Path 3 Eval Of Thyroid

Front 1

EVALUATION OF THYROID - WHITLEY - FRIDAY FEB 2

Front 3

what type of relationship exists between TSH and free T4 levels?

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inverse log relationship - small alterations in free T4 produce a much larger response in serum TSH

Front 4

what is the preferred screening test for evaluating thyrometabolic states, and why?

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TSH test - excludes thyroid disease, detects disease, and indicates mild disease and thyroxine suppression in differentiated cancer patients

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at what age are TSH concentrations high than normal?

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in children, especially first week of life

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what drugs decrease and increas TSH secretion (2,1)?

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decrease: 1) dopamine; 2) glucocorticoids; increase: amiodarone

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how do free T4 levels fluctuate in a euthyroid individual, and how does this relate to levels of binding protein?

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the steady state level remains almost constant, and is independent of binding protein variations

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what is the preferred type of test for measuring free T4?

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immunoassay

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why does a total T4 test not provide adequate clinical information?

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changes in the concentration or affinity of serum binding proteins affect total T4

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besides hyperthyroidism, what can high TT4 values reflect?

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increases in thyroid hormone binding protein (and low TT4 levels may reflect decreases in thyroid hormone binding protein)

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what can increase the amount of thyroid binding protein (examples)?

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pregnancy, oral contraceptives, estrogen therapy, newborn, hereditary TBG increase

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what can decrease the amount of thyroid binding protein (5)?

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renal or GI protein loss, androgen therapy, glucocorticoid excess, cirrhosis, hereditary deficiency

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what value should be reported with every total T4, and what is it?

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free thyroxine estimate - an estimate of free T4, representing the total T4 corrected for abnormalities in the degree of serum protein binding

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what are the units/range for FTI?

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unitles, and has normal range close to normal range for total T4

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when is FTI unreliable?

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1) euthyroid patients with TBG excess or deficiency (congenital); 2) familial dysalbuminemic hyperthyroidism; 3) severe illness; 4) anti-T4 antibodies - this measurement is normal in hyper- and hypothyroid patients, healthy subjects, and subjects with mild abnormalities in binding proteins

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what test was designed to correct for variations in protein binding of T4, and what are the units of this test?

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T3 or T4 resin uptake test (T-uptake), expressed as THBR (thyroid hormone binding ratio)

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how is this test used?

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used with total T4 to calculate a free thyroxine index (FTI = TT4 * THBR)

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what is a total T3 test useful in?

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detection of T3-thyrotoxicosis - not a good general test

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how is most T3 formed?

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by conversion of T4 to T3 in peripheral tissues (80%), 20% is formed in thyroid

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is most T3 protein bound?

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yes, but the free fration is 10X as high as with T4

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what is a free T3 test useful in?

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also useful in diagnosing T3 thyrotoxicosis

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what does an increased reverse T3, with low total T3 suggest?

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nonthyroidal illness rather than hypothyroidism

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what is reverse T3?

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T3 with two iodines on the distal phenyl group (not the one with the NH2/COOH)

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wheres is thyroglobulin stored and what does it serve as?

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stored as colloid in thyroid follicle, serves as prohormone in thyroid hormone synthesis

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what is measurement of Tg most useful in?

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detection of residual/recurrent differentiated thyroid carcinoma following surgical resection and radioiodine ablation

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what else is Tg useful for diagnosing?

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1) diagnosing factitious hyperthyroidism (characterized by non-elevated serum Tg); 2) assessing the activity of inflammatory thyroiditis

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what measurement is a sensitive and specific indicator of autoimmune thyroid diseease?

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measurement of antibodies to thyroid peroxidase

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where is the thyroid peroxidase enzyme located?

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on the surface of the microvilli of thyroid epithelial cells

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what other anti-thyroid andibodies can be tested for (2)?

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1) antithyroglboulin (TgAb); 2) anti-TSH receptor antibodies (TRAb)

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who has a high prevalence of TgAb?

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adults without thyroid disease - it is less frequently positive in autoimmune thyroid disease than TPOAb

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what problem can TgAb cause, and in who?

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present in about 35% of thyroid cancer patients - these antibodies interfere with immunoassays for Tg

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in what two diseases were these antibodies mentioned to be found?

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1) Graves' disease; 2) Hashimoto's thyroiditis

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what do these antibodies do in Graves' disease?

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activate the TSH receptor, resulting in gland enlargement and thyroid hormone overproduction (test is also called TSI (thyroid stimulating immunoglobulins)

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what does it do in Hashimoto's?

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blocks the action of TSH, thus adccounting for the hypothyroidism

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what populations with no overt signs or symptoms should undergo thyroid tests (3)?

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1) newborns; 2) adults at 35, every 5 years; 3) elderly (high risk)

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HYPOTHYROIDISM

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what are clues from lab results that there may be primary hypothyroidism (4)?

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1) hyponatremia; 2) hypercholesteremia; 3) anemia; 4) elevated creatine kinase

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what do low, normal, and high TSH values suggest about hypothyroidism?

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normal values exclude primary hypothyroidism, high values suggest thyroid gland failure, and low values suggest secondary or tertiary hypothyroidism

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what other test and value confirms primary hypothyroidism?

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low free serum T4

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what do slightly high TSH and normal free T4 values suggest?

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subclinical hypothyroidism or recovery from nonthyroidal illness

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what are the value of total and free T3 tests in hypothyroidism?

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not indicated, since normal levels are found in 25% of patients with primary hypothyroidism

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what test has 99% sensitivity for Hashimoto's?

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TPOAb (99% in Hashimoto's, 90 to 95% for other autoimmune thyroid disease)

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what are optimal screening tests for subclinical hypothyroidism (2)?

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1) TSH; 2) TPOAb

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after initiating or changing L-T4 replacement therapy, what happens to serum TSH?

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6 to 8 weeks are needed for serum TSH to reach a new steady state%

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what more reliably indicates new thyroid status during this period?

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serum free T4

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what should be measured, and how often, to monitor clinical euthyroidism (replacement therapy)?

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TSH should be measured 1 to 2 times per year

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what may low TSH levels raise the risk for (2)?

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1) bone resoprtion (osteoporosis); 2) cardiac arrhythmias (especially atrial fibrillation)

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what should be measured in patients suspected of noncompliance, and what values should these patients have?

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TSH and free T4 - these values should be high in noncompliant patients

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what test and result indicates secondary (central) hypothyroidism?

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free serum T4 is used to make this diagnosis - it will be low

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what will TSH be like?

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subnormal, inappropriately normal (for low free T4), or sometimes elevated

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why may it be elevated?

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due to secretion of biologically inactive, but immunoreactive, TSH isoforms

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what test differentiates between secondary and tertiary hypothyroidism?

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TRH test - TRH is given, and if TSH doesn't increase, hypothyroidism is secondary to hypopituitarism - if there is a response, the problem is with the hypothalamus

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what effect may mild hypothyroidism have on pregnancy?

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can have detrimental effect - fetal loss and infant IQ decrease

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what test is used for pre-pregnancy and first trimester screening?

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serum TSH

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what may be necessary for pregnant patients receiving L-T4 replacement therapy?

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increased doses, to maintain normal TSH

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***see flowchart on hypothyroidism***

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HYPERTHYROIDISM (THYROTOXICOSIS)

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what are laboratory value clues to hyperthyroidism (5)?

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1) hypercalcemia; 2) hyperphosphatemia; 3) hyperglycemia; 4) hypercholesterolemia; 5) elevated alkaline phosphatase

Front 63

what is the first test done to evaluate primary hyperthyroidism, and what level is observed in primary hyperthyroidism?

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profoundly low/undetectable level (<0.01 mU/L) observed in primary hyperthyroidism - low level is also suspicious (<0.1 mU/L)

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what does a normal level mean, and what can a high level be consistent with?

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normal level excludes primary hyperthyroidism, and a high level is consistent with TSH-secreting tumor or reistance to thyroid hormones

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what test and result confirms hyperthyroidism?

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elevated free T4 level

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what TSH and T4 levels may suggest subclinical hyperthyroidism, T3 thyrotoxicosis, or nonthyroidal illness?

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low TSH level and normal level of free T4

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what does a low T3 value suggest?

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nonthyroidal illness

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what does a normal T3 level suggest?

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subclinical hyperthyroidism

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what does a high T3 level suggest?

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confirms T3 thyrotoxicosis

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why may there be more T3 than T4?

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autonomic toxic adenomas may produce more T3

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what is the rationale for the radioactive iodine uptake test?

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percent uptake of iodine into thyroid gland is proportional to rate of thyroid hormone production

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what is the test used in?

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differential diagnosis of biochemically established hyperthyroidism

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what is the differential diagnosis for increased uptake (5)?

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1) Graves' disease; 2) toxic multinodular goiter; 3) toxic autonomous nodule; 4) trophoblastic tumor; 5) TSH-secreting pituitary tumor

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what is the differential diagnosis for decreased uptake (3)?

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1) thyroiditis; 2) excessive thyroid hormone in medications or food; 3) iodine excess

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what antibody do most patients with Graves' disease have, and what do fewer have?

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most have TPOAb, fewer have TgAb

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in what types of goiter (2) are no circulating antibodies seen?

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solitary or multinodular toxic goiters

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why are TSH receptor antibodies measured during last trimester of pregnancy?

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to predict possible occurrence of neonatal or fetal thyrotoxicosis secondary to transplacental passage of maternal antibodies

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in what conditions will high serum hCG be seen?

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1) molar pregnancy; 2) choriocarcinoma; 3) hyperemesis gravidarum

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what test is used to monitor effectiveness of antithyroid medication during the first 2-3 months of treatment?

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serum free T4

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what are serum TSH values useful for, and what are they like in early suppression therapy?

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not an accurate measurement of thyroid status - often remains low for several months after normalization of T4 and T3 concentrations

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what may overtreatment with suppression therapy lead to?

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hypothyroidism

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what is a marker for a TSH-secreting pituitary tumor, but not with resistance to thyroid hormone?

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increase in the alpha-subunit of TSH (this increases with TSH secreting tumor, but not resistance to thyroid hormone)

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what will happen when TRH is administered to patients with TSH-secreting tumors?

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no increase in serum TSH

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***see flowchart on hyperthyroidism***

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NONTHYROIDAL ILLNESS (SICK EUTHYROID SYNDROME)

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what is NTI/sick euthyroid syndrome?

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disorder characterized by thyroid hormone excess or deficiency in the absence of thyroid disease

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what are some causes of euthyroid hyper- or hypothyroxinemia (4)?

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1) acute/chronic illness; 2) alterations in binding proteins; 3) actions of drugs; 4) peripheral resistance to thyroid hormones

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what is the clinical problem?

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TSH and free T4 have reduced specificity for detecting thyroid dysfunction when patients are seriously ill, causing considerable diagnostic confusion

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what might low levels of total and free T3 result from?

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impaired conversion of T4 to T3 in peripheral tissues

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what may raised levels of serum free T3 indicate, in what patients?

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useful indicator of hyperthyroidism in a hospitalized patient

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what was said about normal or low T3 in these patients?

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does not rule out hyperthyroidism

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what is serum free T4 like normally in sick euthyroid syndrome?

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usually normal

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what can be used for confirmation when a free T4 immunoassay result is abnormal in a hospitalized patient?

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reflex total T4

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in severe illness, what may total serum T4 be like?

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low

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what should one be suspicious of, if there is a low total T4 in a patient not in intesive care?

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hypothyroidism

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what may be true if both total and freee T4 are abnormal, in the same direction?

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thyroid condition may be present

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what if the total and free T4 are discordant?

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thee free T4 abnormality is probably not due to thyroid dysfunction, but is more likely a result of the illness, medications, or an artifact of the test

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what medications (2) were said to directly inhibit pituitary TSH secretion?

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1) dopamine; 2) glucocorticoids

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what are serum TSH levels like in most euthyroid sick patients?

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normal

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what may serum TSH levels be like in acute illness?

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mildly suppressed

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when may TSH be elevated in NTI?

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during the recovery phase (transient rebound effect)

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what will TSH reference level be like in the hospitalized setting?

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widened (0.05 - 10.0 m/UL)

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what is the most useful test combination to detect thyroid dysfunction in a sick hospitalize patient?

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TSH plus free T4

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when should diagnostic testing be done, whenever possible?

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deferred until the illness has resolved

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what is the exception?

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when patient's history or clinical features suggest the presence of hyroid dysfunction

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THYROID CANCER

Front 111

what type of cancer is serum TSH considered a growth factor for?

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DTC (differentiated thyroid carcinoma)

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what test should suppress TSH to subnormal values?

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L-T4

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what happens ot serum TG following successful therapy of DC?

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falls to undetectable levels

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what does presence of Tg after thyroidectomy and ablation indicate?

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pathognomonic for the presence of residual or recurrent tumor

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what can interfere with immunoassays for Tg, and cause falsely low or high serum Tg values?

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TgAb

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what misjudgement of Tg (from TgAb) is a seroius concern?

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underestimation is particuarly serious, and has potential to mask metastatic disease

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what do serum measurements of TgAb have prognostic value for monitoring, and what levels indicate what problem?

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the treatment of TgAb DTC patients - increasing levels are often the earliest sign of residual or recurrent tumor

Front 118

what test is used to detect cells containing Tg mRNA, and what may this test be useful in doing?

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RT-PCR (reverse transcriptase PCR) - may help overcome limitations of current Tg/TgAb methods

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what is used to identify patients with familial medullary thyroid carcinoma?

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RET proto-oncogene analysis

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what other patients can be identified with this method?

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those with MEN II and III

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what is used less frequently to diagnose MTC?

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measurements of serum calcitonisn

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what is thyroid storm, how is it diagnosed, and what is the mortality (with treatment)?

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a life-threatening condition characterized by an exaggeration of the manifestations of thyrotoxicosis - diagnosis is clinically based, 30% mortality even with treatments

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what is myxedema coma, and when is treatment initiated?

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a life-threatening condition characterized by exaggerated hypothyroidism - treatment is initiated without waiting for lab reults