Thyroid Gland Physiology Notes

Thyroid Gland Introduction

• Thyroid is an endocrine gland situated at the root of the neck on either side of the trachea. It has two lobes, which are connected in the middle by an isthmus.
• Normally, the weight of thyroid is about 20-40 gm in adults but it is subjected to variations even under physiological conditions. Thyroid is larger in females than in males.
• The structure and the function of the thyroid gland change in different stages of the sexual cycle in females. Its function increases slightly during pregnancy and lactation and decreases during menopause.
• Thyroid gland starts functioning in the fetal life itself. However, the maximum activity of the gland is achieved only after puberty. Diseases of thyroid gland are more common in females than in males.

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Histology Of Thyroid Gland

• The thyroid gland is composed of large number of closed follicles. The follicles are lined with cuboidal epithelial cells, which are called the follicular cells. The follicular cavity is filled with a colloidal substance known as thyroglobulin which is secreted by the follicular cells.
• Follicular cells secrete tetraiodothyronine (T₄ or thyroxine) and tri-iodothyronine (T₃). In between the follicles, the parafollicular cells are present. These cells secrete calcitonin.
• Thyroid receives very rich blood supply. The amount of blood received by thyroid per minute is five times more than its weight.

Hormones Of Thyroid Gland

Thyroid gland secretes three hormones:

1. Tetraiodothyronine – T₄ (thyroxine)
2. Tri-iodothyronine – T₃
3. Calcitonin.

• Chemistry and Potency: Both T₄ and T₃ are iodine-containing derivatives of amino acid tyrosine. T₄ is otherwise known as thyroxine and it forms about 90% of the total secretion, whereas, T₃ is only 9-10%. But the potency of T₃ is four times more than that of T₄.
• Duration of Action:
  • T₄ acts for longer period than T₃. The duration of T₄ action is four times more than T₃ action. This is because of the difference in the affinity of these hormones to plasma proteins.
  • T₃ has less affinity for plasma proteins and combines loosely with them so that it is released quickly. T₄ has more affinity and strongly binds with plasma proteins so that it is released slowly. Therefore, T₃ acts on the target cells immediately and T₄ acts slowly.
• Half-life: The thyroid hormones have long half-life. T₄ has a long half-life of 7 days. The half-life of T₃ is varying between 10 and 24 hours.

Synthesis Of Thyroid Hormones

• Synthesis of thyroid hormones takes place in thyroglobulin present in the follicular cavity. Iodine and tyrosine are essential for the formation of thyroid hormones. Iodine is consumed through diet. It is converted into iodide and absorbed from Gl tract. Tyrosine is also consumed through diet and is absorbed from the Gl tract.
• For the synthesis of normal quantities of thyroid hormones, approximately 1 mg of iodine is required per week or about 50 mg per year. To prevent iodine deficiency, common table salt is iodized with one part of sodium iodide to every 100,000 parts of sodium chloride.

Stages Of Synthesis Of Thyroid Hormones: Various stages involved in the synthesis of thyroid hormones are:

1. Thyroglobulin synthesis
2. Iodide trapping or iodide pump
3. Oxidation of iodide
4. iodination of tyrosine
5. Coupling reactions.

1. Thyroglobulin Synthesis

• The endoplasmic reticulum and Golgi apparatus in the follicular cells of the thyroid gland synthesize and secrete a large glycoprotein molecule called thyroglobulin.
• Each thyroglobulin molecule contains 140 molecules of amino acid tyrosine. Synthesis of thyroglobulin occurs continuously. After synthesis, the thyroglobulin is stored in the follicle.

2. Iodide Trapping or Iodide Pump

• Iodide is transported actively from the blood into the follicular cell against the electrochemical gradient by a process called iodide trapping.
• A sodium-iodide symport pump called iodide pump carries iodide along with sodium into the follicular cell. From here, iodide is transported into the follicular cavity by an iodide-chloride pump called pendrin.
• Normally, iodide is 30 times more concentrated in the thyroid gland than in the blood. However, during hyperactivity of the thyroid gland, the concentric iodide increases 200 times more.

3. Oxidation of the Iodide:

• Iodide must be oxidized to elementary iodine because only iodine is capable of combining with tyrosine to form thyroid hormones. The oxidation of iodide into iodine occurs inside the follicular cells.
• The process of oxidation is promoted by the enzyme thyroid peroxidase. The absence or inactivity of thyroid peroxidase can totally stop the production of thyroid hormones.

4. Iodination of Tyrosine

• The combination of iodine with tyrosine is known as iodination. It takes place in the follicle within thyroglobulin. First, iodine is released from follicular cells into the follicular cavity where it binds with thyroglobulin.
• This process is called the organification of thyroglobulin. Tyrosine is already present in thyroglobulin. Within thyroglobulin, iodine combines with tyrosine.
• The binding of iodine with tyrosine is a very slow process. However, the enzyme iodinase secreted by the follicular cells accelerates the process.
• lodination of tyrosine occurs in several stages. Tyrosine is iodized first into monoiodotyrosine (MIT) and later into di-iodotyrosine (DIT). MIT and DIT are called iodothyronine residues.

5. Coupling Reactions

• The iodotyrosin resides get coupled with one another through the reactions called coupling reactions. The coupling occurs in different configurations to give rise to different thyroid hormones.
• One molecule of DIT and one molecule of MIT combine to form tri-iodothyronine (T₃)
• Sometimes one molecule of MIT and one molecule of DIT combine to produce another form of T₃ called reverse T₃ or rT₃. Reverse T₃ is only 1% of thyroid output
• Two molecules of DIT combine to form tetraiodo- thyronine (T₄) which is thyroxine.

Tyrosine + I = Monoiodotyrosine (MIT)

MIT + l₂ = Di-iodotyrosine (DIT)

DIT + MIT = Tri-iodothyronine (T₃)

MIT + DIT = Reverse T₃

DIT + DIT = Tetraiodothyronine or Thyroxine (T₄)

Storage Of Thyroid Hormones

• After synthesis, the thyroid hormones remain in the form of vesicles within thyroglobulin. Each thyroglobulin molecule contains 5 or 6 molecules of thyroxine.
• There is also an average of 1 tri-iodothyronine molecule for every 10 molecules of thyroxine. In this way, i.e. in combination with thyroglobulin, the thyroid hormones can be stored for several months.
• And, thyroid gland is unique in this, as it is the only endocrine gland that can store its hormones for a long period of about 4 months. So, when the synthesis of thyroid hormone stops, the signs, and symptoms of deficiency do not appear for about 4 months.

Release Of Thyroid Hormones From The Thyroid Gland

Thyroglobulin itself is not released into the bloodstream. On the other hand, the hormones are first cleaved from the thyroglobulin. The release of thyroid hormones into the blood occurs through a series of activities:

1. The plasma membrane of the follicular cell sends foot-like extensions called pseudopods, which close around the thyroglobulin-hormone complex. A receptor-like substance called megalin which is present in the membrane of follicular cells mediates this process
2. The pseudopods convert thyroglobulin – hormone complex into small pinocytic vesicles
3. Then, the lysosomes of the cell fuse with the vesicles
4. The lysosomes contain some digestive enzymes like proteinases which digest (proteolysis) the thyroglobulin and release the hormones
5. Now, the hormones diffuse through the base of the follicular cell and enter the capillaries.

• Only T₃ and T₄ are released into the blood. In the peripheral tissues T₄ is converted into T₃. A small amount: of reverse T₃ is also formed. Reverse T₃ is biologically inactive form of T₃ that is produced when T₄ is converted into T₃.
• The MIT and DIT are not released into blood. These iodotyrosine residues are deiodinated by an enzyme called iodotyrosine deiodinase resulting in release of iodine.
• The iodine is reutilized by the follicular cells for synthesis of thyroid hormones. During congenital absence of iodotyrosine deiodinase, MIT and DIT are excreted in urine and the symptoms of iodine deficiency develop.

Rate Of Secretion: The rate of secretion of thyroid hormones per day:

Thyroxine: 80-90 pg

Tri-iodothyronine: 4-5 pg

Reverse T₃: 1-2 pg

Transport Of Thyroid Hormones In The Blood

• The thyroid hormones are transported in The blood in combination with the plasma proteins.
• The normal plasma level of total T₃ is 0.12 pg/dL and that of total T₄ is 8 pg/dL.
• Thyroid hormones are transported in the blood by three types of proteins:

1. Thyroxine binding globulin (TBG)
2. Thyroxine-binding prealbumin (TBPA)
3. Albumin.

1. Thyroxine Binding Globulin (TBG): It is a glycoprotein and its concentration in the blood is 1-1.5 mg/dL. It has a great affinity for thyroxine and about one-third of the hormone combines strongly with this protein.

2. Thyroxine Binding Prealbumin (TBPA): TBPA transports one-fourth of the thyroid hormones. It is also called transthyretin (TTR).

3. Albumin: Albumin transports about one-tenth of the thyroid hormones.

Metabolism Of Thyroid Hormones: Thyroid hormones are metabolized by several methods. Degradation of thyroid hormones by deamination and decarboxylase reactions occurs in the peripheral tissues and liver. Degradation by conjugation with sulfate or glucuronic acid occurs in liver. Conjugation also occurs if; kidney to a lesser degree.

Mode Of Action Of Thyroid Hormones

• After entering the peripheral tissues (particularly the liver, muscle, and kidney) most of the T₄ is deiodinated to form T₃. So it is believed that the true intracellular hormor is principally T₃ rather than T₄.
• Moreover, T₃ is found freely in the plasma and T₄ is usually bound with plasma proteins. So, at the site of action, T₃ acts more quickly than T₄. Thyroid hormones act by activating the genes.
• In addition, the thyroid hormone also acts at mitochondrial level by stimulating the synthesis of proteins and RNA.

The sequence of events of the mode of action of thyroid hormones:

• Before acting on the genes to increase genetic transcription, almost all the T₄ molecules are converted into T₃ molecules
• T₃ has got a very high binding affinity for the cellular thyroid hormone receptors (TR). The receptors are either attached to DNA genetic strands or in close proximity to them
• The TR is always bound to another receptor called retinoid X receptor (RXR). The exact role of RXR is not clear. Thyroid hormones bind with receptors and form the hormone-receptor complex
• This complex initiates the transcription process by activating the enzymes such as RNA polymerase and phosphoprotein kinases
• It also stimulates the synthesis of nuclear proteins. Thus, a large number of mRNA is formed, which activate the ribosomes to synthesize the new proteins
• The new proteins are involved in many activities including enzymatic actions.

Functions Of Thyroid Hormones

Thyroid hormones have two major effects on the body:

1. To increase the overall metabolic rate in the body
2. To stimulate growth in children.

The actions of thyroid hormones are:

1. On Basal Metabolic Rate
   • Thyroxine increases the metabolic activities of almost all tissues of the body except brain, retina, spleen, testes, and lungs. It increases the basal metabolic rate (BMR) by increasing the oxygen consumption of the tissues.
   • It also increases the rate of utilization of foodstuffs in the peripheral cells. The action that increases the BMR is called calorigenic action.
   • In hyperthyroidism BMR increases by about 60-100% above the normal level and in hypothyroidism it falls by 20-40% below the normal level.
2. On Protein Metabolism: Thyroid hormone increases the synthesis of proteins in the cells. The protein synthesis is accelerated by the following ways:
   1. By Increasing the Translation of RNA: Thyroid hormone increases the translation of RNA in the cells. Because of this, the ribosomes are activated and more proteins are synthesized.
   2. By Increasing the Transcription of DNA to RNA: Thyroid hormone also stimulates the transcription of DNA to RNA. This in turn accelerates the synthesis of proteins in the cells.
   3. By Increasing the Activity of Mitochondria:
      • In addition to acting at the nucleus, thyroid hormone acts at the mitochondrial level also. It increases the number and the activity of mitochondria in most of the cells of the body.
      • Thyroid hormone accelerates the synthesis of RNA and other substances from mitochondria by activating series of enzymes. In turn, the mitochondria increase the production of ATP, which is utilized for energy required for cellular activities.
      • Though thyroxine increases synthesis of protein, it also causes catabolism of proteins.
   4. By Increasing the Activity of Cellular Enzymes: Thyroid hormones also increase the activity of at least 100 or more intracellular enzymes such as alpha glycerophosphate dehydrogenase and oxidative enzymes. These enzymes accelerate the metabolism of proteins and the carbohydrates.
3. On Carbohydrate Metabolism: Thyroxine stimulates almost all processes involved in the metabolism of carbohydrate.
   • Thyroxine:
     1. Increases the absorption of glucose from Gl tract
     2. Enhances the glucose uptake by the cells, by accelerating the transport of glucose through the cell membrane
     3. Increases the breakdown of glycogen into glucose
     4. Accelerates gluconeogenesis.
4. On Fat Metabolism: Thyroxine decreases the fat storage by mobilizing it from adipose tissues and fat depots. The mobilized fat is converted into free fatty acid and transported by blood. Thus, thyroxine increases the free fatty acid level in blood.
5. On Plasma And Liver Fats
   • Even though there is an increase in the blood level of free by acids, thyroxine specifically decreases the cholesterol, phospholipids, and triglyceride levels in the plasma. So, in hyposecretion of thyroxine, the cholesterol level in plasma increases resulting in atherosclerosis.
   • Thyroxine also increases deposition of fats in the liver leading to fatty liver. Thyroxine decreases plasma cholesterol level by increasing its excretion from liver cells into bile. Cholesterol enters the intestine through bile and, then it is excreted through the feces.
6. On Vitamin Metabolism: Thyroxine increases the formation of many enzymes. Since the vitamins form the essential parts of the enzymes it is believed that the vitamins may be utilized during the formation of the enzymes. Hence, vitamin deficiency is possible during hypersecretion of thyroxine.
7. On Body Temperature: Thyroid hormone increases the heat production in the body by accelerating various cellular metabolic processes and increasing BMR. It is called thyroid hormone-induced thermogenesis. During hypersecretion of thyroxine, the body temperature increases greatly resulting in excess sweating.
8. On Growth
   • Thyroid hormones have general and specific effects on growth. Lack of thyroxine arrests the growth and increase in thyroxine secretion accelerates the growth of the body especially in growing children.
   • At the same time, the closure of epiphysis occurs at an early age under the influence of thyroxine. So, the height of the individual may be slightly less.
     Thyroxine is more important to promote growth and development of the brain during fetal life and the first few years of postnatal life.
9. Effect On Body Weight: Thyroxine is essential for maintaining the weight of the body. Increase in thyroxine secretion decreases the body weight and fat storage, and a decrease in thyroxine secretion increases the body weight because of fat deposition.
10. Effect On Blood: Thyroxine increases the production of RBCs. It is one of the important general factors necessary for erythro- poiesis. Thyroxine accelerates the process of erythropoiesis and increases blood volume. So, polycythemia is common in hyperthyroidism.
11. On Cardiovascular System: Thyroxine increases overall activity of cardiovascular system:
    1. On Heart Rate: Thyroxine has a direct effect on heart and increases heart rate. It is an important clinical investigation for diagnosis of hypothyroidism and hyperthyroidism.
    2. On the Force of Contraction of the Heart:
       • Due to its effect on enzymatic activity, thyroxine generally increases the force of contraction of the heart. But in hyperthyroidism or in thyrotoxicosis, the heart may become weak due to excess activity and protein catabolism.
       • So, the patient may die of cardiac decompensation. Cardiac decompensation refers to failure of the heart to maintain adequate circulation associated with dyspnea, venous engorgement (veins overfilled with blood), and edema.
    3. On Blood Vessels: Due to increased metabolic activity by thyroxine, a large quantity of metabolites is produced. The metabolites cause vasodilatation and so, the blood flow increases.
    4. On Arterial Blood Pressure: Because of increase in rate and force of contraction of the heart, increase in blood volume and blood flow by the influence of thyroxine, cardiac output increases. This in turn, increases the blood pressure. But, generally, the mean pressure is not altered. Systolic pressure increases and the diastolic pressure decreases. So, only the pulse pressure increases.
12. Effect On Respiration
    • Thyroxine increases the rate and force of respiration indirectly. The increased metabolic rate (caused by thyroxine) increases the demand for oxygen and formation of excess carbon dioxide.
    • These two factors stimulate the respiratory centers to increase the rate and force of respiration.
13. On Gastrointestinal Tract: Generally, thyroxine increases the appetite and food tasks. It also increases the secretions and movements of GI tract. So hypersecretion of thyroxine causes diarrhea and the lack of thyroxine causes constipation.
14. On Central Nervous System: Thyroxine is very essential for the development and maintenance of normal functioning of the central nervous system.
    1. On Development of Central Nervous System: Thyroxine is very important to promote growth and development of the brain during fetal life and during the first few years of postnatal life. Thyroid deficiency in infants results in abnormal development of synapses, defective myelination and mental retardation.
    2. On the Normal Function of Central Nervous System:
       • Thyroxine is a stimulating factor for the central nervous system particularly, the brain. Thus, the normal functioning of the brain needs the presence of thyroxine. Thyroxine also increases the blood flow to brain.
       • Thus, during the hypersecretion of thyroxine there is excess stimulation of the central nervous system. So, the person is likely to have extreme nervousness and may develop psychoneurotic problems such as anxiety complexes, excess worries, or paranoid thoughts (the persons think without justification, that other people are plotting or conspiring against them or harassing them).
       • Hyposecretion of thyroxine leads to lethargy and somnolence (excess sleep).
15. On Skeletal Muscle
    • Thyroxine is essential for the normal activity of the skeletal muscles. Slight increase in thyroxine level makes the muscles to work with more vigor.
    • But, hypersecretion of thyroxine causes weakness of the muscles due to the catabolism of proteins. This condition is called thyrotoxic myopathy.
    • The muscles relax very slowly after the contraction. Hyperthyroidism also causes fine muscular tremor. The tremor occurs at the frequency of 10-15 times per second. It is due to the thyroxine-induced excess neuronal activity, which controls the muscle. And, the lack of thyroxine makes the muscles more sluggish.
16. On Sleep: Hypersecretion of thyroxine causes excessive stimulation of the muscles and central nervous system. So, the person feels tired, exhausted, and feeis like sleeping. But, the person cannot sleep because of the stimulatory effect of thyroxine on neurons. On the other hand, hyposecretion of thyroxine causes somnolence,
17. On Sexual Function
    • A normal thyroxine level is essential for normal sexual function. In men, hyposecretion of thyroid hormones leads to complete loss of libido (sexual drive). And hypersecretion of thyroid hormones leads to impotence.
    • In women, hyposecretion of thyroid hormones causes menorrhagia and polymenorrhea. In some women, it causes irregular menstruation and occasionally amenorrhea. Hypersecretion of thyroid hormones in women leads to oligomenorrhea and sometimes amenorrhea.
18. On Other Endocrine Glands: Because of its metabolic effects, thyroxine increases the demand for secretion of other endocrine glands.

Regulation Of Secretion Of Thyroid Hormones

Many factors are involved in the regulation of thyroid secretion.

Factors increasing the secretion of thyroid hormones:

1. Low basal metabolic rate
2. Leptin
3. α melanocyte-stimulating hormone

Factors decreasing the secretion of thyroid hormones:

1. Excess iodide intake
2. Stress
3. Somatostatin
4. Glucocorticoids
5. Dopamine.

All these factors act through the pathway as given. The secretion of thyroid hormones is controlled by anterior pituitary and hypothalamus through a feedback mechanism.

Role Of Pituitary Gland

• Thyroid Stimulating Hormone: Thyroid stimulating hormone (TSH) secreted by anterior pituitary is the major factor regulating the synthesis and release of thyroid hormones. It is also necessary for the growth and the secretory activity of the thyroid gland. Thus, TSH influences every stage of formation and release of thyroid hormones.
• Chemistry: TSH is a peptide hormone with one a chain and one chain.
• Half-life and Plasma Level: Its half-life is about 60 minutes. The normal plasma level of TSH is approximately 2 U/mL.
• Actions of TSH
  • TSH increases:
    • The number of thyroid cells, which are cuboidal in nature, then it converts them into columnar cells and causes the development of thyroid follicles
    • The size and secretory activity of the cells
    • The iodide pump and iodide trapping in the cells
    • The thyroglobulin secretion into the follicles
    • lodination of tyrosine and coupling to form the hormones
    • Proteolysis of the thyroglobulin, by which, the release of hormone is enhanced and the colloidal substance is decreased.
  • The immediate effect of TSH is proteolysis of the thyroglobulin, by which, thyroxine is released within 30 minutes. The effect of TSH on other stages in thyroxine synthesis takes place after some hours, days, or weeks.
• Mode of Action of TSH: TSH acts through cyclic AMP mechanism.

Role Of Hypothalamus

• Hypothalamus regulates thyroid secretion by controlling TSH secretion through thyrotropic releasing hormone (TRH). TRH is secreted by the nerve endings in the median eminence of hypothalamus.
• From the hypothalamus, it is transported through the hypothalami-hypophyseal portal vessels to the anterior pituitary. After reaching the pituitary gland, the TRH causes the release of TSH.

Feedback Control: Thyroid hormones regulate their own secretion through negative feedback control by inhibiting the release of TRH from the hypothalamus and TSH from anterior pituitary.

Role Of Iodide:

• Iodide is an important factor regulating the synthesis of thyroid hormones. When the dietary level of iodine is moderate, the blood level of thyroid hormones is normal.
• However, when iodine intake is high, the enzymes necessary for the synthesis of thyroid hormones are inhibited by iodide itself resulting in the suppression of hormone synthesis. This effect of iodide is called the Wolff-Chaikoff effect.

Role Of Other Factors

• Many other factors are involved in the regulation of thyroid secretion in accordance to the needs of the body. Leptin (from adipose tissue) and a melanocyte-stimulating hormone (from the pituitary) increase the release of TRH and synthesis of T₄. The low body temperature also stimulates the synthesis of thyroid hormones.
• However, this happens only in infants. Stress, somatostatin, glucocorticoids, and dopamine decrease the secretion of T₄ by inhibiting the release of TRH.

Applied Physiology Disorders Of Thyroid Gland

1. Hyperthyroidism: Increased secretion of thyroid hormones is called hyperthyroidism. One of the causes of hyperthyroidism is Graves’ disease, which is an autoimmune disease. In addition, hyperthyroidism occurs because of other causes also.

• Causes for Hyperthyroidism
  1. Graves’ disease
     • Graves’ disease is an autoimmune disease and it is the moot common cause of hyperthyroidism. Normally, thyroid Simulating hormone (TSH) combines with surface acceptors of thyroid cells and causes the synthesis and secretion of thyroid hormones.
     • In Graves’ disease, the B lymphocytes (plasma cells) produce autoimmune antibodies called thyroid-stimulating autoantibodies (BTSAB).
     • These antibodies act like TSH by binding with membrane receptors of TSH and activating cAMP system of the thyroid follicular cells. This results in hypersecretion of thyroid hormones.
     • The antibodies act for a long time even up to 12 hours in contrast to that of TSH, which lasts only for an hour or so. The high concentration of thyroid hormones caused by the antibodies suppresses the TSH production also.
     • So, the concentration of TSH is low or almost zero in the plasma of most of hyperthyroid patients.
  2. Thyroid adenoma
     • Sometimes, a localized tumor develops in the thyroid tissue. It is known as thyroid adenoma and it secretes large quantities of thyroid hormones. It is not associated with autoimmunity. As far as this adenoma remains active, the other parts of thyroid gland cannot secrete the hormone. This is because the hormone secreted from adenoma depresses the production of TSH.
• Signs and Symptoms of Hyperthyroidism
  • Intolerance to heat is a common symptom in hyperthyroidism. It is because the body produces lot of heat due to increased basal metabolic rate caused by excess of thyroxine
  • Increased sweating occurs due to vasodilatation
  • Body weight decreases due to fat mobilization
  • Increased motility of Gl tract causes diarrhea
  • Excess protein catabolism causes muscular weakness
  • Symptoms like nervousness, extreme fatigue, inability to sleep, mild tremor in the hands, and psychoneurotic symptoms such as hyperexcitability, extreme anxiety, or worry are very common in hyperthyroidism. All these symptoms are due to the excess stimulation of neurons in the central nervous system
  • Enlargement of the thyroid gland, which is called the toxic goiter
  • Oligomenorrhea or amenorrhea
  • Exophthalmos
  • Polycythemia
  • Tachycardia and atrial fibrillation
  • Systolic hypertension
  • Cardiac failure.
• Exophthalmos: The protrusion of eyeballs is called exophthalmos. Most, but not all hyperthyroid patients develop some degree-protrusion of eyeballs.
  • Causes for exophthalmos
    • Exophthalmos in hyperthyroidism is due to the edematous swelling of the retro-orbital tissues and degenerative changes in the extraocular muscles. The autoimmune disease also is believed to cause exophthalmos.
    • Severe exophthalmic conditions lead to blindness because of two reasons:
      1. Protrusion of the eyeball stretches and damages the optic nerve resulting in blindness or
      2. Due to the protrusion of eyeballs, the eyelids cannot be closed completely while blinking or during sleep. So, the constant exposure of the eyeball to atmosphere causes dryness of the cornea leading to irritation and infection. It finally results in ulceration of the cornea leading to blindness.

2. Hypothyroidism: Decreased secretion of thyroid hormones is called hypothyroidism. Hypothyroidism leads to myxedema in adults and cretinism in children.

• Myxedema: It is hypothyroidism in adults characterized by generalized edematous appearance.
  • Causes for myxedema
    • Myxedema occurs due to diseases of thyroid gland, genetic disorder,s or iodine deficiency. In addition, it is also caused by a deficiency of thyroid stimulating hormone or thyrotropic releasing hormone.
    • The common cause of myxedema is the autoimmune disease called Hashimoto’s thyroiditis which is common in late middle-aged women.
    • In most of the patients it starts with glandular inflammation called thyroiditis caused by autoimmune antibodies. Later it leads to destruction of the glands.
  • Signs and symptoms of myxedema: Typical feature of this disorder is an edematous appearance throughout the body. It is associated with the following symptoms:
    • Swelling of the face
    • Bagginess under the eyes
    • Nonpitting type of edema, i.e. when pressed, it does not make pits and the edema is hard. It is because of the accumulation of proteins with hyaluronic acid and chondroitin sulfate, which from a hard tissue with increased accumulation of fluid.
• Atherosclerosis: It is the hardening of the walls arteries because of the accumulation of fat deposits and other substances. In myxedema, it occurs because of an increased plasma level of cholesterol which leads to the deposition of cholesterol on the walls of the arteries.
  • Atherosclerosis produces arteriosclerosis which refers to the thickening and stiffening of arterial wall. Arteriosclerosis causes hypertension.
  • Other general features of hypothyroidism in adults are:
    1. Anemia
    2. Fatigue and muscular sluggishness
    3. Extreme somnolence with sleeping up to 14-16 hours per day
    4. Menorrhagia and polymenorrhea
    5. Decreased cardiovascular functions such as reduction in rate and force of contraction of the heart, cardiac output, and blood volume
    6. Increase in body weight
    7. Constipation
    8. Mental sluggishness
    9. Depressed hair growth
    10. Scaliness of the skin
    11. Frog like husky voice
    12. Cold intolerance.
• Cretinism: Cretinism is hypothyroidism in children characterized by stunted growth.
  • Causes for cretinism: Cretinism occurs due to congenital absence of thyroid gland, genetic disorder, or lack of iodine in the diet.
  • Features of cretinism
    • A newborn baby with thyroid deficiency may appear normal at the time of birth because thyroxine might have been supplied from the mother. But a few weeks after birth, the baby starts developing the signs like sluggish movements and croaking sound while crying. Unless treated immediately, the baby will be mentally retarded permanently.
    • Skeletal growth is more affected than the soft tissues. So, there is stunted growth with bloated body. The tongue becomes so big, that it hangs down with dripping of saliva. The big tongue obstructs swallowing and breathing. The tongue produces characteristic guttural breathing that may sometimes choke the baby.
  • Cretin vs dwarf: A cretin is different from pituitary dwarf. In cretinism, there is mental retardation and the different parts of the body- are disproportionate. Whereas, in dwarfism, the development of nervous system is normal and the parts of the body are proportionate. The reproductive function is affected in cretinism and in dwarfism, it may be normal.

3. Goiter: Goiter means enlargement of the thyroid gland. It occurs both in hypothyroidism and hyperthyroidism.

• Goiter in Hyperthyroidism – Toxic Goiter: Toxic goiter is the enlargement of thyroid gland with increased secretion of thyroid hormones caused by thyroid tumor. Because of increased number of hormone-secreting cells of the tumor the hormone level increases to a very great extent hence, it is called toxic goiter.
• Goiter in Hypothyroidism – Nontoxic Goiter: Nontoxic goiter is the enlargement of thyroid gland without increase in hormone secretion. It is also called hypothyroid goiter. Based on the cause, the nontoxic hypothyroid goiter is classified into two types.
  1. Endemic colloid goiter
  2. Idiopathic nontoxic goiter.
     1. Endemic colloid goiter
        • It is the nontoxic goiter caused by iodine deficiency. It is also called iodine deficiency goiter. Iodine deficiency occurs when intake is less than 50 pg /day. Because of lack of iodine, there is no formation of hormones. By feedback mechanism, the hypothalamus and anterior pituitary are stimulated.
        • It increases the secretion of I PH and TSH. The TSH then causes the thyroid cells ic to secrete tremendous amounts of thyroglobulin into the tote. As there are no hormones to be cleaved, the thyroglobulin remains as it is and, gets accumulated in the follicles of the gland. This increases the size of gland.
        • In certain areas of the world, especially in the Swiss Alps, Andes, Great Lakes region of United States, and in India particularly in Kashmir Valley, the soil does not contain enough iodine.
        • Therefore, the foodstuffs also do not contain iodine. The endemic colloid goiter was very common in these parts of the world before the introduction of iodized salts.
     2. Idiopathic nontoxic goiter:
        • It is the goiter due to unknown cause. Enlargement of thyroid gland occurs even without iodine deficiency. The exact cause is not known. It is suggested that these patients are affected first by thyroiditis, which reduces the synthesis of thyroid hormones. Therefore, the secretion of TSH increases causing increase in the size of the gland.
        • In some persons, the abnormal enzyme system leads to goiter. In these persons, the goiter develops due to the deficiency of enzymes like peroxidase, iodine, and deiodinase, which are required for thyroid hormone synthesis.
        • Some foodstuffs contain goiterogenic substances (goitrogens) such as goitrin. These substances contain antithyroid substances like propylthiouracil. Goitrogens suppress the synthesis of thyroid hormones.
        • Therefore, TSH secretion increases resulting in enlargement of the gland. Such goitrogens are found in vegetables like turnips and cabbages. Soybean also contains some amount of goitrogens.
        • The goitrogens become active only during low iodine intake.

Treatment For Thyroid Disorders

Treatment For Hyperthyroidism

• Surgical Removal
  • Hyperthyroidism can be treated by antithyroid substances. However, in advanced cases, the thyroid gland must be removed. The surgical removal of thyroid gland is called thyroidectomy.
  • Before surgery, the patient is prepared by reducing the basal metabolic rate. It is done by injecting propylthiouracil for several weeks until basal metabolic rate reaches almost the basal level.
  • The high concentration of iodides is administered for two weeks. It decreases the size of the gland and blood supply to a very great extent. Because of these precautions, the mortality after the operation decreases very much.
• Antithyroid Substances: The drugs, which suppress the secretion of thyroid hormones, are called the antithyroid substances. The three well known antithyroid substances are:
  1. Thiocyanate
  2. Thiourylenes
  3. High concentration of inorganic iodides.

1. Thiocyanate: Thiocyanate prevents synthesis of thyroxine by inhibiting iodide trapping. The active pump, which transports iodide into the thyroid cells, can transport thiocyanate ions also. So administration of thiocyanate in high concentrations causes competitive inhibition of iodide transport into the cell. And, iodide trapping is inhibited leading to the inhibition of synthesis of thyroxine.

2. Thiourylenes:

• The thiourylenes are the thiourea-related substances such as propylthiouracil and methimazole which prevent the formation of thyroid hormone from iodides and tyrosine.
• It is achieved partly by blocking peroxidase enzyme activity and partly by blocking the coupling of iodinated tyrosine to form either T₃ or T₄.
• During the use of these two antithyroid substances, even though the synthesis of thyroid hormone is inhibited, the formation of thyroglobulin is not stopped.
• The deficiency of the hormone increases the TSH secretion, which increases the size of thyroid gland with more secretion of thyroglobulin. Thyroglobulin accumulates in the gland and causes enlargement of the gland resulting in nontoxic goiter.

3. High concentrations of inorganic iodides

• iodides in high concentration decrease all phases of thyroid activity, including the release of hormones. So, the size of the gland is also reduced with decreased blood supply.
• Because of this, iodides are frequently administered to hyperthyroid patients for 2 or 3 weeks prior to surgical removal of the thyroid gland.

Treatment For Hypothyroidism: The only treatment for hypothyroidism is the administration of thyroid extract or ingestion of pure thyroxine in the form of tablets orally.

Thyroid Function Tests

• The following tests are commonly done to assess the functional status of thyroid gland:
• For the usual case of hyperthyroidism or hypothyroidism, the most accurate diagnostic test is direct measurement of the concentration of “free” thyroid hormones in the plasma, i.e. T₃ and T₄.
• Measurement of basal metabolic rate: In hyperthyroidism, it is usually increased by about 30-60%. Basal metabolic rate is decreased in hypothyroidism by 20-40%.
• The measurement of TRH and TSH: There is almost total absence of these two hormones in hyperthyroidism. It is because of negative feedback mechanism by the increased level of thyroid hormones.