Thyroid Hormones- Dr. Chintan

Functions• The thyroid hormones increase the metabolic activities

of almost all the tissues of the body. The BMR is increased.

• The rate of utilization of foods for energy is greatly accelerated. Although the rate of protein synthesis is increased, at the same time the rate of protein catabolism is also increased.

• The growth rate of young people is greatly accelerated. The mental processes are excited, and the activities of most of the other endocrine glands are increased.

Functions• mitochondria in most cells of the increase in size as well as number

- the total membrane surface area of the mitochondria increases – more ATP

• ↑ Na+ K+ ATPase activity - ↑ transport of both sodium and potassium ions through the cell membranes – more energy – more heat

• Growth - the effect of thyroid hormone on growth is manifest mainly in growing children. In those who are hypothyroid, the rate of growth is greatly retarded. In those who are hyperthyroid, excessive skeletal growth often occurs, causing the child to become considerably taller at an earlier age - amphibian metamorphosis

• To promote growth and development of the brain during fetal life and for the first few years of postnatal life – mental retardation

Metabolic Functions• Carbohydrate Metabolism - rapid uptake of glucose by the cells, ↑

glycolysis, ↑ gluconeogenesis, ↑ rate of absorption from the GIT, and ↑ insulin secretion

• Fat Metabolism - lipids are mobilized rapidly from the fat tissue, which ↓ the fat stores of the body. Also ↑ the free fatty acid concentration in the plasma and ↑ the oxidation of free fatty acids by the cells

• ↑ thyroid hormone - ↓ the concentrations of cholesterol (secretion in the bile and loss in the feces), phospholipids, and triglycerides in the plasma, it ↑ the free fatty acids.

• ↓ thyroid secretion - ↑ the plasma concentrations of cholesterol, phospholipids, and triglycerides & causes excessive deposition of fat in the liver - atherosclerosis

Metabolic, CVS• Thyroid hormone ↑ the quantities of many bodily enzymes

and because vitamins are essential parts of some of the enzymes or coenzymes, thyroid hormone causes ↑ need for vitamins – deficiency

• ↑ thyroid hormone - ↑ BMR - ↓ body weight–↑ appetite

• CVS – ↑ metabolism in the tissues causes more rapid utilization of oxygen & release of greater quantities of metabolic end products – vasodilation - ↑ blood flow.

• blood flow ↑ in the skin for heat elimination

• ↑ blood flow - ↑ cardiac output

CVS, RS, GIT• ↑ in HR – resting tachycardia

• ↑ in heart strength – long term failure due to ↑ in CO

• MAP unchanged – SBP ↑, DBP ↓ - PP ↑

• RS - ↑ the rate and depth of respiration

• GIT - ↑ appetite and food intake - ↑ secretion of the digestive juices - ↑ GIT motility – diarrhea & constipation

Nerve, Muscle, Sleep• CNS – excitation - extreme nervousness - anxiety complexes - extreme

worry – paranoia – restless – Reaction time

• Muscle - stamina, strength ↑ - long term weak due to protein catabolism – vice versa sluggish, relax slowly

• Hyperthyroidism – Fine (not coarse) muscle tremor - tremor can be observe by placing a sheet of paper on the extended fingers and noting the degree of vibration of the paper

• Sleep - the hyperthyroid subject often has a feeling of constant tiredness, but because of the excitable effects of thyroid hormone on the synapses, it is difficult to sleep

• extreme somnolence is characteristic of hypothyroidism, with sleep sometimes lasting 12 to 14 hours a day

Endocrine, Sexual• Endocrine - ↑ need of insulin, PTH, glucocorticoids -

Relation to Catecholamines

• Sexual Function - In men, lack of thyroid hormone is likely to cause loss of libido - great excesses of the hormone, sometimes cause impotence

• In women, lack of thyroid hormone often causes menorrhagia, polymenorrhea, irregular periods, amenorrhea, decreased libido - hyperthyroid woman, oligomenorrhea, amenorrhea

• Milk secretion is decreased in hypothyroidism and stimulated by thyroid hormones

Physiologic effects of thyroid hormones • Heart: Chronotropic, Increase number and affinity of β

adrenergic receptors – Inotropic, Enhance responses to circulating Catecholamines.

• Adipose tissue: Catabolic - Stimulate lipolysis. • Muscle: Catabolic - Increase protein breakdown. • Bone: Developmental - Promote normal growth and

skeletal development. • Nervous system: Developmental - Promote normal brain

development. • Gut: Metabolic - Increase rate of carbohydrate absorption. • Lipoprotein: Metabolic - Stimulate formation of LDL

receptors. • Other: Calorigenic - Stimulate oxygen consumption by

metabolically active tissues - Increase metabolic rate.

Regulation• TSH – thyrotropin - anterior pituitary hormone, a

glycoprotein with a molecular weight of about 28,000 - cAMP

• 1st 30 minutes• 1. Increased proteolysis of the thyroglobulin

• Hours, days, weeks• 2. Increased activity of the iodide pump - iodide trapping• 3. Increased iodination of tyrosine to form the thyroid

hormones• 4. Increased size, number and increased secretory activity

of the thyroid cells• 5. change from cuboidal to columnar cells

Regulation• hypothalamic hormone, thyrotropin-releasing hormone

(TRH), which is secreted by nerve endings in the median eminence of the hypothalamus - tripeptide amide

• Phospholipase second messenger system

• Exposure to cold - ↑ TRH, TSH - excitation of the hypothalamic centers for body temperature control

• Excitement and anxiety — conditions that greatly stimulate the sympathetic nervous system—cause an acute ↓ in secretion of TSH

• Negative feedback

Antithyroid Substances• Thiocyanate Ions Decrease Iodide Trapping• The same active pump that transports iodide ions into the

thyroid cells can also pump thiocyanate ions, perchlorate ions, and nitrate ions - competitive inhibition

• ↓ T3, T4 - ↑ TSH from Ant. Pituitary via negative feedback – enlarged thyroid gland – goiter

• Propylthiouracil ↓ Thyroid Hormone Formation• Propylthiouracil, methimazole and carbimazole - block the

peroxidase enzyme that is required for iodination of tyrosine - block the coupling of two iodinated tyrosines - goiter

Antithyroid Substances• Iodides in High Concentrations ↓ Thyroid Activity, Gland

Size, Blood flow

• reduce the rate of iodide trapping

• normal endocytosis of colloid from the follicles by the thyroid glandular cells is paralyzed

• frequently administered to patients for 2 to 3 weeks before surgical removal of the thyroid gland to decrease the amount of bleeding

• Wolff - Chaikoff effect

Applied - Hyperthyroidism• Toxic Goiter, Thyrotoxicosis, Graves’ Disease

• thyroid gland is increased 2 to 3 times normal size, with tremendous hyperplasia - 5 to 15 times increase in hormone secretion

• TSH low or zero – negative feedback

• immunoglobulin antibodies that bind with the same membrane receptors that bind TSH - induce continual activation of the cAMP system of the cells, with resultant development of hyperthyroidism – thyroid stimulating immunoglobulin

• Autoimmunity

Applied - Hyperthyroidism• Thyroid Adenoma – localized tumor – not autoimmune

• Symptoms of Hyperthyroidism• (1) a high state of excitability, • (2) intolerance to heat, • (3) increased sweating, • (4) mild to extreme weight loss (Obesity Rx ????), • (5) varying degrees of diarrhea, • (6) muscle weakness, • (7) nervousness or other psychic disorders,• (8) extreme fatigue but inability to sleep, and• (9) tremor of the hands.

Hyperthyroidism - symptoms• Exophthalmos - autoimmune process - improved with

treatment

• protrusion of the eyeballs - stretching the optic nerve enough to damage vision

• eyes are damaged because the eyelids do not close completely when the person blinks or is asleep. As a result, the epithelial surfaces of the eyes become dry and irritated and often infected, resulting in ulceration of the cornea.

• Edematous swelling of the retro-orbital tissues and degenerative changes in the extra ocular muscles

Diagnostic Tests for Hyperthyroidism• direct measurement of the concentration of “free” T4 &

T3 in the plasma, using radioimmunoassay

• BMR is usually increased to +30 to +60 in severe hyperthyroidism

• no or low plasma TSH

• high TSI in thyrotoxicosis

• low TSI in thyroid adenoma

Rx of Hyperthyroidism• surgical removal of the thyroid gland – thyroidectomy

• Prepare the patient before surgery

• by administering Propylthiouracil, usually for several weeks, until the BMR has returned to normal.

• Then, administration of high concentrations of iodides for 1 to 2 weeks before operation causes the gland to regress in size and its blood supply to diminish

• Rx of the Hyperplastic Thyroid Gland with Radioactive Iodine - 5 millicuries of radioactive iodine

Hypothyroidism• autoimmunity against the thyroid gland - immunity

destroys the gland

• First autoimmune “thyroiditis,” - progressive deterioration and finally fibrosis of the gland

• Endemic Colloid Goiter Caused by Dietary Iodide Deficiency

• Lack of iodine prevents production of both T3 & T4 - no hormone is available to inhibit production of TSH – pituitary secretes excessively large quantities of TSH – stimulation of thyroid cells to secrete tremendous amounts of thyroglobulin colloid into the follicles, and the gland grows larger and larger

Hypothyroidism• Idiopathic Nontoxic Colloid Goiter

• Thyroiditis causes slight hypothyroidism, which then leads to increased TSH secretion and progressive growth of the noninflamed portions of the gland

• nodular, with some portions of the gland growing while other portions are being destroyed by thyroiditis

• 1. Deficient iodide-trapping mechanism, • 2. Deficient peroxidase system, • 3. Deficient coupling of iodinated tyrosines in the thyroglobulin

molecule, • 4. Deficiency of the deiodinase enzyme

• foods contain Goitrogenic substances - cabbage

Hypothyroidism• fatigue and extreme somnolence, • extreme muscular sluggishness,• slowed heart rate, • decreased cardiac output,• decreased blood volume, • increased body weight, • constipation, • mental sluggishness, • depressed growth of hair and scaliness of the skin,• development of a froglike rough voice, • carotenemia• Myxedema - myxedema madness

Hypothyroidism• Myxedema• Looseness under the eyes and swelling of the face• greatly increased quantities of hyaluronic acid and

chondroitin sulfate bound with protein form excessive tissue gel in the interstitial spaces

• edema is the nonpitting type• Atherosclerosis - PVD, CAD - early death.

• Diagnostic Tests in Hypothyroidism - The free thyroxine in the blood is low - The BMR in myxedema ranges between -30 and -50

• Rx of Hypothyroidism - daily oral ingestion of a tablet or more containing thyroxine

Hypothyroidism - Cretinism• extreme hypothyroidism during fetal life, infancy, or childhood• failure of body growth and by mental retardation• congenital cretinism - genetic defect - iodine lack in the diet

(endemic cretinism)

• A neonate - normal appearance - supplied with some thyroid hormone by the mother - few weeks after birth, the neonate’s movements become sluggish and both physical and mental growth begin to be greatly retarded.

• unless the cretinism is treated within a few weeks after birth, mental growth remains permanently retarded

• obese, stout and short – more soft tissue growth than bones - deep breathing due to large tongue – idiotic look

Thank You…