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Thyroid: I Thyroid Gland and Thyroid Hormones


Thyroid: I Thyroid Gland and Thyroid Hormones
Clinical scenario
Nodular thyroid disease is common, affecting approximately 5% of the female population over the age of 50. Women are affected more commonly than men and the incidence increases with age. A 59-year-old lady, Mrs RB, presented with a long history of a swelling in the anterior neck. This had gradually increased in size over the years and had now become quite obviously visible. She had no dysphagia or dyspnoea, the thyroid gland was not painful, she did not have a hoarse voice and there was no history of previous radiotherapy treatment to the neck. She had no symptoms to suggest abnormal thyroid hormone production and on examination she was clinically euthyroid. The thyroid gland was asymmetrically enlarged with a 3 × 4 cm nodule palpable in the right lobe together with three other palpable nodules. The gland moved freely on swallowing and there was no associated lymphadenopathy. Her thyroid function tests were normal as follows: fT4 18.3 pmol/L; TSH 0.85 mU/L; thyroid antibodies negative. Thyroid ultrasound scanning revealed a multinodular goitre. Fine-needle aspiration of the dominant nodule was performed and cytology of the aspirate showed no evidence of malignant cells. She decided to undergo conservative management with regular clinical follow-up.

Clinical management of patients with nodular thyroid disease depends upon excluding the presence of malignant disease and then treating the goitre according to its size, patient preference and the likelihood of compression of other structures in the neck and mediastinum (Fig. 13a). In patients with compressive symptoms, CT scanning will reveal the extent of pressure on adjoining structures in the neck.

Thyroid: I Thyroid Gland and Thyroid Hormones, Thyroid gland: anatomy and structure, Thyroid hormones, Mechanism of action of thyroid hormone

Thyroid gland: anatomy and structure In humans, the thyroid gland is situated anteriorly in the neck (Fig. 13b), and its function is the synthesis and secretion of the thyroid hormones thyroxine (T4) and tri-iodothyronine (T3). These hormones are essential for normal development and growth and for homoeostasis in the body by regulating energy production. The parathyroid glands, which secrete parathyroid hormone (see Chapter 49) are embedded in the thyroid gland, and the parafollicular cells, which are scattered between the thyroid follicles, produce calcitonin (see Chapter 50). The human thyroid gland begins to develop at around 4 weeks after conception, and moves down the neck while forming its characteristic bilobular structure, which is completed by the third trimester.
In the normal adult, the gland has two lobes, weighs around 25 g and is situated close to the trachea (Fig. 13b). The gland is composed of well over a million clusters of cells, or follicles. These are spherical and consist of cells surrounding a central space containing a jelly-like substance known as colloid, whose function is to store thyroid hormones prior to their secretion. Each thyroid cell has three functions: (i) exocrine, because it secretes substances into the colloid; (ii) absorptive, because it takes up substances from the colloid by pinocytosis; and (iii) endocrine, because it secretes hormones directly into the bloodstream.

Thyroid hormones
Synthesis. The follicle cells have in their basement membrane an iodide-trapping mechanism which pumps dietary iodide into the cell (Fig.13c). The pump is very powerful, and the cell can concentrate iodide to 25–50 times its concentration in the plasma. Thyroid iodine content is normally around 600 μg/g tissue.

Uptake enhancers include: (i) TSH; (ii) iodine deficiency; (iii) TSH receptor antibodies; and (iv) autoregulation. Uptake inhibitors include: (i) I ions; (ii) cardiac glycosides (e.g. digoxin); (iii) thiocyanate (SCN); and (iv) perchlorate (PClO). Inside the cell, iodide is rapidly oxidized by a peroxidase system to the more reactive iodine, which immediately reacts with tyrosine residues on a thyroid glycoprotein called thyroglobulin, to form monoiodotyrosyl (T1) or diiodotyrosyl (T2) thyroglobulin. These then couple to form tri-iodothyronine (T3) or thyroxine (T4) residues (Fig. 13d), still attached to thy-roglobulin, which is stored in the colloid (i.e. Tl + T2 = T3;
T2 + T2 = T4). This process is stimulated by TSH.
Under TSH stimulation, colloid droplets are taken back up into the cell cytoplasm by micropinocytosis, where they fuse with lysosomes and are proteolysed to release the residues from the glycoprotein. T1 and T2 are rapidly deiodinated by halogenases, and the liberated iodine is recycled in the follicle cell. Tri-iodothyronine and thyroxine (Fig. 13e) are released into the circulation, where they are bound to plasma proteins, including thyroxine-binding globulin (TGB), thyroxine-binding prealbumin (TBPA) and albumin (see Chapter 15). Most is bound and physiologically inactive, while only the free fraction is active. Metabolism (Fig. 13e). The thyroid secretes a total of 80–100 μg of T3 and T4 per day, and the ratio of T4:T3 is about 20:1. Although both T3 and T4 circulate, the tissues obtain 90% of their T3 by deiodinating T4. Iodide liberated from thyroid hormone is excreted in the urine or is recirculated to the thyroid, where it is concentrated by the trapping mechanism. About one-third of T4 leaving the plasma is conjugated with glucuronide or sulphate in the liver and excreted in the bile. A small proportion of the free T4 is reabsorbed via the enterohepatic circulation. The half-life of T4 in the plasma is about 6–7 days; that of T3 is very much shorter, being about 1 day. T3 is much more potent than is T4.

Mechanism of action of thyroid hormone. There are multiple sites of action of T3 in the cell. At the membrane, the hormone stimulates the Na+/K+–ATPase pump, resulting in increased uptake of amino acids and glucose, which causes calorigenesis (heat production). T3 combines with specific receptors on mitochondria to generate energy and with intranuclear receptors which are transcription modulators, resulting in altered protein synthesis.