Much confusion occurs when interpreting the TFTs since sometimes normal results require treatment, and sometimes abnormal results do not require treatment. The most important criteria in deciding what should be done in terms of therapy strategy should be the patient's clinical status.

Thyroid disorders are common in India which is why thyroid function tests (TFTs) are very commonly ordered during endocrine panel testing. Here is a quick run through of the common TFTs performed and what the results mean for making a diagnosis. 

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Thyroid Function Tests

Thyroid-stimulating hormone (TSH)

This should be the first test done on anyone suspected of thyroid disorders. Even inconspicuous thyroid dysfunction can significantly elevate TSH levels. TSH assays are reliable since third-generation chemiluminescent assays can detect both significant low levels and high levels of TSH. Many times, a normal TSH can halt the further need of thyroid testing.

Serum thyroxine (T4)

In hyperthyroid patients, T4 levels are used to assess the severity of hyperthyroxinemia since most of these patients will have high T4 levels. In some cases, TSH levels may remain suppressed for extended periods during the treatment period and hence may not be a good indicator of thyroid function.

A clinically euthyroid patient may have subclinical hyperthyroidism, which can only be confirmed with T4 level testing. In cases of secondary hypothyroidism suspicion, the serum TSH may be normal despite low levels of serum T4 and this warrants the assessment of other pituitary functions.

Serum triiodothyronine (T3)

T3 level estimation is usually not required nor helpful in clinical practice since T3 has a short half-life and T3 levels tend to remain normal. However, in 5% of patients with Graves' disease (GD), T3 toxicosis needs to be ruled out by assessing T3 levels in patients with hyperthyroid clinical features with low TSH and normal T4.

Free triiodothyronine (free T3) and free thyroxine (free T4)

In conditions which involve changes in thyroid-binding globulin (TBG) levels, measuring the free T3 and free T4 is useful. TBG may increase, and the free T3 and free T4 may mirror this change but without an increase in hormone activity. Conversely, false lowering of the free T3 and free T4 may also be seen with lowered TBG levels in certain conditions.

Antithyroid antibodies

The antithyroid peroxidase (anti-TPO) antibody, antithyroglobulin antibody, and the TSH receptor antibodies are produced against the thyroid antigens. Patients with subclinical hypothyroidism should be checked for anti-TPO antibodies. Autoimmune thyroiditis can also be identified with anti-TPO antibodies when assessing nodular thyroid disease.

The TSH receptor antibody (TSHR-Ab) levels can confirm GD when radioactive iodine uptake cannot be done. The TSHR-Ab can also assist in foreseeing the course and treatment response in GD. It can also assess the risk of fetal thyrotoxicosis in pregnant women with GD and also help to diagnose euthyroid ophthalmopathy.

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Thyroid Pathophysiology

Primary hypothyroidism and hyperthyroidism

When the problem lies at the level of the thyroid, this is known as primary hypothyroidism, and in which low levels of T4 and T3 are seen and high levels of TSH are seen. High levels of TSH in most cases try to drive the thyroid to produce normal levels of thyroid hormones. In contrast, in primary hyperthyroidism low levels of TSH are seen due to the suppression from the excessive secretion of thyroid hormones.

Secondary hypothyroidism and hyperthyroidism

In these abnormalities, the problem is at the level of the hypothalamus or the pituitary gland. Remember that TSH may be normal even in cases of low T4 levels and these patients will require thyroid hormone replacement. The TSH levels regarded as apparently normal, are in reality inappropriately low. Thyroxine dosage adjustments can be made by monitoring T4 levels.

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Pregnancy and Thyroid Function

Levels of T4 are higher in pregnancy with a matching lowering of serum TSH as expected. In pregnancy, these recommendations should be borne in mind:

• T4 should be 1.5 x the upper limit of normal
• Assessed thyroid functions every 6 weeks

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Subclinical Hypothyroidism /Hyperthyroidism

TSH level is low in subclinical hypothyroidism. Normal T4 levels are seen in subclinical hyperthyroidism. Clinical euthyroidism may be seen. Treat subclinical hypothyroidism if TSH >10 mIU/ml. Also consider treatment for subclinical hypothyroidism if TSH is between 4.5 to 10 mIU/ml if the patient is pregnant, planning pregnancy, in infertility, in mood disorders, in depression, or if there are high levels of TPO antibodies.

When to treat?

FACTOR	TSH (<0.1 µU/L)	TSH (<0.1 to 0.5 µU/L)*
Age above 65	Yes	Consider treating
Age below 65 with comorbidities
Heart Disease	Yes	Consider treating
Osteoporosis	Yes	No
Menopause	Consider treating	Consider treating
Hyperthyroid symptoms	Yes	Consider treating
Age below 65 with no symptoms	Consider treating	No

*Where 0.5µU/Lis the lower limit of the normal range

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Sick Euthyroid Syndrome/Non-thyroid Illness Syndrome

In a patient with a coexisting serious non-thyroid illness, the syndrome of abnormal TFTs with no real thyroid disorders is known as sick euthyroid syndrome. TSH may be normal or low but both T4 and T3 are elevated. When someone has a critical illness they exhibit a high metabolic demand, and their body tries to save energy by lowering metabolism so that tissue energy expenditure is reduced and made available to the vital organs. This can be achieved partly by lowering thyroid hormone production. As such T3 levels become reduced and concurrently T4 levels rise. Reverse T3, an inactive form of T3 levels also rise. Levothyroxine replacement therapy is not recommended in such patients as per the latest guidelines. 

Article was originally published on October 15, 2018.