Thyroid Pathology Flashcards
What is Thyrotoxicosis?
Hypermetabolic state caused by elevated circulating levels of free T3/T4
What are 4 examples of disorders of Thyrotoxicosis NOT associated with hyperthyroidism?
Granulomatous Thyroiditis (De Quervain)
Subacute Lymphoctyic Thyroiditis
Struma Ovarii
Factitious Thyrotoxicosis
What are the major Sx’s of hyperthyroidism?
Increased BMR, tachycardia, tremor, hyperstimulation of gut, wide staring gaze, osteoporosis
What is a thyroid storm?
Abrupt onset of severe hyperthyroidism with fever and tachycardia
*Medical emergency
What is apathetic hyperthyroidism?
Thyrotoxicosis in older adults that is seen only via lab work-up for unexplained weight loss or worsening CV disease
What would the lab findings be for apathetic hyperthyroidism?
Low serum TSH
Increased free T4
How much of the thyroid will take up radioactive iodine in Graves disease?
The whole gland (diffuse)
How much of the thyroid will take up radioactive iodine in a toxic adenoma?
Increased uptake in a solitary nodule
How much of the thyroid will take up radioactive iodine in thyroiditis?
Decreased uptake
Sx’s = mental retardation, short stature, coarse facial features, protruding tongue, umbilical hernia in children
Cretinism (hypothyroidism)
Sx’s = apathy, fatigue, mental sluggishness, cold intolerance, overweight, cool/pale skin, coarse facial features, cold intolerance in adult
Myxedema (hypothyroidism)
What can hypothyroidism do to cholesterol levels?
Increased total cholesterol
Increased LDL
What would the lab findings be in primary hypothyroidism?
Increased serum TSH
Decreased free T4
Which test is most sensitive for screening for hypothyroidism?
TSH
What would lab findings be in secondary hypothyroidism?
Decreased serum TSH
Decreased free T4
What is the difference between primary and secondary hypothyroidism?
Secondary is caused by pituitary or hypothalamic failure
What is Hashimoto thyroiditis?
Autoimmune destruction of thyroid gland leading to gradual thyroid failure (hypothyroidism)
Which Abs are found in Hashimoto thyroiditis?
Anti-microsomal
Anti-thyroid peroxidase
Anti-thyroglobulin
Which gene defects are associated with Hashimoto thyroiditis?
CTLA4
PTPN22
Morphology = Diffusely enlarged thyroid with atrophic follicles and Hurthle cell metaplasia
Hashimoto thyroiditis
Which cancer are pts at increased risk for if they Hashimoto thyroiditis?
Marginal zone B-cell lymphoma
What is the common presentation of a pt with Hashimoto thyroiditis?
Painless, symmetrically enlarged thyroid
Painless, mild hyperthyroidism that may cause a goiter and is the cause of Postpartum Thyroiditis
Subacute Lymphocytic Thyroiditis
Morphology = patchy distribution and collapse of thyroid follicles with NO fibrosis or Hurthle cell metaplasia
Subacute Lymphocytic Thyroiditis
1/3 of pts with _____ will evolve into overt hypothyroidism?
Subacute Lymphocytic Thyroiditis
What is another name for Granulomatous Thyroiditis?
De Quervain’s Thyroiditis
What is Granulomatous Thyroiditis?
Immune response triggered by a viral infection
Sx’s = painful, enlarged thyroid occurring after a URI causing transient hyperthyroidism for 2-6 weeks
Granulomatous Thyroiditis
What is the Tx for Granulomatous Thyroiditis?
Self-limited
Morphology = enlarged, firm thyroid stuck to surrounding structures with aggregates of lymphocytes, macrophages, and plasma cells, and damaged follicles
Granulomatous Thyroiditis
What are the lab values in Granulomatous Thyroiditis?
Low serum TSH
High serum T3/T4
What is the radioactive iodine uptake like in Granulomatous Thyroiditis?
Decreased uptake
What is Riedel Thyroiditis?
Extensive fibrosis of the thyroid and surrounding structures due to IgG4-related sclerosing disease (can affect other organs)
Form of Autoimmune IgG4-related sclerosing disease?
Riedel Thyroiditis
What is the most common cause of thyroid pain?
Granulomatous Thyroiditis
What is the most common cause of endogenous hyperthyroidism?
Graves disease
What is Graves disease?
Elevated T3/T4 due to stimulation of TSH receptors via Thyroid-Stimulating Immunoglobulin (TSI) and TSH receptor blocking Abs
What polymorphisms are associated with Graves disease?
CTLA4
PTPN22
HLA-DR3
What are the major Sx’s of Graves disease?
Diffuse thyroid enlargement, Hyperthyroidism
Exophthalmos
Infiltrative dermopathy (pretibial myxedema)
What is the pathogenesis of exophthalmos?
Orbital preadipocytes express TSH receptor –> increased volume of retroorbital CT and extraocular muscles
Morphology = Symmetric thyroid enlargement with tall, crowded follicular cells that lack a fibrovascular core, and pale colloid with scalloped margins
Graves disease
What are the lab values seen in Graves disease?
Low serum TSH
High free T3/T4
What is the radioactive iodine uptake like in Graves disease?
Diffusely taken up
What is the Tx for Graves disease?
ß-blockers
Decrease thyroid hormone synthesis
Surgery
Where are diffuse nontoxic goiters endemic?
Andes and Himalayas
When do sporadic diffuse nontoxic goiters typically arise?
Puberty or young adult life
What are the lab values seen in diffuse nontoxic goiters?
Elevated TSH
Normal T3/T4
Most Sx’s of diffuse nontoxic goiters are due to what?
Mass effect
What are multinodular goiters?
Long-standing simple goiters that convert to multinodular goiters
What is the radioactive iodine uptake like in multinodular goiters?
Uneven uptake, may find “hot” nodule
How do you evaluate the dominant nodule in multinodular goiters?
Fine needle aspiration (FNA)
What is Plummer Syndrome?
When a nodule in a long-standing goiter becomes autonomous and produces hyperthyroidism
What is another name for Plummer Syndrome?
Toxic Multinodular Goiter
Which clues help to decide if a neoplasm is most likely neoplastic?
Solitary nodule
Found in younger pts
Found in males
History of radiation to head/neck
Which clues help to decide if a neoplasm is most likely benign?
Multiple nodules
Found in older pts
Found in females
Presence of “hot” spots
What is the best way to evaluate thyroid nodules?
Fine needle aspiration
Sx’s = unilateral, painless mass that are generally non-functional
Follicular adenomas
Morphology = solitary, encapsulated, well-demarcated lesions with uniform-appearing follicles and may see Hurthle cell metaplasia
Follicular adenomas
What is the name for a Follicular adenoma if Hurthle cell metaplasia is seen?
Hurthle cell adenoma
What do you look at to confirm a definitive Dx of Follicular adenoma?
Integrity of the capsule
What increases the risk of developing Papillary carcinomas?
Exposure to ionizing radiation in early life
What increases the risk of developing Follicular carcinomas?
Dietary iodine deficiency
What gene mutations are seen in Follicular and Anaplastic carcinomas?
RAS
PI3K
PTEN
What gene mutation is seen in Papillary carcinoma?
BRAF
Morphology = areas of fibrosis and calcification with large overlapping nuclei having a clear/empty appearance (Ground glass or Orphan Annie Eye nuclei), and pseudo-inclusions
Papillary carcinoma
Morphology = large, overlapping nuclei having a clear/empty appearance with follicular architecture
Follicular variant of PTC
Morphology = Tall columnar cells with intensely eosinophilic cytoplasm lining the papillary structures
Tall-cell variant of PTC
What mutations are associated with Tall-cell variant of PTC?
BRAF mutation
RET/PTC translocation
Sx’s = asymptomatic thyroid nodules, possible cervical lymph node mass, hoarseness, dysphagia, cough, and dyspnea
Papillary carcinoma
Which organ does metastasis usually occur to in Papillary carcinoma?
Lung
What is the Tx for Papillary carcinoma?
Surgery
Radiation
Which form of Papillary carcinoma has a poorer prognosis?
Tall-cell variant in older pts
What factors contribute to the prognosis of Papillary carcinoma?
Age
Extrathyroid extension
Metastasis
Morphology = single nodule containing small follicles with uniform cells (no nuclei like those in PTC) and may have Hurthle cell metaplasia
Follicular carcinoma
What distinguishes Follicular adenoma VS carcinoma?
Carcinoma has invasion into/beyond the capsule
Sx’s = slow growing, painless nodule with “cold” nodules
Follicular carcinoma
What areas are most likely to have metastases in Follicular carcinoma?
Bone
Lungs
Liver
What determines prognosis of Follicular carcinoma?
Extend of invasion and stage at presentation
What is the Tx for Follicular carcinoma?
Surgery + radioactive iodine
Thyroid hormone administration
What is serum product is used to monitor tumor recurrence in Follicular carcinoma?
Serum thyroglobulin
Sx’s = rapidly enlarging neck mass with dyspnea, dysphagia, hoarseness, and cough
Anaplastic thyroid carcinoma
Morphology = Undifferentiated, highly aggressive tumors
Anaplastic thyroid carcioma
What is the Tx for Anaplastic thyroid carcinoma
There is no effective therapy
How do Anaplastic thyroid carcinomas arise?
De novo
Dedifferentiation of papillary or follicular carcinomas
What type of tumor is a neuroendocrine neoplasm derived from C (parafollicular) cells
Medullary thyroid carcinomas
What are the familial forms of Medullary thyroid carcinomas associated with?
MEN 2A/2B
Familial Medullary Thyroid Carcinoma
What gene mutation is seen in 1/2 of sporadic cases of Medullary thyroid carcinoma?
RET
What is the presentation difference between sporadic and familial Medullary thyroid carcinoma?
Sporadic = single nodule Familial = multiple b/l foci
Medullary thyroid carcinomas will stain + for?
Calcitonin
What can be seen deposited in the stroma in Medullary thyroid carcinomas?
Amyloid
What are the major Sx’s of sporadic Medullary thyroid carcinoma?
Paraneoplastic syndrome (diarrhea due to VIP) and normal Ca levels
What is a useful tumor marker that is secreted in sporadic Medullary thyroid carcinoma?
Carcinoembryonic Ag (CAE)
Pts diagnosed with MEN 2B are often given _____ as prophylactic Tx for Medullary thyroid cancer?
Thyroidectomy
Morphology = cyst lined by stratified squamous epithelium in midline of neck
High-lying thyroglossal duct cyst
Morphology = cyst lined by epithelium resembling thyroidal acinar epithelium in midline of neck
Low-lying thyroglossal duct cyst