Thyroid Gland Pathology Flashcards
What are some probable causes of primary hyperthyroidism?
- Diffuse hyperplasia (Graves disease)
- Hyperfunctioning multinodular goiter
- Hyperfunctioning thyroid adenoma
What is a probable cause of secondary hyperthyroidism?
- Pituitary adenoma
What can be looked at to determine primary from secondary hyperthyroidism ?
- TSH levels
- Low TSH means primary
- High TSH means secondary
What may prompt someone with hyperthyroidism to go see the doctor?
- Palpitations or tachycardia
- Perspiration
- Facial flushing
- Exophthalmos
What is apathetic hyperthyroidism?
- Older adults with masked symptomatology
- Unexplained weight loss
- Cardiovascular disease
What is regular hyperthyroidism?
- Symptoms as seen in the hyperthyroidism
- Jittery
- Palpitations
What is thyroid storm?
- Abrupt onset of thyrotoxicosis
What is seen in thyroid storm?
- Fever
- Cardiac manifestations
- GI symptoms
- Precipitating history
What cardiac manifestations may be seen in a thyroid storm?
- Tachycardia
- CHF
What GI symptoms may be seen in a thyroid storm?
- Diarrhea
- Jaundice
What precipitating history may cause a thyroid storm?
- Pregnancy/postpartum
- Hemithyroidectomy
- Drugs: amiodarone
What are some treatment options of thyroid storm?
- Beta blockers
- High doses of iodide
- Thioamide
- Radioiodine ablation
- Surgery
What is Graves disease characterized by?
- Hyperthyroidism with gland enlargement
- Infiltrative ophthalmopathy
- Pretibial myxedema
What is the pathogenesis of Graves disease?
- Lymphocytes invade preorbital space
- Fibroblasts have TSH receptors
- EOM swelling
- Matrix accumulates
- Adipocytes expand
What is pretibial myxedema?
- Infiltrative dermopathy
- Scaly, indurated skin
What are the serum levels of thyroid hormones in Graves disease?
- T3/T4: HIGH
- TSH: LOW
- TSI: HIGH
What is the presentation of congenital hypothyroidism?
- Mental retardation
- Growth retardation
- Coarse facial features
- Umbilical hernias
Where is congenital hypothyroidism seen?
- Where there is endemic areas without iodine supplementation
What is myxedema?
- Hypothyroidism in the adult/older child
What is the clinical presentation of myxedema?
- Mental and physical sluggishness (slowing)
- Weight gain
- Cold intolerance
- Cardiac effect (lower output and hypercholesterolemia)
What causes hashimoto thyroditis?
- Autoantibodies against Thyroglobulin and Thyroid Peroxidase (TPO)
What is the progression to hypothyroidism in Hashimoto thyroiditis?
- Immune mediated insult –> hyperactivity and enlargement –> follicular cell exhaustion causing hypothyroidism
What is seen on histology in Hashimoto thyroiditis?
- Lymphocytic infiltrate with germinal centers
- Atrophic follicle cells with eosinophilic change (Hürthle cell metaplasia)
What is subacute lymphocytic thyroiditis?
- Typically a transient period of thyroid hormone irregularities
What is Granulomatous thyroiditis?
- Painful
- Granulomata
- Viral in origin??
- Sometimes lumped in with subacute thyroiditis
What is Riedel thyroiditis?
- Fibrosing process
- Extends from the thyroid into adjacent tissue
What is the cause of Riedel thyroiditis?
- Unknown (IgG4-related)
What is the thyroid state in Riedel thyroiditis?
- Euthyroid
What causes endemic goiters?
- Iodine deficiency
What are some goitrogens?
- Cassava root
- Brassicaceae (broccoli, cauliflower, cabbage)
Who is most likely to have a sporadic goiter?
- Females
What are some symptoms of a goiter due to mass effect?
- Dysphagia
- Hoarseness
- Stridor
- SVC syndrome
Why are there multinodular goiters?
- Hyperplasia, regression (involution) cycle
- Varied response of nodules to stimuli
- Neoplastic nature of some nodules (adenomas)
What is radioisotope scanning?
- A modality to determine if a specific nodule is responsible for hyperfunction
What is a hot nodule? How is it treated?
- Hyperfunctioning nodule
- Treated with radioactive iodide or excised
What is a cold neoplasm? How is it treated?
- Could be a neoplasm
- Need to do further workup like U/S
What are some benign neoplasms of the thyroid?
- Hyperplastic (adenomatoid) nodules
- Follicular adenomas
What are some malignant neoplasms of the thyroid?
- Papillary thyroid carcinoma
- Follicular/Hürthle cell carcinoma
- Anaplastic carcinoma
- Medullary carcinoma
What is a follicular adenoma?
- Discrete clonal population of follicular cells with ‘Thyroid autonomy”
- Benign but need to make sure there is an intact capsule
- No nuclear features of papillary carcinoma
What is a papillary thyroid carcinoma?
- Majority of malignant tumors of the thyroid glands
- Most occur between 25-50
How does a papillary thyroid carcinoma present?
- Typically without symptoms
- Palpable nodule
- Ultrasound
What does histology show for a papillary thyroid carcinoma?
- Enlarged nuclei with “clear” appearance
- “Orphan Annie Eye nuclei”
What is the follicular variant of PTC?
- Follicular architecture, but nuclear features of papillary carcinoma
- Fewer cases have RET-PTC rearrangements or BRAF mutations
- More cases with RAS mutations
What is the tall cell variant of PTC?
- Older patients
- Aggressive
What is the diffuse sclerosing variant of PTC?
- Kids and young adults
- Greater incidence of distant metastasis to lung, brain, bone, and liver
- Shorter periods of disease-free survival
- Mortality rate isn’t that bad despite the likelihood of distant metastasis
What is follicular carcinoma?
- Follicular neoplasm with invasive properties
- Less common than papillary
- More common in areas with goiter from iodide deficiency
What mutations are seen in follicular carcinoma?
- RAS mutations - not specific
- PAX8/PPARG mutations - more characteristic
What are the two types of invasion seen with follicular carcinoma?
- Invasion of the capsule (mushroom cloud)
- Angioinvasion
What are some therapeutic options for differentiated thyroid carcinoma?
- Surgery
- Radioactive iodine
- If refractory: chemotherapy or tyrosine kinase inhibitors
What is special about using radioactive iodine in differentiated thyroid carcinoma?
- The radioactive iodine will even target the metastasis due to the similar cell components
What is anaplastic carcinoma?
- Uncommon
- Tend to occur in elderly patients
- Highly aggressive
- Present with mass effect
- Die within a year of local invasion
What are the genetics with papillary carcinoma?
- RET/PTC rearrangements –> constitutive tyrosine kinase activity
- BRAF gain of function mutations –> MAP kinase signaling
What are the genetics with follicular carcinoma?
- PAX8-PPARG
What are the genetics with follicular neoplasms?
- RAS
- PTEN
What are the genetics with anaplastic carcinoma?
- TP53
What are C cells responsible for?
- Calcitonin secretion
What stain is done to help identify C cells?
- Calcitonin immunohistochemistry
What is medullary carcinoma?
- Neuroendocrine carcinoma derived from C cells
- Blue cells with dispersed chromatin
- Amyloid
- C cell hyperplasia
What is the sporadic form of MTC?
- 70-80% of all MTCs
- Unifocal tumors
- Mean age is 50
- Aggressive
What is the familial form of MTC?
- BEST prognosis of all forms
- Multifocal
- Mean age is 43
What proto-oncogene is associated with MTC?
- RET on chromosome 10
