Thyroid Flashcards

Question

what is the most common thyroid carcinoma?

Answer 1

papillary (\>85%)

Answer 2

blood loss anesthesia rsik transient hyperthyroid/thyroid storm (from TH release) hypoparathyroidism - transient or permanent recurrent laryngeal nerve damage (hoarseness) hypothyroid

Answer 3

for hyperthyroid 10 drops daily for up to 10 days before surgery decrease vascularity of the thyroid gland and surgical blood loss must treat with goitrogen first - iodine MAY exacerbate hyperthyroid

Answer 4

binding of a hormone to a serum protein renders it inactive only free hormone is able to enter cells increasing binding proteins increases total hormone concentration but NOT of the active portion

Answer 5

papillary carcinoma classic intranuclear pseudoinclusions . There are intra-nuclear inclusions which are cytoplasmic extensions into the nucleus. It is sort of an optical illusion that looks like a hole when cytoplasm goes in even though there are no holes. Nuclear clearing plus nuclear groups plus inclusions are pathomnemonic of papillary carcinoma. These things that are typical tend to pop up on exams.

Answer 6

if mom is euthyroid - good prognosis if Rx at birth, develop normally until birth, rarely found on fetal u/s if mom is hypothyroid - usually iodine deficiency, more severe mental retardation, poorer prognosis (less respinsive to Rx), deaf mutism and rigidiy hypothyroidism and goiter impaired cognitive function retarded mental and physical development impaired growth (short stature) increased infant mortality low birth weight, spontaneous abortion, decreased mortality congenital abnormalities deaf-mutism

Answer 7

"silent thyroiditis" **due to release of pre-formed thyroid hormone (low reactive iodine uptake, self limited - subsides in a few weeks!)** goiterous thyroid enlargement and mild hyperthyroidism less common post partum and middle aged variant of hashimotos (1/3 evolve into hypothyroid, majoriyt have circulating anti thyroid abs)

Answer 8

more side effects with PTU - use methimazole EXCEPT use PTU in pregnancy both can harm fetus

Answer 9

graves disease diffusely and symmetrically enlarged gland with beefy red parenchyma

Answer 10

150 mcg (200 if pregnant)

Answer 11

RET mutations - lead to activation of the reeceptor

Answer 12

chrominc autoimmune thyroiditis chronic inflammatory autoimmune disease characterized by destruction of the thyroid gland with acquired defect in thyroid immune synthesis

Answer 13

neuroendocrine tumor derivd from C (parafollicular) cells secrete calcitionin can be sporadic or associated with MEN (familial)

Answer 14

natural from animals diff amts of everything in diff batches endocrinologists don't like it!!

Answer 15

-3’ and 5’ ionidation of inner ring (2 purple circles on the inner ring) are both required for activity, but only one outer iodine is need for activity, so both T3 and T4 are active

Answer 16

most common ause of endogenous hyperthyroidism F\> M ab binds to TSH receptor in the thyroid and stimulates the thyroid gland to produce too much thyroid hormone

Answer 17

high TSH low T4 [anti-thyroglobulin, anti-thyroid peroxidase]

Answer 18

for hyperthyroid usefull in all etiologies of hyper, start ASAP even before determinimg cause decrase symptoms caused by icreased beta-adrenergic tone decrease vasculariyt of thyroid

Answer 19

water insoluble long half life (T4-8d, T3-1d) circulates bound to proteins!! **TBG** (thyroid binding protein) **Tyroid binding prealbumin** **albumin**

Answer 20

in colloid, when 2 iodines bound to a tyrosine ring DIT + MIT = T3 DIT + DIT = T4 if not made into TH, recycle iodine and tyrosine

Answer 21

repeated episodes of hyperplasia and involutionlead to long standing preceded by diffuse goiter endemic or sporadic forms older individuals as late complication of simple goiter may be really big! compress esophagus

Answer 22

1. u/s and fna 2. fna sample submitted for molecular testing 3. cold nodules by radionucleotide scan 4. suspected tumors need surgical resection - entire capsule should be evalulated histologically for capsular and vascular invasion

Answer 23

taking too much thyroid hormone - T4, T3, both

Answer 24

rare fibrosing process ## Footnote Riedel’s thyroiditis is a very rare disease where the thyroid gland becomes fibrotic and stuck to other neck organs. It can be confused with an anaplastic carcinoma. It is associated with another strange disease, idiopathic fibrosis in the retroperitoneal area.

Answer 25

psammoma body - papillary carcinoma calcified structures (tumor cell necrosis) Psammoma calcifications in papillary carcinomas. These tumors grow so slowly that as they grow they start dying and outgrow their blood supply. They form lamellar calcifications, or psammoma bodies.

Answer 26

papillary carcinoma papillary architecture and overlapping oval nuclei with clearing are seen Nuclear clearing plus nuclear groups plus inclusions are pathomnemonic of papillary carcinoma. These things that are typical tend to pop up on exams.

Answer 27

5' generate T3 - Type 2 (activator): in pituitary - only 5’ à generates active T3

Answer 28

no nodules endemic or sporadic in childhood - cretinism in adulthood - euthyroid can turn into multinodular goiter with repeated cycles (hyperplasia and involution)

Answer 29

Again, T3 and T4 feedback to the thyroid to inhibit TSH secretion T4 works b/c de-iodinase in pituitary converting T4à T3

Answer 30

genetic testing for thyroid nodules to reduce genetic testing more info than afirma

Answer 31

in L thyroxine - give it diff properties because only need a tiny amount may have sensitivities or allergies may affect bioavailability

Answer 32

T3! rarely only if deiodinase enzyme type 1 deficiency - deiodinates outer ring of T4 to form T3 or if patient's really want it

Answer 33

PTU methimazole goitrogens!

Answer 34

meds (PTU or methimazole, beta blockers, stable iodine) radioactive iodine (gradual) surgery (usually prep

Answer 35

**benign** **solitary**, discrete, well demarcated nodule cmpressing the surrounding tissue derived from follicular epithelium presents as a **painless** mass **adenoma vs carcinoma**: vascular and capsular invasion!! cells inside look the same, call it a "follicular neoplasm" then remove t in surgery and look at it again and if invaded capsule it is a carcinoma, if didn't it is an adenoma

Answer 36

elevated TSH level (\>4) normal T3, T4 few or no signs of hypothyroidism may increase risk of CV disease (increased Ch, LDL, athercsclerosis, MI)

Answer 37

fetal thyroid does not function before 12 wks TH can cross the placenta in small amts - necessary for normal growth and development, nerve and mental function better mental function w normal maternal TSH

Answer 38

solitry nodule toxic ademoma

Answer 39

increase Na/K ATPase increase O2 consumption increase heat production increase BMR 1)in the case of BMR, too much thyroid hormone leads to increased heat production (these people will feel hot) vs. less production (pts will feel cold). One way to do this is by increasing the number of Na/K ATPases on the plasma membrane

Answer 40

graves disease - FNA sheets of benign follicular cells - hyperfuncitoning You would see benign follicular cells in sheets called fire flares. These cytoplasmic extensions pink in color tells you that the cells are actively secreting thyroid hormones. It’s a sign of hyperfunctioning state. You can see them here as well (Pink blob on right) This is colloid.

Answer 41

medullary carcinoma polygonal/spindle cells arranged in nests, follicles amyloid common - results from altered calcitonin proteins will stain positive for calcitonin

Answer 42

Hashimoto - atrophic, small gland ## Footnote In later stages, the gland shrinks due to fibrosis and scarring. This is the hypothyroid stage of the disease.

Answer 43

from pituitary binds to TSH receptor on the thyroid follicular epithelium which causes acivation of G proteins and cAMP mediated synthesis and release of T3 and T4 At Every level of TH synthesis/secretion, TSH stimulates via GPCR mechanism -It also increases DNA, RNA, protein, and phospholipid secretion à increased cell size, cell number, and number of follicles At normal levels of TSH, this is not relevant. However, with excessive TSH -à develop goiter, because all of the trophic hormones can stimulate the gland to **hypertrophy**

Answer 44

Most follicular carcinomas look like this. They look like adenoma with a capsule, but there’s a little bit of capsular invasion. This is normal thyroid (right), this is your nodule (left), this is your capsule (magenta curve down the middle). Inside of it looks like an adenoma but it is pushing through (up towards right upper corner). This is capsular invasion so by definition this is follicular carcinoma.

Answer 45

•Tertiary disorders result from hypothalamic dysfunction.

Answer 46

Activation of the THR (receptor)’s activity requires: 1) dimerization with the retinoid X receptor (RXR). 2) They bind to the Thyroid response element (TRE) 3) Stimulation or inhibition of a whole variety of genes

Answer 47

•Secondary disorders are the result of pituitary dysfunction

Answer 48

assoc w thyroid ca tonsils, acne, chernbyl

Answer 49

activate and/or degrade ## Footnote Deiodination is a pathway of degradation, but also this pathway of degradation leads to activation in the case of TH à diodinases can determine whether the hormone is inactive or active Here, T4 can be converted to T3, but it can also be converted to rT3 (inactive). Eventually free thyronine can be generated Another pathway of inactivation: in liver and kidney, T3 and T4 can undergo glucuronidation to solubilize them for excretion through the urine

Answer 50

Anti-TSHR (TR ab) Thyroid stimulating Ig (TSI) TSH-binding inhibitor igs (TBII) other auto-abs

Answer 51

1. diffusely enlarged and vascular thyroid, sometimes with thrill and bruits 2. exophthalmos - protursion of eyes 3. infiltrative dermopathy - localized skin lesions

Answer 52

adenoma vs carcinoma: vascular and capsular invasion!! cells inside look the same, call it a "follicular neoplasm" then remove t in surgery and look at it again and if invaded capsule it is a carcinoma, if didn't it is an adenoma adenomas have less mutations (**RAS, PIK3CA**) adenomas are **not** forerunners of follicular carcinomas but some may arise from preexisting follicular adenomas

Answer 53

excess synthesis and secretion of thyroid hormones by the thyroid gland

Answer 54

enlargement of thyroid gland due to imapired synthesis of hormones compensatory elevation of TSH --\> hypertrophy and hyperplasia --\> enlargement of thyroid gland --\> diffuse non toxic or multinodular goiter **iodine deficiency** is most common cause - overcome with thyroid enlargement --\> euthyroid state! USUALLY

Answer 55

1. Synthesis of TG, extrusion into follicular lumen 2. Na/I cotransport 3. Oxidation of I- to I2 4. Organification of I2 into MIT and DIT 5. Coupling reaction of MIT and DIT to T3 and T4 6. Endocytosis of TG back into follicular cell 7. Hydrolysis of T4 and T3; Enter circulation 8. Deiodination of residual MIT and DIT - recycling of I- and tyrosine OR 1) Iodine uptake 2) Thyroglobulin secretion into lumen (look at right side of diagram) 3) Peroxidase enzymes here shown 4) When gland stimulated by TSH à 1) new thyroid hormone made 2) and existing thyroid hormone present in thyroidglobulin is endocytosed back into the cell (as thyroidglobulin) where it merges with the a lysosome that hydrolyzes the proteinà T3 + T4 released ● 5)There are also some mono- and diiodotyrosines whose iodines are recycled for future use (deiodination) ●

Answer 56

BRAF point mutation

Answer 57

hashimotos exuberant lymphoplasmacytic infiltrate . Lymphocytes form follicles. You would see a lymph node with germinal centers These are follicular cells, but in contrast to normal follicular cells, they get these pink eosinophilic granular cytoplasm due to accumulations of cytoplasmic mitochondria. This is a typical look. They are called **Hurthle cells** or oxyphilic cells. The combination of this lymphoplasmacytic inflammation with this Hurthle cell change is indicative of Hashimoto Thyroiditis. Confirm it with serum antithyroid antibodies.

Answer 58

deiodinases that convert T4 to T3 are selenoproteins thyroid has more selenium than any other organs need trace amounts

Answer 59

lack thyroid hormone receptor or mutant thyroid receptor all have goiters because high TSH

Answer 60

1. deficiency in spil leached by glaciation 2. contaminants in water (glaciation) 3. low selenium levels in soil

Answer 61

T3: one outer iodine; active

Answer 62

1) Follicles: consist of epithelial cells (green cells) making thyroid hormones (T3, T4). 2) Follicles surround a lumen where thyroid hormones are stored being readily accessible in case you need it

Answer 63

papillary carcioma

Answer 64

lymphoma rapidly enlargining mass appears as fleshy and tan

Answer 65

used to dip cow teats with iodine based germicide to decrease risk of mastitis now better about contamination

Answer 66

also subacute and dequervain **granulomatous** related to viral or post viral inflammation self limited \*\***sudden** painful thyroid enlargement, hyperthyroidism returm to normal thyroid function

Answer 67

initiates or sustains differentiation and growth - stim formation of proteins which helps tissue growth and brain development incomplete mental and physical development (Cretin) if untreated hypothyroid in puberty also effects puberty

Answer 68

nl cells: **growth receptor signalling pathways** are transiently activated by binding of soluble GF ligands to TKs which result in autophosphorylation and signal transduction events --\> activation of **RAS, MAPK, PI2K** GOF in these pathways lead to constituitive activation --\> **excessive cell proliferation and increased cell survival**

Answer 69

thyroiditis

Answer 70

After Iodine pumped into the cell, Iodine then comes to the apical side where Pendrine shuttles iodine into the lumen where its converted to iodide

Answer 71

lymphoma diffuse large cell lymphoma often arises in background of lymphocytic or hashimoto thyroiditis Here’s an example of diffuse large cell lymphoma. It is important to recognize this because treatment is obviously different from other cancers of the thyroid gland.

Answer 72

Increased binding protein (BP)à fall in free T3à causes increased pituitary secretion of TSHà normalizes free-T3 levels Which is why lower BP levels do not affect the level of effective T3 hormone

Answer 73

Another level of regulation: Thyroid hormone in pre-pro state is thyroglobulin (pro state would be T4, inactive/low activity) This (bottom right molecule) is how T4 would be stored in the colloid (lumen of the follicle)à as a part of a larger molecule called thyroglobulin

Answer 74

Na/I Symport plasma membrane protein on the basolateral membrane of follicular cells which catalyzes the accumulation of iodine into thyroid cells against a chemical and electrical gradient (concentrate I 20-40x) TSH upregulates NIS gene expression stimulating iodine uptake \*first step in thyroid hormone formation requires E (Na/K ATPase

Answer 75

T4: two outer iodine ; active

Answer 76

2) Lipids: 1) Increases lipolysis (mobilization of fatty acids from adipocytes) 2) increases lipogenesis (generation of fatty acids within adipocytes) --whether lipolysis or lipogenesis predominates depends on how much TH is there --So if you’re euthyroid (nromal), they will balance each other out --If you’re hyperthyroid, will increase lipolysis (afternoon lecturer will go over this) and see Sx of hyperthyroidism

Answer 77

profound hypothyroidism in older chukdhood/adults clinical symptoms dep on leel of hormone and age of onset slowing activiity, fatigue, apathy, SOB, weight gain, constipation, decreased sweating can lead to myxedema coma (poor prognisis) hypothermia, sepsis, MI, hypotension

Answer 78

neutropenia liver disease (fulminant) vasculitis

Answer 79

inhibits 5'-deiodinase ennxyme (which convers T4 to T3)

Answer 80

3) Protein synthesis (normally levels à stimulates protein synthesis): 1) High levelsà stimulates protein catabolism

Answer 81

In goiter we see a lot of colloid, histiocytes, lymphocytes, and sheets of benign follicular cells 1. abundant colloid 2. macrophages (inflam) 3. sheets of benign follicular cells

Answer 82

5 inactivate T3 and T4 --Type 3 (inactivator): in brain, placenta, skin) Only 5 à only generates

Answer 83

from thyroid itself

Answer 84

most common thyroid ca presents as painless nodule or neck mass (metastasis) or enlarged LN (may be first presentation solid white firm mass, encapsulated or ill defined excellent prognosis metastasis is lyphatic to neck nodes

Answer 85

sudden and severe exacrerbation of hyperthroidism usually pre-existing hyperthyroidism (graves) acute elevationof catecholamines due to infection, surgeru, any form of stress fever cardiac (tachy, arrhytmia, CHF) GI (ab pain, nausea, diarrhea) neuro and psych (coma, termor, psychosis) **medical emergency** - can die from arrhythmias

Answer 86

Undifferentiated carcinoma is a very aggressive tumor that presents as a rapidly enlarging mass. It is seen in older patients. Mean survival is 6 months. It just is a very ugly tumor and a very aggressive disease.

Answer 87

Thyroid peroxidase is located on the surface of this membrane (pointing to “Exocytosis”/red arrow pointing to the left) ## Footnote It’s the same enzyme that: 1) oxidizes the iodide and causes organification (iodine being added to carbon compounds) 2) Causes conjugation or condensation of two of these 1) Iodide (pointing at I- directly left of yellow square/pendrin in the mid-left area of the diagram) is oxidized to form iodine. 2) It’s placed onto tyrosines, which are then condensed or conjugated

Answer 88

for maturation! can lead to severe mental retardation if not enough

Answer 89

1. anti-thyroglubulin (TG) 2. anti-thyroperxidase (TPO) 3. anti-TSH receptor

Answer 90

growth formation, bone maturation permissive for action of GH

Answer 91

most common cause of sporadic hypothyroidism in areas with adequate iodine intake 1. painless enlargement of thyroid gland (goiter) 2. gradual development of hypothyroidism in a middle aged woman

Answer 92

increase glucose absorption, glycogenolysis, gluconeogenesis, lipolysis, protein synthesis ## Footnote 1) Glucose (TH considered a diabetogenic hormone by antagonizing insulin effects) 1) increases glucose absorption from the gut, so will need to monitor glucose serum levels 2) increases glycogenolysisà increases glucose levels 3) Also increases gluconeogenesisàincreased glucose levels

Answer 93

test uses thyroid cells obtained at the time of FNA to screeen for genes that are associated for thyroid ca - only for indeterminate nodules likely to be benign vs might be cancerous - prevent unnecessary thyroid surgery@

Answer 94

inhibit thyroperoxidase enzyme (which normally acts on TH by oxidizing iodide to iodine facilitating iodines addition to tyrosine

Answer 95

Formerly thought that T4 was the major hormone (90% of production), but T3 is more active. T4 is active, but need 10x as many T4 to equal a T3 response Why is T4 produced so much? It is de-ionidated peripherally in other organs (primarily kidney and liver) to activate it (increase its activity?)

Answer 96

osteoporosis! ## Footnote -while some TH needed for normal bone formation, too much will cause bone resorption à osteoporosis

Answer 97

pretibial myxedema assocoated with graves' disease

Answer 98

future therapy! may be useful for graves, cancer TSH receptor agonist and antagonist

Thyroid Flashcards

(126 cards)