Thyroid Panel Flashcards
What are thyroid stimulating hormones used to differentiate? What are the normal values?
Used to diagnose primary hypothyroidism and differentiate it from secondary (pituitary) and tertiary (hypothalamus) hypothyroidism
TSH monitors exogenous thyroid replacement or suppression as well
Normal: 2-10 µU/mL
Where is TSH secreted from?
TSH is secreted by the pituitary gland
What causes the release of TSH?
stimulation by thyroid releasing hormone (TRH) from the hypothalamus
Low levels of triiodothyronine (T3) and thyroxine (T4) stimulate?
TRH and TSH
What is primary hypothyroidism?
condition in which a defect in the thyroid gland leads to reduced production of thyroid hormone.
TSH is high, low levels of triiodothyronine (T3) and thyroxine (T4) being produced.
What is secondary hypothyroidism?
the pituitary gland does not create enough TSH to induce the thyroid gland
What is tertiary hypothyroidism?
Results when the hypothalamus fails to produce sufficient TRH.
Explain the feedback loops involved with the thyroid
What is the goal of thyroid replacement therapy?
Goal of thyroid replacement is to provide enough thyroid medication so that TSH secretion is low normal, indicating a euthyroid state.
What is the goal of thyroid suppression and how is it achieved?
Goal of thyroid suppression is to completely suppress the thyroid gland and TSH secretion by providing excessive thyroid medication – this is used to decrease the size of a thyroid goiter.
Goal is to give enough medication to keep TSH less than 2 for replacement and even lower if thyroid suppression is the goal.
A decreased T4 and elevated or normal TSH can indicate what?
Thyroid disorder
A decreased T4 with a decreased TSH can indicate what?
Pituitary disorder
Interfering Factors of TSH
Recent radioisotope administration may affect test results
Severe illness may cause decreased TSH
Diurnal variation in TSH – basal levels at 10 AM while highest levels (2-3 times basal levels) at 10 PM
Drugs that increase levels include antithyroid meds, lithium, potassium iodide, and TSH injection
Drugs that decrease levels include aspirin, NSAIDS, steroids, and T3
Causes of increased levels of TSH
Primary hypothyroidism (thyroid dysfunction), thyroiditis, thyroid agenesis, congenital cretinism, large doses of iodine, radioactive iodine injection, surgical ablation of thyroid, severe and chronic illnesses – inadequate thyroid hormones stimulate release of TSH from anterior pituitary to cause TSH to rise
Pituitary TSH secreting tumor
Causes of decreased levels of TSH
Secondary or tertiary hypothyroidism due to pituitary or hypothalamus dysfunction, respectively – diseases of hypothalamus decrease secretion of TRH which is a major factor that determines TSH production and secretion. Diseases of the pituitary decrease production of TSH
Hyperthyroidism – increased levels of thyroid hormones inhibit release of TSH
Suppressive doses of thyroid medication
Factitious hyperthyroidism – patients take thyroid medication without a prescription
What does TSH stimulating test differentiate?
Used to differentiate between primary and secondary/tertiary hypothyroidism
How does the TSH stimulating test differentiate between primary and secondary or tertiary hypothyroidism?
Normal patients and patients with secondary/tertiary hypothyroidism can increase thyroid function when exogenous TSH is given.
Patients with primary hypothyroidism due to a diseased thyroid cannot increase thyroid function when TSH is given – their thyroid gland is inadequate and cannot function
What is the procedure for the TSH stimulating test?
obtain baseline levels of radioactive iodine uptake (RAIU) or T4. Administer TSH IM for 3 days. Repeat measurement of RAIU or T4
A Pt undergoing a TSH stimulating test has a 5% rise in RAIU and a 0.5 mcg/dL rise in T4. What type of hypothyroidism does this indicate?
Primary hypothyroidism
Patients with less than 10% increase in RAIU or less than a 1.5 mcg/dL rise in thyroxine (T4) have primary hypothyroidism
A Pt undergoing a TSH stimulating test has a 20% rise in RAIU. What type of hypothyroidism does this indicate?
Secondary or Tertiary
If the hypothyroidism is caused by inadequate pituitary secretion of TSH or hypothalamic secretion of TRH, the RAIU should increase by at least 10% and T4 levels should rise 1.5 mcg/dL or more
Causes of decreased levels in TSH stimulating test
Primary hypothyroidism, thyroiditis, thyroid agenesis, congenital cretinism, large doses of iodine, radioactive iodine injection, surgical ablation of thyroid, severe and chronic illnesses – thyroid is unable to increase T4 levels or RAIU
Causes of increased levels in TSH stimulating test
Secondary/tertiary hypothyroidism (pituitary or hypothalamus dysfunction) – thyroid is capable of producing T4 and RAIU, but the pituitary/hypothalamic stimulation is inadequate for appropriate stimulation, so when TSH is given, T4 and RAIU increase significantly
What does the Thyrotropin releasing hormone (TRH) evaluate?
Assists in evaluation of hyper- and hypothyroidism, especially hypo-
Also aids in detecting primary, secondary, and tertiary hypothyroidism
TRH test assesses the anterior pituitary gland by its secretion of TSH in response to an IV injection of TRH
A Pt has an IV bolus of TRH administered. The TSH is measured 30 minutes later and found to 1.2 times the baseline value. What does this indicate?
Hyperthyroidism
In hyperthyroidism, either a slight increase or no increase in TSH is seen because pituitary TSH production is suppressed by excess circulating thyroxine (T4) and triiodothyronine (T3)
Describe the procedure for performing a TRH test?
Give the patient an IV bolus of TRH. Measure their TSH 30 minutes later.
Normal is a prompt rise in TSH to twice the baseline value in 30 minutes.
A Pt has an IV bolus of TRH administered. The TSH is measured 30 minutes later and found to 4 times the baseline value. What does this indicate?
Primary hypothryoidism
In primary hypothyroidism (thyroid gland failure) the increase in the TSH level is two or more times the normal result
A Pt has an IV bolus of TRH administered. The TSH is measured 30 minutes later and found to be the same as the baseline value. What does this indicate?
Secondary hypothyroidism
In secondary hypothyroidism (anterior pituitary failure), no TSH response occurs
A Pt has multiple IV boli of TRH administered. The TSH is measured rises after the fourth dose. What does this indicate?
Tertiary hypothyroidism
Tertiary hypothyroidism (hypothalamic failure) may be diagnosed by a delayed rise in TSH, and multiple injections of TRH may be needed to induce the appropriate TSH response
Interfering factors of TRH test
Normal response may be exaggerated in women
Normal response may be less than expected in elderly
Pregnancy may increase the response
Drugs that may modify the TSH response include antithyroid drugs, aspirin, steroids, estrogen, and T4
What results indicate Hyperthryoidism from TRH test?
Hyperthyroidism – pituitary already is maximally suppressed by high levels of T3 and T4, so the pituitary response to TRH will be blunted and stimulated TSH levels will be less than double
What results indicate primary hypothryoidism from the TRH test?
Primary hypothyroidism (thyroid disease) – TSH is already stimulated by lack of T3 and T4, so stimulation will be maximized by TRH and stimulated TSH will be more than double the baseline
What results indicate Secondary hypothyroidism from the TRH test?
Secondary hypothyroidism (pituitary disease) – diseased pituitary unable to produce TSH, no matter how much the stimulation, so TSH will not double after TRH stimulation
What results indicate tertiary hypothryoidism from the TRH test?
Tertiary hypothyroidism (hypothalamus disease) – pituitary is functioning normally. If TRH is given, the pituitary will respond normally and produce twice the TSH level
How does psychiatric primary depression affect TSH?
Psychiatric primary depression – TSH response is blunted in most patients, whereas other types of depression have normal TRH induced TSH response.
What is Thyroxine Binding Globulin (TBG)?
The major thyroid hormone protein carrier
When is the TBG test used and what are the normal values?
Test is used in patients with abnormal total T3 and T4 levels
Normal range 1.7-3.6 mg/dL
Describe how TBG is measured
Assays of T4 and T3 measure the total of the bound and unbound thyroid hormones, most of which are bound to TBG.
The unbound hormone is metabolically active
What do increased TBG levels indicate?
With increased TBG levels, more hormone is bound to the protein so less free metabolically active hormone is available.
TSH is then stimulated to produce higher levels of thyroid hormones to compensate, so T3 and T4 levels increase but do not cause hyperthyroidism as the increase is just to compensate for the increased TBG
TBG interfering factors?
Previous administration of diagnostic radioisotopes
Drugs that increase TBG include estrogens, methadone, oral contraceptives, and tamoxifen
Drugs that decrease TBG include androgens, phenytoin, propranolol, and steroids
Causes of increased levels of TBG
Pregnancy, estrogen replacement therapy, estrogen producing tumors – all proteins are increased with increased estrogen
Infectious hepatitis
Genetic increase of TBG
Acute intermittent porphyria
Causes of decreased levels of TBG
Protein losing enteropathy, nephropathy, or malnutrition – decreased protein levels
Testosterone producing tumors – testosterone decreases TBG
Ovarian failure – reduced estrogens causes TBG to be reduced
Major stress
What is the Total T4 used for? What are the normal and critical values?
One of the first tests done for assessing thyroid function.
Used to diagnose and monitor thyroid replacement and suppressive therapy
Normal: 4-12 mcg/dL
Critical values
< 2 mcg/dL if myxedema coma is possible
> 20 mcg/dL if thyroid storm is possible
How are thyroid hormones formed?
Thyroid hormones are produced when tyrosine combines with iodine to form monoiodotyrosine. This complex picks up another iodine to become diiodotyrosine. Two of these combine to form tetraiodothyronine (T4). If a diiodotyrosine combines with a monoiodotyrosine, then triiodothyronine (T3) is formed.
What percent of thyroid hormone is T4?
T4 makes up ~90%
What protein binds most thyroid hormone?
Thyroxine binding globulin (TBG) binds most of the thyroid hormone with a little binding to albumin and prealbumin
Interfering factors of Total T4
T4 levels increase after iodinated contrast x-ray studies
Pregnancy increases levels
Drugs that increase levels include amphetamines, estrogens, heroin, iodinated contrast media, iodine, methadone, oral contraceptives
Drugs that decrease levels include anabolic steroids, androgens, anti-inflammatories, antithyroid drugs (PTU), barbiturates, furosemide, lithium, phenytoin, propranolol
Causes of increased Total T4
Familial dysalbuminemic hyperthyroxinemia – genetically defective form of albumin that binds tightly to T4 so the bound form is increased. Patient is not hyperthyroid as the protein bound T4 is not active
TBG increase (pregnancy, hepatitis, congenital hyperproteinemia) – assay measures both the bound and unbound so an elevated TBG will cause an elevation of T4
Primary hyperthyroid states (Grave’s disease, toxic thyroid adenoma) – increased T4 despite lack of TSH stimulation
Acute thyroiditis – thyroid secretes increased T4 during acute inflammatory stages, but in latter stages the thyroid may become burned out and the patient will develop hypothyroidism
Factitious hyperthyroidism – patients who self-administer thyroxine will have elevated levels
Struma ovarii – ectopic thyroid tissue in ovary or anywhere else produces excess T4
Causes of decreased Total T4
Protein malnutrition and other protein depleted states (nephrotic syndrome) – TBG and albumin decrease
Hypothyroid states (cretinism, surgical ablation, myxedema) – Thyroid cannot produce adequate T4 despite stimulation
Pituitary insufficiency – Insufficient TSH produced
Hypothalamic failure – Insufficient TRH produced
Iodine insufficiency – iodine is the basic raw material for T4. T4 cannot be produced without it. Very rare with iodine in table salt
Nonthyroid illnesses (renal failure, Cushing disease, cirrhosis, surgery, advanced cancer)
What is the Free T4 test used for? What are the normal values?
FT4 evaluates thyroid function in patients with protein abnormalities that could affect the total T4 levels.
Used to diagnose thyroid function and monitor replacement and suppressive therapy.
Normal: 0.8-2.8 ng/dL
Greater than normal levels indicate hyperthyroid states and low levels are seen in hypothyroid states
What % of T4 is not bound (free)?
1-5%
In a patient with a low Total T4 and a possibility of hypoproteinemia, what test should you run to confirm hypothyroidism?
Free T4
If the Free T4 is normal they do not have hypothyroidism
Interfering factors for Free T4
Exogenously administered thyroxine will cause elevated FT4 results
Drugs that increase FT4 include aspirin, heparin, and propranolol
Drugs that decrease FT4 levels include furosemide, phenytoin, and methadone.
Causes of increased levels of Free T4
Primary hyperthyroid states (Grave’s disease, toxic thyroid adenoma) – increased T4 despite lack of TSH stimulation
Acute thyroiditis – thyroid secretes increased T4 during acute inflammatory stages, but in latter stages the thyroid may become burned out and the patient will develop hypothyroidism
Factitious hyperthyroidism – patients who self-administer thyroxine will have elevated levels
Struma ovarii – ectopic thyroid tissue in ovary or anywhere else produces excess T4
Causes of decreased levels of Free T4
- *Hypothyroid states** (cretinism, surgical ablation, myxedema) –
- *Thyroid cannot produce adequate T4** despite stimulation
Pituitary insufficiency – Insufficient TSH produced
Hypothalamic failure – Insufficient TRH produced
Iodine insufficiency – iodine is the basic raw material for T4. T4 cannot be produced without it. Very rare with iodine in table salt
Nonthyroid illnesses (renal failure, Cushing disease, cirrhosis, surgery, advanced cancer)
What is the Free Thyroxine index (FTI) used for? What are the normal values?
Used to diagnose hyper- and hypothyroidism
FTI corrects for changes in thyroid hormone binding serum proteins that can affect total T4 levels
Normal 0.8-2.4 ng/dL
What is the formula used to calculate FTI?
FTI = (T3 uptake) X (measured T4 )
A patient presents with hyperproteinemia, would this affect the FTI result?
NO
FTI is not affected by thyroxine binding globulin (TBG) abnormalities so correlates more closely with the true hormonal status than total T4 or T3 measurements
High FTI suggests?
Hyperthyroidism
Low FTI suggests?
hypothyroidism
Causes of increased FTI
Primary hyperthyroid states (Grave’s disease, toxic thyroid adenoma) – increased T4 despite lack of TSH stimulation
Acute thyroiditis – thyroid secretes increased T4 during acute inflammatory stages, but in latter stages the thyroid may become burned out and the patient will develop hypothyroidism
Factitious hyperthyroidism – patients who self-administer thyroxine will have elevated levels
Struma ovarii – ectopic thyroid tissue in ovary or anywhere else produces excess T4
Causes of decreased FTI
Hypothyroid states (cretinism, surgical ablation, myxedema) –
Thyroid cannot produce adequate T4 despite stimulation
Pituitary insufficiency – Insufficient TSH produced
Hypothalamic failure – Insufficient TRH produced
Iodine insufficiency – iodine is the basic raw material for T4. T4 cannot be produced without it. Very rare with iodine in table salt
Nonthyroid illnesses (renal failure, Cushing disease, cirrhosis, surgery, advanced cancer)
What is the Triiodothyronine (T3) test used for? What are the normal values?
There is an overlap between hypothyroid and normal thyroid states, so T3 levels are mainly used in diagnosing hyperthyroid states.
An elevated T3 indicates hyperthyroidism, especially when T4 is also elevated
Normal range approximately 70-205 ng/dL
If decreased, the patient is hypothyroid
How is T3 formed?
A large portion of T3 is formed in the liver by conversion from T4 .
Which hormone is more stable: T3 or T4?
T4
T3 is less stable than T4 because it is less tightly protein bound
Interfering factors of Triiodothyronine test
Radioisotope administration before the test may alter results
Total T3 is increased in pregnancy because serum proteins are increased. Free T3 is not affected by protein levels
Drugs that cause increased levels include estrogen, methadone, and oral contraceptives
Drugs that decrease levels include anabolic steroids, androgens, phenytoin, propranolol, salicylates
Causes of increased Triiodothyronine
TBG increase (pregnancy, hepatitis, congenital hyperproteinemia)
Primary hyperthyroid states (Grave’s disease, toxic thyroid adenoma) – increased T4 despite lack of TSH stimulation
Acute thyroiditis – thyroid secretes increased T4 during acute inflammatory stages, but in latter stages the thyroid may become burned out and the patient will develop hypothyroidism
Factitious hyperthyroidism – patients who self-administer thyroxine will have elevated levels
Struma ovarii – ectopic thyroid tissue in ovary or anywhere else produces excess T4
Causes of decreased Triiodothyronine
Protein malnutrition and other protein depleted states (nephrotic syndrome)
Hepatic diseases – liver dysfunction may affect T3 levels due to decreased conversion of T4 to T3
Hypothyroid states (cretinism, surgical ablation, myxedema) –
Thyroid cannot produce adequate T4 despite stimulation
Pituitary insufficiency – Insufficient TSH produced
Hypothalamic failure – Insufficient TRH produced
Iodine insufficiency – iodine is the basic raw material for T4. T4 cannot be produced without it. Very rare with iodine in table salt
Nonthyroid illnesses (renal failure, Cushing disease, cirrhosis, surgery, advanced cancer)
How is T3 uptake measured?
Radioactive T3 (RT3 ) is added to patient’s serum along with hormone binding resin.
The lower the T4 , the more RT3 binds on the serum proteins and less on the hormone binding resin. The higher the T4 , the less RT3 can bind to serum proteins and more is available to bind to the resin.
This also depends on the amount of TBG. As TBG increases, the T3 uptake will decrease and as the TBG decreases the T3 uptake will increase assuming T4 stays the same.
Therefore, T4 and T3 uptake must be measured together.
What is T3 uptakes used for? What is the normal range?
Indirect measurement of T4
Normal 24-34%
Interfering factors of T3 uptake
Pregnancy, oral contraceptives, and some genetic disorders cause increased TBG so the thyroid hormone levels may be falsely elevated with normal thyroid function.
Androgens, serious illness, and nephrotic syndrome will lower these proteins causing falsely low thyroid hormones.
Recent radioisotope scans may affect test results
Severe acidosis may increase T3 uptake
Drugs that increase TBG levels include anabolic steroids, heparin, phenytoin, salicylates, thyroid agents, and warfarin
Drugs that decrease levels include antithyroid agents, estrogen, oral contraceptives, and thiazides
Causes of increased leves of T3 uptake
Hyperthyroidism
Hypoproteinemia – fewer TBG binding sites are available for the RT3 , which will bind an increased percentage of resin sites
Familial dysalbuminemic hyperthyroxinemia – defective form of albumin binds T4 tightly so fewer binding sites are available for RT3
Non-thyroid illnesses (renal failure, Cushing disease, cirrhosis, surgery, advanced cancer)
Factitious hyperthyroidism – self-administration of T4 will cause elevated levels so fewer TBG binding sites are available for RT3
Struma ovarii – ectopic thyroid tissue produces excess T4
Causes of decreaed T3 uptake levels
Increase in TBG – more protein binding sites are available for RT3 , so less is bound to resin
Hypothyroid states – inadequate T4 is produced, so levels are decreased
Hepatitis and cirrhosis – have elevated TBG
