Thyroid Panel

Question 1

What are thyroid stimulating hormones used to differentiate? What are the normal values?

Answer 1

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

Question 2

Where is TSH secreted from?

Answer 2

TSH is secreted by the pituitary gland

Question 3

What causes the release of TSH?

Answer 3

stimulation by thyroid releasing hormone (TRH) from the hypothalamus

Question 4

Low levels of triiodothyronine (T3) and thyroxine (T4) stimulate?

Answer 4

TRH and TSH

Question 5

What is primary hypothyroidism?

Answer 5

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.

Question 6

What is secondary hypothyroidism?

Answer 6

the pituitary gland does not create enough TSH to induce the thyroid gland

Question 7

What is tertiary hypothyroidism?

Answer 7

Results when the hypothalamus fails to produce sufficient TRH.

Question 8

Explain the feedback loops involved with the thyroid

Answer 8

Question 9

What is the goal of thyroid replacement therapy?

Answer 9

Goal of thyroid replacement is to provide enough thyroid medication so that TSH secretion is low normal, indicating a euthyroid state.

Question 10

What is the goal of thyroid suppression and how is it achieved?

Answer 10

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.

Question 11

A decreased T4 and elevated or normal TSH can indicate what?

Answer 11

Thyroid disorder

Question 12

A decreased T4 with a decreased TSH can indicate what?

Answer 12

Pituitary disorder

Question 13

Interfering Factors of TSH

Answer 13

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

Question 14

Causes of increased levels of TSH

Answer 14

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

Question 15

Causes of decreased levels of TSH

Answer 15

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

Question 16

What does TSH stimulating test differentiate?

Answer 16

Used to differentiate between primary and secondary/tertiary hypothyroidism

Question 17

How does the TSH stimulating test differentiate between primary and secondary or tertiary hypothyroidism?

Answer 17

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

Question 18

What is the procedure for the TSH stimulating test?

Answer 18

obtain baseline levels of radioactive iodine uptake (RAIU) or T4. Administer TSH IM for 3 days. Repeat measurement of RAIU or T4

Question 19

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?

Answer 19

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

Question 20

A Pt undergoing a TSH stimulating test has a 20% rise in RAIU. What type of hypothyroidism does this indicate?

Answer 20

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

Question 21

Causes of decreased levels in TSH stimulating test

Answer 21

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

Question 22

Causes of increased levels in TSH stimulating test

Answer 22

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

Question 23

What does the Thyrotropin releasing hormone (TRH) evaluate?

Answer 23

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

Question 24

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?

Answer 24

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)

Question 25

Describe the procedure for performing a TRH test?

Answer 25

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.

Question 26

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?

Answer 26

**Primary hypothryoidism** In primary hypothyroidism (thyroid gland failure) the increase in the TSH level is two or more times the normal result

Question 27

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?

Answer 27

**Secondary hypothyroidism** In secondary hypothyroidism (anterior pituitary failure), no TSH response occurs

Question 28

A Pt has multiple IV boli of TRH administered. The TSH is measured rises after the fourth dose. What does this indicate?

Answer 28

**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

Question 29

Interfering factors of TRH test

Answer 29

Normal response may be exaggerated in **women** Normal response may be less than expected in **elderly** **Pregnanc**y may increase the response **Drugs** that may modify the TSH response include antithyroid drugs, aspirin, steroids, estrogen, and T4

Question 30

What results indicate Hyperthryoidism from TRH test?

Answer 30

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

Question 31

What results indicate primary hypothryoidism from the TRH test?

Answer 31

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

Question 32

What results indicate Secondary hypothyroidism from the TRH test?

Answer 32

Secondary hypothyroidism (pituitary disease) – diseased pituitary unable to produce TSH, no matter how much the stimulation, so TSH will not double after TRH stimulation ## Footnote

Question 33

What results indicate tertiary hypothryoidism from the TRH test?

Answer 33

Tertiary hypothyroidism (hypothalamus disease) – pituitary is functioning normally. If TRH is given, the pituitary will respond normally and produce twice the TSH level

Question 34

How does psychiatric primary depression affect TSH?

Answer 34

Psychiatric primary depression – TSH response is blunted in most patients, whereas other types of depression have normal TRH induced TSH response.

Question 35

What is Thyroxine Binding Globulin (TBG)?

Answer 35

The major thyroid hormone protein carrier

Question 36

When is the TBG test used and what are the normal values?

Answer 36

Test is used in patients with abnormal total T3 and T4 levels Normal range 1.7-3.6 mg/dL

Question 37

Describe how TBG is measured

Answer 37

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

Question 38

What do increased TBG levels indicate?

Answer 38

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

Question 39

TBG interfering factors?

Answer 39

**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

Question 40

Causes of increased levels of TBG

Answer 40

**Pregnancy, estrogen replacement therapy, estrogen producing tumors** – all proteins are increased with increased estrogen **Infectious hepatitis** **Genetic increase of TBG** **Acute intermittent porphyria**

Question 41

Causes of decreased levels of TBG

Answer 41

**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**

Question 42

What is the Total T4 used for? What are the normal and critical values?

Answer 42

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

Question 43

How are thyroid hormones formed?

Answer 43

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.

Question 44

What percent of thyroid hormone is T4?

Answer 44

T4 makes up ~90%

Question 45

What protein binds most thyroid hormone?

Answer 45

**Thyroxine binding globulin (TBG)** binds most of the thyroid hormone with a little binding to albumin and prealbumin

Question 46

Interfering factors of Total T4

Answer 46

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

Question 47

Causes of increased Total T4

Answer 47

**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

Question 48

Causes of decreased Total T4

Answer 48

**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)

Question 49

What is the Free T4 test used for? What are the normal values?

Answer 49

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

Question 50

What % of T4 is not bound (free)?

Answer 50

1-5%

Question 51

In a patient with a low Total T4 and a possibility of hypoproteinemia, what test should you run to confirm hypothyroidism?

Answer 51

Free T4 If the Free T4 is normal they do not have hypothyroidism

Question 52

Interfering factors for Free T4

Answer 52

**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.

Question 53

Causes of increased levels of Free T4

Answer 53

**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

Question 54

Causes of decreased levels of Free T4

Answer 54

* *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)

Question 55

What is the Free Thyroxine index (FTI) used for? What are the normal values?

Answer 55

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**

Question 56

What is the formula used to calculate FTI?

Answer 56

FTI = (T3 uptake) X (measured T4 )

Question 57

A patient presents with hyperproteinemia, would this affect the FTI result?

Answer 57

**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

Question 58

High FTI suggests?

Answer 58

Hyperthyroidism

Question 59

Low FTI suggests?

Answer 59

hypothyroidism

Question 60

Causes of increased FTI

Answer 60

**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

Question 61

Causes of decreased FTI

Answer 61

**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)

Question 62

What is the Triiodothyronine (T3) test used for? What are the normal values?

Answer 62

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

Question 63

How is T3 formed?

Answer 63

A large portion of T3 is formed in the liver by conversion from T4 .

Question 64

Which hormone is more stable: T3 or T4?

Answer 64

T4 T3 is less stable than T4 because it is less tightly protein bound

Question 65

Interfering factors of Triiodothyronine test

Answer 65

**Radioisotope administration** before the test may alter results **Total T3 is increased in pregnanc**y 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

Question 66

Causes of increased Triiodothyronine

Answer 66

**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

Question 67

Causes of decreased Triiodothyronine

Answer 67

**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)

Question 68

How is T3 uptake measured?

Answer 68

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.

Question 69

What is T3 uptakes used for? What is the normal range?

Answer 69

Indirect measurement of T4 Normal 24-34%

Question 70

Interfering factors of T3 uptake

Answer 70

**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

Question 71

Causes of increased leves of T3 uptake

Answer 71

**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

Question 72

Causes of decreaed T3 uptake levels

Answer 72

**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