Download Thyroid Gland

Thyroid Gland
Normal
The thyroid gland consists of two bulky lateral lobes connected by a relatively thin isthmus, usually
located below and anterior to the larynx. Normal variations in the structure of the thyroid gland
include the presence of a pyramidal lobe, a remnant of the thyroglossal duct above the isthmus.
The thyroid gland develops from an evagination of the developing pharyngeal epithelium that
descends as part of the thyroglossal duct from the foramen cecum at the base of the tongue to its
normal position in the anterior neck. This pattern of descent explains the occasional presence of
ectopic thyroid tissue, most commonly located at the base of the tongue (lingual thyroid) or at other
sites abnormally high in the neck. Excessive descent leads to substernal thyroid glands. The
clinical significance of these lesions lies in distinguishing them from metastatic thyroid carcinomas
and the extremely rare occasions on which these ectopic sites can develop a primary thyroid
malignancy.[8] Patients with lingual thyroids present an additional problem in that the ectopic thyroid
tissue is sometimes the only thyroid tissue (total migration failure), and removal of the lingual
thyroid results in symptomatic hypothyroidism. Malformations of branchial pouch differentiation
may result in intrathyroidal sites of the thymus or parathyroid glands. The implication of these
deviations becomes evident in the patient who has a total thyroidectomy and subsequently
develops hypoparathyroidism.
The weight of the normal adult thyroid is approximately 15 to 25 gm. The thyroid has a rich
intraglandular capillary network that is supplied by the superior and inferior thyroidal arteries. Nerve
fibers from the cervical sympathetic ganglia indirectly influence thyroid secretion by acting on the
blood vessels. The thyroid is divided by thin fibrous septae into lobules composed of about 20 to 40
evenly dispersed follicles. Normal follicles range from 50 to 500 µm in size, are lined by cuboidal to
low columnar epithelium, and are filled with periodic acid Schiff (PAS)-positive thyroglobulin.
In response to trophic factors from the hypothalamus, TSH (thyrotropin) is released by thyrotrophs
in the anterior pituitary into the circulation. The binding of TSH to its receptor on the thyroid
follicular epithelium results in activation and conformational change in the receptor, allowing it to
associate with a stimulatory G-protein ( Fig. 24-7 ). Activation of the G-protein eventually results in
an increase in intracellular cAMP levels, which stimulates thyroid growth, and hormone synthesis
and release via cAMP-dependent protein kinases. The dissociation of thyroid hormone synthesis
and release from the controlled influence of TSH-signaling pathways results in so-called thyroid
autonomy and hyperfunction (see below).
Figure 24-7 Homeostasis in the hypothalamus-pituitary-thyroid axis and mechanism of action
of thyroid hormones. Secretion of thyroid hormones (T3 and T4) is controlled by trophic factors
secreted by both the hypothalamus and the anterior pituitary. Decreased levels of T3 and T4
stimulate the release of thyrotropin-releasing hormone (TRH) from the hypothalamus and
thyroid-stimulating hormone (TSH) from the anterior pituitary, causing T3 and T4 levels to rise.
Elevated T3 and T4 levels, in turn, suppress the secretion of both TRH and TSH. This
relationship is termed a negative-feedback loop. TSH binds to the TSH receptor on the thyroid
follicular epithelium, which causes activation of G proteins, and cyclic AMP (cAMP)-mediated
synthesis and release of thyroid hormones (T3 and T4). In the periphery, T3 and T4 interact
with the thyroid hormone receptor (TR) to form a hormone-receptor complex that translocates
to the nucleus and binds to so-called thyroid response elements (TREs) on target genes
initiating transcription.
Thyroid follicular epithelial cells convert thyroglobulin into thyroxine (T4) and lesser amounts of
triiodothyronine (T3). T4 and T3 are released into the systemic circulation, where most of these
peptides are reversibly bound to circulating plasma proteins, such as thyroxine-binding globulin
(TBG) and transthyretin, for transport to peripheral tissues. The binding proteins serve to maintain
the serum unbound ("free") T3 and T4 concentrations within narrow limits yet ensure that the
hormones are readily available to the tissues. In the periphery, the majority of free T4 is deiodinated
to T3; the latter binds to thyroid hormone nuclear receptors in target cells with tenfold greater
affinity than does T4 and has proportionately greater activity. The interaction of thyroid hormone
with its nuclear thyroid hormone receptor (TR) results in the formation of a multi-protein
hormone-receptor complex that binds to thyroid hormone response elements (TREs) in target
genes, regulating their transcription (see Fig. 24-7 ).[9] Thyroid hormone has diverse cellular
effects, including up-regulation of carbohydrate and lipid catabolism and stimulation of protein
synthesis in a wide range of cells. The net result of these processes is an increase in the basal
metabolic rate. One of the most important functions of thyroid hormone is its critical role in brain
development, since absence of thyroid hormone during the fetal and neonatal periods may
profoundly interfere with intellectual growth (see below).
The thyroid gland is one of the most responsive organs in the body and contains the largest store
of hormones of any endocrine gland. The gland responds to many stimuli and is in a constant state
of adaptation. During puberty, pregnancy, and physiologic stress from any source, the gland
increases in size and becomes more active. This functional lability is reflected in transient
hyperplasia of the thyroidal epithelium. At this time, thyroglobulin is resorbed, and the follicular cells
become tall and more columnar, sometimes forming small, infolded buds or papillae. When the
stress abates, involution occurs; that is, the height of the epithelium falls, colloid accumulates, and
the follicular cells resume their normal size and architecture. Failure of this normal balance
between hyperplasia and involution can produce major or minor deviations from the usual
histologic pattern.
The function of the thyroid gland can be inhibited by a variety of chemical agents, collectively
referred to as goitrogens. Because they suppress T3 and T4 synthesis, the level of TSH increases,
and subsequent hyperplastic enlargement of the gland (goiter) follows. The antithyroid agent
propylthiouracil inhibits the oxidation of iodide and blocks production of the thyroid hormones;
parenthetically, propylthiouracil also inhibits the peripheral deiodination of circulating T4 into T3,
thus ameliorating symptoms of thyroid hormone excess (see below). Iodide, when given to patients
with thyroid hyperfunction, also blocks the release of thyroid hormones but through different
mechanisms. Iodides in large doses inhibit proteolysis of thyroglobulin. Thus, thyroid hormone is
synthesized and incorporated within increasing amounts of colloid, but it is not released into the
blood.
The thyroid gland follicles also contain a population of parafollicular cells, or C cells, which
synthesize and secrete the hormone calcitonin. This hormone promotes the absorption of calcium
by the skeletal system and inhibits the resorption of bone by osteoclasts.
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