Thyroid labs and imaging Flashcards
Thyroxine (T4)
greatest amount of thyroid hormone
- T4 must be converted to the active hormone T3
Triiodothyronine (T3)
- most biologically active
Calcitonin
produced in parafollicular cells (C cells) of the thyroid
- involved in regulating blood levels of Ca and phosphate by inhibiting osteoclast activity
- decrease resorption of Ca in the kidneys
Thyroid hormone metabolism
- thyroid hormones are poorly soluble in the plasma
- 0.03% of T4 and 0.3% of T3 unbound
- only free T3 and T4 can penetrate cellular membranes and exert biologic activity by interacting w/ nuclear receptors
Where is T4 converted to T3 at?
- *liver, gut, skeletal muscle, brain and thyroid
3 makor plasma proteins responsible for transport?
- TBG- thyroxine binding globulin
- TBPA- thyroxine binding pre-albumin
- albumin
Thyroid fxn tests?
- TSH
- T4 - total serum level
- T3 - total serum level
- Free T4 index - calcultaion of Free T4 (FTI)
- T3 resin uptake (used to calc. FTI)
- thyroglobulin AB (Tg-Ab)
- thyroid peroxidase AB (TPO-Ab)
- TSH receptor ab (Anti-TSHR)
What is the best assessment of thyroid fxn?
- TSH
- assuming steady state conditions and absence of pituitary or hypothalamic disease
- 3rd generation assay is the most sensitive
- direct measurements of serum thyroid hormone levels still impt in some pts
Thyroid ab tests?
- TPO-Ab and Tg-Ab (high concentrations are seen in nearly all pts with Hashimotos thyroiditis)
- TSH receptor stim. AB seen in graves
- TSH receptor blocking Ab seen in atrophic Hashimoto’s thyroiditis and sometimes graves
mechanism of TSH?
- secreted by the pituitary: responds to low levels of thyroid hormones, and responds to TRH (comes from hypothalamus)
TSH testing is used for what?
- dx a thyroid disorder in a person with sxs
- screen newborns for an underactive thyroid
- monitor thyroid replacement therapy in people with hypothyroidism
- dx and monitor female infertility problems
- help evaluate fxn of pituitary gland
- screen adults for thyroid disorders as recommended by American thyroid association
interpretation of TSH normals>
- differ b/t adults, newborns and cord
- will differ from lab to lab
What happens to TSH as you age?
- age related shift towards higher TSH concentrations in older pts
- values will vary depending on lab
When will you see an elevated TSH?
- hypothyroidism
- thyroiditis
- thyroid agenesis (newborns)
- pituitary tumor
- other severe and chronic illnesses
- drug effects: iodine, ad thyroxine (T4)
When will you see a low TSH?
- hyperthyroidism
- damage to pituitary gland that prevents it from making TSH (secondary hypothyroidism)
- hypothalamus insufficiency (tertiary hyperthyroidism)
- taking too much thyroid med for tx of underactive thyroid gland
- drugs: excess T4 therapy, glucocorticoids, L -drops
Importance of T4 (thyroxine)
- prominent thyroid hormone (>90%)
- nearly all of it is transported bound to proteins: TBG, albumin, transthyretin (TBPA)
- only free (unbound) T4 is metabolically active
- total T4 measures bound and free hormone
Total T4 reliable test except for what interfering factors? - this measure both bound and free T4
- decreased by PTU, NSAIDs, androgens, lithium, phenytoin, amidarone, salicylates, corticosteroids, and rifampin
- increased by estrogens, heroin, amphetamines, OCP, pregnancy ( due to increased circulating protein)
When will you see increased Total T4 levels?
- hyperthyroidism
- acute thyroiditis
- conditions causing increased TBG (thyroid binding globulin)
- pregnancy
- meds: estrogens, heroin,, amphetamines, OCPs
When will you see decreased total T4 levels?
- hypothyroid states
- pituitary insufficiency
- hypothalamic failure
- protein malnutrition/depletion
- iodine insufficiency
- numerous other non-thyroid illnesses (CRF, cushings, cirrhosis, advanced cancer)
Why will altered levels of TBG change the value of the total T4?
- direct measurement of thyroxine binding globulin (TBG) can be done and will explain the abnorm. value
- excess TBG or low levels of TBG are found in some families as a hereditary trait. It causes no problem other than falsely elevating or lowering the total T4 level
- these people are frequently misdx as being hyperthyroid or hypothyroid but they don’t have a thyroid problem and they don’t need any tx
What does the free T4 index measure?
indirectly measures unbound T4
- correction of misleading results of total T4 caused by conditions that alter the TBG
- calculated product of the T3 resin uptake and serum T4
- T3 resin uptake measures unoccupied binding sites on TBG, it isn’t a measure of T3
What is a more accurate test to measure Free T4?
- Free T4
fewer interfering factors:
increased by heparin, ASA, and propranolol
decreased by: furosemide, phenytoins - various wats to test free T4 but none of them directly measures unbound T4
Indication for measuring free T4?
- along with TSH, to dx hypo/hyperthyroidism
- monitoring response to therapy along with TSH
- gives a quicker result to response to tehrapy with replacent thyroxine than TSH
Triiodothyronine (Total T3)
- accounts for less than 10% of total thyroid hormone, large proporton formed by peripheral T4 to T3 conversion (liver)
- 70% protein bound
- less accurate test
- interpretation: increased in hyperthyroidism, increased during pregnancy and by OCPs, and estrogens
decreased by androgens, phenytoin, propranolol, high dose salicylates
How do you calculate Free T4 using T3 resin uptake test?
- incubate pt’s serum w/ radiolabeled T3 tracer
- then add an insoluble resin that traps remaining unbound radiolabeled T3
- the value reported is the % tracer bound to the resin
- the number of free binding sites is determined by both binding protein levels and endogenous hormone production
- thyroid hormone binding ratio (THBI) = pts T3 resin/normal pool resin
- T3 resin uptake measures unoccupied binding site on TBG, it isn’t a measure of T3
T3 resin uptake: in hyperthyroidism would be?
- high T4, high T3 resin uptake or THBI, high free index T4
TBG excess would have what T3 resin and T4 levels?
- high T4
- low T3 resin uptake or THBI
- normal free index T4
Hypothyroidism levels of T3 resin and T4?
- low T4, low T3 resin uptake and low free index T4
TBG deficiency levels of T3 resin and T4?
- low T4, high T3 resin, normal free index of T4
What is the Thyroid binding globulin?
- most of thyroid hormones in blood are attached to protein called TBG
- if there is an excess or deficiency of this protein it alters the T4 or T3 measurement but doesn’t affect the action of the hormone
- if the pt appears to have normal thyroid fxn but an unexplained high or low T4 or T3 it may be due to an increase or decrease of TBG
- direct measure can be doen and will explain abnormal value
- excess or low TBG are found in some families as hereditary trait, it causes no problem except falsely elevateing or lowering T4 level
- these pts are frequently misdx as being hyperthyroid or hypothyroid but have not problem
TBG levels
- major thyroid hormone transport protein
- when TBG is elevate, T3 and T4 are elevated
- affects the measurement of total T4/T3
TBG levels are increased by?
- pregnancy
- infectious hepatitis
- estrogens (OC, tamoxifen)
TBG levels are decreased by?
- protein losing conditions
- malnutrition
- major stress (steroids included)
- androgens (testosterone)
- drugs: phenytoin, propanolol
- menopause
What does the Free Thyroxine index (FTI or T7) measure?
- evaluates thyroid fxn in pts with protein abnormalities (low albumin, low or high TBG)
- calculated value, corrects for changes in protein binding, more closely approximates true hormone level
Most common thyroid autoantibodies?
- antithyroid peroxidase (TPO Ab)
- antithyroglobulin (TgAb)
- these abs work against thyroid peroxidase, an enzyme that plays a part in T4 to T3 conversion and synthesis process
- causes chronic inflammation and destruction resulting in chronic thyroiditis
- initially produces a mild hyperthyroidism: eventually leads to hypothyroid condition
Indications for testing for thyroid autoabs?
- hyperthyroid conditions: Hashimotos thyroiditis (if in hyperthyroid state), Graves disease
- hypothyroid conditions: Hashimoto’s thyroiditis, myxedema
Interpretation of thyroid autoantibodies?
- nomral healthy people produce abs especially elderly women
- normal titers:
TSHR antibodies?
- immunoglobulins that stimulate or inhibit thyroid hormone release
- autoimmune process and this can cross the placenta: neonatal hyperthyroidism (especially in neonate whose mother has Graves)
Testing results of TSHR - stim ab
- graves disease (sensitivity 90%)
- TSHR stim Ab decline in graves tx with antihyperthyroid meds
- TSHR stim ab will initially rise after radioiodine tx and then gradually drop although sometimes they may persist for years
- TSHR stim. Ab will completely go away after a thyroidectomy
- used to monitor level of disease and monitor progress of meds
- TSHR blocking ab some pts with hashimoto’s thyroiditis have these - leads to hypothyroidism
What is thyroglobulin?
- protein precursor of thyroid hormones
- levels are low or undetectable with normal thyroid function
When would thyroglobuin levels be elevated?
- thyroiditis
- graves disease
- thyroid cancer
When is thyroglobulin used as a tumor marker of thyroid tissue?
- effectiveness of cancer tx
- residual tissue post-op
- metastasis
When are TSH and free T4 tests done?
- initial labs to establish hypothyroidism or hyperthyroidism, also used to monitor therapy
WHen do you do a FTI (free thyroixine index)??
- this can help determine if true elevatiin or depression of T4 or T3
What does a TBG (thyroxine binding globulin) measure?
- amount of binding proteins
When would you test anti Tg and anti TPO?
- when you are looking for AI diseases such as Hashimotos or graves
When would you do a a TSH stim Ab/ TSH-blocking Ab test?
- in graves disease and hashimotos
What is a thyroglobulin test used for?
tumor marker
When are thyroid nodules brought to attention?
- when noted by pt
- found by provider on PE
- incidentalomas - found during other radiologic procedure (carotid US, neck CT)
Who presents with thyroid cancer the most?
- present in 4-6.5% of nodules
- there is increased prevalence in children, adults 60 yo
- people who have had head or neck irradiation, people with a family hx of thyroid cancer
Steps to dx thyroid nodules?
- first obtaina throrough history and PE
- next measure TSH: if low usually indicates overtt hyperthyroidism
- if high: more suspicious for cancer
- next step: Thyroid US - to confirm presence of nodularity, assess sonographic features of nodule, assess for add. nodules and lymphadenopathy, assess for nodules for suspicious findings
Indications for ultrasound?
- US good at diff. cystic from solid nodules but won’t be able to tell if nodlue benign or malignant, can aid in determining which nodule to bx
- allows accurate measurement of nodule;s size and can determine if a nodule is getting smaller or is growing larger
- aids in performing thyroid FNA bx by improving accuracy if nodule can’t be felt easily on exam
What US characteristics suggest a benign nodule?
- nice sharp edges around nodule
- fluid filled (Cystic) - not live tissue
- multiple nodules (multi-nodular goiter)
- no blood supply - not live tissue
When should a FNA bx be done?
- most accurate method for evaluating thyroid nodules and selecting pts for surgery
- FNA bx of nodules >1-1.5 cm w/ suspicious findings on US
- if there are any RFs nodules =/>0.5 cm are bx
- pts without RFs nodules
What levels of TSH are an indication that a FNA bx is needed?
- when serum TSH is normal or elevated
What should be done if TSH is low?
- this can indicate that there is overt or subclinical hyperthyroidism
- possibility that the nodule is hyperfunctioning, radioactive thyroid scan needs to be done next
- don’t do a FNA, not as suspect
Using a radionuclide thyroid scan?
- uses either a radioactive or iodine tracer and special scanner to measure how much tracer is being absorbed:
- iodine: shouldnt be done on pregnant women because it can cause fetal complications
- technetium-99m (isotope uptake scan)
- some cancers will look hot or warm on technetium scans but cold on iodine scans so it is usually better to do on iodine scans
Process of radinuclide thyroid scan?
- painless procedure
- takes about 30 minutes
- exposes pt to little or no radiation
- somewhat costly
Why would you do a radionuclide thyroid scan?
- to determine functional status of a thyroid nodule
- measure size of goiter prior to tx
- follow up thyroid cancer pts after surgery
- ID nodules and determining if hot or cold
- locating thyroid tissue outside of neck, ex: base of tongue or in chest
- used to select nodules for FNA
How do you interpret a radionuclide thyroid scan?
- gland may concentrate iodine normally but will be unable to convert the iodine to thyroid hormone so iodine tracer preferred
- hot nodule: rapid uptake of iodine or isotope, less likely to be malignant
- cold nodule: little or no uptake of iodine or isotope: more likely to be malignant
Results of a radionuclide thyroid scan?
- 95% of solitary thyroid nodules are benign
What should you consider before doing a thyroid scan?
- if pregnant or breastfeeding
- hx of allergies: iodine, shellfish, bee venom
- meds: thyroid hormones, antithyroid meds, meds that contain iodine: cough syrup, multivitamins, and amiodarone
What will hot and cold nodules look like on a scan?
- hot: darker than rest of thyroid
- cold: can’t see nodule, empty space
What is favored a single nodule or multi-nodular thyroid?
- multi-nodular is good finding
What is a fine needle aspiration (FNA)?
- non-surgical differentiation of malignant and benign nodules
- cost effective, and safe
- results are classified as:
benign, follicular lesion of undetermined significance, follicular neoplasm, suspicious for malignancy, malignant, non-dx
Determining if nodular is benign or malignant with FNA?
- benign: consist of follicular epithelium with variable amount of colloid
- malignant: can determine type: papillary, follicular variant of papillary, medullary, anaplastic, thyroid lymphoma, metastases to thyroid,
- follicular CA and hurtle cell CA can’t be dx clearly by FNA bx (have to go in surgically)
Suspicious findings from FNA
- 10% of FNAs
- not clearly benign nor malignant
- 25% are found to be malignant when undergoing thyroid surgery
- end up being follicular or hurthle cell cancers
- surgery is recommended for suspcious aspiration
Non-dx findings from FNA?
- cytologically inadequate
- repeat FNA under US guidance
- consider core-needle bx
- if still non-dx surgical excision needs to be considered
How is thyroid function best assessed?
- by measuring serum TSH, assuming steady state conditions and absence of pituitary or hypothalamic disease
