Thyroid

Question 1

What cells secrete TSH?

Answer 1

thyrotrope cels in anterior pituitary

Question 2

TSH has an alpha and beta subunit. Which one is unique to TSH

Answer 2

beta

the alpha is identical to that of hCG, LH and FSH

Question 3

What cells hold the receptor for TSH?

Answer 3

thyroid follicular cells - tells them to produce and secrete thyroid hormone

Question 4

What is the best screening test for thyroid disease? Why?

Answer 4

TSH - it will respond to even small changes in free T4

also used to monitor disease

Question 5

Why is it recommended to measure free T4 rather than total T4, total T3 or free T3 to initially assess active hormone levels?

Answer 5

There is 100x more total T4 than T3 and 10x more free T4 as free T3

furthermore, 99.9% of T4 is bound to protein and biologically inactive, so it’s better to measure just the free T4

Question 6

If you do want to measure the T3, sould you measure total or free?

Answer 6

First, you usually don’t need to measure the T3, but there are occasional patients with a T3 toxicosis so if a patient appears hyperthyroid but FT4 is nl, consider checking the T3

in this case, total T3 is preferred over free T3 (it’s an assay availability question)

Question 7

What are the causes of hyperthyroidism?

Answer 7

Graves disease
Hashimoto's
toxic adenoma
toxic multinodular goiter
iodine-induced
trophoblastic disease/germ cell tumors
TSH-producing pituitary adenoma
thyroiditis
exogenous thyroid hormone use
ectopic hyperthyroidism (struma ovarii)

Question 8

After you have a positive TSH screen with high free T4, what tests can be ordered next to determine the cause?

Answer 8

First, if they have an enlarged thyroid, ophthalmopathy and severe HyperT, the diagnosis is Graves and you don’t need to do more testing. Otherwise:

1. thyroid uptake scan
2. thyroid US
3. Measurement of Graves’-related autoantibodies
4. Repeat TSH, free T4

Question 9

What autoantibodies are found in patients with thyroid disease?

Answer 9

1. anti-thyroid peroxidase
2. antithyroglobulin antibodies
3. auto-antibodies to the TSH receptor

Question 10

Which antibodies are MARKERs of autoimmune thyroid damage and which antibodies are actually playing a role in the pathogenesis of disease?

Answer 10

Anti-TPO and Anti-thyroglobulin are just markers

the antibodies to the TSH receptor (thyroid stimulating immunoglobulin TSI) cause Graves’ disease pathology

Question 11

What tests are available to measure thyroid stimulating immunoglobulins?

Answer 11

Two kinds:

1. Quantitation of amount of TSH receptor antibody in patient serum
2. Bioassay to measure the stimulatory effect of the antibodies on TSH-responsive cells

Question 12

What are the pros and cons of the quantitation of the amount of TSH receptor antibody?

Answer 12

pros: quick and less expensive
cons: quantitates stimulating, blocking and neutral TSH receptor antibodies, so can overestimate it

Question 13

What are the pros and cons of the stimulatory bioassay?

Answer 13

pros: specific for detection of stimulating antibodies only
cons: expensive and time-consuming

Question 14

How does the bioassay work?

Answer 14

You take a modified TSH receptor that binds the stimulating antibodies but NOT the blocking antibodies

when they bind, you get an increase in cAMP which then activates a cAMP-responsive promoter that leads to the production of an enzyme called luciferase

the cells incubate with patient serum and normal serum and index or ratio between the two incubations in the amount of yellow luciferase is reported

Question 15

If you have an elevated TSI index, what is the diagnosis?

Answer 15

Graves (even if they have a nodule!!)

Question 16

If a patient has an elevated TSH, but a normal FT4, how do you interpret those results?

Answer 16

Subclinical hypothyroidism

defined by a noraml FT4 in the presence of an elevated TSH

Question 17

What, if anything, should be done next for a patient with subclinical hypothyroidism?

Answer 17

Depends on the TSH

if it’s between 4.5 and 10, don’t treat, but monitor every 6-12 months

check antibodies in case they have an associated autoimmune disease and predict development of overt hypothyroidism

Question 18

What is the likely diagnosis for a patient with hyperthyroidism and positive anti-Tg and anti-TPO antibodies?

Answer 18

Hashimoto’s thyroiditis

TSH receptor blocking antibodies may also be seen with this diagnosis

Question 19

What is the pathophysiology of Hashimoto thyroiditis?

Answer 19

profuse lymphocytic infiltration with lymphoid germinal centers and destruction of thyroid follicles by both B and T cells (but mostly by cyttotoxic T cells). THe antibodies are just markers - they’re not doing the damage.

Question 20

What are the current recommendations for screening for hypothyroidism in nonpregnant adults?

Answer 20

I’ts controversial - no clinical trials exist evaluating effectiveness, but there is a consensus recommendations to screen those with symptoms of hypoT, risk factors for hypoT and patients taking drugs that may impair thyroid function

Question 21

What is the differential for a thyroid nodule?

Answer 21

Benign: MNG, Hashimoto’s, cyst, follicular adenoma, hurthle-cell adenoma

malignant: papillary carcinoma, follicular carc, medullary carc, anaplastic carc, thyroid lymphoma, metastatic carcinoma

Question 22

What testing should be ordered after a thyroid nodule is found on exam?

Answer 22

TSH and thyroid US

Question 23

If you have a nodule and the TSH is abnormal, what is the next step?

Answer 23

radionuclide thyroid scan to see if the nodule is hot or cold

Question 24

If the nodule is cold, what is the next step?

Answer 24

can consider an FNA based on sonographic and clinical criteria

Question 25

If the nodule is hot, what is the next step?

Answer 25

vritually all of them are benign, so you can skip the biopsy and just check FT4 and T3 and treat appropriately

Question 26

What percentage of thyroid nodules are found to be cancerous?

Answer 26

Only 4-6.5% are cancerous

Question 27

What groups have a higher prevalence of cancerous nodules?

Answer 27

children
adults under 30 or over 60
hx of head/neck irradiation
Fam Hx of thyroid Ca

Question 28

What tests could be used to monitor a patient for residual or recurrent thyroid cancer after appropriate treatment?

Answer 28

Formerly used thyroid uptake scans, but now serum thyroglobulin has supplanted the uptake scan as a marker of tumor persistence or recurrence (it’s synthesized only by thyroid follicular cells, so it’s a specific marker for thyroid tissue)