thyroid and adrenal lab med

wher does 90% of T3 and T4 bind after exiting the thyroid

Thyroid Binding Globulin (TBG) in the liver

what are the proteins that T3 and T4 bind to after leaving the thyroid

Thyroid binding globulins, thyroid binding protiens and albumin

which is the more active/potent thyroid hormone and where is it made

T3, mostly made by hepatic and renal deiodination of T4 (some made in thyroid)

which is the less active/potent thyroid hormone and where is it made

T4, made solely in the thyroid

which thyroid hormone is more protein bound and how does this change its onset

T4 (99% protein bound), makes it slow to activate (2-3 days) and slow to inactivate (more in storage)

which thyroid hormone is less protein bound and how does this change its onset

T3, has rapid onset of action (2-3hrs) and rapid inactivation (less in storage)

what are some of the biological effects of T3 and T4 on the body as a whole

affects heart rate, breathing, metabolism of glucose, menstruation, the liver (in lots of ways), bone health and muscle contractions, body temp, body weight, and brain development

what impact do T3 and T4 have on the release of TSH and TRH

the more T3 and T4 the less TSH and TRH released (neg feedback loop)

what is the #1 thyroid function screening test

TSH test (see if theres a thyroid problem at all)

what tests can be done to test for thyroid dysfxn

TSH (testing pituitary function)

T3 and T4 tests for the thyroid directly (can be total T3/T4, free T3/T4 which is a direct measure, free T4 index, or T3U which is controlled by TBG carrier protein and is an indirect measure of free T3/T4)

thyroid antibody tests

calcitonin

thyroglobulin

can thyroid tests be used as the sole measure of thyroid dysfunction

no

what is the most sensitive first line screening test for thyroid disorders

TSH

what does TSH tell us as a lab test

assess pituitary function and reflects long term thyroid status, production is inversely related to thyroid hormones (esp T40

if you have a pt w hyperthyroidism what will their TSH look like

low (bc T3/T4 are high)

if you have a pt w hypothyroidism what will their TSH look like

high (bc T3/T4 are low)

what are the uses of TSH tests

screening, theraputic monitoring (esp for hypothyroidism tx), essential for monitoring suppression therapy in pts w a TSH responsive thyroid tumor

what do we do if TSH is outside the reference range

get a free T4

what does a total T3/T4 test measure

measures both bound and free T3/T4, and is accurate and sensitive to ACUTE changes

what may affect your total T3/T4 readings inaccurately

may be greatly altered by illness/meds because the level of Thyroid Binding Globulins are altered by these things and 99% of thyroid hormones circulate inactive and bound to proteins (mainly the TBG)

when testing the total T3/T4 for a pt w hyperthyroid what will you see? what if its hypothyroid?

T3/T4 correlate well, T3 high and T4 high

T3 has limited utility and may be low if the pts thyroid is fine or may be fine if the pt has hypothyroidism (doesnt correlate as well)

what does a FREE T3/T4 measure

a direct assay that measures unbound hormone levels

what are some of the benefits of measuring free T3/T4 over total T3/T4

no need to separate free from bound hormones

measurements are NOT altered by changes in protein and therefore free is a better indicator of thyroid status

more sensitive and accurate

free levels dont always correlate well to total level measurements

an indirect measure of free T4 levels by correcting for variations in TBG (thyroid binding globulin)

Free T4 Index

if a pt has hypothyroidism what will their Free T4 Index look like

low

if a pt has hyperthyroidism what will their Free T4 Index look like

high

what is the Free T4 Index index calculation

FTI = total T4 X % T3 R-uptake

what are the downsides for a Free T4 Index

its dependent on the amount of TBG, mostly obsolete now due to improvements in free hormone assays

an indirect measure of serum thyroid hormone binding capacity/sites that accounts for binding protein alterations. varies inversely w the number of avalibale free TBG binding sites

T3 resin uptake

how is a T3 resin uptake performed and reported

incubate a pts serum w radiolabeled T3 tracer (that binds to TBG), then adding resin that traps remaining unbound radiolabeled T3

value is reported as % tracer bound to resin

also rarely used due to improved FT4 assays

if a pt has hyperthyroidism would their % in a T3 resin uptake be high or low

high

if a pt has hypothyroidism would their % in a T3 resin uptake be high or low

low

what are antithyroid antibodies

antibodies that develop when the immune system attacks the thyroid gland, which can cause inflammation, damage, and distrup function (results for tests are reported as titers)

where produces calcitonin and what does it do

parafollicular or C-cells in the thyroid

helps in calcium and phosphorus metabolism and homeostasis

in the bone it suppresses reabsorbtion of bone, releasing calcium and phosphorus into the blood

in the kidney it inhibits tubular reabsorbtion of calcium and phosphorus

what are calcitonin labs used for

to determine when to perform a thyroidectomy, assess prognosis, and monitor for recurrence

if you do a thyroidectomy on a pt and their calcitonin is still high afterwards what does that mean

you mightve missed some thyroid tissue or the tissue is coming back or the cancer has metastisized to other areas

what does elevated calcitonin indicate

blood ionized calcium levels strongly stimulate calcitonin secretion, may indicate thyroid hyperplasia or thyroid medullary cancer

a protein made and stored in the thyroid

thyroglobulin (TG)

what is the major use for thyroglobulin labs

tumor marker for thyroid cancer

if you perform a thyroidectomy on a pt and they still have thyroglobulin what does that mean

either you missed some of the thyroid tissue or the cancer is metastatic

what should thyroglobulin measurements also include

measurement of anti-TG antibodies (presence of these autoantibodies = false positive/ negative results)

what factors can interefere w thyroid function immunoassays

meds(biotin, amiodarone, heparin, hormones, salysalate, phenytonin, carbamazepine, OCP’s, steroids)

diet (soy, milk, coffee)

malabsorbtion syndromes

pregnancy/recent illness/stress

age/gender (very active in early infancy and young kids bc growing so much)

lab mistake

causes of hyperthyroidism

Grave’s disease, Toxic Multinodular Goiter, Toxic adenomas (95% of hyperthyroidism pts)

overstimulation of thyroid, genetic mutations (tumor induced), inflammation, infection, injury, extrathyroidal sources (either tissue other than thyroid is making T3/T4 or pt is taking T3/T4 when they shouldnt be)

what are the diagnostic labs for hyperthyroidism

LOW TSH, HIGH T3/T4

what are the main causes of hypothyroidism

autoimmunity (in the US), iodine deficiency (world wide)

what are the diagnostic labs for hypothyroidism

HIGH TSH, LOW T3/T4 (diagnostic if presenting w sx)

one of the most preventable causes of intellectual disability, this can occur during development/infancy and is most often sporadic but can be genetic. testing for this is now part of the newborn screening program

congenital hypothyroidism (“cretinism”)

what causes cretinism

iodine deficiency

how quickly must congenital hypothyroidism (cretinism) be treated

requires rapid diagnosis and treatment (under 2wks) or will cause irreversible neurological problems and growth deficits

a specialty thyroid test with in VIVO administration of radioactive iodine, where the accumulated radioactivity of the thyroid is measured at intervals and a scan examines the anatomic distribution of the iodine within the gland

radioactive iodine uptake and thyroid scan

the procedure of choice to collect specimen for microscopic eval to distinguish benign vs malignant nodules

fine needle aspiration cytology

when are cortisol concentrations highest naturally

in the early morning between 4-8am (therefore a single, random serum test isnt super useful)

what is the optimal specimen for measuring cortisol to gauge adrenal function

24hr urine sample

if you have a low cortisol level in the morning what does that indicate

adrenal insufficiency

what pts do we not do a 24hr urine test for cortisol on

pts w renal impairment

a test that measures how the body reacts to dextamethasone (synthetic glucocorticoid) and is done to assess adrenal function

dextamethasone test

what NORMALLY happens when you give someone who doesnt have cushings dextamethasone

ACTH and CRH secretion are suppressed → cortisol production suppressed/decreased

what is the diagnostic indicator for cushings when doing a dexamethasone suppression test

cortisol 1.8 ug/dL or more = cushings

when is it best to draw ACTH when testing whether cushing syndrome is ACTH dependent or not

draw between midnight and 2am when plasma circulating concentrations at lowest

when is the best time to draw ACTH when determining adrenal insufficiency

draw between 6-8am during its peak (suppressed morning ACTH = excess cortisol secretion)

what is the most useful test in diagnosis of adrenal insufficiency

ACTH stimulation test

a test that measures how well the adrenal glands respond to ACTH like stimulus by measuring cortisol after the ACTH stimulation to assess adrenal function

ACTH stimulation test

cortisol of less than 18 ug/dL after an ACTH stimulation test means what

adrenal insufficiency (no cortisol production after ACTH stimulation)

a disorder of excess cortisol production, more commonly ACTH dependent than not and most commonly caused by the exogenous administration of glucocorticoids

cushings syndrome

a disease of LOW CORTISOL AND HIGH ACTH

addisons disease

causes of addisons

autoimmune, fungal/viral (libe TB), anatomic destruction (like surgery or cancer)

characteristics of addisons

hyperpigmentation of the skin and mucus membranes (caused by degradation of ACTH and its pro-hormone melanin)