6. Release of T4 and T3 into the circulation and recycling processes. Majority of T4 and T3 are liberated from thyroglobulin in the lysosomal pathway in a T4 to T3 ratio of 20:1. They cross the basal membrane and enter the blood and lymphatic capillaries. Most of the released hormones are immediately bound to either a specific plasma protein (54 kilodalton), thyroxinbinding protein (70%), or a nonspecific prealbumin fraction of serum protein (25%), leaving only small amounts (~5%) of free circulating hormones that are metabolically active. Very small amounts of T4 to T3 are released bound to thyroglobulin. Only the follicular cells are capable of producing T4, whereas most T3, which is five times more active than T4, is produced through conversion from T4 by organs such as the kidney, liver, and heart. The free circulating hormones also function in the feedback system that regulates the secretory activity of the thyroid. Once uncoupled from thyroglobulin, DIT and MIT molecules are further deiodinated within the cytoplasm of the follicular cells to release the amino acid tyrosine and iodide, which are then available for recycling.
Thyroid hormones play an essential role in normal fetal development.
In humans, thyroid hormones are essential to normal growth and development. In normal pregnancy, both T3 and T4 cross the placental barrier and are critical in the early stages of brain development. In addition, the fetal thyroid gland begins to function during the 14th week of gestation and also contributes additional thyroid hormones. Thyroid hormone deficiency during fetal development results in irreversible damage to the central nervous system (CNS), causing reduced numbers of neurons, defective myelination, and mental retardation. If maternal thyroid deficiency is present before the development of the fetal thyroid gland, the mental retardation is severe. Recent studies reveal that thyroid hormones also stimulate gene expression for GH in the somatotropes. Therefore, in addition to neural abnormalities, a generalized stunted body growth is typical. The combination of these two abnormalities is called congenital hypothyroidism.
The parathyroid glands are small endocrine glands closely associated with the thyroid. They are ovoid, a few millimeters in diameter, and arranged in two pairs, constituting the superior and inferior parathyroid glands. They are usually located in the connective tissue on the posterior surface of the lateral lobes of the thyroid gland. However, the number and location may vary. In 2% to 10% of individuals, additional glands are associated with the thymus.
Structurally, each parathyroid gland is surrounded by a thin connective tissue capsule that separates it from the thyroid. Septa extend from the capsule into the gland to divide it into poorly defined lobules and to separate the densely packed cords of cells. The connective tissue is more evident in the adult, with the development of fat cells that increase with age and ultimately constitute as much as 60% to 70% of the glandular mass.
The glands receive their blood supply from the inferior thyroid arteries or from anastomoses between the superior and inferior thyroid arteries. Typical of endocrine glands, rich networks of fenestrated blood capillaries and lymphatic capillaries surround the parenchyma of the parathyroids.
Parathyroid glands develop from the endodermal cells derived from the third and fourth branchial pouches.