In this article we will discuss about:-1. Secretion of Thyroid Glands 2. Actions of the Thyroid Gland 3. Regulation 4. Thyroid Function Tests.
Secretion of Thyroid Glands:
The hormones secreted by this gland are:
i. Thyroxine (T4)
ii. Triiodothyronine (T3)
iii. Thyrocalcitonin (calcitonin)
Among the three hormones, the follicular cells of the gland secrete the first two hormones (T3 and T4) and the last one (thyrocalcitonin) is secreted by the parafollicular cells. T4 is also known as tetraiodo-thyronine and gets converted to T3 at the time of action in the target organ. Calcitonin hormone will be discussed along with calcium metabolism.
Biosynthesis of hormone is regulated by the activity of TSH secreted from the anterior pituitary gland. Since it is a tropic hormone, TSH regulates the growth and functioning of thyroid gland.
The following diagram indicates the action of TSH on thyroid gland (Fig. 6.32):
The steps in the biosynthesis of the hormone are (Fig. 6.33):
i. Iodide trapping that is the uptake of iodide by the follicular cells from the plasma against the electrochemical gradient. The hormone TSH secreted by the anterior pituitary gland affects this step. Substances, like thiocyanate, pertechnetate and perchlorate that are examples of antithyroid drugs can inhibit iodide trapping.
ii. Oxidation of iodine:
Occurs inside the follicular cells by the action of the enzyme peroxidase. Drugs like thiouracil and carbimazole can inhibit this step and act as antithyroid drugs.
iii. Organification:
Iodine gets incorporated to tyrosine amino acid present in the colloid and leads to the formation of MIT (Monoiodotyrosine). On further iodination of MIT, there is formation of DIT (Di- iodotyrosine).
iv. Coupling:
Coupling of 2 DIT will lead to the formation of T4 and 1 MIT with 1 DIT will results in T3.
After the synthesis, the hormone with thyroglobulin is stored in the colloid.
There are many substances which have the ability to decrease the amount of thyroxin secreted by the gland. These drugs will be of choice when there is a necessity to decrease the amount of thyroxine secretion in certain pathological situations. Table 6.5 shows the list of antithyroid drugs.
Steps involved in hormonopoiesis of thyroxine:
1. Iodide trapping (active process)
2. Conversion of iodide to molecular iodine. Peroxidase is the enzyme involved.
3. Organification of tyrosine to form MIT and DIT—iodinase.
4. Oxidative coupling of
MIT + DIT—to form T3
DIT + DIT—to form T4
5. Proteolytic separation of T3 and T4 from thyroglobulin— deiodinase
At the time of release of the hormones into circulation, the acinar cells will engulf the thyroglobulin along with the hormones by endocytosis.
In the cells, the hormone will be separated by proteolysis and released into the circulation and thyroglobulin will be retained for further use.
Most of the hormone in circulation is in protein bound form along with thyroid binding globulin (TBG), albumin (TBA), thyroid binding pre-albumin (TBPA) (Table 6.6).
Actions of the Thyroid Gland:
1. Calorigenic Action:
It increases the oxygen consumption in almost all the tissues of the body except adult brain, gonads, lymphoid tissue. Increased metabolic rate increases the heat production in the body. The unit to measure heat energy is calorie (Fig. 6.34).
In normal adult male, the basal metabolic rate (BMR) is about 40 Kcal/sq m BSA/Hr ±15%.
In hyperthyroidism, it can be as much as + 60 to 100%.
In hypothyroidism, it can fall by -40 to -60%. Hence estimation of BMR forms one of the thyroid function tests.
2. Nervous System:
For the growth of the nervous system in the first three years of even during the postnatal period, the action of the thyroxine on brain is essential. The growth of the brain occurs only during this phase after birth.
The growth of the brain includes:
i. Formation of the synapses.
ii. Growth of axon and dendrites and arborization of these processes.
iii. Increase in the number of glial cells.
iv. Myelination of nerve fibers.
In cretin (when thyroxine is deficient from childhood):
1. The brain remains smaller than normal.
2 Number and size of the nerve cells reduced.
3. Arborization of the dendrites is less profuse.
4. Net effect in the child will be marked decrease in IQ.
5. Myelination will be defective.
6. CSF protein content is increased.
Because of these reasons, the action of hormone on the brain is very crucial in the first two to three years of postnatal life. If there is deficiency of the hormone during this period, it can lead to mental retardation. This is associated with delayed milestones during the growth of the infant.
3. On Growth and Development:
It affects the growth and development of other parts of body as well.
The general growth is influenced by the growth hormone of the anterior pituitary gland but thyroxine potentiates the action of the growth hormone and hence the summated effect of these hormones is very much for the linear growth of the body and the growth of other organs.
It also affects the growth of reproductive organs and lack of the hormone may lead to sterility, infantile sex organs in adults and in adult females menstrual problems.
4. Metabolic Actions:
Apart from its action on the oxygen consumption by the tissues, it also influences the metabolism of carbohydrate, fats and proteins.
a. Carbohydrate metabolism:
It acts as a hyperglycemic agent. It increases the blood glucose level by increasing gluconeogenesis and glycogenolysis in the liver. It also enhances the peripheral utilization of glucose.
b. Protein metabolism:
It has both anabolic and catabolic effects. Excess of hormonal level in circulation, catabolism predominates and leads to loss of body weight and muscular weakness. In hypothyroidism, the anabolism suffers and again leads to muscular weakness.
c. Fat metabolism:
It increases lipolysis. Cholesterol synthesis and degradation are both affected by this hormone. The degradation is more dependent on thyroxine than synthesis and hence in hypothyroidism the serum cholesterol level is increased.
d. On mucopolysaccharides:
The excretion of substances, like hyaluronic acid and chondroitin sulphate, is affected by the action of this hormone. Hence, in hypothyroidism, they get deposited in the subcutaneous region giving rise to myxedema.
5. On Systems:
The hormone affects functioning of the different systems of the body.
Some of the systems on which the actions are more pronounced are:
a. CVS:
It increases both the heart rate and force of contraction. It increases the number of beta receptors and affinity of the beta receptors for catecholamine. Hence, the resting heart rate will be more in hyperthyroid subjects. The increase in cardiac output leads to increase of systolic blood pressure (systolic hypertension).
It also increases the blood flow to the skin in order to facilitate the heat loss from the body. It is essential as the hormone increases basal metabolic rate and hence increased heat production. As a result of this cutaneous vasodilatation, the peripheral resistance decreases which will result in fall in diastolic BP.
b. GIT:
Hormone is required for normal secretory aspects and movements of gastrointestinal tract. In hyperthyroidism, the patients suffer from diarrhea and in hypothyroidism the patient may develop constipation.
c. Nervous system:
In adult, it affects the velocity of impulse conduction in the nerve fibers. In hyposecretion state, it results in increased reflex time and vice versa in hyperthyroidism.
Regulation of Thyroid Hormone:
It is brought about by the negative feedback mechanism. There is involvement of hypothalamo- pituitary-thyroid axis (Fig. 6.35).
Increase in free form of hormone in circulation acts on hypothalamus and anterior pituitary gland. Acting on hypothalamus, it decreases the secretion of thyrotropin-releasing hormone (TRF/TRH) and this acts on anterior pituitary decreases secretion of TSH.
Net effect will be decreased TSH from anterior pituitary gland. This decreases the secretion of thyroid hormones from the gland.
Many of the other chemical influences acting on TRH-TSH-Thyroxine (hypothalamo-pituitary-thyroid axis) secretions have been shown in Table 6.7.
Alteration in the temperature can directly act on the hypothalamus to alter the secretion of the hormone.
Thyroid Function Tests:
1. Determination of BMR.
2. Blood cholesterol level.
3. Estimation of protein bound iron (PBI)
4. 131I uptake studies (Figs 6.36, 6.37)
5. Estimation of free T3, T4 and TSH in plasma.
Applied Aspects:
Cretinism (Fig. 6.38 and Table 6.8):
i. Hyposecretion of thyroxine from infancy.
ii. Skeletal growth will be stunted and hence short stature.
iii. Mental retardation due to poor growth of nervous system.
iv. Milestones in the development of child get postponed.
v. Thick protruding tongue and pot belly.
vi. Even after attaining the adolescence, there will not be development of sex organs and hence the sex organs remain infantile.
vii. Facial changes will not correspond with chronological age.
Congenital hypothyroidism could be due to:
i. Maternal iodine deficiency.
ii. Fetal thyroid dysgenesis.
iii. Inborn errors in thyroid hormone synthesis.
iv. Maternal antithyroid antibodies crossing.
v. Fetal hypopituitary hypothyroidism.
Myxedema (Fig. 6.39 and Table 6.9):
i. Hyposecretion of thyroxine in adults.
ii. Person’s basal metabolic rate is grossly reduced. It can be as little as -40 to -60%.
iii. Person cannot withstand cold stress.
iv. Cold dry skin with sparse hair.
v. There will be accumulation of chondroitin sulfate and hyaluronic acid in the subcutaneous region. These substances are osmotically active and hence this results in retention of water also in the subcutaneous region. This results in non-pitting edema (puffiness of face, legs, etc.).
vi. Person will have bradycardia and blood pressure also will be less than normal.
vii. The activity of CNS becomes dull, thereby it may lead to loss of memory and dulling of intelligence and reaction time is prolonged.
viii. There will be increase in the serum cholesterol level.
ix. The reproductive ability of the person suffers and the females may suffer from menorrhagia.
Myxedema could be due to:
i. Hashimoto’s thyroiditis.
ii. Hypothalamic or pituitary destruction.
iii. Nodular goiters.
iv. Surgical removal.
Graves’ disease (Fig. 6.40 and Table 6.10):
i. Hyperthyroidism in adult stage.
ii. Person may show exophthalmos.
iii. Tachycardia and palpitation.
iv. The person may suffer from systolic hypertension.
v. Negative nitrogen balance with loss of wasting of muscle tissue.
vi. CNS symptoms include tremors, hyperreflexia, and psychosis.
vii. The basal metabolic rate may be increased to as much as plus 60 to 100%.
viii. The person cannot withstand heat stress.
ix. Skin will be warm and wet.
x. Serum cholesterol level will be less than normal.
xi. The person may suffer from loss of libido and infertility.
The disease may be because of autoimmunity. The body starts producing antibodies which are known as thyroid-stimulating immunoglobulins (TSI) or long-acting thyroid stimulators (LATS). These antibodies bind to the receptors where TSH normally binds.
They imitate the action of TSH on the gland and hence bring about increased secretion of thyroxine. Since the thyroxine level in circulation is increased, this exerts more negative feedback regulation on anterior pituitary. So TSH secretion from anterior pituitary gland is decreased. This results in decreased concentration of TSH in circulation.
Goiter means enlargement of thyoriod gland. Goiter can be due to hypo- or hyperthyroidism. Endemic goiter (hypothyroidism) usually occurs due to deficiency of iodine (Fig. 6.41). Exophthalmic goiter occurs due to hyperthyroidism.
Features of hyperthyroidism in adult:
i. Heat intolerance.
ii. Tachycardia and palpitations.
iii. Hyperactivity and irritability.
iv. Tremors.
v. Warm wet skin.
vi. Diarrhea.
vii. Oligomenorrhea.
viii. Lid retraction and lid lag.
ix. Weight loss.
Features of hypothyroidism in adult:
i. Cold intolerance.
ii. Bradycardia.
iii. Poor memory and increased reaction time.
iv. Cold dry skin.
v. Constipation.
vi. Menorrhagia.
vii. Diffuse alopecia.
viii. Weight gain.
ix. Hoarse voice.
x. Carpal tunnel syndrome.
Thyroid storm:
Serious thyrotoxicosis.
Features are:
a. Fever.
b. Tachycardia.
c. Psychosis.
d. Confusion.
e. GI tract symptoms.