Thyroid Pathology Flashcards
What is the location of the thyroid gland?
In the anterior neck below the larynx along the thyroglossal duct
What is the histological structure of the thyroid gland?
Composed of lobules containing follicles defined by thin fibrous septa
Each follicle is surrounded by follicular epithelial cells
There are C cells (parafollicular cells) scattered about - these are slightly larger cells with clearer cytoplasm
What is the function of follicular cells?
Secrete thyroglobulin
Produce colloid and thyroid hormones
Control the release of these hormones into the blood
What is the function of C cells?
Secrete calcitonin
What is the process of secretion of thyroid hormones?
TSH from the pituitary gland binds to TSH G-protein coupled receptors on thyroid epithelial cells
This causes an increase in the production of cAMP
cAMP increases production and release of T3 and T4
What is the function of T3 and T4?
Bind to rage cells to increase basal metabolic rate
Describe the negative feedback effect that controls the secretion of thyroid hormones.
Hypothalamus releases TRH which stimulates the anterior pituitary gland to secrete TSH
TSH stimulates thyroid follicular epithelium to secrete T3 and T4
Increased levels of T3 and T4 inhibit the anterior pituitary gland and the hypothalamus to decrease the secretion of TSH and TRH
What do TRH and TSH stand for?
TRH - thyrotropin releasing hormone
TSH - thyroid stimulating hormone
What are the main examples of autoimmune thyroiditis?
Hashimoto’s thyroiditis (hypofunction)
Grave’s disease (hyperfunction)
What are the common features of autoimmune thyroiditis?
Increased incidence in family members
Susceptibility associated with the HLA haplotype
Association with other autoimmune diseases
What are non-immune related causes of inflammation of the thyroid?
Palpation Subacute lymphocytic De Quervain's Infection Riedel's
What is thyrotoxicosis?
When symptoms and signs occur as a result of excess T3 and T4
What are the causes of thyrotoxicosis?
Hyperthyroidism Hyperfunctioning nodules and tumours TSH secreting pituitary adenomas Thyroiditis Ectopic production Facticious
What is Grave’s disease?
An autoimmune disorder of thyroid gland hyperactivity
Who are commonly affected by Grave’s disease?
Women (10 times more than men)
20-40 years old
What is the action of anti-TSH receptor antibodies?
Act to stimulate receptors and mimic the effect of TSH
What are the anti-TSH receptor antibodies?
Thyroid stimulating immunoglobulin
Thyroid growth stimulating immunoglobulin
TSH binding inhibitor immunoglobulin
What triad of features are classic of Grave’s disease?
Diffuse enlargement of the thyroid
Eye changes (exophthalmus)
Pretibial myxoedema
Which histological changes occur in Grave’s disease?
Most follicles contain little or no thyroglobulin, and where there is thyroglobulin, there aren areas of pallor at the edges
In between follicles is abundant lymphocyte invasion
What is hypothyroidism?
Symptoms and signs due to low levels of T3 and T4
What are the causes of hypothyroidism?
Hashimoto's thyroiditis (autoimmune) Iodine deficiency Drugs (e.g. lithium) Post-therapy (surgery, irradiation) Congenital abnormalities Born errors of metabolism
What are secondary and tertiary hypothyroidism?
A result of pituitary or hypothalamus pathology respectively
What is Hashimoto’s thyroiditis?
Gradual failure of thyroid function?
Who commonly present with Hashimoto’s thyroiditis?
Women (10-20 times more than men)
45-60 years old
Which antibodies are associated with Hashimoto’s thyroiditis?
Anti-thyroid antibodies (anti-thyroglobulin and anti-peroxidase)
What is the pathogenesis of Hashimoto’s thyroiditis?
CD8+ cells cause destruction of thyroid epithelium
Cytokines recruit macrophages that damage thyroid follicles
Thyroid follicles atrophy
Progressive fibrosis
What histological features can be seen in Hashimoto’s thyroiditis?
Prominent lymphoid infiltration
Lymphoid follicles with reactive appearing germinal centres
Islands of residual normal thyroid follicles containing thyroglobulin
What may precede hypothyroidism?
Transient hyperfunction (Hashitoxicosis)
What is there an increased risk of in Hashimoto’s thyroiditis?
B cell non-Hodgekin’s lymphoma
What is a goitre?
Any enlargement of the thyroid gland
What are goitres usually caused by?
Lack of dietary iodine
Lack of bioavailability of iodine
How does a goitre form?
Reduced T3/T4 production causes rise in TSH, stimulating gland enlargement
Who commonly present with diffuse goitres?
Women
Puberty-aged and young adults
What will thyroid hormone levels be like in a diffuse goitre?
T3 and T4 usually normal
TSH often high or upper limit of normal
What are the different types of goitre?
Diffuse
Multi-nodular
What is a multi-nodular goitre?
One that has evolved from a long-standing simple goitre due to recurrent hyperplasia and involution
What effects can a large multi-nodular goitre cause?
Airway obstruction
Dysphagia
Compression of vessels
What are the thyroid neoplasms?
Follicular adenoma Papillary carcinoma Follicular carcinoma Medullary carcinoma Anaplastic carcinoma
What is the description of a follicular adenoma?
Discrete solitary mass
What are the symptoms of a follicular adenoma?
Usually asymptomatic and incidental finding
Local symptoms e.g. dysphagia if large
What is the pathology of a follicular adenoma?
Encapsulated by a surrounding collagen cuff
Composed of neoplastic thyroid follicles
Usually non-function but can secrete thyroid hormones
What are follicular adenoma usually caused by?
Mutations of the TSHR signalling pathway
What is themes common thyroid carcinoma?
Papillary carcinoma
What are the causes of thyroid carcinomas?
Ionising radiation (papillary carcinoma) Iodine deficiency (follicular carcinoma) MEN2 (medullary carcinoma)
Describe the pathology of papillary carcinomas
Usually a solitary nodule in the thyroid, can be multifactorial, often cystic, may be calcified
What are the symptoms and signs of papillary carcinomas?
Lesion in the thyroid gland or cervical lymph node mass Hoarseness Dysphagia Cough Dysphnoea
How do papillary carcinomas spread?
Lymph node metastasis
Uncommonly haematogenous spread, usually to lung
What is the prognosis for papillary carcinomas?
Good - survival at 10 years is 95%+
Prognosis worse as age increases, if there is extra-thyroid extension or if distant metastases
Who commonly present with follicular carcinomas?
Women
40s and 50s
Describe the pathology of follicular carcinomas
Usually a single nodule
Slowly enlarging, painless, non-functional
What is the spread of follicular carcinomas?
Rarely lymphatic spread
Can have haematogenous spread to bone, lungs, liver
Do follicular carcinomas commonly spread locally?
Yes - can be widely or minimally invasive
What are features of a widely invasive follicular carcinoma?
More solid architechture
Less follicular architecture
More mitotic activity
What are the features of a minimally invasive follicular carcinoma?
Follicular architecture (well differentiated)
May have part surrounding capsule
Difficult to distinguish from adenoma
What is the prognosis of follicular carcinomas?
Depends on extent of invasion and stage at presentation
If high stage - 50% mortality at 10 years
If minimally invasive - >90% survival at 10 years
What do medullary thyroid carcinomas derive from?
C cells
What are the types of medullary thyroid carcinomas?
Sporadic (70%)
Associated with multiple endocrine neoplasia (MEN2a or 2b)
Familial medullary carcinoma
Who usually presents with medullary thyroid carcinomas?
Can be very young if associated with MEN
Adults in 40s and 50s
What is the difference between sporadic and familial medullary thyroid carcinomas?
Sporadic - solitary nodules
Familial - bilateral or multicentric
Describe the pathology of medullary thyroid carcinomas?
Composed of spindle or polygonal cells arranged in nests, trabeculae or follicles
How do medullary thyroid carcinomas present?
Neck mass with local effects (dysphagia, hoarseness, airway compromise) Paraneoplastic syndrome (diarrhoea, Cushing's)
What is the treatment for medullary thyroid carcinomas?
Total thyroidectomy
What is the prognosis for medullary thyroid carcinomas?
5 and 10 year survival overall about 80% and 73%
35% recurrence in patients who get a total thyroidectomy
What are the good and poor prognostic factors for medullary thyroid carcinomas?
Good: young age, female, small tumour size, confined to thyroid with no meastases
Poor: necrosis, many mitosis, squamous metaplasia, MEN2b
What are anapaestic carcinomas?
Undifferentiated and aggressive tumours
Usually present in older patients
Can occur in patients with history of differentiated thyroid carcinoma
Rapid growth and involvement of neck structures
