Thyroid disease is a medical condition that affects the function of the thyroid gland (the endocrine organ found at the front of the neck that produces thyroid hormones). The symptoms of the disease vary depending on the type. There are four general types: 1) hypothyroidism (low function) caused by not having enough thyroid hormones; 2) hyperthyroidism (high function) caused by having too much of the hormones; 3) structural abnormalities, most commonly an enlargement of the gland; and 4) tumours which can be benign or cancerous. Common hypothyroid symptoms include fatigue, low energy, weight gain, inability to tolerate the cold, slow heart rate, dry skin and constipation. Common hyperthyroid symptoms include irritability, weight loss, fast heartbeat, heat intolerance, diarrhoea, and enlargement of the thyroid. In both hypothyroidism and hyperthyroidism, there may be swelling of a part of the neck, which is also known as goiter.

Both Thyroglobulin and T4 are produced by the thyroid gland, while TSH, produced by the pituitary gland activated their production. All three can be measured to monitor thyroid glandular function.

Thyroglobulin

Thyroglobulin is the predominant protein produced by the gland. This glycoprotein is the precursor of thyroid hormones tri-iodothyroxine (T3) and thyroxine (T4). In addition, it serves as a storage protein for iodide that ensures sufficiency of this essential element. Thus, the Thyroglobulin levels may serve as a marker for Iodine deficiency. Thyroglobulin is also produced by thyroid cancer, and its levels are commonly used to monitor the treatment of cancer patients who have undergone thyroidectomy. Because Thyroglobulin is also produced by the non-cancerous state of the gland, it is not suitable as a diagnostic cancer biomarker. Blood thyroglobulin levels can also be elevated in some cases of Grave’s disease.

Thyroxine (T4)

The thyroid gland produces the tyrosine-based hormone Thyroxine, also called T4 for its four iodine moieties from its precursor Thyroglobulin. T4 levels are in high abundance in the blood, but only after a de-ionidation step (to become T3) its potency becomes 3-4 times higher as a hormone. This conversion can happen either in the gland or in the target cells. The levels of T4 are 14-20 times higher than T3 levels. Thus, the metabolism of carbohydrates, lipids and proteins is regulated by the fine-tuning of T3 levels.

Both T3 and T4 act together with its precursor Thyroglobulin as Iodine reservoir in the thyroid. Iodine deficiency leads to increased T4 levels and increased size of the gland. In the foetus and during childhood, the hormones are also critical for functions such as brain development, neuronal differentiation, and formation of neural processes.

Thyroid-Stimulating Hormone (TSH)

TSH (a.k.a Thyrotropin) is a glycoprotein hormone secreted by the anterior pituitary gland. It activates the thyroid gland to secrete T4 (converted to T3 in the liver), thus being a key regulator of normal development and metabolism.  The levels of T3 and T4 inversely feedback to the levels of TSH. Thus, serum TSH levels are measured to diagnose and manage thyroid disorders. It is important for clinical applications to recognize that TSH levels are subject to circadian and ultradian rhythms.