Hormones of the thyroid gland

The thyroid gland is located in the neck and is attached to the trachea just below the larynx. Internally, the gland is composed of a large number of follicles filled with thyroglobulin, the storage form of thyroxin.

The production of thyroxin requires iodine.

Iodine is actively transported into the thyroid gland, where the concentration can become as much as 25 times that of blood. If iodine is lacking in the diet, the thyroid gland enlarges, producing a goiter.

Goiter is a swelling in the thyroid gland which can lead to a swelling of the neck or larynx. Goiter is a term that refers to an enlargement of the thyroid and can be associated with a thyroid gland that is functioning properly or not.

Worldwide, over 90% cases of goiter are caused by iodine

deficiency.

Toxic goiters will present with symptoms of thyrotoxicosis

such as palpitations, hyperactivity, weight loss despite

increased appetite, and heat intolerance.

When there is a low level of thyroxin in the blood, a condition

called hypothyroidism, the anterior pituitary is stimulated to

produce TSH. TSH causes the thyroid to increase in size so

that enough thyroxin usually is produced. In this case,

enlargement continues because enough thyroxin is never

produced.

Signs and symptoms of hypothyroidism Hypothyroidism can be associated with the

following symptoms:

Early Cold intolerance, Constipation, Weight

gain and water retention, Bradycardia, Fatigue, Decreased sweating, Muscle cramps and joint pain, Dry, itchy skin, Thin brittle fingernails, Depression, Poor muscle tone, Female infertility, Hyperprolactinemia and Elevated serum cholesterol

Late Goiter, Slow speech, Dry puffy skin, Thinning of the

outer third of the eyebrows, Abnormal menstrual cycles, Low basal body temperature, Thyroid-Related Depression.

THE HYPOTHALAMUS-PITUITARY-THYROID CONTROL RELATIONSHIP

TRH (thyroid-releasing hormone) stimulates the anterior pituitary.

TSH (thyroid-stimulating hormone) stimulates the thyroid to secrete thyroxin.

The level of thyroxin in the body is negatively controlled in 3 ways:

a. The level of TSH exerts feedback control over the hypothalamus;

b. The level of thyroxin exerts feedback control over the anterior pituitary; and

c. The level of thyroxin exerts feedback control over the hypothalamus. In this way, thyroxin controls its own secretion.

Thyroxin Thyroxin increases the

metabolic rate. It does not have a target organ; instead, it stimulates most of the cells of the body to metabolize at a faster rate.

• If the thyroid fails to develop properly, a condition called cretinism results.

• Cretins are short, stocky persons who have had extreme hypothyroidism since infancy and/or childhood.

Thyroxin therapy can initiate growth, but unless treatment is begun within the first two months of life, mental retardation results.

The occurrence of hypothyroidism in adults produces the condition known as myxedema, which is characterized by laziness, weight gain, loss of hair, slowed pulse rate, decreased body temperature, and thickness and puffiness of the skin.

In the case of hyperthyroidism (too much thyroxin), the thyroid gland is enlarged and overactive, causing a goiter to form and the eyes to protrude because of edema in the tissues of the eye sockets and swelling of muscles that move the eyes. This type of goiter is called exophthalmic goiter.The patient with exophthalmic goiter usually becomes hyperactive, nervous, irritable, and suffers from insomnia. Removal or destruction of a portion of the thyroid by means of radioactive iodine sometimes is effective in curing the condition.

Preparations of thyroid hormones are useful for replacement therapy in cretinism or myxedema.

These preparations are also employed to prevent myxedema in cases when the thyroid gland must be surgically removed.

Sodium levothyroxine is the sodium salt of the levo isomer of thyroxine, an active physiologic principle obtained from the thyroid gland of domesticated animals used for food by humans. It can also be prepared synthetically.

USES AND DOSE. Sodium levothyroxine is classed as a thyroid

hormone. It is used for replacement therapy of reduced or completely

absent thyroid function (manifested as myxedema, cretinism, and mild

forms of hypothyroidism). Consistent potency, prolonged duration of

action, and easily monitored plasma levels prompt many authorities to

consider levothyroxine the agent of choice for thyroid replacement

therapy. The usual dose is 25 to 300 g once a day.

PRESCRIPTION PRODUCTS. Levothroid®, Synthroid®,

Synthrox®, and Syroxine®.

Calcitonin• In addition to thyroxin, the thyroid gland also produces the hormone

calcitonin.

• Calcitonin is a polypeptide containing 32 amino acid residues.

• The preparation used in therapy is a synthetic salmon calcitonin. Salmon calcitonin elicits 20-fold or more activity on a molar basis than human or porcine calcitonins; the apparent increased potency may be caused, in part, by a greater affinity for receptor sites and thus a slower rate of degradation and a longer duration of action.

• This hormone helps to regulate the calcium level in the blood and opposes the action of parathyroid hormone. Since This hormone exerts a hypocalcemic effect by suppressing bone resorption and by inhibiting tubular reabsorption of calcium in the kidneys.

• PRESCRIPTION PRODUCTS. Calcimar®

Parathyroid GlandThe parathyroid glands are embedded in the

posterior surface of the thyroid gland.Under the influence of parathyroid hormone (PTH),

also called parathormone, the calcium level in blood increases and the phosphate level decreases.

The parathyroid hormone (parathyrin) is a straight-chain polypeptide containing 83 amino acid residues and has a molecular weight of approximately 9500.

A portion of the molecule that contains only 35 amino acid residues can elicit the significant physiologic activity of the hormone.

The essential 35-amino acid subunit of human parathyroid hormone differs in 5 or 6 of its amino acid residues from the animal parathyroid hormones that are available through the meat-packing industry.

The hormone stimulates the absorption of calcium from the gut, the retention of calcium by the kidneys, and the demineralization of bone.

In other words, PTH promotes the activity of osteoclasts, the bone-resorbing cells.

Although this also raises the level of phosphate in the blood, PTH acts on the kidneys to excrete phosphate in the urine.

When a woman stops producing the female sex hormone estrogen following menopause, she is more likely to suffer from osteoporosis, characterized by a thinning of the bones. Therefore, Calcitonin can be used to treat postmenopausal osteoporosis.

If insufficient PTH is produced, the level of calcium in blood drops, resulting in tetany.

In tetany, the body shakes from continuous muscle contraction; because calcium plays an important role in both nervous conduction and muscle contraction.

The level of PTH secretion is controlled by a feedback mechanism involving calcium.

When the calcium level rises, PTH secretion is inhibited, and when the calcium level lowers, PTH secretion is stimulated.

Thyroid and parathyroid glandsa. The thyroid is located in the

neck in front of the trachea, b. The 4 parathyroid glands are

embedded in the posterior surface of the thyroid gland. Yet, the parathyroid and thyroid glands have no anatomical or physiological connection with one another,

c. Regulation of parathyroid hormone (PTH) secretion. A low blood level of calcium causes the parathyroids to secrete PTH, which causes the kidneys and the gut to retain calcium and osteoclasts to break down bone. The end result is an increased level of calcium in the blood. A high blood level of calcium inhibits secretion of PTH.

Its principal effect involves bone resorption and calcium release, but it also promotes absorption of calcium from the gut and renal tubules.

Parathyroid hormone is inactivated in the intestinal tract, but it has been used parenterally in medicine for blood-calcium maintenance in cases of parathyroid tetany.

Pancreatic hormonesThe pancreas is a long organ that lies

transversely in the abdomen between the kidneys and near the duodenum of the small intestine.

It is composed of two types of tissue— exocrine, which produces and secretes digestive juices that go by way of the pancreatic duct and the common duct to the small intestine, and endocrine, called the islets of Langerhans, which produces and secretes the hormones insulin and glucagon directly into the blood.

Insulin is secreted when there is a high level of glucose in blood, which usually occurs just after eating. It is produced from -cells.Insulin has three different actions: 1. It stimulates liver and muscle cells to take

up and metabolize glucose. 2. It stimulates the liver and the muscles to

store glucose as glycogen.3. It promotes the buildup of fats and proteins

and inhibits their use as an energy source. Therefore, insulin is a hormone that promotes storage of nutrients so that they are on hand during leaner times. It also helps to lower the blood glucose level.

Insulin is a polypeptide with a molecular weight of 5734. It contains 48 amino acid residues (including 3 cystine residues) that are arranged in 2 linear chains connected by disulfide linkages.

Insulin has been studied more extensively than any other polypeptide hormone. One of the interesting observations resulting from these studies is the variation in amino acid residues 8, 9, and 10, depending on the origin of the insulin.

Structures of insulin from several mammals

The amino acid sequence in these 3 positions has no effect on the normal physiologic properties of the polypeptide.

The distinctive amino acid residue 30 of the larger peptide chain of human insulin is apparently without physiologic significance because an analog lacking amino acid residues 26 to 30 retains activity.

The disulfide bonds that link the 2 peptide chains are major obstacles to the feasible synthesis of insulin.

Insulin is digested by proteolytic enzymes (a common property of polypeptide hormones), and it is ineffective when given orally.

Commercial production of human insulin has been achieved using two independent approaches:

1. Pork insulin is converted to human insulin by replacing enzymatically the terminal alanine amino acid residue with threonine.

2. Recombinant DNA techniques have also been used for microbial synthesis.

Insulin injection is a sterile, neutral solution of the active principle of the pancreas that affects the metabolism of glucose. Insulin injection contains 40, 100, or 500 USP insulin units in each ml.

It is a prompt-acting preparation with a peak of action at 2 to 5 hours.

Insulin preparations, must be labeled to indicate the nature (beef and pork, beef, pork, or human) of the insulin; when a product meets the standards for purified insulin, this must also be indicated on the label.

PROPRIETARY PRODUCTS. purified beef: Beef Regular Iletin II®; purified pork: Actrapid®, Pork Regular Iletin II®, and Velosulin®; human: Humulin R®.

Glucagon is secreted from the pancreas between eating, and its effects are opposite to those of insulin. Glucagon stimulates the breakdown of stored nutrients and causes the blood sugar level to rise.

It is produced from -cells.

Glucagon and insulin, both polypeptide hormones, exert counterbalancing actions on carbohydrate metabolism in the body.

Glucagon is a straight-chained polypeptide containing 29 amino acid residues with a molecular weight of 3485.

Glucagon can be used in diagnosis and in the treatment of hypoglycemia.

Contrary effects of insulin and glucagon

When the blood glucose level is high, the pancreas secretes insulin. Insulin promotes the storage of glucose as glycogen and the synthesis of proteins and fats. Therefore, insulin lowers the blood glucose level. When the blood glucose level is low, the pancreas secretes glucagon. Glucagon acts in opposition to insulin in all respects; therefore, glucagon raises the blood glucose level.

DIABETES MELLITUSThe symptoms of diabetes mellitus (sugar diabetes) include the following:1. Sugar in the urine2. Frequent, copious urination3. Abnormal thirst4. Rapid loss of weight5. General weakness6. Drowsiness and fatigue7. Itching of the genitals and the skin8. Visual disturbances, blurring9. Skin disorders, such as boils, carbuncles, and

infection

Many symptoms of diabetes mellitus develop because sugar is

not being metabolized by the cells. The liver fails to store

glucose as glycogen, and all the cells fail to utilize glucose as an

energy source. This means that the blood glucose level rises

very high after eating, causing glucose to be excreted in the

urine. More water than usual therefore is excreted so that the

diabetic is extremely thirsty.

Since carbohydrate is not being metabolized, the body turns to

the breakdown of protein and fat for energy. Unfortunately, the

breakdown of these molecules leads to the buildup of acids in

the blood (acidosis) and to respiratory distress. It is the latter

that eventually can cause coma and death of the diabetic. The

symptoms that lead to coma develop slowly.

Type I diabetesThere are two types of diabetes. In type I

diabetes, formerly called juvenile-onset diabetes, the pancreas is not producing insulin. Therefore, the patient must have daily insulin injections.

Obviously, insulin injections are not the same as a fully functioning pancreas that responds on demand to high glucose level by supplying insulin. For this reason, some doctors advocate an islet cell transplant.

Type II diabetesIn type II diabetes, formerly called maturity-onset

diabetes, now known to occur in obese people of any

age, the pancreas is producing insulin, but the cells do

not respond to it. At first, the cells lack the receptors

necessary to detect the presence of insulin, and later,

the cells are even incapable of taking up glucose.

If type II diabetes is untreated, the results can be as serious as type I diabetes. Diabetics are prone to blindness, kidney disease, and circulatory disorders, including strokes.

Pregnancy carries an increased risk of diabetic coma, and the child of a diabetic is somewhat more likely to be stillborn or to die shortly after birth. It is important, therefore, to prevent or to at least control type II diabetes. The best defense is a nonfattening diet and regular exercise. If that fails, there are oral drugs that make the cells more sensitive to the effects of insulin or that stimulate the pancreas to make more of it.