Laboratory evaluation of thyroid gland functional activity

Professor, Doctor of Medical Sciences
Alvils Helds

Current laboratory testing methods allow to provide objective information on thyroid functional activity, which through proper evaluation of the information obtained, provides early diagnosis of various thyroid diseases and also adequate treatment.
Unfortunately, the really necessary examinations are often not chosen, and the results are not always correctly interpreted. There are three trends.
The first – too few laboratory tests are selected to evaluate the functional activity of the thyroid gland. For example, thyroid hyper-function is based only on blood TSH concentration reduction.
The second – choose too many tests that duplicate one another without substantial additional information but only unnecessarily increases the cost of laboratory diagnosis. For example, the laboratory is ordered to perform both the total concentration of thyroxine (T4) and triiodothyronine (J3) in blood and the transport protein-free (“free) levels of this hormone concentration.
The third – from a number of parameters that can be determined in laboratories those are chosen that may change due to various reasons not related to the thyroid gland functions but it does not ordain to identify indicators which are less subject to fluctuations. For example, it is preferable to determine the total concentration of thyroxine and triiodothynine in blood, which unlike non-protein-bound of the same hormone concentrations can vary under the influence of different extrathyreoidal factors.

A small amount of information on thyroid hormones is useful to select properly the necessary laboratory examinations and to adequately interpret them. The thyroid gland produces three hormones – thyroxin (T4), triiodothyronine (T3) and calcitonin. During 24-hours 90 micrograms of T4 and 32 micrograms of T3 are formed in humans with average weight. It should be noted that all T4 (100%) is synthesized in the thyroid gland, while T3 accounts for only 20% in the thyroid gland, the remainder in the parietal tissues from T4. In the case of thyroid gland diseases and in some other situations, the development of T3 in the periphery may change. For example, in the case of fasting and severe chronic diseases, less active T3 occurs in the periphery but more in patients with hypothyroidism.

The biological effects of thyroid hormone determine their binding to the target organ cell nuclear receptors. The T3 binding is 10 – 15 times higher which also determines the most significant operational effect. However, T3 is metabolized much faster; its half-life is 0.75 days, while for T4 it is 7 days. It is important to know that only T4 and T3 protein-free amounts (Free T4, Free T3) are involved in the metabolism of substances, but 99.98% T4 and 99.70% T3 are bound to proteins. Thus, to judge about the effect of this hormone in the body, we need to look for fluctuations in very low concentrations of free hormones, which once caused great problems to laboratory experts, but now have been resolved.

After this short introduction, let’s move to the recommendations on choosing hormone tests that would provide adequate information on the functional state of the thyroid gland. Thyroid-stimulating hormone (TSH, TTH). It is produced in the pituitary gland; it regulates the functional activity of the thyroid gland by the reverse feedback principle. If there is shortage of the thyroid hormone in the body, the TSH begins to be exacerbated to eliminate the deficit by stimulating the thyroid gland. If these hormones are too many TSH excretion decreases. Treatment of hyperthyroidism preserves a reduced TSH concentration for several weeks after reaching euthyreosis. High-doses of glucocorticoids and dopamine preparations reduce TSH level.

TSH testing indications:

  • As a screening method to further investigate people suspected of thyroid gland pathology,
  • Diagnosis and therapy control of primary hypothyroidism (basic process in the thyroid gland),
  • Hyperthyroidism (thyrotoxicosis) diagnosis of the first laboratory stage

FT4 testing indications:

  • To patients with hypothyroidism together with TSH,
  • To hypothyroidism patients, both while diagnosing and during treatment.

FT3 testing indications:

  • Diagnosis of hypothyroidism in patients (combined with FT4, since 2 to 5% of all hypothyroidism patients have T3 toxicity without increased FT4 concentration,
  • During treatment in the absence of T3 toxicosis, FT3 detection is not indicated.

In very rare cases there may be Free T4 and Free T3 concentration increase in the blood to normal or slightly elevated TSH concentration back-ground without a hypothyroidism clinical picture – a thyroid hormone resistance syndrome.

Thyroid gland laboratory tests during pregnancy

Evaluation of thyroid gland functional activity is important both for ensuring normal pregnancy and for normal development of the child. Erroneous decision and wrong choice of treatment is often a cause of spontaneous abortions or abnormalities in the development of the fetus.

The following issues are important in practical work:

  • How can thyroid hormones and TSH parameters change during pregnancy in a healthy woman?

The answer: total T4 and total T3 concentration in the blood should not be controlled, as it may increase due to the increased production of transport globulins. The TSH concentration in 18% of pregnant women decreases until the 20th week of pregnancy. FT4 and FT3 concentration in the blood increases slightly (due to increased production of HCG). However, in such cases the onset of clinical symptoms of hyperthyroidism should be evaluated.

  • What should be the parameters of TSH in patients with hypothyroidism during pregnancy?

The answer: the first three months of pregnancy are the most important for normal development of the fetus. During this time, TSH should be monitored once a month. The dose of L-thyroxin should be normally increased so that the TSH concentration in the blood would be below 2.5 mU/L. After that, the TSH control should be performed every second month.

  • What should be thyroid hormones and TSH indicators in the treatment of hyperthyroidism during pregnancy?

The answer: FT4 – within reference ranges, TSH below 4 mU/L.

Thyroid gland laboratory tests for the evaluation of autoimmune processes.

The most common causes of thyroid gland abnormalities are autoimmune processes. The thyroid gland is the only organ in which cell proliferation and function-simulating antibodies can also occur alongside the defective thyroid antibodies that form the core element. These two processes quite often take place simultaneously, and yet many of the mechanisms are not fully understood, but laboratory information is also expanding to the needs of the practitioner. In Latvia it is now possible to check Anti Thyreoperoxidase antibodies (Anti TPO) and thyroglobulin antibodies(Anti TG) level in the blood. Anti TPO better than Anti TG correlates with autoimmune processes in the thyroid gland, informing about the process in the cell and its nucleus. However, it should be noted that sometimes there are patients with a convincing autoimmune process in the thyroid gland and a high level of Anti TG in the blood, while Anti TPO is only slightly elevated. Such a phenomenon has not been convincingly explained yet. Quite often the level in the blood of greatly increased autoantibodies is incorrectly interpreted. For example, the patient has a clinical picture of an autoimmune thyreotoxicosis (Grave’s disease) with a corresponding change in hormones. There is also significantly increased autoantibody concentration in the blood and the diagnosis is changed to the diagnosis of chronic lymphoid thyroiditis. Sometimes there are difficulties in differential diagnosis. Therefore, it should be taken into account that in autoimmune thyrotoxicosis patients in the thyroid gland alongside with a stimulating process, there is also a degrading process. It is evidenced by significantly increased autoantibody level in 80% of cases.

In order to obtain information on thyroid immune diseases in practical everyday life, it would be important to check:

  • Anti TPO. A slight increase in the concentration of these antibodies still does not indicate an autoimmune process. The number of hundreds and thousands of U/mL, is of importance. The analysis should be performed if the autoimmune process is suspected and if hypothyroidism has been diagnosed and its cause has not been clarified. If the concentration has increased significantly, frequent repeated analyses provide little additional information. In families with a history of thyroid diseases the analysis should be recommended when pregnancy occurs.
  • Anti TG. It is less important than the above mentioned. Diagnostic significance together with TG concentration in the blood, after thyroid cancer treatment.
  • Anti TSH receptor antibodies. It is a relatively new analysis which provides information on thyroid stimulating antibodies. This analysis is recommended to justify diagnosis of autoimmune thyrotoxicosis (in absence of a convincing clinical picture). It has a prognostic role for patients with progressive autoimmune ophtalmopathy, as well as in the discontinuation of antithyroid therapy with antithyroid drugs. It is recommended to check these parameters for autoimmune thyrotoxicosis in pregnant women for 26 – 28 weeks to diagnose fetal thyrotoxicosis before birth.
  • Thyroglobulin (Tg) concentration in the blood. It is of a low diagnostic value as the concentration virtually is increased in all thyroid diseases. It is mandatory to be regularly checked after thyroid cancer therapy.
  • Calcitotin concentration in the blood should be detected if there is a nodular goiter and suspicion of glandular medullary cancer in one of the knots.