The Pathology of Thyroid Gland Flashcards
What is the structure of the thyroid like?
The thyroid has a right and left lobe, which are connected by a narrow isthmus
Can a NORMAL thyroid be palpated during a physial examination?
It cannot easily be palpated
What is the epithelium of the thyroid gland?
Lined by a cuboidal epithelium and filled with pink, homogenous colloid
What does the interstitium of the thyroid contain?
C cells, but it is not prominent
What is hyperthyroidism?
Increased levels of circulating thyroid hormone
What are the main types of hyperthyroidism? (3)
- Abnormal thyroid stimulator –> Grave’s disease
- Intrinsic disease of the thyroid gland –> Toxic multinodular Goiter or functional adenoma
- Excess TSH production by the pituitary adenoma (rare)
What is thyrotoxicosis?
Hypermetabolic state due to elevated circulating levels of T3 and T4
What are the primary causes of hyperthyroidism? (4)
- Diffuse toxic hyperplasia (Grave’s disease)
- Hyperfunctioning multinodular goiter
- Hyperfunctioning adenoma
- Iodine-induced hyperthyroidism
What are the secondary causes of hyperthyroidism?
TSH-secreting pituitary adenoma (rare)
What do the signs and symptoms of hyperthyroidism reflect?
A hypermetabolic state of target tissues
What are the constitutional symptoms of hyperthyroidism?
Skin: soft, warm, and flushed –> heat intolerance and excessive sweating
Increased sympathetic activity and hypermetabolism –> weight loss despite an increase in appetite
What are the GI symptoms of hyperthyroidism?
Stimulation of the gut:
Hypermotility –> fat malabsorption & diarrhea
What are the cardiac symptoms of hyperthyroidism?
Palpitations and tachycardia
Older adult patients with pre-existing heart disease may develop congestive heart failure
What are the neuromuscular symptoms of hyperthyroidism?
Nervousness, tremor, and irritability (sympathetic overactivity)
Nearly 50% of patients develop proximal muscle weakness (thyroid myopathy)
What are the ocular manifestations of hyperthyroidism?
Wide, staring gaze and lid lag
What is Grave’s disease?
The most common cause of endogenous hyperthyroidism (diffuse toxic goiter)
Autoimmune disorder resulting in increased synthesis & release of thyroid hormones
What is the ratio of women to men developing Grave’s disease?
Female: Male
8:1
What is the common age group for developing Grave’s disease?
20 to 40 years of age
What is the triad of manifestation for Grave’s disease?
Thryrotoxicosis
Infiltrative ophtalmopathy
Localized, infiltrative dermopathy –> sometimes designated pretibial myxedema
What causes thyrotoxicosis in Grave’s diseasE?
Diffusely enlarged, hyper-functional thyroid
What is the result of infiltrative ophthalmopathy in Grave’s disease?
Exophthalmos
What % of patients with Grave’s disease present with thyrotoxicosis?
100% –> All of the patients
What % of patients with Grave’s disease present with infiltrative ophthalmopathy?
40%
What is Grave’s disease caused by?
Autoantibodies against TSH receptor that bind to, and stimulate, thyroid follicular cells independent of endogenous trophic hormones
What is the pathogenesis of Grave’s disease?
- Breakdown in self-tolerance to thyroid autoantigens (TSH receptor)
- Production of multiple autoantibodies
- Thyroid-stimulating immunoglobulin –> IgG antibody binds to TSH receptor and mimics the action of TSH, stimulating adenyl cyclase –> Increased release of thyroid hormones
OR
Thyroid-growth stimulating immunoglobulin –> Abs directed against TSH receptor –> Proliferation of thyroid follicular epithelium
OR
TSH binding inhibitor immunoglobulins –> Anti-TSH receptor antibodies prevent TSH from binding to its thyroid epithelial cels –> Inhibit thyroid cell function
What is the pathogenesis of Grave’s disease ophthalmopathy?
The volume of retroorbital connective tissues and extraocular muscles is increased
What causes the increased volume of retroorbital connective tissue and extraocular muscles? (4)
- Marked infiltration of the retroorbital space by mononuclear cells (predominantly T cells)
- Inflammatory edema and swelling of extraocular muscles
- Accumulation of extracellular matrix components, specifically hydrophilic glycosaminoglycans
- Increased number of adipocytes (fatty infiltration)
What are examples of glycosaminoglycans?
Hyaluronic acid and chondroitin sulfate
What are the gross features of Grave’s disease?
The thyroid gland is symmetrically enlarged (35 –> 100g)
The cut surface: firm & dark red
What is the effect of Grave’s opthalmopathy?
Changes displace the eyeball forward, potentially interfering with the function of the extraocular muscles
What are the microscopic features of Grave’s disease?
Follicular epithelial cells: tall, columnar, and more crowded than usual
Colloid within follicular lumen: pale, with scalloped margins
Interstitium: lymphoid infiltrates (consisting predominantly of T cells, with fewer B cells and mature plasma cells)
What is cretinism?
Hypothyroidism developing in infancy or early childhood
What are the different types of cretinism?
Endemic cretinism
Sporadic cretinism
What is endemic cretinism?
Dietary iodine deficiency is endemic (mountainous areas)
What is sporadic cretinism?
Enzyme defects that interfere withy thyroid hormone synthesis
What is cretinism characterised by? (5)
- Mental retardation
- SHort stature with skeletal abnormalities
- Coarse facial features
- Enlarged tongue
- Umbilical hernia
Why is mental retardation a sign of cretinism?
Cretinism –> hypothyroidism –> low levels of thyroid hormones in the mother –> decreased levels of T3 and T4 passing through the placenta onto the fetus
What is myxedema?
Also known as Gull disease
Hypothyroidism in older children or adults
What are the clinical features of Myxedema? (9)
Decreased basal metabolic rate and decreased stimulation of sympathetic nervous system:
1. Accumulation of glycosaminoglycans in skin and soft tissue
2. Weight gain despite the loss of appetite
3. Slowing of mental activity
4. Muscle weakness
5. Cold intolerance with decreased sweating
6. Bradycardia with decreased cardiac output, leading to shortness of breath and fatigue
7. Oligomenorrhea
8. Hypercholesterolemia
9. Constipation
What will the accumulation of glycosaminoglycans in skin and soft tissue cause in cases of myxedema?
Deepening of the voice and large tongue
What is thyroiditis?
Heterogenous group of inflammatory disorders if the thyroid gland
What are the most common examples of Thyroiditis? (3)
- Hashimoto thyroiditis (chronic lymphocytic thyroiditis)
- Granulomatous thyroiditis
- Subacute lymphocytic thyroiditis
What is Granulomatous thyroiditis?
Self-limited disease, probably secondary to viral infection like influenza or adenovirus
What characterizes Granulomatous thyroiditis?
Pain and the presence of granulomatous inflammation in the thyroid
What is Subacute lymphocytic thyroiditis?
Self-limited disease, occurs after pregnancy (postpartum thyroiditis)
What characterizes Subacute lymphocytic thyroiditis?
Typically painless, characterized by lymphocytic inflammation in the thyroid
What is Hashimoto thyroiditis?
Gradual thyroid failure secondary to autoimmune destruction of the thyroid gland
What is the most common cause of hypothyroidism?
Hashimoto thyroiditis
What is the female: male ratio of Hashimoto thyroiditis?
Female: male –> 10:1
Older Female: male –> 20:1
What is the age group affected by Hashimoto thyroiditis?
45 to 65
Can Hashimoto thyroiditis occur in chidlren?
Yes but it is less common
What is the pathogenesis of Hashimoto thyroiditis?
Circulating autoantibodies against thyroid agents –> the immune response leads to progressive depletion of thyroid epithelial cells (thyrocytes) –> and replacement by mononuclear cell infiltration and fibrosis
What activates the CD4 lymphocytes sensitized to thyroid antigens?
Initiated by viral and bacterial infection, which leads to the proliferation of autoreactive cytotoxic CD8+
What do the activated CD4 cells also recruit in Hashimoto thyroiditis?
They recruit autoreactive B cells to produce antibodies against thyroid agents
What are the antithyroid antibodies?
Antithyroglobulin
Antithyroid peroxidase antibodies
What are the gross features of Hashimoto thyroiditis?
Diffusely & symmetrically enlarged gland (6 0 to 200g)
What is the cut surface of Hashimoto’s thyroiditis?
Pale and grey-tan and fleshly with vaguely nodular pattern
What are the microscopic examination of Hashimoto thyroiditis like?
The parenchyma: infiltration of mononuclear inflammatory (small lymphocytes, plasma cells, and well-developed germinal centres)
The follicles: atrophic, metaplasia of epithelial cells (abundant eosinophilic, granular cytoplasm –> Hurthle or oxyphil cells)
What are Hurthle cells like?
- Abundant eosinophilic cytoplasm
- Round central nuclei
- Single prominent nucleus
What are the clinical presentations of Hashimoto thyroiditis?
Painless enlargement of the thyroid, usually associated with some degree of hypothyroidism, which develops gradually often seen in middle-aged women
What may Hashimoto thyroiditis be preceded by?
Transient thyrotoxicosis is caused by disruption of thyroid follicles, with the secondary release of thyroid
During this phase, free T4 and T3 concentrations are elevated, TSH is diminished and radioactiveiodine uptake is decreased
What happens as hypothyroisism seupervenes?
T3 and T4 levels progressively fall, accompanied by a compensatory increase in TSH
What does neoplasm of the thyroid usually present as?
As a distinct, solitary nodule
Which nodule types are more likely to be neoplastic?
- Solitary nodules rather than multiple nodules
- Nodules in younger patients than those in older patients
- Nodules in males than those in females
Where is increased uptake “hot” nodule seen?
In Grave’s disease or nodular goiter
Where is decreased uptake “cold” nodule seen?
In adenoma and cracinoma
What are adenomas of the thyroid?
Benign neoplasms derived from follicular epithelium (Follicular adenoma)
Typically is solitary encapsulated neoplasms
Which age group do adenomas of the thyroid appear in?
40 to 50 year olds
What is the female: male ratio of adenomas of the thyroid?
Female: male
7:1
What is the pathogenesis of the adenomas of the thyroid?
Driver mutations in the TSH receptor signaling pathway play an important role in the pathogenesis of toxic adenomas:
1. Activating (gain-of-function) somatic mutations in the gene encoding the TSH receptor itslef or alpha-subunit of Gs
2. Follicular cells secrete thyroid hormone independent of TSH stimulation (thyroid autonomy)
3. Symptomatic hyperthyroidism, with a “hot” thyroid nodule seen on imaging
What is the gross feature morphology of adenoma?
Solitary, circumscribed (1 to 3 cm) surrounded by a thin fibrous capsule
What is the cut surface of adenoma like?
- Soft & paler than surrounding gland
- Haemorrhage, fibrosis and cystic change
What are the microscopic features of adenomas?
- Bening proliferation of follicles surrounded by a follicular capsule
- Th constituent cells are arranged in uniform follicles that contain colloid
- Papillary growth patterns
What could be the suspicion surrounding papillary growth patterns?
Suspicion for an encapsulated papillary carcinoma
What is papillary thyroid carcinoma (PTC)?
It is derived from the thyroid follicular epithelium, and it accounts for more than 85% of the cases of thyroid cancer
What are the risk factors for papillary thyroid carcinoma?
- Exposure to ionizing radiation in childhood (Chernobyl)
- Genetic factors:
a. High risk (10x) because of first degree relations
What is the pathogenesis of papillary thyroid carcinoma?
- Somatic rearrangements of receptor tyrosine kinase (RET) protooncogene on chromosome 10
OR - Point mutation of the B-type Raf kinas (BRAF) gene
What % of PTC cases are due to RET protooncogene?
30%
What % of PCT cases are due to BRAF gene?
60%
What is the gross feature morphology of PCT?
- Solitary or multifocal lesions
- May be well-circumscribed and even encapsulated
- Infiltrate the adjacent parenchyma with ill-defined margins
- The lesions may contain areas of fibrosis, and calcification and often are cystic
What is the cut surface of PTC like?
Granular and sometimes contain grossly discernible pale tan papillary foci
What are the microscopic features of PCT?
- Branching papillae having fibrovascular stalk covered by a single to multiple layers of CUBOIDAL epithelial cells
- The nuclei –> contained finely dispersed chromatin, which imparts an optically clear appearance
What kind of structures are seen within the papillae of PCT?
Psammoma bodies –> concentrically calcified
What is the nucleus of the PCT like?
Ground glass or “Orphan Annie eye” nuclei
What is a medullary carcinoma?
Neuroendocrine neoplasms derived from the parafollicular cells (C cells) of the thyroid –> 5%
What do medullary carcinomas secrete?
Calcitonin
What can high levels of calcitonin produced by the medullary carcinomas lead to?
Hypocalcemia
What does calcitonin deposit as in medullary carcinomas?
As amyloid
How do medullary carcinomas arise?
Sporadically in about 70% of cases
Familial cases occurring in the setting of MEN syndrome 2A or 2B
Both associate with mutations in the RET oncogene
What is the distinctive characteristic of medullary carcinomas?
Amyloid deposition in adjusted stroma
