Dysfunction of the thyroid gland causes some of the most common endocrine disorders seen by the physician. Thyrotoxicosis (hyperthyroidism) is a consequence of excess thyroid hormone; a deficiency of thyroid hormone causes hypothyroidism (myxedema). Thyroid dysfunction is frequently manifested clinically by a swelling (enlargement) of the gland, a condition referred to as goiter formation.
The thyroid gland arises embryologically from the fourth pharyngeal pouch. The lateral components combine to develop the easily palpable, butterfly shaped mature thyroid gland (20 gm). The lateral lobes (2 × 3 cm) partially hidden by the sternocleidomastoid muscles, are connected by the isthmus, which sits just below the cricoid cartilage. A pyramidal lobe is present in about 30 per cent; it extends upward from the isthmus lateral to the trachea. The gland consists of spherical follicles (acini) lined by epithelial tissue and filled with colloid. This substance consists of thyroglobulin, the storage from of T4 (thyroxine), T3 (3,5,3‘-triiodothyronine), and the precursors MIT (monoiodothyronine) and DIT (diiodothyronine). Other functioning cells of neural crest origin located in the parafollicular area of the thyroid (C cells) secrete calcitonin.
Iodide, a substrate for thyroid hormone synthesis, also plays an auto-regulatory role in the metabolism of the thyroid gland. The normal gland contains approximately 10,000 µg of iodine, which is predominantly organically bound. The minimal daily requirement of iodine is only about 200 µg (renal loss replacement). Iodide deficiency is a rare occurrence in the iodide-replete western world but remains the most common cause of goiter (endemic goiter) in the world. Many patients with endemic goiter are mentally deficient owing to hypothyroidism dating from birth (cretinism) or suffer from retarded musculoskeletal development owing to thyroid hormone deficiency during childhood.
The thyroid gland concentrates iodide through a unique trapping mechanism to maintain a cell-to-plasma iodide ratio of about 50 to 1. Trapped iodide is rapidly oxidized by peroxidase to iodine and subsequently undergoes organification by iodinating tyrosine residues on thyroglobulin to from MIT and DIT. Coupling of these compounds results in the formation of T3 and T4. The secretory process is initiated by pinocytosis of thyroglobulin from the follicular lumen followed by the release of T4 and T3 from their storage from by proteolysis induced by lysosomal enzymes. The active hormones T4 and T3 are then secreted into the circulation. The thyroid gland is the only source for T4, whereas it contributes only about 20 per cent of the T3 produced daily.
A number of chemicals interfere with thyroid gland metabolism. These effects have been exploited for therapeutic purpose in the case of propylthiouracil (PTU) and methimazole. Both drugs effectively block thyroid hormone synthesis and are utilized clinically in the treatment of hyperthyroidism. Agents that are preferentially trapped by the thyroid (iodide, pertechnetate) are used diagnostically for gland imaging. Pharmacologic amounts of iodide will also inhibit thyroid gland synthesis and release of hormones. This inhibitory effect is generally of short duration in normal people, but if sustained it can lead to hypothyroidism and compensatory goiter formation. Lithium has a similar effect to that of iodide. Its extensive use in manic-depressive illness has led to significant problem with hypothyroidism in this patient group.
Thyroid hormones circulate in two forms, protein bound and free. Thyroxine-binding globulin (TBG), the principal carrier, binds about 70 per cent of the thyroid hormones under normal conditions. Other carrier proteins, thyroxine-binding pre-albumin (TBPA) and albumin, play a lesser role. A small but very important quantity of T4 (0.03 per cent) and T3 (0.3 per cent) is free and remain in rapid equilibrium with the protein-bound fraction. The metabolic state of the patient correlates with the free component rather than the total (bound) thyroid hormone level. Alterations in serum TBG concentration are common and account for the majority of changes in serum total T4 not attributable to hyper or hypothyroidism (Table 1).
These changes in serum total T4 levels are not accompanied by changes in the free T4 concentration. Thus a measurement of free T4 or an index of free T4 is obligatory under these conditions in order to interpret accurately significance of a change in the total hormone value.
Table 1. Alterations in thyroxine-binding globulin (TBG) concentration
T4 = serum thyroxine level; FT4 = serum level free (unbound)thyroxine; TBG = thyroxine-binding globuin.
Dr. Afsaneh Jeddi