Clinical Pathology - Thyroid Funct

Front 1

NORMAL THYROID GLAND WEIGHS

Back 1

15-25 gm

Front 2

___ synthesize and secrete calcition

Back 2

C-cells or parafollicular cells

Front 3

normal hypothalamic-pituitary-thyroid (HPT) axis

Back 3

hypothalamus - TRH
pituitary - TSH (thyrotropin)
thyroid - thyroid hormone

Front 4

iodine enters the follicular cells (under TSH stimulation) in the form of __

Back 4

inorganic iodide
- it is transformed into thyroxine (T4) and 3,5,3'-triiodiothyronine (t3)

Front 5

__% of T4 is made directly by the thyroid

__% of T3 is made directly by the thyroid

Back 5

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

Front 6

If 85 micrograms of T4 are produced daily, then about __ micrograms of T3 are produced daily

Back 6

8.5

T4 production is 10 times that of T3

Front 7

Thyroid hormones circulate attached to plasma proteins.

Back 7

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!)

Front 8

Primary hypothyroidism is most commonly ___

Back 8

iatrogenic
- failure of the thyroid gland itself to secrete adequate thyroid hormone

Front 9

Iodide transport into follicular cells is influenced by serum idodide levels

Back 9

iodide deficiency - increases pump activity

iodide excess - ihibits iodide uptake

Front 10

T4 and T3 are produced by combining __

Back 10

DIT + DIT = T4

DIT + MIT = T3

Front 11

About 50% of T4 is monodeiodinated in teh 5'-position to form T3, while about 40% is deiodinated to form __

Back 11

reverse T3 (rT3)
- biologically inactive
- circulates bound to TBG
- short halflife (4 hrs)
- considered a disposal pathway in peripheral metabolism of T4

Front 12

When there is abundant iodide available, which is preferentially produced? DIT or MIT

Back 12

DIT
- leading to greater T4 production

When iodide is less available, then more MIT is produced with DIT, leading to greater T3 production directly

Front 13

TSH is a glycoprotein with covalently linked __ and __ subunits

Back 13

alpha and beta subunits
- alpha is same as that of LH, FSH, and HCG
- beta confers thryoid specificity

Front 14

American thryoid association (ATA) recommends that third generation TSH assays should be able to quantitate TSH in the ___ range with an interassay CV of __%

Back 14

0.010-0.020 mIU/L
20% or less

Front 15

Third generation, nonisotopic immunometric TSH assays using a chemiluminescent label, are __ sensitive compared to radioimmunoassays

Back 15

1000 times more sensitive

Front 16

nml TSH level

Back 16

0.5-5.0 mIU/L

Front 17

All patients with hyperthyroidism have low TSH levels?

Back 17

No, although the vast majority do.

Exceptions: patients with rare TSH-producing tumor or pituitary resistance to thyroid hormone

Front 18

subclinical hyperthryoidism

Back 18

low TSH with normal levels of T4 and T3

Front 19

Most patients with hypothyroidism, TSH levels are __

Back 19

- elevated TSH, except in those with pit or hypothal disorders

Front 20

subclinical hypothyroidism

Back 20

elevated TSH with nml levels of T4 and T3 and free T4

Front 21

Important cause of increased and decreased TSH levels (don't forget)

Back 21

nonthyroidal disease
- acute illness, TSH tends to be low
- resolution of illness, TSH rises to within or above nml
- ultimately nml again

Front 22

When assessing thyroid funciton, __ should be evaluated in conjunction with TSH level

Back 22

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

Front 23

When should you order TSH plus FT3?

Back 23

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

Front 24

T4 thyrotoxicosis

Back 24

NOT COMMON!

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

Front 25

Severe nonthyroidal illness is associated with __ T4 and T3 syndrome

Back 25

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

Front 26

Euthyroid hyperthyroxinemia

Back 26

increased serum total T4 with nml TSH, in otherwise euthryoid patient

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

No physiologic effect, becasue the FT4 is nml!!

Front 27

Assessment using T3 uptake along with total T4 was used to evaluate __

Back 27

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

Front 28

Direct measure of FT4 by immunoassay vs. FT4 by equilibrium dialysis

Which is more accurate

Back 28

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

Front 29

Although 10 times more T4 is produced daily compared to T3, there is __ T3 bound in circulation

Back 29

less T3 is bound to proteins in circulation
- a relatively greater proportion of T3 is free compared to free T4

Front 30

T3 levels can be WNL in hyperthyroid patients if __

Back 30

- coexistent nonthyroidal disease or on drugs that decrease conversion of T4 to T3 (propranolol or amiodarone)

Front 31

T3 thyrotoxicosis

Back 31

- 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

Front 32

In general, is the measurement of serum T3 useful in evaluating pts suspected of having hypothyroidism?

Back 32

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)

Front 33

serum thyroglobulin (Tg) level reflects what?

Back 33

- 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

Front 34

Tg level helps in diagnosing thyrotoxicosis factitia

Back 34

Patients with thyrotoxicosis factitia have UNDETECTABLE levels of Tg in contrast to a high level in pts with other causes of thyrotoxicosis

Front 35

Tg is (not or is) helpful in monitoring recurrence of undifferentiated or medullary thyroid carcinoma?

Back 35

Not

Front 36

T3 is measured by __

Back 36

- immunoassay
-

Front 37

__% of patients with hyperthyroidism have elevated T3 and T4

Back 37

90%

T3 or T4 thyrotoxicosis are uncommon

Front 38

thyroxin binding globulin (TBG) may be useful to measure if ___

Back 38

- 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

Front 39

Pencillin, salicylates, heparin can all __ T4

Back 39

(among other drugs) can dissociated T4 from TBG

Front 40

There are 3 thyroid autoantigens responsible for autoimmune thyroid disease

Back 40

- thyroperoxidase (TPO)
- thyroglobulin (Tg)
- TSH receptor (TR)

Front 41

anti-TPO autoAb are responsible for __

Back 41

- tissue injury in Hashimoto's and atrophic thyroiditis

Front 42

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

Back 42

- should always order an anti-Tg antibody level; even a low titer Ab could interview with Tg evaluation

Front 43

In Grave's disease, __% have anti-TSH receptor Ab

Back 43

85%

Front 44

which test is best for assessing dietary iodine intake?

Back 44

-urinary iodine excretion (UI) provides and accurate estimate of dietary iodine intake
- most of ingested iodine is excreted in the urine

Front 45

hypothyroidism in newborns; screening?

Back 45

1 in 3000-5000

Screening
- 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

Front 46

Severe nonthyroidal illness (NTI) and affects on thyroid hormone levels

Back 46

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

Front 47

HCG has a weak thyroid stimulating activity

Back 47

- 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

Front 48

Estrogen can lead to ___ thyroxine binding globulin (TBG) levels

Back 48

elevated TBG with increased TOTAL T3 and T4, but nml TSH, FT3 and FT4

Front 49

Propranolol __ conversion of T4 to T3 in periphhery

Back 49

inhibits
- one reason it is used to treat thyrotoxicosis

Front 50

Detection of subclinical hyperthyroidism is particularly important in patients over the age of __

Back 50

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

Front 51

American Thyroid Assoc recommends screening for thyroid disease at __

Back 51

- 35 years old, every 5 years

Front 52

Which test should be used to monitor pts receiving thyroid hormone therapy?

Back 52

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

Front 53

__% of medullary thryoid carcinomas are hereditary (MEN__ and MEN__)

Back 53

25% are hereditary
- MEN2A and MEN2B
autosomal dominant multiglandular disorders

Front 54

Pentagastrin (Pg) test

Back 54

- provocative test used to detect abnormally high calcitonin levels to predict presence or absence of MTC or other C cell abn