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54 Cards in this Set

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  • Back
15-25 gm
___ synthesize and secrete calcition
C-cells or parafollicular cells
normal hypothalamic-pituitary-thyroid (HPT) axis
hypothalamus - TRH
pituitary - TSH (thyrotropin)
thyroid - thyroid hormone
iodine enters the follicular cells (under TSH stimulation) in the form of __
inorganic iodide
- it is transformed into thyroxine (T4) and 3,5,3'-triiodiothyronine (t3)
__% of T4 is made directly by the thyroid

__% of T3 is made directly by the thyroid
100% of T4 is made directly by the thyroid

Only 20% of T3 is made directly by the thyroid; 80% is produced enzymatically in nonthyroidal tissues by 5'-monodeiodination of T4
If 85 micrograms of T4 are produced daily, then about __ micrograms of T3 are produced daily

T4 production is 10 times that of T3
Thyroid hormones circulate attached to plasma proteins.
T4 is bound to:
- 70% thyroxine-binding globulin (TBG)
- 20% transthyretin (prealbumin)
- 10% ablumin

Most of T3 is bound to TGB (but with tenfold less affinity as compared to T4 binding)

Small % of T4 and T3 is unbound (Free component is the metabolically active component!)
Primary hypothyroidism is most commonly ___
- failure of the thyroid gland itself to secrete adequate thyroid hormone
Iodide transport into follicular cells is influenced by serum idodide levels
iodide deficiency - increases pump activity

iodide excess - ihibits iodide uptake
T4 and T3 are produced by combining __
DIT + DIT = T4

DIT + MIT = T3
About 50% of T4 is monodeiodinated in teh 5'-position to form T3, while about 40% is deiodinated to form __
reverse T3 (rT3)
- biologically inactive
- circulates bound to TBG
- short halflife (4 hrs)
- considered a disposal pathway in peripheral metabolism of T4
When there is abundant iodide available, which is preferentially produced? DIT or MIT
- leading to greater T4 production

When iodide is less available, then more MIT is produced with DIT, leading to greater T3 production directly
TSH is a glycoprotein with covalently linked __ and __ subunits
alpha and beta subunits
- alpha is same as that of LH, FSH, and HCG
- beta confers thryoid specificity
American thryoid association (ATA) recommends that third generation TSH assays should be able to quantitate TSH in the ___ range with an interassay CV of __%
0.010-0.020 mIU/L
20% or less
Third generation, nonisotopic immunometric TSH assays using a chemiluminescent label, are __ sensitive compared to radioimmunoassays
1000 times more sensitive
nml TSH level
0.5-5.0 mIU/L
All patients with hyperthyroidism have low TSH levels?
No, although the vast majority do.

Exceptions: patients with rare TSH-producing tumor or pituitary resistance to thyroid hormone
subclinical hyperthryoidism
low TSH with normal levels of T4 and T3
Most patients with hypothyroidism, TSH levels are __
- elevated TSH, except in those with pit or hypothal disorders
subclinical hypothyroidism
elevated TSH with nml levels of T4 and T3 and free T4
Important cause of increased and decreased TSH levels (don't forget)
nonthyroidal disease
- acute illness, TSH tends to be low
- resolution of illness, TSH rises to within or above nml
- ultimately nml again
When assessing thyroid funciton, __ should be evaluated in conjunction with TSH level
TSH and free T4(FT4)
- TSH alone assumes there is an intact HPT axis and that the patient has stable thyroid function

Example: TSH-dependent hyperthyroidism; increased TSH with increased FT4; if TSH was evaluated alone, it would look like hypothyroidism
When should you order TSH plus FT3?
if there is suspected hyperthyroidism, because they could have T3 thyrotoxicosis which is often associated with normal to low-normal T4!!

TSH and FT4 could give a subclinical hyperthryoidism picture, when in fact the patients has T3 thyrotoxicosis
T4 thyrotoxicosis

low TSH
high FT4
nml or low FT3!

Can occur in patients with iodine-induced T4 thyrotoxicosis, with beta-blockers, amiodarone or large doses of steroids, or in thyrotoxic paitents with nonthyroidal illnesses
Severe nonthyroidal illness is associated with __ T4 and T3 syndrome
low T4 and T3 syndrome
- adaptive response to reduce metabolic demands and conserve protein stores

- believed to be due to a maladaptive inhibition of TRH
Euthyroid hyperthyroxinemia
increased serum total T4 with nml TSH, in otherwise euthryoid patient

- increased binding proteins a/w certain drugs(estrogen therapy) and medical condidtions (liver disease)

No physiologic effect, becasue the FT4 is nml!!
Assessment using T3 uptake along with total T4 was used to evaluate __
biologically active FT4

- uptake result is a relative measurement of the unoccupied binding sites of all cirulating proteins
-- high uptake result means less protein bound in vivo

A free thyoxine index (FTI) is calcuated:

T3-uptake of patient/mean T3-uptake of reference range x patient's total T4

FTI is an estimate of FT4

This method has been largely replaced by direct measurement of FT4
Direct measure of FT4 by immunoassay vs. FT4 by equilibrium dialysis

Which is more accurate
equil dail is more accurate, however, the direct FT4 immunoassay is sufficient for most clinical situations

It is when there are marked abn or changes in protein binding that can lead to unreliable direct FT4 measurements that the more accurate FT4 by equilibrium dialysis should be used
Although 10 times more T4 is produced daily compared to T3, there is __ T3 bound in circulation
less T3 is bound to proteins in circulation
- a relatively greater proportion of T3 is free compared to free T4
T3 levels can be WNL in hyperthyroid patients if __
- coexistent nonthyroidal disease or on drugs that decrease conversion of T4 to T3 (propranolol or amiodarone)
T3 thyrotoxicosis
- uncommon (1-4% of thyrotoxic patients), except in regions with iodine deficiency where it is more common

- Although most pts have Grave's dz, it can be seen with toxic nodular goiter, toxic adenoma

- hyperthyroidism with low TSH, high T3, but nml T4 and FT4

Note: elevated T3 with nml T4 can also been seen in early treated hyperthyroidism or during relapse after treatment
In general, is the measurement of serum T3 useful in evaluating pts suspected of having hypothyroidism?
No, 15-30% of hypothyroid patients may have normal T3 levels

- in severe hypothyroidism, decreased T3 levels are seen

- also you can have a low T3 due to a number of nonthyroidal illnesses (remember that 80% of T3 is produced enzymatically in nonthyroidal tissues)
serum thyroglobulin (Tg) level reflects what?
- thyroid gland mass
- thyroid injury
- TSH receptor stimulation

increased Tg
- Grave's dz
- thyroiditis
- nodular goiter

Not routinely measured, but used for:

- monitoring thyroid cancer recurrence
Tg level helps in diagnosing thyrotoxicosis factitia
Patients with thyrotoxicosis factitia have UNDETECTABLE levels of Tg in contrast to a high level in pts with other causes of thyrotoxicosis
Tg is (not or is) helpful in monitoring recurrence of undifferentiated or medullary thyroid carcinoma?
T3 is measured by __
- immunoassay
__% of patients with hyperthyroidism have elevated T3 and T4

T3 or T4 thyrotoxicosis are uncommon
thyroxin binding globulin (TBG) may be useful to measure if ___
- other thyroid studies do not make sense; clinical picture doesn't fit lab findings

- there are deficiencies (partial or complete) as well as variants with decreased affinity of T3 or T4
- can also have excess TBG
Pencillin, salicylates, heparin can all __ T4
(among other drugs) can dissociated T4 from TBG
There are 3 thyroid autoantigens responsible for autoimmune thyroid disease
- thyroperoxidase (TPO)
- thyroglobulin (Tg)
- TSH receptor (TR)
anti-TPO autoAb are responsible for __
- tissue injury in Hashimoto's and atrophic thyroiditis
Note: when measureing thyroglobulin (Tg) for follow-up after thyroid ca (for example), what else should be ordered to ensure appropriate interpretation of Tg levels
- should always order an anti-Tg antibody level; even a low titer Ab could interview with Tg evaluation
In Grave's disease, __% have anti-TSH receptor Ab
which test is best for assessing dietary iodine intake?
-urinary iodine excretion (UI) provides and accurate estimate of dietary iodine intake
- most of ingested iodine is excreted in the urine
hypothyroidism in newborns; screening?
1 in 3000-5000

- measure T4 and TSH, performed on dry blood spots or cord serum

Early detection is critical to prevent severe mental retardation a/w thyroid hormone deficiency

Note: very low birth weight infants should be retested at 2 and 4-6 weeks to detect late onset transient hypothyroidism
Severe nonthyroidal illness (NTI) and affects on thyroid hormone levels
Acute - rapid fall in total and free T3

Eventually - fall in T4 (note T4 that is really low, <2 ng/dL, is a/w a poor px)

Referred to as euthyroid sick syndrome or low T4 syndrome;

Typically see:
acute illness:
- low-nml or low TSH
- nml or low-nml T4
- very low T3

Then TSH rises to WNL or above

With normalization of values with resolution of illness
HCG has a weak thyroid stimulating activity
- homology with TSH

Peak rise in HCG and nadir in TSH occur together at about 10-12 weeks EGA
- most cases, the subsequent increase in FT4 is still WNL
- in 20% of nml pregnancies, TSH can be low
- RARELY (2%)the FT4 is high enough to be supranormal with sign and symptoms of thyrotoxicosis (GESTATIONAL TRANSIENT THYROTOXICOSIS), frequently occurs along with first trimester hyperemesis gravidarum
Estrogen can lead to ___ thyroxine binding globulin (TBG) levels
elevated TBG with increased TOTAL T3 and T4, but nml TSH, FT3 and FT4
Propranolol __ conversion of T4 to T3 in periphhery
- one reason it is used to treat thyrotoxicosis
Detection of subclinical hyperthyroidism is particularly important in patients over the age of __
60 years old
- increased risk of A-fib, cardiovascular mortality, and osteoporosis

- minimal thyroid hormone excess can cause A-fib and stimulate osteoclastic activity in bone causing osteoporosis
American Thyroid Assoc recommends screening for thyroid disease at __
- 35 years old, every 5 years
Which test should be used to monitor pts receiving thyroid hormone therapy?
TSH! annually once stable

- can check a TSH and FT4 if concerned about intermitent compliance

Must wait 6 weeks prior to checking TSH after a change in L-T4
__% of medullary thryoid carcinomas are hereditary (MEN__ and MEN__)
25% are hereditary
- MEN2A and MEN2B
autosomal dominant multiglandular disorders
Pentagastrin (Pg) test
- provocative test used to detect abnormally high calcitonin levels to predict presence or absence of MTC or other C cell abn