo and Hyperthyroidism

◘ Important ◘ Notes ◘ Explanation

 Know the ways in which thyroid disorders present.

Hypothyroidism Thyrotoxicosis Thyroiditis

Causes classified into:

Cretinism • In infants or early childhood

Myxedema • In older child or adult.

NOT ASSOCIATED WITH HYPERTHYROIDISIM:

These diseases include conditions that result in:

Subacute granulomatous (de Quervain) thyroiditis:

The thyroid parenchyma contains a dense

Reviewed by : Team Leaders :

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