Path: Thyroid & Parathyroid

Question 1

What are thyroid function assays?

Answer 1

very sensitive
TSH most clinically useful
can measure thyroid hormone binding ratio and then T3-resin uptake test
multiplying THBR by total T3 or T4 gives free T3 and T4 index

Question 2

What are causes of thyrotoxicosis associated w hyperthyroidism?

Answer 2

diffuse toxic hyperplasia (Graves)
hyperfunctioning multinodular goiter or adenoma
TSH-secreting pit adenoma

Question 3

What are causes of thyrotoxicosis not associated w hyperthyroidism?

Answer 3

thyroiditis - damage follicles which release preformed T3 and T4
struma ovarii (thyroid tissue in ovarian teratoma)
exogenous thyroxin intake, drugs

Question 4

What is thyroid storm?

Answer 4

abrupt severe thyrotoxicosis due to increased catecholamines - can lead to arrhythmia and death

Question 5

What are causes of hypothyroidism?

Answer 5

iodine def*
congenital defect/dev abnormalities
drugs (lithium binds same transporter as iodine)
hashimoto
postablative
pit or hypothalamic failure

Question 6

What is cretinism?

Answer 6

inadequate thyroid hormone levels during dev - impaired skeletal and CNS dev –> short, retardation, coarse facial features, protruding tongue/belly, sparse hair

Question 7

What are other thyroiditis dzs in addition to hashimotos?

Answer 7

subacute granulomatous (de Quervain) - women 30-50, after viral inf, pain, granulomas and fibrosis
subacute lymphocytic - postpartum, often recurs w each pregnancy
Reidel: maybe autoimmune, fibrosis of thyroid and neck
palpation

Question 8

What drives the pathology of Hashimoto?

Answer 8

cd4 T cells against thyroid antigens like thyroid peroxidase, TSH receptor, and thyroglobulin - destroys follicular epithelial cells (transient burst of thyrotoxicosis before hypothyroidism values)

Question 9

What 3 things do the CD4 T cells do in hashimotos?

Answer 9

attract macrophages to destroy thymocytes
induce CD8 T cells to destroy thymocytes
induce plasma cell release of Ab that coat thyrocytes and cause NK attack

Question 10

What are the histologic/gross features of Hashimotos?

Answer 10

lymphoid follicles and GCs, macrophages, plasma cells, enlarged gland, Hurthle cells, fibrosis and atrophy eventually, *increased risk of diffuse large B cell lymphoma
grossly thyroid becomes lobulated

Question 11

What 3 antibodies are found in Graves?

Answer 11

thyroid-stimulating IgG - mimics TSH and lasts longer
Thyroid growth stimulating Ig - stimulate growth of follicles
TSH binding inhibitory Ig - prevents TSH binding to receptor, sometimes stimulates it, sometimes inhibits (transient hypothyroidism)

Question 12

What are the different classifications of goiters?

Answer 12

diffuse vs. multinodular

simple (no thyrotoxicosis, no large nodules) vs. toxic

Question 13

What is the histology of a nodular goiter?

Answer 13

maybe crowded hyperplastic columnar epithelial cells forming papillary structures, increased amts of colloid (colloid goiters), nodules w/i fibrous capsules, variable sized follicles

Question 14

What features are common in multinodular goiters?

Answer 14

areas of hemorrhage, fibrosis and cystic change

Question 15

What are signs suggesting malignancy risk of a thyroid nodule?

Answer 15

solitary, young patient, males, previous radiation treatments of neck, cold (non-functioning) nodule on thyroid scan

Question 16

What are the general features of follicular adenomas?

Answer 16

usually women, middle age
asymptomatic except for lump
cold on scan
encapsulated - displaces normal tissue to side
many have mutations in RAS proteins

Question 17

What are cellular features of follicular adenoma?

Answer 17

look like normal follicular cells
no invasion or metastasis
can have hurthle cell change

Question 18

What are the general features of papillary carcinomas?

Answer 18

often hx of radiation exposure
asymptomatic except for lump
cold on scan
tendency to be multifocal, spread to cervical lymph nodes, invade soft tissues of neck
hematogenous spread is rare

Question 19

What are the microscopic features of papillary carcinoma?

Answer 19

papillary structures, fibrosis, orphan annie nuclei, nuclear grooves, nuclear psuedo-inclusions, psamomma bodies, may invade local structures

Question 20

What is the prognosis of papillary carcinoma?

Answer 20

slow growing, usually good, high survival rate

Question 21

What are the genetics behind papillary carcinomas?

Answer 21

translocation of RET and PTC genes –> fusion protein activates MAP kinase pathway
point mutation V600E in BRAF –> MAP kinase activation
BRAF more specific, and worse prognosis

Question 22

What are the general features of follicular carcinoma?

Answer 22

cold scan, usually doesn’t infiltrate local structures, metastasis by blood to lungs, bone, liver, not usually in cervical lymph nodes

Question 23

What are the cellular features of follicular carcinoma?

Answer 23

resemble normal thyroid and adenoma except:
thicker capsule, invade local vessels, invade capsule
need to look at ENTIRE capsule

Question 24

What are the genetics behind follicular carcinomas?

Answer 24

point mutations in RAS activate MAPK path

translocations b/w PAX-8 and PPARgamma

Question 25

What are the general features of medullary carcinoma?

Answer 25

neuroendocrine origin, not follicular, of parafollicular C cells
secrete calcitonin that may lower blood Ca, but still cold scan
sporadic or familial (MEN 2A, 2B)
RET gene mutations
metastasize to lung, liver, bone
fair prognosis - half at ten years

Question 26

What are cellular features of medullary carcinoma?

Answer 26

solid, lobular, trabecular growth
round, polygonal spindle cells w salt and pepper chromatin
amyloid deposits
necrosis and hemorrhage

Question 27

What are the features of anaplastic (undifferentiated) carcinoma?

Answer 27

highly malignant, poor prognosis
rapid enlargement, invasive, metastases
usually older women
cold scan
often background of previous carcinoma or multinodular goiter
atypical spindle or giant cells

Question 28

What are the features of the normal parathyroid?

Answer 28

chief and oxyphil cells
no ant pit or hypothalamic input - regulate themselves by monitoring serum Ca
PTH increases serum Ca

Question 29

What is secondary hyperparathyroidism usually due to?

Answer 29

renal failure

Question 30

What are classic symptoms of hyperparathyroid patients?

Answer 30

painful bones (osteoporosis and osteitis fibrosa cystica), renal stones, ab groans, psychic moans (depression, lethargy)
also proximal muscle weakness and polyuria

Question 31

What are the features of parathyroid adenoma?

Answer 31

common in younger women
usually solitary, secretes PTH, more chief cells
encapsulated pushes normal tissue aside
other 3 atrophy due to negative feedback
increased uptake on sestamibi scan

Question 32

What are the features of primary parathyroid hyperplasia?

Answer 32

4 enlarged, hyperactive glands
also in younger women
sporadic or part of MEN syndromes
diffuse hypertrophy w loss of fat

Question 33

What are the features of parathyroid carcinoma?

Answer 33

solitary tumor in one gland, other 3 atrophy
cells more often chief than oxyphil
higher serum Ca levels
malignant - invades or metastasizes

Question 34

What is the pathophysiology of secondary hyperparathyroidism?

Answer 34

kidney failure –> increased serum PO4 –> decreased Ca –> increased PTH

Question 35

What are the features of secondary hyperparathyroidism?

Answer 35

symptoms less severe than primary
all four glands hypertrophy
chief and clear cells predominate, fat content down
metastatic calcification in peripheral tissues
calciphylaxis - tissue ischemia from calcified vessels (esp in skin)

Question 36

What are the features of hypoparathyroidism?

Answer 36

hereditary or acquired
acquired usually surgically induced
reduced serum Ca causes muscle spasms, tingling, tetany, arrhythmias, seizures