Molecule

Thyroid Function Tests - What do they reveal?
 

What is 'normal'?  What is 'optimal' ?  Are they Accurate?

How a Thyroid Condition is Diagnosed

 

There are many diseases and illnesses that present themselves in a similar way, therefore it can be difficult for a doctor to make a quick diagnosis. Thyroid disorders can produce a multitude of symptoms relating to any or every part of the body. The type of symptoms a person experiences depends on human individuality, which is influenced by our genetics, upbringing, environment, diet and lifestyle.

 

When your health problems become a concern and you know that something is wrong it is extremely important to find a doctor (or specialist) with whom you feel completely comfortable. Communication needs to be open and honest and there should be a willingness to work together to restore your health. A doctor who is approachable with good listening skills would be a bonus.

 

It is not uncommon to get to your doctor and then forget most of the important details you were going to tell him or her. This is probably a classic hypothyroid trait, if the truth be told. It would therefore be wise to take in a prepared sheet of paper with a list of symptoms that you have, including your past medical history, and also any information on your family history. It is extremely important to write down every symptom that you can think of, even if it seems silly or minor, as it may give the doctor some vital clues to what is causing your ill health.

 

 If a doctor suspects that your thyroid gland may be malfunctioning and causing your symptoms, he or she will use three main strategies to confirm the diagnosis. These include:

 

  1.  – Careful observation and assessment of physical and mental signs and symptoms.

  2.  – Careful evaluation of laboratory blood values, i.e.: Thyroid Function Test (TFT).

  3.  – Conducting a thyroid antibodies blood test.

 

Careful clinical analysis and blood testing together will provide a clearer picture of a person’s thyroid function and whether lifestyle interventions, nutritional supplementation or other treatments are required.

Clinical Presentation

 

Your doctor is trained to listen to your story, and record your symptoms and family history. He or she will ask you questions to clarify details and gain further information to achieve a better understanding of your health status. After making relevant notes, your doctor will examine you and look for physical and mental signs that may relate to your health concerns. If a particular thyroid disorder is suspected from what you have described, your doctor will look for signs that are the most indicative of that specific condition.

 

For Hypothyroidism, the type of objective signs that your doctor can observe or measure may include the following: A slow weak pulse may be felt, and blood pressure may be low or too high. Your skin may feel dry and cold to touch, and your fingernails may be white or brittle. Your hair may look dry and lifeless and the outer third of your eyebrows may be thinning or missing. Your facial features and other body parts may appear swollen and puffy, and your doctor may have noticed that you have gained weight over recent months. Your movements and reflexes may be slow, not to mention your thought processes with a slowing of speech. You may generally appear tired, listless and emotionally drained. A swollen thyroid gland may be seen or felt which can be a good indicator that something is not right with the thyroid gland.

For Hyperthyroidism, your doctor may observe and measure the following: A strong fast heart beat and pulse, with possible arrhythmias detected. Blood pressure may be higher than normal and body temperature may be slightly elevated. Your skin may appear more flushed and warm, your hair fine and sparse, and your hands more swollen, hot and clammy.  You may appear more wound up, anxious and shaky, talking faster, and have more rapid reflexes. You may generally appear more emotional, exhausted and frustrated with life, and to top it off you may feel a constant lump in your throat, having greater difficulty in swallowing and breathing. These specific cluster of symptoms would be a good indicator that an overactive thyroid could be the culprit.

 

Through careful observation, a sensitive doctor will notice and record these relevant findings, and will then request further tests to establish a clear diagnosis. A direct test for thyroid function involves taking blood and determining the levels of thyroid hormones circulating in the bloodstream. Other indirect tests may also be particularly helpful, such as, blood cholesterol levels, liver function, ESR (Erythrocyte Sedimentation Rate), and urinary iodine levels.

 

Body Temperature

 

Some doctors believe that monitoring a person’s average body temperature also helps in establishing the correct diagnosis. If body temperature is consistently too low or too high, a person’s metabolic rate may have changed, and sometimes thyroid function is responsible. Body temperature, along with measuring pulse rate and blood pressure is important, as these variables can indicate that something is wrong. They are also valuable when treating a thyroid condition as they usually return to normal when thyroid hormone levels are optimised.

Laboratory Blood Testing

 

Modern blood testing of thyroid hormone levels is seen as an essential component in diagnosing thyroid disease. The diagnosis is usually confirmed by abnormal blood test results. A thyroid function test (TFT) is ordered by a doctor to analyse serum thyroid hormone levels and thereby to assess how well the thyroid gland is working. Initially pathology laboratories will conduct a TSH (Thyroid Stimulating Hormone) test. TSH is released by the pituitary gland in the brain, to control the levels of thyroid hormones in the bloodstream. If the thyroid gland becomes more underactive or overactive, the levels of TSH will change. If the TSH level rises or falls outside of the normal reference range, further tests will be performed, measuring free thyroxine (T4) levels, and free triiodothyronine (T3) levels. These are the primary hormones produced by the thyroid gland to control cellular metabolism. If blood levels of circulating thyroid hormones are outside of the normal reference ranges, a thyroid antibody test may also be performed to determine the cause of these abnormal levels. This is the standard protocol for measuring thyroid hormone levels in Australia.

ThyroidTest_38663266_M.jpg

When T4 and T3 decrease, TSH rises

                   ---------

When T4 and T3 increase, TSH falls

Immunoassay Techniques

 

Immunoassay techniques for diagnosing thyroid disorders measure the amount of circulating thyroid hormones in the blood very accurately. Normal reference ranges have been developed for various hormones based on the healthy population. The reference ranges for TSH, T4 and T3 will differ slightly from one laboratory to another, depending on the laboratory’s assay methods (methods of analysis). Any blood test results that show hormone levels outside of these ranges usually indicate a thyroid problem.

 

The greater proportion of thyroid hormones are bound to proteins in the bloodstream and have no affect on the body. Less than one percent of thyroid hormones are unbound, or ‘free’, and it is these free hormones that are active and able to control the metabolism of the body, at the cellular level. Laboratories can measure the total T4 and T3 hormones, which include the bound and free hormones together. They can also measure free T4 (fT4), and free T3 (fT3), to assess the levels of active hormone. Most modern testing uses the free hormone tests.

 

When analysing the results of a thyroid function test, it is vital to refer to the reference range that is given from that particular laboratory. Here is an example of the reference ranges of a full thyroid function test, taken from one pathology lab.

Full Thyroid Function Test

Standard Reference Range:        Optimal

TSH: 0.30 - 5.00 mIU/L           0.3 - 2.5 mIU/L

T4: 11 – 23 pmoI/L                 15 - 23 pmol/L

T3: 3.5 – 6.7  pmoI/L               5 - 6.7 pmol/L         

Further diagnostic tests include:

Anti-TPO antibodies: <35 IU/mL

Anti-Tg Antibodies: <35 IU/mL

TSH Receptor Antibodies: 0.00 - 1.75 IU/L

Reverse T3:  11 - 21 ng/dl

The testing of TSH alone is inadequate for the diagnosis and management of thyroid conditions. Clinical evaluation along with full laboratory tests is a better indicator of thyroid function. The physical and mental signs and symptoms of thyroid disease are very revealing of how well the body is functioning.

Full Thyroid Function Test 

 

Blood testing remains a problematic method for diagnosing various thyroid conditions. Many people have, what is interpreted to be, normal blood test results, but still experience significant symptoms of thyroid failure or disease. A person may not always present as a classic textbook case, but this does not rule out the possibility that thyroid dysfunction is the cause of their health problems.

 

To gain a clearer assessment of a person’s thyroid function, a full thyroid function test should be completed, which includes TSH, fT4 and fT3 levels. The measurement of thyroid antibody levels is also important in determining whether a disease process is present. In time this autoimmune process may cause the thyroid gland to fail or malfunction and lead to permanent hypothyroidism or hyperthyroidism. The testing of TSH alone is inadequate for the diagnosis and management of thyroid conditions. Clinical evaluation along with full laboratory tests is a better indicator of thyroid function. The physical and mental signs and symptoms of thyroid disease are very revealing of how well the body is functioning.

Recent developments are challenging the standard approaches to diagnosing and treating thyroid disorders. Current research is indicating that the reference ranges for TSH values are too wide, especially at the upper end. The majority of the healthy population, with normal thyroid function, have TSH values in the lower end of the reference range. This raises the question whether TSH values in the mid to upper end of the scale are actually ‘normal’.

TFT Population Studies

 

The American Association of Clinical Endocrinologists, Thyroid Awareness Month 2001, January 2001, commented on TSH values:   

"AACE encourages patients whose TSH is outside the normal range (.5-5.0uU/ml) to see an endocrinologist for treatment and thyroid disease management. Even though a TSH level between 3.0 and 5.0uU/ml is in the normal range, it should be considered suspect since it may signal a case of evolving thyroid underactivity."

 

Prof A P Weetman, in an article in the British Medical Journal, 19 April 1997, discussed thyroid screening and subclinical disease:

"...even within the reference range of around 0.5-4.5 mU/l, a high thyroid stimulating hormone concentration (>2 mU/l) was associated with an increased risk of future hypothyroidism. The simplest explanation is that thyroid disease is so common that many people predisposed to thyroid failure are included in a laboratory's reference population, which raises the question whether thyroxine replacement is adequate in patients with thyroid stimulating hormone levels above 2 mU/l."

The Norwegian Study

 

In 2002, a Norwegian study (European Journal of Endocrinology, 2000, 143 639-647) tested the TSH value of 65,000 people, in an attempt to establish a range of values for TSH that can be expected in the healthy population. A survey was conducted to exclude any individuals with a history of thyroid disease. Blood samples were also taken to exclude individuals who had positive thyroid antibodies accompanied by a TSH value above 4 - on a nominated reference range of 0.2 to 4.5mIU/L. The study however did include people with positive thyroid antibodies if their TSH reading was 4 or less. The reference range covered 95% of the healthy population with the lowest and highest 2.5% of readings being excluded.

 

The results of this survey are shown on the following chart and reveal that the normal TSH readings of the healthy population are not evenly distributed, but fall heavily towards the lower end of the ‘normal’ reference range. The centre of the normal reference range for the test kit used was 2.35, but 85% of the healthy population had a TSH value below this point. The median value was at 1.50, with 50% of the population on each side of this point. The most common value was 1.25. When looking at the results, the lowest reference point, which excluded the bottom 2.5% of the population, was at 0.48. The highest reference point, which excluded the top 2.5 % of the population, was at 3.6. This range of 0.48 to 3.6 is much narrower than the test kit’s reference range of 0.2 to 4.5, and the narrowing would potentially have been even more pronounced if all people presenting with any sign of thyroid illness had been excluded.

 TSH Distribution Chart

TFT chart.jpg

These results strongly suggest that the normal reference ranges for TSH values are too wide, and blood levels in the upper half of the range have a low probability of being normal, especially for a person who is symptomatic and has a history of thyroid disease.

 

A proportion of the people used in this study did have positive thyroid antibody results, but were still included because their TSH value was under 4. If all subjects used in this survey were proven to be completely free of any sign of thyroid disease, then the TSH results may have been even more revealing of the healthy population, and the determined range for ‘normal’ would have even narrower limits.

"In the future, it is likely that the upper limit of the serum TSH euthyroid reference range will be reduced to 2.5 mIU/L because >95% of rigorously screened normal euthyroid volunteers have serum TSH values between 0.4 and 2.5 mIU/L.” 

The National Academy of Clinical Biochemistry - NACB

The National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines, 2002, reported the following:

 

“Over the last two decades, the upper reference limit for TSH has steadily declined from ~10 to approximately ~4.0-4.5 mIU/L. This decrease reflects a number of factors including the improved sensitivity and specificity of current monoclonal antibody based immunometric assays, the recognition that normal TSH values are log-distributed and importantly, improvements in the sensitivity and specificity of the thyroid antibody tests that are used to pre-screen subjects. The recent follow-up study of the Whickham cohort has found that individuals with a serum TSH >2.0 mIU/L at their primary evaluation had an increased odds ratio of developing hypothyroidism over the next 20 years, especially if thyroid antibodies were elevated. An increased odds-ratio for hypothyroidism was even seen in antibody-negative subjects. It is likely that such subjects had low levels of thyroid antibodies that could not be detected by the insensitive microsomal antibody agglutination tests used in the initial study. Even the current sensitive TPOAb immunoassays may not identify all individuals with occult [hidden] thyroid insufficiency. In the future, it is likely that the upper limit of the serum TSH euthyroid reference range will be reduced to 2.5 mIU/L because >95% of rigorously screened normal euthyroid volunteers have serum TSH values between 0.4 and 2.5 mIU/L.” 

 

Generally speaking, the Norwegian study has revealed some interesting data, which could affect the diagnosis and treatment for people suffering with hypothyroidism. It tends to suggests that TSH values that fall within the mid to high end of the normal reference range should be treated with more suspicion than they currently are. Similarly, when thyroid hormone replacement is required, serum TSH levels should be returned to the lower half of the reference range, as this is where the majority of healthy people have their TSH levels. Simply aiming for somewhere in the middle of the range may not be the best method for correcting a person’s TSH levels to where it is best for them. A good target point would be around 1.0 to 1.5, keeping in mind that some people will feel better slightly under or over this target. Finding an individual personal set point is of utmost importance.

 

It needs to be emphasized that a person becomes symptomatic when the concentration of their thyroid hormones are no longer at their personal set point. A ‘normal’ population reference range is used to determine the probability that a person’s current levels are adequate. However, it is very possible for a person to be within the ‘normal’ population range but nowhere near their personal set point. A person will only feel completely well when their thyroid hormone levels are within the narrow margin, which is their ‘normal’ range.

 

The following appeared in a report in the Journal of Clinical Endocrinology and Metabolism, 2002 March; 87(3): 1068-72:

 

“Our data indicate that each individual has a unique thyroid function. The individual reference ranges for test results were narrow, compared with group reference ranges used to develop laboratory reference ranges. Accordingly, a test result within laboratory reference limits is not necessarily normal for an individual.”

 

In the Medical Journal of Australia, 2001, Dr John Walsh and Dr Bronwyn Stuckey discussed what is the optimal treatment for hypothyroidism according to the latest research:

 

"There is evidence that individuals have different set points in the relationship between serum thyroxine, T3 and TSH concentrations. The reference range for TSH is wide (typically 0.3-4.0mU/L) and not normally distributed, with a mean and median in the lower part of the range, at about 1.5mU/L. Thus, a serum TSH concentration of 4.0mU/L, although within the reference range, might reflect significant undertreatment for a patient whose optimal thyroxine replacement dose would result in a serum TSH concentration of 0.4mU/L."

 

TFTs are Not the 'Be All' and 'End All'

Finally, it needs to be stated, that Thyroid Function Tests only measure the circulating levels of thyroid hormones within the blood stream, and provide only a general indication of overall thyroid function. This test does not indicate what is happening at the cellular level within a person's body, and how well they are utilising the thyroid hormones available. A doctor cannot diagnose a patient as 'normal' by a simple blood test alone. Neither can the reliance on a computer generated response be adequate in diagnosing and managing a patient's thyroid condition. Clinical signs and symptoms are more revealing of what is happening internally, and these need to be assessed carefully. It is often wrongly assumed that once a person's thyroid hormones have been normalised within a reference range, that they will no longer have any more symptoms of the disease, and if they do, then it must be due to something else.

What has been coming to light over the past 2 decades, is that many thyroid patients have underlying issues that impact the way their body responds to thyroid hormones which is not evident in any standard blood tests. It is not uncommon for thyroid patients to have a poor response to thyroid medications and have continued symptoms despite having optimised their hormone levels. What is often overlooked, and poorly understood by the medical profession, is problems relating to the synthesis and absorption of thyroid hormones, abnormal transport and binding to receptor sites, poor conversion of T4 into T3, and the important role of the gut and liver in providing sufficient thyroid hormones to target organs. Any one of these things can greatly impact upon a person's metabolism and cellular responsiveness, and leave them in a hypo metabolic state at the cellular level. Diet, nutrition, supplementation, and other health interventions to improve responsiveness and provide adequate active thyroid hormones needs to be considered. Thyroxine, T4 alone therapy, may be insufficient in restoring a person's health, and T3, the most metabolically active hormone may need to be included in the treatment regime. This highlights the importance of always having T3 and T4 levels assessed along with TSH when monitoring treatment progress. The longer a person remains with ‘suboptimal’ thyroid hormone levels and unresolved thyroid symptoms, the worse their condition will become, and the risk of developing more serious health problems may rise.

Summary:

Thyroid disorders can produce a multitude of signs and symptoms relating to any or every part of the body. Obtaining the correct diagnosis and finding adequate treatment and monitoring can sometimes be a challenge. Thyroid functions tests provide a general overview of thyroid function and circulating thyroid hormone levels, and can provide an initial indication of a malfunctioning gland. However, clinical symptoms speak louder than blood test results alone, and doctors should never lose the art of careful clinical analysis and assessment.  A full thyroid function test should always include TSH, fT4, fT3 and thyroid antibodies. These blood results, alongside clinical symptoms and responsiveness, should be considered together to gain a more comprehensive understanding of the metabolic changes within a person's body. Optimising all thyroid hormones to find an individual's personal setpoint is a first crucial step in treating the disease, along with addressing underlying triggers and causes, in restoring the body to health. If doctors only follow basic recommendations, and a TSH blood test result is the only method of assessment used to determine thyroid function, then many individuals suffering with thyroid disease will be left undiagnosed, misdiagnosed, untreated, or inadequately managed.

References:

 

[1] American Association of Clinical Endocrinologists, "New Campaign Urges People to "Think Thyroid" at Critical Life Stages and Get Tested", Thyroid Awareness Month 2001, January 2001  

               

[2] Prof A P Weetman, "Fortnightly review: Hypothyroidism: screening and subclinical disease", British Medical Journal, 19 April 1997; 314: 1175.

http://www.bmj.com/cgi/content/full/314/7088/1175

 

[3] LM Demers PhD FACB, CA Spencer PhD FACB, NACB: “Laboratory Support for the Diagnosis and Monitoring of Thyroid Disease”. The National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines, 2002.[3]

https://www.aacc.org/-/media/Files/Science-and-Practice/Practice-Guidelines/Thyroid-Disease/ThyroidArchived2010.pdf?la=en&hash=0556298535B60C441FBB6AC742E3A4652E0332F8

 

[4] Stig Andersen et al, “Narrow Individual Variations in Serum T4 and T3 in Normal Subjects: A Clue to the Understanding of Subclinical Thyroid Disease”. Journal of Clinical Endocrinology and Metabolism, 2002 March; 87(3):1068-72

https://academic.oup.com/jcem/article/87/3/1068/2846746

 

[5]  Drs John P Walsh and Bronwyn G A Stuckey, "What is the optimal treatment for hypothyroidism?" Medical Journal of Australia, 2001;174:141-143 [Thyroid Australia, Thyroid Flyer, 2:4, October 2001.]