Thyroid Gland

last authored:
last reviewed:

 

 

Introduction

The thyroid is an important endocrine gland located below the larynx, in front of the trachea. The two bulky lobes of the thyroid wrap part of the way around the trachea, connected by the isthmus. The four small parathyroid glands are embedded in the back of the thyroid, and the recurrent paryngeal nerves run closely alongside the thyroid.

 

The adult thyroid is normally 15-25 gm, and is divided into 20-40 evenly dispersed follicles by thin fibrous septae. Follicles range from 50-500 µm in size and are comprised of cuboidal or low columnar epithelium. Follicles surround colloid.

 

The thyroid produces two main hormones. Thyroxine (T₄) and its more active counterpart triidothyronine (T₃) regulate body metabolism, while calcitonin decreases the rate of bone breakdown.

return to top

 

 

 

Physiologic Functions

Thyroxine (T4) and Triidotheronine (T3)

Thyroid hormones have wide-ranging metabolic effects on liver, kidney, muscle, and other tissues. Many of these increase the adrenaline response.

 

Metabolism: Thyroxine's increases ATP production in nearly all cells, raising the basal metabolic rate (BMR). Carbohydrate and lipid catabolism is increased.

 

Cardiovascular System: Thyroxine is ionotropic and chronotropic, increasing cardiac output.

• acts on myosin
• increases systole and diasole

Sympathetic Nervous System: increases adrenergic receptors in skeletal muscle, adipose tissue, and lymphocytes.

 

 

Regulation of Secretion

The hypothalamus secretes TRH, or thyrotropin-releasing hormone, into the median eminence. This hormone diffuses to the anterior pituitary, where GPCRs on thyrotrophs respond by secreting TSH into the circulation. Somatostatin and dopamine, released from the hypothalamus, can inhibit TSH release from the pituitary.

 

TSH binds to the GPCR TSH receptor on thyroid follicular cells, activating adenylyl cyclase and cAMP. This stimulates thyroid growth and causes synthesis and release of thyroid hormones T₃ and T₄. T3 and T4 provide negative feedback to the hypothalamus and pituitary.

Conditions that increase TRH and TSH include:

• cold temperatures

 

During puberty, pregnancy, and physiologic stress, the thyroid increases in size through transient hyperplasia and becomes more active. Follicular cells become taller and more columnar, sometimes forming small inward folds or papillae.

 

 

T₃ and T₄ Biosynthesis

Iodide is taken up by thyroid follicular cells via a Na/I symporter. TSH binding induces synthesis of thyroglobulin fromtyrosine, which is deposited in the colloid for storage and combination with iodide to produce T₃ and T₄. Once returned to the cytosol, T₃ and T₄ are cleaved and released into the circulation.

T 1/2 is about 1 week for T4.

 

 

Peripheral Effects

Transport

Both T₃ and T₄ are transported bound to thyroixin-binding globulin (TBG) and enter cells by transport of diffusion. This keeps free levels low while maintaining a ready supply of hormone. While T4 levels are higher, T3 is 10x more active, and once inside the cytosol of target cells, T4 is converted to T3. Conversion in both ways is possible.

 

 

 

Cellular Signaling

Thyroid hormones are not steroids, but they are lipid soluble and activate nuclear receptors to activate transcription.

T3 and T4 bind to the thyroid hormone receptor, a member of the nuclear receptor superfamily. It dimerizes with the retinoic acid receptor and binds to TREs on the DNA, activating mulitiple targets including Na-K ATPase, beta adrenergic receptors in the heart, and proteins mediating thermogenesis and lipolysis.

 

 

 

Inhibition of Production

The thyroid can be inhibited by a variety of agents which suppress T3 and T4 synthesis. This increases levels of TSH, leading to hyperplastic enlargement and goiter formation.

Propylthiouracil inhibits the oxidation of iodide and blocks production of thyroid hormones.

 

 

 

Calcitonin

Calcitonin, is produced by parafollicular (C) cells of the thyroid.

a thyroid hormone, increases bone density by increasing bone uptake of calcium and decreasing bone breakdown by osteoclasts.

High blood levels of calcium increase calcitonin release, facilitating its uptake by bone.

Calcitonin is particularly important for the growth and development of children, and once adulthood hits, response to calcitonin decreases.

While calcitonin is not necessary for normal calcium homeostasis, it acts to decrease plasma calcium levels in two ways:

• inhibits bone osteoclasts, decreasing calcium and phosphate resorption
• increases kidney excretion of calcium by decreasing tubular resorption

Calcitonin is being used as a treatment for osteoporosis, acting to reduce trabecular bone loss and risk of fracture.

 

Calcitonin can also be used for acute compression fractures for pain control.

 

 

Resources and References

return to top