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85 Cards in this Set

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What embryonic tissue is the fetal thyroid formed from?

If a newborn baby's TSH is measured and comes out at 500, what developmental defect do you suspect?
Pharyngeal epithelium that then migrates down (gets pulled down as heart moves).

Super hypothyroid- suspect pharyngeal epithelium didn't form.
What is the role of Somatostatin in The H-P-Thyroid axis?
It inhibits TSH release slightly (also remember, it inhibits GH secretion).
What are the three tiers or regulation of thyroid hormone synthesis?
1. Hypothalamus- TRH (inc. TSH and PRL)- sensitive to T3>T4 feedback

2. Pituitary- TSH- glycoprotein (shares a subunit with FSH/LH, B subunit specific). Inc T4

3. IODINE! Na-I symporter transports I- from blood into thyroid cell (excreted by kidney)
Why must you wait till 48hrs after birth to test TSH function in a newborn?

What is the effect of leptin on TRH? What about cortisol?
TRH is stimulated by the cold, so must wait till baby is sufficiently acclimated to temp. before drawing a level.

Leptin increases TRH, Cortisol/Stress inhibits TRH.
What is the structure of a thyroid follicle?

Why is it not good to take too much I-? What molecule catalyzes iodination?
Lumen containing TG surrounded by folliclar cells.

Too much I will suppress synthesis and function of symporter and stop thyroid synthesis for a while.

*TPO or thyroid peroxidase catalyzes iodination and coupling
Describe the steps in Synthesis and secretion of Thyroid Hormone.
1. I- from diet is transported into follicle (Na-I symporter NIS)
2. Iodine oxidized by Thyroid Peroxidase (TPO)
3. Organification and coupling. I- added to tyrosine and coupled (T3, T4)
4. Endocytosis of Iodinated TG and proteolysis to make T4, T3
5. Secretion into circulation
What are some differences between T3 and T4?

What is "Reverse T3"?
T4= prohormone, 4 Iodines, more abundant, doesn't bind as tightly to receptor; half life is 7 days.

T3= 3 Iodinated tyrosines, binds 10x tighter to receptor, much less common, half life is 1 day.

Reverse T3: Inactive T3
What is Thyroid binding globulin?
Glycoprotein that binds T4/T3.
Has a single binding site (either T3 or T4).

Estrogen increase it's synthesis, Androgens increase clearance.
Babies have increased Total T4 levels at birth. Should you be worried?
No. It is natural for babies to have increased TBG (cranked out at 3rd trimester), so they have elevated Total T4s. Check TSH- it is normal.
What would the Total T4 and TSH levels be in the case of classic TBG deficiency?

What about if there was a tumor squashing the pituitary gland?
Classic TBG deficiency- low total T4, but free T4 and TSH normal.

Tumor- low TSH, low Free T4. Secondary hypothyroidism.
What are the 3 Deiodinase enzymes?

What is their function and where are they found?
*cleave either outside or inside Iodine on rings

- Type 1 5'- found in periphery (liver, kidney, etc), provides most of circulating T3 (inner ring provides rT3 and T2)

-Type 2 5'= found in brain and pituitary, maintains intracellular T3 level for feedback

-Type 3 5'= only in placenta, infantile hemangioma (tumor)- inactivates T4 to rT3, thus protecting fetus from mom's circulating T4. Should not be expressed post-natally.
What are the two Thyroid hormone receptor genes and where are they found?

What is their mechanism of action?
TRa (brain), TRB (liver, tissues).

Nuclear receptors. Dimerizes with retinoid-X-receptor. Usually it's sitting on TRE (thyroid response element) but it's inactive until T3 comes along and knocks off a co-repressor, promoting transcription.
What is the role of Thyroid Hormone in the fetus?

What about after birth?
Growth + Development= neural, CNS, and somatic growth. Increased thyroid hormone in 1st trimester

*Metabolism= basic functions of cell, apetite, carb and fat metabolism, protein synthesis, inc. Beta receptor expression, etc.
T or F

Iodine deficiency is the most common cause of hypothyroidism in developing countries.
True!
What two transporters are specific to T4/T3?
Even though T4/T3 are small and lipophilic, still need transporter!

MCT family- MCT8 and MCT10 (monocarboxylate transporter)
What one test is the best initial assessment for thyroid function?
TSH!!
Provide the relative value of FT4 and TSH in the following scenarios:

-Primary Hypothyroidism
-Subclinical Hypothyroidism
- Secondary Hypothyroidism
Primary: T4 low, TSH high (compensatory)

Subclinical: T4 normal, TSH high (mild decrease in T4 upregulate TSH so it normalizes T4 levels)

Secondary: TSH low, T4 low (central problem)
What is "Cretinism""?

What is "Myxedema"?
Cretinism= hypothyroidism in infancy (congenital)- clinical features of large goiter, short stature (impaired skeletal development), mental retardation (impaired CNS development)

Myxedema= severe/complicated hypothyroidism or, more specifically, the skin manifestations of severe hypothyroidism
Is the thyroid radioisotope scan a good diagnostic test for hypothyroidism? Why or why not?

What about thyroid ultrasound and biopsy?
Neither are good.

Radioisotope scan- thyroid might not take up iodine if TSH is low.

Ultrasound/Biopsy- good for nodules or goiters but not useful for diagnosing hypothyroidism
Would a TSH level alone be enough to diagnose secondary hypothyroidism? why or why not?
No. For secondary hypothyroidism you also want a Free T4. This is because a person might have low TSH due to high T4 feedback (ex: thyroid adenoma). You want to rule this out if you suspect secondary cause.
Which is more common regarding Hypothyroidism:

Subclinical or Overt?
Primary or Secondary?
Women or Men?
Younger or older age?
Subclinical > Overt
Primary >> Secondary (500:1)
Women 10x> Men
Prevalence increases with age

*also note: higher prevalence with other autoimmune conditions
What are some classic clincal features of hypothyroidism?

Do you expect to see a large or small thyroid?
Trick question- thyroid variable (goiter or atrophic)

- dry coarse skin (decreased sweating, thin epidermis)
- flat emotionless face, loss of end of eyebrow, yellowish skin
- lethargy, fatigue
- decreased appetite, weight gain, constipation
Why do people with hypothyroidism often have puffy faces, hands, and feet and "non pitting edema"?
Decreased Thyroid hormone increases dermal glycosaminoglycan which increases water content (thickening of skin, edema).

*non-pitting: skin bounces back if you press into it
What is the cause of yellow tinge/pallor in the face of hypothyroid patients?

What other skin/hair/nail changes might these patients identify?
Increased carotene

-brittle nails, hair
- loss of scalp hair & alopecia
- lateral brow thinning
In patients with hypothyroidism, what cardiovascular features might you be concerned about?

What about pulmonary?
Cardio: heart rate decrease, contractility decrease. They can get diastolic hypertension.

Fluid accumulation: membranes get leaky
- pericardial and pleural effusions
- dyspnea and decreased strength of respiratory muscle
What musculoskeletal and neurologic findings might be seen in patients with Hypothyroidism?
- Musculoskeletal- carpal tunnel, n. entrapment (increased glycoprotein and H20 in wrist). myopathy (proximal muscle)

- Decreased memory/concentration. Dementia, psychosis, etc.
What is the most common cause of hypothyroidism in the developing world?

What about in the U.S.?
Iodine deficiency (thyroid enlarges to compensate because low T3/T4 so TSH levels skyrocket to compensate).

US- autoimmune
Why is it necessary for all newborns to undergo routine thyroid screening?

How do newborns with congenital hypothyroidism make it to birth if they're making no T3/T4?
They could have congenital hypothyroidism (gene mutation)- either dysgenesis or thyroid or biosynthetic defect (less common).

*if hormones not given immediately, permanent neurological damage can result since T4/T3 needed for myelination.

Mom's T4 is protective in utero.
If a woman is noted to have circulating thyroid antibodies, does she immediately have to get treatment for an autoimmune disease?

What are the major thyroidal antigens in these diseases?
No. About 10% of women have circulating thyroid antibodies but NORMAL thyroid function.

TPO, TG (thyroglobulin), and TSH-receptor
What is the pathological hallmark of Hashimoto's thyroiditis?

What serum antigen levels are most commonly seen in this condition and also have the greatest risk of hypothyroidism?
Lymphocytic infiltration (it's an autoimmune condition)

TPO (thyroid peroxidase)- 90% of patients have these antibodies, also 4x inc. risk of hypothyroidism
What are the classic findings in Silent Thyroiditis?

How long does it last and what is the prognosis for most people?
Painless, TRANSIENT thyrotoxicosis (inc. thyroid hormone), followed by TRANSIENT hypothyroidism

~4-7 mo, majority return to euthyroid state
Why is it that in patients with silent thyroiditis, radioiodine uptake is LOW in the hyperthyroid state?
Patients with hyperthyroid have inflamed, non-functional thyroids. The high T4 that they are churning out shuts off TSH so basically you don't uptake Iodine.
Why does Post-Partum Thyroiditis occur?

How long after pregnancy are women at risk?
During pregnancy, autoimmune activity is low. After pregnancy there is a lot of autoimmunity rebound.

At risk for up to 12 mo. post delivery.* do NOT give mom's radioiodine test!!!
What is the hallmark feature of subacute thyroiditis?

How does it appear pathalogically?
aka. deQuervain's
classic feature= neck pain related to thyroid inflammation (usually post-infectious)

Multinucleated giant cell, occasional granulomas, infiltration of polys
Why would you give thyroid hormone replacement to a person who has a goiter?

What is the consensus treatment of choice for hypothyroidism? why?
T4/T3 supplementation would cause feedback to decrease TSH, thus decrease stimulation to thyroid gland.

L-T4 (levothyroxine): physiologic so no side effects, cheap
Why is L-T4 a better recommended treatment than L-T3?
L-T4 has longer half life (7) than L-T3 and great success rate. Almost always results in stable FT4, FT3, and TSH levels.
What are the risks of L-T4 therapy?

How does the need for L-T4 change with pregnancy? with age?
- Hyperthyroidism, Hypothyroidism
- Angina, MI, Arrhythmias
- Allergy to dye in tables

Requirement DECREASES with age, INCREASES with pregnancy (30-50%)
What are the L-T4 treatment goals for Primary hypothyroidism? Secondary hypothyroidism?
Primary- get to normal TSH

Secondary- get to normal FT4 (the TSH is of no value since pituitary is the problem).
What is thyrotoxicosis?

How does this differ from hyperthyroidism?
Thyrotoxicosis= thyroid hormone excess

Hyperthyroidism= thyroid hormone excess from increased synthesis & release of thyroid hormone
With respect to Hyperthyroidism, what are the relative levels of FT4, FT3, and TSH for:

- Primary Hyperthyroidism
- Subclinical Hyperthyroidism
- Secondary Hyperthyroidism
Primary= FT3- high, FT4- high, TSH low

Secondary= FT3-high, FT4- high, TSH high

Subclinical= FT3- nl, FT4- nl, TSH low (minor increases in T3/T4 will feedback and reduce TSH)
What is the most common cause of thyrotoxicosis?

Is it more common in men or women?
Grave's Disease

More common in women (10x>men)
What is the relationship of hCG and thyroid?
- hCG-producing tumor can also cause thyrotoxicosis

- Gestational thyrotoxicosis: placenta produces hCG, high levels can stimulate thryoid

*hcG and TSH share the same alpha unit (unique beta) so there is homology between the two
What is the pathogenesis of Grave's disease?
Immunoglobulins (thyroid receptor antibodies)- bind to TSH receptor

Most antibodies activate receptor but some block it. Can cause cytokine release (inflammation, fibroblast activation) and Glycosaminoglycan production (edema).
What are symptoms of thyrotoxicosis?
Sxs: hyperactivity, irritability, insomnia, sweating, palpitation, fatigue, weakness, weight loss, frequent bowel movement, amenorrhea, tremor
What thyrotoxic sign is seen especially in Asian Males?

What cardiovascular signs are associated with thyrotoxicosis?
Neurological manifestation: Hypokalemic periodic paralysis

Tachycardia, palpitations, A fib., bounding pulse, worsening of CHF and angina
What skin changes might occur in a patient with overactive thyroid hormone production?
- Warm, moist, sweating skin
- Fine hair, diffuse alopecia (interestingly- same thing with hypothyroidism)
- DERMOPATHY: Pretibial myxedema, Acropachy (clubbing/widening of fingers)

skin discoloration, plaque development, edema
What is the effect of thyroid hormone excess on the bone?

What might you pick up using a stethoscope, on the physical exam?
Inc. T3/T4 enhances bone resorption (causes osteopenia & osteoporosis) in older patients

Listen for thrill, bruit, due to increased vascularity over thyroid gland
What is the cause of lid retraction (stare) in thyrotoxicosis?

What about exophthalmos and other graves orbitopathies?
Thyroxine increases sympathetic activity.

Also get: scleral injection, periorbital edema, proptosis, abnormal EOMs due to cross reactivity of antibodies with those in eyes
What does a Grave's disease thyroid feel like? What does it look like on radioiodine scans?
A diffuse goiter can feel firm/ rubbery.

May pick up a thrill/bruit while listening with stethoscope.

Scan shows homogenous pattern of high Radioiodine uptake.
A patient with an untreated endemic goiter relocates to the U.S where there is abundant iodine. All of a sudden, he starts to demonstrate signs & sxs of hyperthyroidism. What syndrome is this an example of?
Jod-Basedow
Hyperthyroidism following administration of Iodine (can cause Thyroid Storm)

'Jod' = German for Iodine
A patient with an acute overactive thyroid gland gets iodine loaded for treatment. Within hours, the toxic levels of thyroid hormone drop.

What principle is demonstrated by this treatment?
Wolff-Chaikoff effect
- iodine loading will acutely reduce stored T3/T4 and decrease synthesis of these hormones
- eventually (within weeks), there will be an escape from this phenomenon
What is "Apathetic Thyrotoxicosis"?
Symptoms are different in elderly person:
- apathy, lethargy, weight loss, depression, etc.
-may be accompanied by A fib

*not as commonly seen= hyperphagia, sweating, warm skin, etc.
What are the four standard treatments for Hyperthyroidism (Grave's disease and toxic nodules)?
- Thionamides
- I-131
- Surgical excision
- Beta blockers (adjunctive therapy)
Name some thionamides?

How do they work?
MMI (Methimazole)
PTU (propylthiouracil)

Inhibitis thyroid peroxidase (TPO) activity
- PTU inhibits T4 to T3 conversion

*give PTU in 1st trimester only (MMI may be teratogenic and PTU can cause hepatitis)
What dose of Radioactive Iodine would you give for diagnostic purposes? For therapeutic?
Diagnostic 0.1 mCi

Therapeutic 100+ mCi (give a lot more to target the gland and burn it (causes tissue damage, necrosis, atrophy, fibrosis)
What is the difference between Iodine-123 and I-131?

Which is better for diagnostic purposes and which is better for treatment?
I-123: short 1/2 life, mainly gamma ray emission (B-particles can destroy neighboring tissue)- DIAGNOSTIC

I-131: long half life, very useful for treatment b/c has high B particle emission (has some gamma as well)
What is a thyroid nodule?
Solid or cystic area of thyroid tissue proliferation.
What are some signs and symptoms of nodules?
- Small nodules= asymptomatic
- Large nodules= compress laryngeal n (hoarseness)
- substernal extension (interfere with heart and vascular structures)
- tracheal deviation
- Pemberton sign
What is the Pemberton Sign and how is it elicited?
Facial flushing & dilation of cervical veins upon lifting arms

- compression of jugulars due to large thyroid obstruction. Lack of venous return.
What is a thyroglossal cyst and where might you find it?
Ectopic thyroid tissue that follows the path of normal thyroid descent during embryonic development. Often times found between base of tongue and thyroid gland.
T or F

95% of thyroid nodules are benign?
True!

Many found at autopsy or during ultrasound. Now a days we are seeing more because of more imaging.
Most non-neoplastic nodules or pseudo-nodules are caused by....?

What are the most common kinds of thyroid cancers?
Inflammation (infiltration of lymphocytes)

Papillary >Follicular > Medullary > Anaplastic
What are the four pathalogic classifications of thyroid nodules?
1. Non-neoplastic
2. Benign neoplasm (nonfunctioning adenomas)
3. Malignant neoplasm
4. Nonthyroidal (ex: parathyroidal adenoma)
Mutations in what three growth factors/ oncogenes are implicated in thyroid adenomas?
1. RAS (oncogene)- most common

2. Sodium Iodine Symporter (mutation causes hypofunctioning nodule)

3. TSH receptor (mutation cause overactive nodules)
What are characteristics of thyroid adenomas?
- encapsulated
- orderly architecture
- few mitoses
- no lymphatic/ arterial invasion
- often looks like normal thyroid

*basically non malignant!
What is the best test to do to see the anatomy, location, and size of a thyroid gland/nodule?
Ultrasound. Has resolution of 1 mm!
What would a cystic nodule look like on ultrasound?
Simple cystic= filled with liquid colloid, hypoechoic (dark). Might be surrounded by thick, solid wall that is more hyperechoic.
What are the features of a thyroid nodule that would make one suspicious for malignancy?
- IRREGULAR shape (spiculated, not smooth like egg)
- MICROCALCIFICATIONS
- intranodular CHAOTIC VASCULARITY (normally organized vascularity on periphery)
- INVASION into nearby tissue
- solid or complex nodule (vs. cystic which is usually benign)
Will the radioactive iodine uptake increase or decrease in the following scenarios:

- Grave's disease
- Hypothyroidism
- Iodine deficiency
- Cold nodule
- Hot nodule
- Graves: increase (overactive)
- Hypothyroidism: increase (low FT4, high TSH, stimulates uptake)
- Iodine deficiency: stimulate uptake
- Cold nodule: decrease uptake
- Hot nodule: increase uptake
Describe how a thyroid scan is performed.
1. I131 or I123 is taken orally
2. X ray taken after 24 hours

Hot nodules- generally not biopsied, just treat. Cold nodules are biopsied (16% chance of being cancer- frequently have mutation in Na-I symp.)
What is the role of the CT/MRI scan in thyroid nodules?
CT/ MRI- To see relationship of thyroid gland to surrounding structures.

Tracheal compression, deviation, substernal extension, mediastinal lymphnodes

*NOT for size/characteristics of nodules.
What is the single most important test to diagnose thyroid cancer?
Biopsy!
Why do we care about benign thyroid nodules?
They aren't malignant but they can cause mass effect (pressure, hoarsness, esthetic problems, difficulty swallowing/breathing, etc.)

*may also have potential to turn into malignant nodule or can be HOT (hyperthyroid)
Describe the 4 treatments used for thyroid nodules.
1. Surgery

2. I-131 radioiodine (potent gamma rays, toxic nodules that uptake I-)

3. Percutaneous EtOH injection (for cystic nodule- aspirate cyst and fill with ethanol)

4. Radiofrequency ablation and laser (can cause burn, hematoma, and vocal cord palsy)
What percent of thyroid nodules are actually malignant?

What is the incidence of thyroid cancer like? What about the mortality?
5% of thyroid cancers are actually malignant

Incidence= rising (may be more diagnostic imaging)

Mortality= falling (great treatment options, slow growing cancer, easy target)
What age group is most at risk for malignancy in thyroid nodule?

What other epidemiological factors can increase one's risk for malignancy?
<20, and >70
Male > female
FHx- MEN1, MEN2, Cowden, Familial polyposis coli
PMHx of head/neck irradiation
Iodine deficiency

*Exposure to Ionizing radiation (ex: chernobyl)- dose of exposure and age at exposure (younger = worse)
When do you biopsy a thyroid nodule?

Are the majority of cancerous nodules cold or hot? why?
>1 cm or radiation hx, family hx, risk factors

Majority are COLD- hypofunctioning, de-differentiated cells (don't take up iodine)
What is the most common type of thyroid cancer?

What are some characteristics and what is it's prognosis?
Papillary cancer (90% of total)
-Multifocal
- Lymphatogenous spread to neck, lymphnodes
- rare distant mets
- Large, pale irregular nuclei and "PSAMMOMA body" - laminated micro calcified spheres (seen on ultrasound)

- Excellent Prognosis
How can you tell a follicular adenoma from a follicular carcinoma?

What are some features of this cancer?
Undistinguishable for the most part! Must make a diagnosis based on invasiveness of vasculature and capsule. No microscopic features.

- unifocal
- distant hematogenous spread to lungs
What type of thyroid cancer has the worst prognosis and is the most aggressive?

What type of thyroid cancer is diagnosed using CEA antigens and looks like sheets of cells separated by pink staining "amyloid-like" substance?
Anaplastic- undiffereniated, worst prognosis- usually in pt with long standing goiter. Death in <36 mo.

Medullary cancer (parafollicular C cells, calcitonin and carcinoembryonic antigen used for diagnostic purpose).
Chronic, underlying Hashimoto's thyroiditis can be a set up for what kind of thyroid cancer?
Lymphoma
Lymphocytic invasion of thyroid follicles and blood vessels.
What are two ways in which TSH stimulation can be given (so that radioactive iodine uptake is increased for treatment)?

After therapy, what diagnostic test do you want to do?
1. Hypothyroidism (stop thyroid hormone)
2. Recombinant TSH (thyrogen)


Post-therapy I-131 scan (to determine if there are mets)
What is the typical treatment for papillary and follicular cancer?

What is the exception to this rule?
Typically- surgical resection, sometimes total thyroidectomy

Exception= if papillary cancer is <1cm, unifocal, or no distant mets. Then remove half a thyroid and no iodine ablation therapy.
Why is it indicated to give L-T4 after a surgery for follicular and papillary cancer?

What level is it critical to take at a post surgery follow-up and why?
If TSH is elevated, it will promote growth of any leftover cells. So give L-T4 as suppressive therapy.

Thyroglobulin level. Should be undetectable post thyroidectomy since there are no thyroid cells to produce it.
Why can we not use radioactive Iodine ablation treatment for Medullary carcinomas?

What is used instead?
C cells do not uptake Iodine so we can't use radioactive treatment.

Surgery and external beam radiation (for mets).

*note: anaplastic prognosis is even worse, just do debulking surgery. Radiation not effective.