Thyroid Flashcards
What cells secrete TSH?
thyrotrope cels in anterior pituitary
TSH has an alpha and beta subunit. Which one is unique to TSH
beta
the alpha is identical to that of hCG, LH and FSH
What cells hold the receptor for TSH?
thyroid follicular cells - tells them to produce and secrete thyroid hormone
What is the best screening test for thyroid disease? Why?
TSH - it will respond to even small changes in free T4
also used to monitor disease
Why is it recommended to measure free T4 rather than total T4, total T3 or free T3 to initially assess active hormone levels?
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
If you do want to measure the T3, sould you measure total or free?
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)
What are the causes of hyperthyroidism?
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)
After you have a positive TSH screen with high free T4, what tests can be ordered next to determine the cause?
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:
- thyroid uptake scan
- thyroid US
- Measurement of Graves’-related autoantibodies
- Repeat TSH, free T4
What autoantibodies are found in patients with thyroid disease?
- anti-thyroid peroxidase
- antithyroglobulin antibodies
- auto-antibodies to the TSH receptor
Which antibodies are MARKERs of autoimmune thyroid damage and which antibodies are actually playing a role in the pathogenesis of disease?
Anti-TPO and Anti-thyroglobulin are just markers
the antibodies to the TSH receptor (thyroid stimulating immunoglobulin TSI) cause Graves’ disease pathology
What tests are available to measure thyroid stimulating immunoglobulins?
Two kinds:
- Quantitation of amount of TSH receptor antibody in patient serum
- Bioassay to measure the stimulatory effect of the antibodies on TSH-responsive cells
What are the pros and cons of the quantitation of the amount of TSH receptor antibody?
pros: quick and less expensive
cons: quantitates stimulating, blocking and neutral TSH receptor antibodies, so can overestimate it
What are the pros and cons of the stimulatory bioassay?
pros: specific for detection of stimulating antibodies only
cons: expensive and time-consuming
How does the bioassay work?
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
If you have an elevated TSI index, what is the diagnosis?
Graves (even if they have a nodule!!)
If a patient has an elevated TSH, but a normal FT4, how do you interpret those results?
Subclinical hypothyroidism
defined by a noraml FT4 in the presence of an elevated TSH
What, if anything, should be done next for a patient with subclinical hypothyroidism?
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
What is the likely diagnosis for a patient with hyperthyroidism and positive anti-Tg and anti-TPO antibodies?
Hashimoto’s thyroiditis
TSH receptor blocking antibodies may also be seen with this diagnosis
What is the pathophysiology of Hashimoto thyroiditis?
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.
What are the current recommendations for screening for hypothyroidism in nonpregnant adults?
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
What is the differential for a thyroid nodule?
Benign: MNG, Hashimoto’s, cyst, follicular adenoma, hurthle-cell adenoma
malignant: papillary carcinoma, follicular carc, medullary carc, anaplastic carc, thyroid lymphoma, metastatic carcinoma
What testing should be ordered after a thyroid nodule is found on exam?
TSH and thyroid US
If you have a nodule and the TSH is abnormal, what is the next step?
radionuclide thyroid scan to see if the nodule is hot or cold
If the nodule is cold, what is the next step?
can consider an FNA based on sonographic and clinical criteria
If the nodule is hot, what is the next step?
vritually all of them are benign, so you can skip the biopsy and just check FT4 and T3 and treat appropriately
What percentage of thyroid nodules are found to be cancerous?
Only 4-6.5% are cancerous
What groups have a higher prevalence of cancerous nodules?
children
adults under 30 or over 60
hx of head/neck irradiation
Fam Hx of thyroid Ca
What tests could be used to monitor a patient for residual or recurrent thyroid cancer after appropriate treatment?
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)
