Thyroid Studies

T4 (thyroxine) is the prohormone

T3 (triiodothyronine) is the ACTIVE hormone

what is the difference between T3/T4?

in thyroglobulin in the follicular cells of the thyroid

where are T3 and T4 stored?

proteins

95% of T3/T4 is bound to...

in the periphery

where does most conversion of T4 to T3 occur?

TRH, TSH

to begin to start secreting thyroid hormone, ___ is released by the hypothalamus, which triggers ____ to be secreted by the AP

circulatory system and target tissues

TSH secretion from the pituitary causes T4/T3 to be released into...

T4 is converted into T3 in peripheral tissues

after T3/T4 are released into the bloodstream, what happens?

TRH release is INCREASED

More TRH --> more release of TSH --> more relese of T4/T3

how does the body respond when T4/T3 are low in the circulation?

TRH release is DECREASED

Less TRH --> decreased release of TSH --> decreased release of T4 and T3

how does the body respond when T4/T3 are high in the circulation?

thyroid stimulating hormone

total T4 and total T3

free T4 and free T3

what is included in basic thyroid testing?

thyroglobulin

antithyroglobulin antibody

antithyroid perixodase antibody (anti-TPO)

what is included in advanced thyroid testing?

diagnosing hypothyroidism and hyperthyroidism

differentiating primary thyroid disease from secondary and tertiary thyroid disease

monitoring effectiveness of medication for hypo or hyperthyroidism

TSH is often the first line test used for...

a slight decrease in free T4 leads to disproportionately large increase in TSH

--> helpful in determining even SMALL changes

how does a slight decrease in free T4 affect TSH levels?

pituitary or hypothalamic disease is known or suspected

hospitalized patients

in what circumstances is TSH not a very helpful diagnostic tool?

Lithium (causes decreased T4/T3 release from the thyroid)

what medications increase TSH levels?

dopamine agonists (Bromocriptine), high dose steroids

what medications decrease TSH levels?

biotin supplements (also elevate T4/T3)

what medications provide one with falsely low TSH levels?

decreased TSH in first trimester

how do TSH levels change in pregnancy?

primary hypothyroidism

TSH secreting pituitary tumor

euthyroid sick syndrome (maybe)

what are some conditions that cause increased TSH?

secondary hypothyroidism

tertiary hypothyroidism

primary hyperthyroidism

suppression from thyroid medication

biotin supplement

euthyroid sick syndrome (maybe)

what are some conditions that cause decreased TSH?

T4

90% of circulating thyroid hormone is...

thyroxine-binding protein (TBG)

--> hormones are NOT active

T4/T3 are primarily bound to what protein?

both bound and unbound T4/T3

total T4/T3 measures....

only unbound T4/T3 (metabolically active)

free T4/T3 measures....

causes increased TBG --> more hormone bound to protein --> FALSE increase in TOTAL T4 (free T4 would be normal)

how does pregnancy affect T4/T3 levels?

lithium

what medication leads to decreased levels of T4/T3?

biotin supplement

what medication leads to falsely elevated T4/T3

hyperthyroidism

acute thyroiditis

toxic multinodular goiter

biotin supplement (false elevation)

what conditions lead to increased T4/T3 levels?

hypothyroid state

pituitary insufficiency

hypothalamic failure

euthyroid sick syndrome

what conditions lead to decreased T4/T3 levels?

failure of the thyroid to produce T3 and T4

what is the pathophysiology behind primary hypothyroidism?

Hashimoto's thyroiditis

what is the most common cause of primary hypothyroidism?

antibodies to thyroid peroxidase (TPO) and thyroglobulin

90% of the patients with Hashimoto's thyroiditis have a high concentration of...

failure of the pituitary gland to secrete TSH when appropriately stimulated by the hypothalamus

what is the pathophysiology of secondary hypothyroidism?

failure of the hypothalamus to respond to low levels of T4/T3

--> TRH NOT released to stimulate the AP to release TSH

what is the pathophysiology of tertiary hypothyroidism?

order a TSH

what is the first step in working up hypothyroidism

serum free T4 (could also do TSH with reflex free T4)

in the workup of hypothyroidism, if a TSH is high, one should measure a...

central hypothyroidism

if one's TSH is normal but you suspect hypothyroidism, one can check free T4 to assess for...

primary hypothyroidism

if one has a high TSH and a low free T4, that indicates....

subclinical hypothyroidism

if one has a high TSH and a normal free T4, that indicates....

central hypothyroidism (secondary/tertiary)

if one has a low or normal TSH and a low free T4, that indicates....

pituitary function as a whole (FSH, LH, prolacin, estradiol, testosterone, IGF-1, urinary cortisol)

--> cannot just use TSH to make this diagnosis

if one suspects secondary/tertiary hypothyroidism, one should assess...

Grave's disease

what is the most common cause of hyperthyroidism?

autoimmune disorder that causes stimulation of TSH receptor AB

--> causes increased thyroid gland growth

--> increases thyroid hormone production and release

what is Grave's disease?

toxic multi-nodular goiter

toxic adenoma

acute thyroiditis (post-viral, postpartum)

pituitary adenoms

what are some other less common causes of hyperthyroidism

order a TSH

what is the first step in working up hyperthyroidism

free T4 and free T3 (or order TSH with reflex free T4/T3)

if one's TSH is low in the workup of hyperthyroidism, one should order....

overt hyperthyroidism

if one has a low TSH, high free T4 and free T3, that indicates...

T3 thyrotoxicosis

if one has a low TSH, high free T3 but normal free T4, that indicates...

T4 thyrotoxicosis

if one has a low TSH, high free T4 but normal free T3, that indicates...

subclinical hyperthyroidism

if one has a low TSH, normal free T4 and free T3, that indicates...

pituitary adenoma

if one has a normal or high TSH, high free T4 and/or free T3, that indicates...

Euthyroid sick syndrome

abnormal findings on thyroid function tests that occur in the setting of a nonthyroidal illness, without preexisting hypothalamic-pituitary and thyroid gland dysfunction.

cytokines decrease activity of enzyme responsible for converting T4 --> T3 in the periphery

--> as severity worsens, the hypothalamic-pituitary-thyroid pathway is disrupted

felt to be a possibly protective mechanism to help prevent excessive tissue catabolism

what is the pathophysiology behind euthyroid sick syndrome?

critically ill patient

one should try to avoid checking thyroid function in a...

TSH normal

T4 normal

T3 LOW

initial lab work in one with euthyroid sick syndrome?

TSH LOW (occasionally high)

T4 LOW

T3 LOW

what is the most severe set of labs one with euthyroid sick syndrome can have?

4 weeks

--> majority will have normal TSH/thyroid function upon retesting

in a patient with euthyroid sick syndrome, labs should be rechecked in...

Thyroglobulin

precursor to thyroid hormone made by both healthy and malignant thyroid cells

differentiated thyroid cancer for persistent or recurrent disease AFTER initial initial surgical therapy

thyroglobulin is used to monitor patients with....

thyroid cancer

thyroglobulin is NOT used to diagnose...

an autoimmune thyroid disease

--> order in conjucntion with antithyroid peroxidase antibody

antithyroglobulin antibody can be used when one suspects...

overt hypothyroidism

if antithyroglobulin antibody is high in one with subclinical hypothyroidism, it is more likely to become...

treated thyroid cancer

--> Tg AB present, then Tg can't be used to reliably track cancer recurrence

antithyroglobulin antibody is ordered with thyroglobulin in patients with...

Hashimoto's thyroiditis

Grave's disease

Thyroid carcinoma

Other autoimmune conditions

can occur in healthy individuals

causes of antithyroglobulin antibody elevation

ordered with thyroglobulin antibody to increase sensitivity of test when assessing patients with subclinical disease to determine likelihood of becoming overt disease

why would one order thyroid peroxidase antibody?