DIFFICULTIES IN LAB. DIFFICULTIES IN LAB. DIAGNOSIS OF DIAGNOSIS OF THYROID DISEASETHYROID DISEASE

ByByProf. Moustafa RizkProf. Moustafa Rizk

Prof. of Clinical PathologyProf. of Clinical PathologyFaculty of Medicine, University of AlexandriaFaculty of Medicine, University of Alexandria..

Common Thyroid Problems

[1] Those concerning the production of hormone (too much, or too little) . [2] Those due to increased growth of the thyroid causing compression of important neck structures or simply appearing as a mass in the neck. [3] The formation of nodules or lumps within the thyroid which are worrisome for the presence of thyroid cancer. [4] Those which are cancerous.

Common Tests to Examine Thyroid Gland Function

No one single laboratory test is 100% accurate in diagnosing all types of thyroid disease; however,a combination of two or more tests can usually detect even the slightest abnormality of thyroid function

Total T4 For example, a low

T4 level could mean a diseased thyroid gland or a non-functioning pituitary gland which is not stimulating the thyroid to produce T4.

Total T4

Since the pituitary gland would normally release TSH if the T4 is low, a high TSH level would confirm that the thyroid gland (not the pituitary gland) is responsible for the hypothyroidism, a condition sometimes called primary hypothyroidism.

Total T4

If the T4 level is low and TSH is not elevated, the pituitary gland is more likely to be the cause for the hypothyroidism.

Total T4

Elevation or decrease in serum T4 may be due to change in TBG level and not reflect clinical hyperthyroidism or hypothyroidism.

Total T4T4 levels may be elevated with increased

concentrations of TBG:

Administration of oral contraceptives Pregnancy Infectious and chronic active hepatitis Biliary cirrhosis Congenital increase in TBG levels.

Total T4T4 may be reduced when TBG levels

are decreased: Nephrotic syndrome, Androgen therapy Glucocorticoid therapy Major systemic illness Congenital decrease of TBG

Total T4

Drugs which compete for protein binding sites, such as phenylbutazone, diphenylhydantoin or salicylates, can result in a depressed T4 measurement.

Serum T4 levels in neonates and infants are higher than values in the normal adult, due to the increased concentration of TBG in neonate serum.

Thyroid Binding Globulin

If a patient appears to have normal thyroid function, but an unexplained high or low T4, or T3, it may be due to an increase or decrease of TBG. Direct measurement of TBG can be done and will explain the abnormal value.

Free Thyroxine Index

T4 values should be normalized for individual variations in thyroxine binding protein (TBP) capacity. The Free Thyroxine Index (FTI) is conventionally used to achieve this measurement

Free Thyroxine Index

The Free thyroxine index is a calculation we used to do before the FT4 test came out on the market. By measuring serum total T4 and the T3 uptake we were able to figure out how much of the free T4 was bound and how much was free, so it was sort of a “prediction" of how much FT4 was available.

Free Thyroid Hormone

Since only the free or non-TBG bound T4 results in clinical changes in the patient, it is best to measure the Free-T4 rather than the total T4.

Free Thyroid Hormone

Free T3 and Free T4 levels are the only accurate measure of the actual active thyroid hormone levels in the blood.

It is relatively common to find the Free T4 and Free T3 hormone levels below normal when TSH is in its normal range, even in the low end of its normal range.

When patients with these lab values are treated, tremendous improvement , and a reduction of the classic hypothyroid symptoms

Free Thyroid Hormone

FT3 is typically elevated to a greater degree than free T4 (FT4) in Graves' disease and in toxic adenomas. In contrast, levels of FT4 are elevated to a greater degree than FT3 in toxic multinodular goiter and excessive T4 therapy.

FT3 is useful in distinguishing these forms of hyperthyroidism.

FT3 may also be important in monitoring patients on antithyroid therapy, where treatment is focused on reducing the T3 production and the T4 conversion to T3.

Old Laboratory Tests Unreliable Most all older thyroid function panels

include the following: Total T4 T3 Uptake (a count of the proteins

that bind up  both T4 and T3) Free Thyroxine Index (FTI).

These tests should be abandoned because they are unreliable as gauges of thyroid function .

Total T3

Thyroxine (T4) represents 80% of the thyroid hormone produced by the normal gland and generally represents the overall function of the gland. The other 20% is triiodothyronine measured as T3 by immunoassay.

Sometimes the diseased thyroid gland will start producing very high levels of T3 but still produce normal levels of T4.

Total T3

Clinically, measurements of serum T3 concentration are especially valuable in diagnosing hyperthyroidism and in following the course of therapy for this disorder .

Total T3 measurements may be valuable when hyperthyroidism is suspected and the free T4 estimate is normal.

Total T3

Dietary iodide deficiency results in inadequate production of thyroid hormones despite the presence of normal thyroid tissue.

In these cases, the serum T4 concentration is often low, while the TSH concentration is elevated. However, in iodine deficiency, these results, together with a normal or slightly elevated serum T3, are indicative of euthyroid status in most individuals.

TSH

When the thyroid gland becomes inefficient such as in early hypothyroidism, the TSH becomes elevated even though the T4 and T3 may still be within the "normal" range.

This rise in TSH represents the pituitary gland's response to a drop in circulating thyroid hormone; it is usually the first indication of thyroid gland failure.

How is it used? 

diagnose a thyroid disorder in a person with symptoms,

screen healthy adults for thyroid disorders as recommended by the American Thyroid Association,

screen newborns for an underactive thyroid,  monitor thyroid replacement therapy in people

with hypothyroidism diagnose and monitor female infertility problems.  

TSH

A high TSH result often means an underactive thyroid gland caused by failure of the gland (hypothyroidism).

Rarely, a high TSH result can indicate a problem with the pituitary gland, such as a tumor, in what is known as secondary hyperthyroidism.

A high TSH value can also occur in people with underactive thyroid glands who have been receiving too little thyroid hormone medication.

TSH

A low TSH result can indicate an overactive thyroid gland (hyperthyroidism).

A low TSH result can also indicate damage to the pituitary gland that prevents it from producing TSH.

A low TSH result can also occur in people with an underactive thyroid gland who are receiving too much thyroid hormone medication.

TSH

When the doctor adjusts the dose of thyroid hormone , The patient must wait at least one to two months before he goes to lab to check his TSH again, so that his new dose can have its full effect.

TRH Test

A baseline TSH of 5 or less usually goes up to 10-20 after giving an injection of TRH.

Patients with too much thyroid hormone (thyroxine or triiodothyronine) will not show a rise in TSH when given TRH.

TRH Test

Patients who show too much response to TRH (TSH rises greater than 40) may be hypothyroid.

This test is also used patients who are taking thyroid replacement to see if they are on sufficient medication.

It is sometimes used to measure if the pituitary gland is functioning.

Is there is a need to stop taking thyroid pills for

these tests?

Most thyroid pills have a half life of 7 days which means they must be stopped for four weeks (five half lives) before accurate thyroid testing is possible.

Thyroid Antibodies

Some people are found to have antibodies against their own thyroid tissue. A condition known as Hashimoto's Thyroiditis is associated with a high level of these thyroid autoantibodies in the blood. Whether the antibodies cause the disease or whether the disease causes the antibodies is not known

Common Thyroid Diseases

1- Hypothyroidism 2- Hyperthyroidism 3- Goiters

5-Solitary Thyroid Nodules,

4-Thyroiditis

6-cancer

1-Hypothyroidism Hypothyroidism is a

condition in which the body lacks sufficient thyroid hormone. Hypothyroidism is more common than you would believe...and, millions of people are currently hypothyroid and don't know it

There are two fairly common causes of

hypothyroidism. The first is a result of previous (or currently

ongoing) inflammation of the thyroid gland which leaves a large percentage of the cells of the thyroid damaged (or dead) and incapable of producing sufficient hormone. The most common cause of thyroid gland failure is called autoimmune thyroiditis (also called Hashimoto's thyroiditis), a form of thyroid inflammation caused by the patient's own immune system.

The second major cause is the broad category of "medical treatments". The treatment of many thyroid conditions warrants surgical removal of a portion or all of the thyroid gland. If the total mass of thyroid producing cells left within the body are not enough to meat the needs of the body, the patient will develop hypothyroidism.

Hypothyroidism Diagnosis

The idea is to measure blood levels of T4 or FT4 and TSH. In the typical person with an under-active thyroid gland, the blood level of T4 and FT4 will be low, while the TSH level will be high.

In the more rare case of hypothyroidism due to pituitary failure, the thyroid hormone T4 will be low, but the TSH level will also be low.

. The real question in this situation is what is wrong with the pituitary?

The next question is: When is low too low, and when is high too high? Blood levels have "normal" ranges, but other factors need to be taken into account as well, such as the presence or absence of symptoms.

Levels should be discussed with the patient’s doctor so interpretation can be of help (or not?) .

Although the majority of individuals with hypothyroidism will be easy to diagnose with these simple blood tests, many millions will have this disease in mild to moderate forms which are more difficult to diagnose.

In other words, some patients with very "mild" deviations in their thyroid laboratory test results will feel just fine while others will be quite symptomatic.

It is important to help the patient to FEEL better, not just make his lab results better

2- Hyperthyroidism

Hyperthyroidism is a condition caused by the effects of too much thyroid hormone on tissues of the body.

Hyperthyroidism Causes

The most common underlying cause of hyperthyroidism is Graves' disease. Graves' disease is classified as an autoimmune disease.

The antibodies that the patient's immune system makes attach to specific activating sites on thyroid gland which in turn cause the thyroid to make more hormone.

Hyperthyroidism can also be caused by a single nodule within the thyroid instead of the entire thyroid.

Thyroiditis, can lead to the release of excess amounts of thyroid hormones that are normally stored in the gland .

3-Thyroid Goiter The term nontoxic goiter refers to enlargement of the

thyroid which is not associated with overproduction of thyroid hormone or malignancy.

The thyroid can become very large so that it can easily be seen as a mass in the neck.

A diet deficient in iodine can cause a goiter but this is rarely the cause because of the readily available iodine in our diets.

A more common cause of goiter is an increase in TSH in response to a defect in normal hormone synthesis within the thyroid gland causing the thyroid to enlarge. This enlargement usually takes many years to become manifest.

4-Thyroiditis

Hashimoto's Thyroiditis (also called autoimmune or chronic lymphocytic thyroiditis) is the most common type of thyroiditis

During the course of this disease, the cells of the thyroid becomes inefficient in converting iodine into thyroid hormone and "compensates" by enlarging.

Hashimoto's ThyroiditisAs the disease progresses, the TSH

increases since the pituitary is trying to induce the thyroid to make more hormone, the T4 falls since the thyroid can't make it, and the patient becomes hypothyroid.

Thyroid antibodies are present in 95% of patients with Hashimoto's Thyroiditis and serve as a useful "marker" in identifying the disease without thyroid biopsy or surgery

De Quervain's Thyroiditis

The thyroid gland generally swells rapidly and is very painful and tender. The gland discharges thyroid hormone into the blood and the patients become hyperthyroid; however the gland quits taking up iodine (radioactive iodine uptake is very low) and the hyperthyroidism generally resolves over the next several weeks.

Thyroid antibodies are not present in the blood, but the sedimentation rate, which measures inflammation, is very high.

5-Thyroid Nodules Three questions that should be answered

about all thyroid nodules: Is the nodule one of the few that are

cancerous ? Is the nodule causing trouble by pressing

on other structures in the neck ? Is the nodule making too much thyroid

hormone ? presence of hyperthyroidism or hypothyroidism favors a benign nodule

Thyroid fine needle aspiration (FNA) biopsy is the only non-surgical method which can differentiate malignant and benign nodules.

Thyroid cancer Calcitonin Thyroglobulin Calcium and ionized calcium Parathormon

HOW TO APPROACH

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