Anatomy and Physiology

Thyroid Gland

Figure
1: Thyroid Gland

The thyroid gland is a ductless alveolar gland. It regulates growth, metabolism and energy use. It
is the far largest gland in the neck and shaped in the form of a butterfly located in the throat in front of
the larynx. It is comprised of two halves, known as lobes, which are attached by a band of thyroid tissue
called the isthmus.

The major functional cells of the thyroid are the follicular cells. These are arranged into hollow
spheres that form a functional unit termed a follicle. Within these follicles is a central lumen containing
colloid; the extracellular storage site for thyroid hormone. Colloid is composed largely of thyroglobulin
(Tg) a glycoprotein involved in thyroid hormone synthesis. Parafollicular C cells secrete calcitonin, a
hormone involved in calcium regulation.

Hypothalamic-pituitary-thyroid axis

Thyroid hormone release is controlled by the hypothalamic-pituitary-thyroid axis.

1. Thyrotropin releasing hormone

TRH is secreted from the paraventricular nucleus of the hypothalamus. As the name suggests it is a
tropic hormone i.e one that acts upon another endocrine gland. It reaches the anterior pituitary via the
hypophyseal portal system. Here it causes the release of thyroid stimulating hormone.

2. Thyroid stimulating hormone

TSH, produced by the thyrotrophs of the anterior pituitary, is released following stimulation by TRH.
Transported in the blood, TSH acts upon the thyroid gland promoting the synthesis and release of
thyroid hormone.

3. Triiodothyronine and thyroxine

The thyroid is stimulated to synthesize and release thyroid hormone by TSH. The thyroid produces two
hormones, thyroxine (T4) and triiodothyronine (T3). These thyroid hormones complete a negative
feedback loop through the suppression of TRH and TSH release. Though T3 is more biologically active
than its counterpart T4, secreted thyroid hormone is 90% T4. Peripherally much of T4 is converted to T3.
Both are highly lipophilic, act on intracellular receptors and bind to thyroxine-binding globulin (TBG) in
the blood. Only the ‘free pool’ is active: <0.1% T4 and <1% of T3.

The effects to T3/T4 are numerous:

 BMR: increases the basal metabolic rate.

 Metabolism: it has anabolic effects at low serum levels and catabolic effects at higher levels.
 Growth: increases release and effect of GH and IGF-1.
 Cardiovascular: increases the heart rate and contractility through increasing sensitivity to
catecholamines.

Thyroid hormone synthesis

Thyroid hormone has two constituents, tyrosine and iodine. Tyrosine (amino acid) is synthesized by the
body while iodine is obtained in the diet and reduced to iodide before being absorbed in the small
intestines. These building blocks are assembled on the glycoprotein thyroglobulin (Tg) and synthesis
occurs in the central colloid.

1. Preparation

Iodide enters the cell across the basolateral membrane via a sodium symporter. This process is driven by
secondary active transport mediated by a Na+/K+-ATPase pump. At the luminal membrane, iodide is
activated by thyroperoxidase (TPO) before entering the colloid via the ion exchanger Pendrin.

Thyroglobulin, containing tyrosine, is produced by Golgi complexes and the endoplasmic reticulum in
the follicular cells. The thyroglobulin/tyrosine complex is exocytosed across the luminal membrane into
the colloid.

2. Synthesis

Within the colloid, one iodide may attach to a tyrosine (attached to a thyroglobulin) to form
monoiodotyrosine (MIT). This reaction is catalysed by TPO. A second iodide may attach to MIT to form
di-iodotyrosine (DIT). Coupling of MIT and DIT yield the thyroid hormones. One MIT and one DIT gives
triiodothyronine (T3) while two DITs give thyroxine (T4).

3. Release

When stimulated (by TSH) the surrounding follicular cells phagocytose a portion of the colloid. Once
within the follicular cell, this vesicle is subject to lysosomes which act to release the T3/T4 from Tg.
The thyroid hormones T3/T4 may then diffuse into the blood stream. Any remaining MIT and DIT is
deiodinated (a reaction catalysed by iodinase) and recycled.

Calcitonin

Calcitonin is produced by the parafollicular C cells. Calcitonin release is stimulated by increases in serum
calcium. It acts to lower calcium through its action on numerous tissues:

 Intestines: Reduces calcium absorption

 Bones: Stimulates osteoblasts, inhibits osteoclasts
 Kidneys: Inhibits phosphate reabsorption

It is not an essential hormone, following thyroidectomy no hormonal replacement of calcitonin is

required.