The thyroid gland is an endocrine organ that regulates important processes in the metabolism, growth and cardiac function. However, the function of the thyroid gland itself must also be controlled. In order to understand the causes and symptoms of over- and under-functions of the thyroid, you should understand the regulatory mechanisms and effects of thyroid hormones.

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What is the Thyroid? – Anatomy

The thyroid or glandula thyroidea is an organ of the neck, which is located at the junction between the larynx and the trachea. With its flap areas it encloses the dexter and sinister lobe, the trachea and extends backwards toward the esophagus. Both flap areas are connected with each other via the Isthmus glandulae thyroideae. This can continue cranially as lobus pyramidalis, which is a relic of the migration of the tongue base.

Histologically the thyroid gland is made up of follicles. They are round structures, enclosed by thyrocytes, in which the synthesis of hormones takes place. This can be seen in the colloid that fills the follicles. Slumped follicles or cell clusters, in which no lumen can be distinguished, identify the secreting state. The epithelial cells are then isoprismatic, while they appear flattened in the stored form.

The arterial supply of the thyroid for one occurs cranially via a superior thyroid artery from the external carotid artery and secondly, caudally from the inferior thyroid artery from the truncus thyreocervicalis. A plexus thyroideus impar takes care of venous drainage, which mostly drains the blood into the V. brachiocephalica sinsitra.

A very important topographic relationship is the proximity to the recurrent laryngeal nerve, which runs dorsally along both thyroid lobes. Due to this, thyroid surgery must be performed with extreme caution. An injury of the nerve can result in hoarseness (unilateral lesion), and worst-case scenario in breathlessness (bilateral lesion).

Regulation Axis – Control from Above

The hypothalamus produces TRH, the thyrotropin-releasing hormone. It is a tripeptide, which has emerged from its precursor molecule via limited proteolysis. In addition to the concentration of thyroid hormones in the blood, even cold can be a stimulus for the secretion of TRH. Since TRH is a hydrophilic hormone, it binds to membrane receptors in the pituitary gland s and stimulates the formation and secretion of TSH (thyroidin stimulating hormone).

This is also hydrophilic and binds to receptors in the thyroid gland, which then receive more iodine and synthesize triiodothyronine (T3) and thyroxine (T4). Through TSH the growth of the thyroid gland is also induced. For the purposes of negative feedback, T3 and T4 inhibit the secretion of TRH as well as TSH; TSH also inhibits TRH secretion.

T3 and T4 Synthesis – The Main Task of the Thyroid

In the thyroid gland, iodine is actively added (via sodium-iodide symporters) and elemental iodine is gained via perodidase. In the colloid of the thyroid, iodine is linked to thyreoglobulin. This takes places at the numerous thyroxin residues of the globulin. A residue may be mono- or dual iodinated. They have the name mono- or diiodotyrosine, and represent the storage form of thyroid hormones.

If they are secreted, an intra-molecular coupling of the jodthyroxine residue takes place, which is also referred to as iodine oxidation. An iodinated thyroxin residue is bonded to another via an oxygen bridge. Therefore, this is not considered a peptide bond! The following products can occur during iodine oxidation:

  • Dijodthyrosin + Dijodthyrosin = T4
  • Dijodthyrosin + Monojodthyrosin = T3
  • Monojodthyrosin + Dijodthyrosin = rT3 = reverse T3

The rT3 is an inactive molecule, and is absorbed and dismantled in the thyrocytes.
T3 and T4 are released into the blood and transported bound to TBG (thyroxin-binding globulin), prealbumin or albumin, because they are lipophilic hormones.

The concentration of T4 in the blood is 20x higher than that of T3, although T3 is 3x more effective. Approximately 30 % of the T4 is therefore converted into T3 via deiodase. That makes up about 80 % of the total T3 in the blood, only about 20 % was secreted directly. The background to this subsequent conversion lies in the half-life of both molecules. T3 has a half-life of just one day; T4 on the other hand has a half-life of one week! Therefore, it is extremely useful to release more T4, which remains longer in the blood. In order to utilize the higher efficacy of T3, T4 is converted into T3.

Effects of Thyroid Hormones

Thyroxin binds to intracellular, nuclear receptors, which simultaneously are transcription factors. Together with other activators, the hormone-receptor complex binds to TREs (thyroid hormone responsive elements) of the DNA. This activates the synthesis of certain proteins.

T3 and T4 act on three major areas in the body: metabolism, growth and cardiac function. They increase the activity of sodium-potassium ATPase, so that the basal metabolic rate is increased. This goes hand in hand with increased oxygen consumption. An uncoupling of the respiratory chain leads to an increased heat production. In addition, the organism is stimulated to anabolism: Gluconeogenesis, glycogen, lipolysis and glycolysis are increased.

Through the induction of HMG-CoA reductase the cholesterol formation and connective tissue metabolism increases. T3 and T4 stimulate growth hormone production in the pituitary gland and thus promote the embryonic brain development. Therefore, pregnant and lactating women may have increased iodine needs.

The thyroid hormones perpetrate a contractility and frequency increasing action on the cardiac function. This is done by the induction of β-receptor formation, so that the catecholamine sensitivity is increased. Likewise, the myocyte forms increased myosin after stimulation and also contributes to an increased contractile force.

Functional Disorders – Small Gland, but Far-Reaching Consequences

Based on the knowledge about the effects of thyroid hormones, the consequences that follow a functional disorder of the endocrine organ can be easily deduced.
Hyperthyroidism is a condition in which too much T3 and T4 are produced. Accordingly, the effects amplified (compare above):

  • Weight loss (slender figure)
  • Increased appetite
  • Anxiety, sleep disorder
  • Heat intolerance (warm hands)
  • Increased perspiration
  • Increased bowel movements to diarrhea
  • Tremors
  • Tachycardia
  • Hypertension
  • Greasy hair, hair loss
  • Cycle or fertility disorder

If too little T3 and T4 are produced, whether due to an iodine deficiency or a dysfunction, this is called hypothyroidism. The effects are reduced accordingly:

  • Mental and physical degradation, concentration disturbances
  • Disinterest, lack of motivation, depression
  • Increased need for sleep
  • Cretinism (when innate): mental retardation, dwarfism, speech disorders
  • Constipation tendency
  • Cold intolerance
  • Bradycardia
  • Myxedema
  • Goiter (enlarged thyroid)
  • Dry skin, brittle hair
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