Thyroid for Dummies (10 page)

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Part I: Understanding the Thyroid

Checking Blood Levels

of Thyroid Hormones

Numerous blood tests are available to measure thyroid function, but the most accurate and sensitive tests for determining thyroid function are the
free thyroxine
(FT4) and the
thyroid-stimulating hormone
(TSH) tests, both of which are described in this section. (Free thyroxine is the tiny portion of thyroid hormone in the blood that is not bound to protein and is therefore free to enter your cells; refer to Chapter 3.) The vast majority of people are accurately diagnosed with these tests. If you’re undergoing screening for thyroid function and your doctor wants to order just one test to start, that test is usually the TSH due to its accuracy and the fact that it’s a simple blood test.

Many doctors practising today learned about thyroid disease years ago, when only older tests were available, and they still use them. Just in case your doctor orders such tests or in case you have copies of old test results that you want to understand, this section also explains how some of the older tests work.

Total thyroxine

The
total thyroxine
or
TT4
test (sometimes called the
T4 immunoassay
) measures all the T4 thyroid hormone in a given quantity of blood. But, most of the hormone measured (more than 99 per cent) is inactive because it is bound to protein (refer to Chapter 3). So, by itself, this test does not tell you how much thyroid activity is present. This test can only give a more accurate picture of active thyroid hormone function if the test is combined with a test that measures what per cent of the total thyroxine is bound and what per cent is free.

Seeing what raises TT4

The total thyroxine test is also deceiving at times. Many drugs and clinical states raise the level of TT4 in your blood, by raising the amount of thyroxine-binding protein present, although they don’t impact the amount of free thyroxine. Some of the drugs that can raise the level of TT4 in your blood include: ߜ
Oestrogen hormones:
Used in hormone replacement therapy (HRT) and the oral contraceptive pill

ߜ
Amiodarone:
A drug used for the heart

ߜ
Amphetamines:
Stimulant drugs

ߜ
Methadone:
An opiate drug

ߜ
Phenothiazines:
A class of drugs used to treat some psychiatric conditions, such as schizophrenia

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Some clinical states that raise TT4 levels include:

ߜ High oestrogen states, such as pregnancy

ߜ Acute illness, such as AIDS or hepatitis

ߜ Acute psychiatric problems

Understanding what lowers TT4

Conversely, some drugs and physical conditions tend to lower the results of a TT4 test by reducing the amount of thyroxine-binding protein you make, without affecting the amount of free thyroxine in your circulation. The drugs that have this impact include:

ߜ
Androgens:
Male hormones taken to build muscle ߜ
Corticosteroids:
Usually given to reduce inflammation ߜ
Nicotinic acid:
Given to lower harmful blood fats Physical conditions that can lower TT4 levels include: ߜ Severe chronic illness, such as kidney failure or liver failure ߜ Starvation or severe malnutrition

Some medicines, such as non-steroidal anti-inflammatory drugs (NSAIDs), phenytoin (used to treat epilepsy), and aspirin, can also displace thyroid hormones from their binding proteins to reduce the total but not the free thyroid hormone concentrations, once a new steady state is reached. So, if thyroid status is tested in someone taking one of these drugs who isn’t in a steady state with their treatment (perhaps because they recently started therapy or the dose was recently changed) the results are misleading.

Looking at what’s normal for TT4

The normal range of TT4 is usually around 60–160 nmol/L (nanomoles per litre) of blood.

Different laboratories may use different techniques to perform the same test, resulting in slightly different normal values. Even when they use the same technique, slight variations in the normal values often appear from lab to lab.

Each lab uses its own reference group of people without thyroid disease who act as guinea pigs for the lab to draw up their normal range. Most test result sheets include the laboratory’s reference range next to the person’s own individual blood test result, which makes interpreting what’s happening easier.

With the availability of reliable tests for free T4, the justification for laboratories to continue using the TT4 test is diminishing.

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Part I: Understanding the Thyroid

How the resin T3 uptake is done

When radioactive T3 or T4 is mixed with your

expressed as the per cent of radioactivity found

blood in a test tube, it combines with the binding

on the resin, compared to the original radioac-

sites on the thyroxine-binding proteins. Your

tivity that was added. The more binding sites

blood is then exposed to a substance called a

available on your proteins, the lower the resin

resin that binds the unbound T3 or T4, and the

uptake result, and vice versa.

resin is measured for radioactivity. The result is

If your doctor chooses to use the total thyroxine test to monitor your thyroid function, however, he first makes certain that you aren’t taking any of the drugs or experiencing any of the physical conditions listed in this section. In addition, your doctor must also order the next test, the resin T3 uptake, to get a complete picture of how much of the total T4 measured is tied up to protein, and how much remains free and active in your circulation.

Resin T3 uptake

The
resin T3 uptake
test is now virtually obsolete. This test measures whether your thyroxine-binding proteins have a lot of spare sites for T3 hormone (active thyroid hormone) to bind on to. This occurs when the TT4 is low (and therefore taking up very few of the sites) or when the binding protein levels are very high.

The effect of any of the drugs or physical conditions that reduce the binding sites (flip back to the section ‘Understanding what lowers TT4’) – thus, causing a low TT4 measurement – leaves very few binding sites for any more thyroid hormone to bind to. If T3 is added to a sample of that blood, little T3 can bind, leaving a lot of measurable free T3. The resin T3 uptake is therefore high. Any of the drugs or clinical states that raise the binding sites (refer back to the section ‘Seeing what raises TT4’) – thus, causing an increased TT4 level –

also leaves a lot of binding sites available for added T3. The amount of free T3

measured is then low, giving a decreased resin T3 uptake. The usual result of a resin T3 uptake is 25–35 per cent depending on the laboratory.

Free thyroxine index

As the previous sections discuss, the total thyroxine (TT4) test and the resin T3

uptake are used together for greatest value, as several drugs and physical conditions can alter the results of the TT4 test (and also alter the resin T3 uptake results). The impact of such drugs and physical conditions always affects the TT4 and resin T3 uptake results in opposite directions: If the TT4 is depressed, then the resin T3 uptake is high; if the TT4 is elevated, the resin T3 uptake is low.

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To help wrap these findings up in one useful result, doctors multiply the TT4 level by the resin T3 uptake. The result is called the
free thyroxine index
(FT4I)
and, depending on the laboratory, the normal range is around 20–63 on the index. A result below the usual reference range for a laboratory indicates low thyroid function, while a result above the usual reference range indicates increased thyroid function.

Even when you are taking one of the drugs or experiencing one of the physical conditions listed in the ‘Total thyroxine’ section, the free thyroxine index is within the normal range if your thyroid is functioning normally.

Free thyroxine (FT4)

The
free thyroxine
(FT4 or sometimes fT4) test is the best way to measure the amount of free thyroid hormone in your blood. This test measures the 0.03

per cent of T4 that is not bound to protein – the T4 that is free to interact with your cells (refer to Chapter 2). All the factors that can change the amount of total thyroxine in your system, such as the drugs and physical conditions listed earlier in this chapter, do not affect the amount of FT4 in your blood. Depending upon the test method that is used by the particular laboratory, the usual FT4 level is around 9.0 to 25 pmol/L (picomols per litre).

The level of FT4 in your blood is high if you have hyperthyroidism and low if you have hypothyroidism. (As Chapter 6 explains in more detail, in rare cases, a person with hyperthyroidism has too much T3 rather than too much T4 in his blood. In these rare instances, an FT4 test could come back normal or even low.) The FT4 is not a perfect test, because certain conditions do arise that make the FT4 level appear abnormal when the patient actually has normal thyroid function. Fortunately, these conditions are easily recognised. They include the following:

ߜ Having severe chronic illness (not thyroid disease), such as kidney or liver failure, may slightly decrease FT4.

ߜ Producing or ingesting large amounts of T3 – through excessive thyroid medication, for example – decreases FT4.

ߜ Having a rare condition, often hereditary such as one of the rare inherited conditions discussed in Chapter 17, in which there is a resistance to T4, causing high levels of FT4 in someone who is not yet hyperthyroid.

ߜ Receiving the drug heparin to prevent blood clotting may slightly increase FT4.

ߜ Having an acute illness, such as AIDS or hepatitis, may briefly elevate FT4 as binding proteins suddenly fall.

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Part I: Understanding the Thyroid

Free triiodothyronine (FT3)

The
free triiodothyronine (FT3)
test measures the free T3 hormone in the blood. This test is rarely necessary, except in the situation where a person is obviously hyperthyroid, yet their FT4 test result is normal. The usual level of FT3 is 3.5 to 7.7 pmol/L (picomols per litre). Someone with hyperthyroidism has a high FT3 result, while a person with hypothyroidism has a low FT3 value.

Thyroid-stimulating hormone (TSH)

In most circumstances, the
thyroid-stimulating hormone (TSH)
test is the most sensitive test of thyroid function. The body’s own negative feedback system means that TSH rises when the T4 level in the blood falls, and the TSH falls when the T4 rises (refer to Chapter 3). The assays that measure TSH are among the most accurate clinical techniques currently available, making them a reliable test to measure thyroid function. If you have hyperthyroidism, your TSH level is low (because TSH production is suppressed by the high level of T4 in your blood). If you have hypothyroidism, your TSH level is high (because your body is trying to stimulate production of more T4).

Seeing what lowers TSH levels

Many different conditions can cause a reduction in your TSH level, and having a low TSH does not necessarily mean that you have hyperthyroidism. The factors that can decrease your TSH include:

ߜ Receiving excessive treatment with T3 or T4 hormone ߜ Developing thyroid nodules, which make excessive T3 or T4 (see Chapter 6)

ߜ During the first three months of pregnancy. (A hormone called
human
chorionic gonadotrophin
is produced during this time, which has TSH-like properties and stimulates the production of T4, thereby suppressing TSH.) ߜ Suffering from the cancers known as
choriocarcinoma
or molar pregnancy, both of which are associated with the production of large amounts of the hormone, human chorionic gonadotrophin

ߜ Having a pituitary tumour that destroys TSH producing cells ߜ Developing Euthyroid (normal thyroid function) Graves’ disease, where hyperthyroidism is present in the thyroid but the thyroid is not making levels of T4 that are excessive (see Chapter 5)

ߜ Suffering from acute depression

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Understanding what raises TSH levels

Several conditions can cause an increase in your TSH level, even if your thyroid is not underactive. The following conditions have to be considered when a high TSH is found:

ߜ Presence of a pituitary tumour involving the cells that make TSH

ߜ Recovery from a severe illness

ߜ Insufficient dietary iodine

ߜ Resistance to the action of T4

ߜ Failure of the adrenal gland to make adrenal hormone ߜ Psychiatric illness

Looking at what’s normal for TSH

Depending on the particular laboratory doing the test, a normal TSH level is 0.3–4.5 µU/ml (microunits per millilitre).

Many of the conditions listed in this section are temporary, meaning that a person’s TSH levels return to normal in time. Other conditions, such as a pituitary tumour, require action (in this case, the removal of the tumour) to restore the TSH to its normal level.

Sometimes, a condition that suppresses production of TSH, such as hyperthyroidism, produces a low TSH level for a period of time even after you’ve returned to a normal metabolic state with treatment. The FT4 is normal, but the TSH remains low. This instance is one occasion when the TSH is not a reliable guide to thyroid function, so the FT4 is used instead.

After your doctor establishes a diagnosis for a thyroid problem, you may have repeated TSH tests during the course of your treatment to monitor your progress. If you are having treatment for hyperthyroidism, however, repeated TSH tests are not always the most effective way to monitor progress, because your TSH may not recover for a long time after your metabolism returns to normal.