thyroid gland

thyroid gland The thyroid gland secretes hormones which are necessary for normal growth and development from fetal life onwards, and for maintenance of normal metabolism in the adult body.

The gland is located just below the larynx and attached to the front of the trachea. The adult gland weighs 10–20 g and consists of two relatively flat oval lobes linked by an isthmus. It is so named because of its resemblance to the classical shield (thureos) used by the ancient Greeks. However, unlike the shield, in any one individual the thyroid is generally asymmetric, with the right lobe being significantly larger than the left. The gland is usually larger in women than in men and it increases slightly in size during pregnancy. This is exploited as an early pregnancy test in some African communities: the neck of a bride is adorned with a tight necklace and pregnancy is indicated when in due course the necklace is broken by the swelling thyroid gland.

The embryonic thyroid originated in the floor of the pharynx and it can be detected as a midline thickening, as early as day 24. By weeks 6–7 the characteristic bilobed structure can be distinguished. At about this time, the gland becomes detached from the pharynx and the developing tissue mass descends into the neck. The two lobes finally come to rest on either side of the trachea with the joining isthmus lying across the front of it. Occasionally the thyroid fails to descend, or may descend too far; the fully developed gland is then found below the root of the tongue or within the thorax. Such developmental abnormalities do not necessarily affect thyroid function.

During its descent down the neck the developing thyroid incorporates ‘C-cells’ into its tissue mass; also two pairs of discrete parathyroid glands become attached to the back surface of the thyroid gland itself. These secrete hormones which regulate the concentration of calcium in the blood: the C-cells secrete the protein calcitonin, and the parathyroids the protein parathyroid hormone. Neither of these are regarded as thyroid hormones since they are not produced by the main mass of thyroid tissue; the latter consists of spherical follicles where the thyroid hormones are synthesized and stored.

The major functional and structural unit of the thyroid is the thyroid follicle. There are many thousands of follicles, and their individual sizes vary considerably, ranging in diameter from 20 to 100 μm (2/100–1/10 mm). A rich network of fenestrated capillary blood vessels surrounds small groups of follicles and there is an impressively high rate of blood flow through the gland as a whole (per unit mass, the flow is twice the flow through the kidneys, which themselves have a much greater blood supply than other organs relative to their size). The even greater flow through an overactive thyroid produces a ‘bruit’ which can be heard when a stethoscope is placed over the gland. The high blood flow ensures an adequate supply of blood-borne nutrients to the follicles — in particular the delivery of iodide derived from the diet — as well as uptake of the thyroid hormones into the bloodstream.

The unique biochemical characteristic of thyroid follicular cells is their ability to concentrate and to utilize dietary iodide. The cell possesses an iodide ‘pump’ which enables it to accumulate iodide internally, so that it can achieve a concentration twenty- to a hundred-fold higher than that in the circulating blood. Two other tissues which share a closely related embryonic origin with the thyroid (some cells of the stomach lining and the salivary glands) also possess this pumping mechanism, but the thyroid is unique in its ability to retain and utilize the iodide for the biosynthesis of its hormones. These hormones are small molecules derived from the amino acid tyrosine and they have iodine incorporated into their structures. There are two thyroid hormones, which have either 3 or 4 atoms of iodine per molecule; they are known respectively as T₃ (tri-iodothyronine) and T₄ (thyroxine). Both are synthesized within the thyroid follicles and secreted into the bloodstream when the cells are stimulated to extrude them by the thyroid stimulation hormone (TSH) from the pituitary gland. The thyroid hormones in the circulation in turn regulate the production of TSH by the pituitary, switching off TSH production when the appropriate level of T_3/T₄ is attained in the blood. Thus the ‘pituitary–thyroid axis’ is a classical example of a negative feedback system.

Following the accumulation of iodine in the follicular cells, the T₃ and T₄ are first synthesized separately and are then incorporated into a much larger molecule known as thyroglobulin. This large glycoprotein, which is sometimes referred to as ‘colloid’ is stored in the hollow interior of each follicle. If a thyroid gland which has been removed is cut across and gently squeezed, the colloid can be observed leaking from the transected follicles as a glistening yellowish fluid. TSH stimulates the release of the T₃ and T₄ from the thyroglobulin so that the hormones can be secreted from the cells into the bloodstream in a regulated fashion. This hormone storage system is unique in endocrine physiology; it ensures that there is a two-month supply of thyroid hormones in the event that a person encounters an iodine deficient environment. This occurs in many parts of the world, such as some mountainous regions in China and India. However, this capacity to store thyroid hormones within the follicles as thyroglobulin becomes disadvantageous if an individual inadvertently ingests radioactive iodine. This occurred after the huge release into the atmosphere of radioactive isotopes, including radioiodine, during the week following the Chernobyl accident on 26 April 1986. The natural storage of the radioiodine in the follicles delays clearance of the ingested radionuclide and concentrates the damaging radiation on the thyroid. In Belarus and the Ukraine this resulted in a major increase in the incidence of thyroid cancer in the 1990s amongst children born before the accident.

Thyroid hormones circulate in the blood in minute concentrations (nanomolar — of the order of 10^-9 × molecular weight per litre). Although this is very low compared with many blood constituents such as glucose or sodium ions, which circulate at millimolar concentrations (a million times greater), it is high relative to hormones in general. The blood concentrations of the thyroid hormones are tightly regulated by TSH and remain very stable in a healthy individual over prolonged periods. Thyroid hormones are relatively insoluble in water and this has two important consequences. Firstly, in the circulation more than 99% of them are linked to specific ‘binding proteins’; this prolongs their half-life in blood, and since the binding is reversible, maintains a biologically active ‘reservoir’ in the circulation. Secondly, on arrival at a target cell, the hormones, being relatively soluble in lipid, are able to cross the plasma membrane of the cell and then bind to specific receptors associated with gene regulation in the nucleus of the cell.

Thyroid hormones regulate the activities of almost all cells in the body. They exert three main classes of action. Firstly they control the basal metabolic rate (BMR). Secondly they influence cell differentiation and growth. Thirdly they may modify the action of other hormones, extending their importance still more widely. Thus a lack of thyroid hormones is manifested in diverse ways. In the developing fetus an inadequate supply leads to impaired brain development with the danger of the infant being borne a cretin. In an adult there is a depressed BMR with attendant lethargy. By contrast, excess thyroid hormones raise the BMR and may lead to cardiac problems due to potentiation by thyroid hormone of the effects of adrenaline.

T₃, the form of thyroid hormone which contains only 3 atoms of iodine per molecule, is now considered to be the physiologically active hormone, and T₄ to be a precursor of T₃, which can be converted to T₃ by specific enzymes within the target cells. Since T₄ circulates at a concentration about a hundred-fold higher than that of T₃, it can therefore be considered to be a storage form of the active hormone. Thus the thyroid system as a whole is designed to buffer any possibility of a reduction in the adequate supply of T₃ to target cells: large reserves are maintained in the thyroglobulin stored in the follicles, in the T₃ and T₄ attached to the circulating binding proteins, and in T₄ itself.

N. J. Marshall

See endocrine.See also goitre; hormones; hyperthyroidism; hypothyroidism.