Path: Thyroid & Parathyroid Flashcards
What are thyroid function assays?
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
What are causes of thyrotoxicosis associated w hyperthyroidism?
diffuse toxic hyperplasia (Graves)
hyperfunctioning multinodular goiter or adenoma
TSH-secreting pit adenoma
What are causes of thyrotoxicosis not associated w hyperthyroidism?
thyroiditis - damage follicles which release preformed T3 and T4 struma ovarii (thyroid tissue in ovarian teratoma) exogenous thyroxin intake, drugs
What is thyroid storm?
abrupt severe thyrotoxicosis due to increased catecholamines - can lead to arrhythmia and death
What are causes of hypothyroidism?
iodine def* congenital defect/dev abnormalities drugs (lithium binds same transporter as iodine) hashimoto postablative pit or hypothalamic failure
What is cretinism?
inadequate thyroid hormone levels during dev - impaired skeletal and CNS dev –> short, retardation, coarse facial features, protruding tongue/belly, sparse hair
What are other thyroiditis dzs in addition to hashimotos?
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
What drives the pathology of Hashimoto?
cd4 T cells against thyroid antigens like thyroid peroxidase, TSH receptor, and thyroglobulin - destroys follicular epithelial cells (transient burst of thyrotoxicosis before hypothyroidism values)
What 3 things do the CD4 T cells do in hashimotos?
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
What are the histologic/gross features of Hashimotos?
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
What 3 antibodies are found in Graves?
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)
What are the different classifications of goiters?
diffuse vs. multinodular
simple (no thyrotoxicosis, no large nodules) vs. toxic
What is the histology of a nodular goiter?
maybe crowded hyperplastic columnar epithelial cells forming papillary structures, increased amts of colloid (colloid goiters), nodules w/i fibrous capsules, variable sized follicles
What features are common in multinodular goiters?
areas of hemorrhage, fibrosis and cystic change
What are signs suggesting malignancy risk of a thyroid nodule?
solitary, young patient, males, previous radiation treatments of neck, cold (non-functioning) nodule on thyroid scan
What are the general features of follicular adenomas?
usually women, middle age asymptomatic except for lump cold on scan encapsulated - displaces normal tissue to side many have mutations in RAS proteins
What are cellular features of follicular adenoma?
look like normal follicular cells
no invasion or metastasis
can have hurthle cell change
What are the general features of papillary carcinomas?
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
What are the microscopic features of papillary carcinoma?
papillary structures, fibrosis, orphan annie nuclei, nuclear grooves, nuclear psuedo-inclusions, psamomma bodies, may invade local structures
What is the prognosis of papillary carcinoma?
slow growing, usually good, high survival rate
What are the genetics behind papillary carcinomas?
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
What are the general features of follicular carcinoma?
cold scan, usually doesn’t infiltrate local structures, metastasis by blood to lungs, bone, liver, not usually in cervical lymph nodes
What are the cellular features of follicular carcinoma?
resemble normal thyroid and adenoma except:
thicker capsule, invade local vessels, invade capsule
need to look at ENTIRE capsule
What are the genetics behind follicular carcinomas?
point mutations in RAS activate MAPK path
translocations b/w PAX-8 and PPARgamma
What are the general features of medullary carcinoma?
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
What are cellular features of medullary carcinoma?
solid, lobular, trabecular growth
round, polygonal spindle cells w salt and pepper chromatin
amyloid deposits
necrosis and hemorrhage
What are the features of anaplastic (undifferentiated) carcinoma?
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
What are the features of the normal parathyroid?
chief and oxyphil cells
no ant pit or hypothalamic input - regulate themselves by monitoring serum Ca
PTH increases serum Ca
What is secondary hyperparathyroidism usually due to?
renal failure
What are classic symptoms of hyperparathyroid patients?
painful bones (osteoporosis and osteitis fibrosa cystica), renal stones, ab groans, psychic moans (depression, lethargy) also proximal muscle weakness and polyuria
What are the features of parathyroid adenoma?
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
What are the features of primary parathyroid hyperplasia?
4 enlarged, hyperactive glands
also in younger women
sporadic or part of MEN syndromes
diffuse hypertrophy w loss of fat
What are the features of parathyroid carcinoma?
solitary tumor in one gland, other 3 atrophy
cells more often chief than oxyphil
higher serum Ca levels
malignant - invades or metastasizes
What is the pathophysiology of secondary hyperparathyroidism?
kidney failure –> increased serum PO4 –> decreased Ca –> increased PTH
What are the features of secondary hyperparathyroidism?
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)
What are the features of hypoparathyroidism?
hereditary or acquired
acquired usually surgically induced
reduced serum Ca causes muscle spasms, tingling, tetany, arrhythmias, seizures
