Thyroid Function Tests

Thyroid Function Tests

The thyroid gland is directly controlled by the pituitary gland in a feed back mechanism. The hypothalamus secretes TRH (thyrotropin-­releasing hormone) that steadily acts on the pituitary gland to produce and release TSH (thyroid-stimulating hormone).
TSH acts on the thyroid follicles to synthesize and release T4 and T3 into the blood stream; they are rapidly bound and transported by circulating thyroid binding globulin (TBG), albumin and prealbumin.
An equilibrium exchange occurs between free and bound hormone. The relatively small quantity of free T4 (0.05 % of plasma T4) and T3 (0.2 % of plasma T3) has a major biological effect on the rate of oxygen consumption and heat production in the tissues. They also play a critical role in growth, development and sexual maturation.
Tri-iodothyronine (T3) is the biologically active hormone. A small fraction of T3 is formed in the thyroid, but the major portion is formed by peripheral deiodination of T4, mainly by the liver, kidneys and muscle.
Investigations for thyroid status:
The tests used to investigate thyroid dysfunction can be grouped into:
Tests which establish the presence thyroid dysfunction e.g. Plasma TSH and thyroid hormone (T4 and T3) measurements.
* Plasma total T4 and total T3: Conditions causing elevation of plasma TBG e.g. pregnancy or administration of oral contraceptives lead to false elevation of T4 and T3, while lowering of TBG levels e.g. protein loosing states, cause a false lowering of T4 and T3.
* Plasma free thyroxine (free T4 and free T3): Plasma free T4 provides a more sensitive and a more specific index of thyroid status than plasma total T4 and T3. Plasma free T3 is of limited value in the diagnosis of hypothyroidism as its level is often normal in these patients.
* TSH assay: High levels are found in primary hypothyroidism and low or very low levels are found in primary hyperthyroidism (below 0.1 mU/L). Low and high levels may be found with euthyroid status in cases of non-thyroidal illness.

Tests for the integrity of hypothalamo pituitary axis. These include:
* TSH stimulation tests can be performed by injection of TSH, which corrects secondary hypothyroidism but not primary hypothyroidism.
* The TRH test: In normal subjects, after I.V. TRH, serum TSH increases by more than 2 mIU/L above the basal level at 20 min. and returns towards the basal values at 60 min. Patients with T3-receptor defect (end organ resistance) show TSH response to TRH test. Absent response is found in:
Hyperthyroidism due to TSH secreting tumor.
Primary hyperthyroidism.
Hypopituitarism.

Tests to elucidate the cause of thyroid dysfunction i.e. thyroid auto-antibodies and serum thyroglobulin measurements.
* Thyroid auto-antibodies: Several types of antibodies to thyroid tissue have been detected in serum of patients with thyroid disease, examples are:
Complement-fixing antibodies in 80% of patients with Hashimoto’s thyroiditis.
Anti-thyroglobulin antibodies and antimicrosomal antibodies (anti-thyroid peroxidase) in patients with Hashimoto's thyroiditis and (long acting thyroid stimulator).
Thyrotrophin-receptor antibodies present in the serum of patients with Grave's disease.

Laboratory findings in thyroid disorders

* Hyperthyroidism (thyrotoxicosis)
TSH is usually very low, very rarely, it may be elevated (TSH secreting tumor).
Total and free T4 and T3 are elevated.
Occasionally, only T3 is elevated (T3 toxicosis).
Plasma T3, T4 can be used to follow the treatment with antithyroid drugs. Measurement of plasma TSH is not a reliable guide for thyroid status during the first 4 to 6 months of treatment (TSH still be suppressed).
* Adult hypothyroidism:
- TSH is high in primary hypothyroidism but low in secondary hypothyroidism.
- Plasma total and free T4, T3 and FTI are low.
- An elevated TSH with normal T4, T3 occur early in the course of the disease (premyxedema).
- Hypercholesterolemia
* Neonatal hypothyroidism (cretinism):
- Raised TSH levels above 30 mu/L with low T4 (< 6.0 μg/dl) on the third day of life (in a normal neonate). These tests should be performed as parameter of neonatal screening programs.