Physiology of the thyroid gland

Question 1

What is a goiter?

Answer 1

• It is an enlargement of the thyroid gland due to overstimulation, it can be due to hypothyroidism, hyperthyroidism (goiter), or euthyroid (like in pregnancy, due to oversecretion of hormones)
• Simple nontoxic goiter (Euthyroid goiter), which may be diffuse or nodular, is noncancerous hypertrophy of the thyroid without hyperthyroidism, hypothyroidism, or inflammation.
  Except in severe iodine deficiency, thyroid function is normal and patients are asymptomatic except for an obviously enlarged, nontender thyroid

Question 2

Describe the structure and function of the thyroid gland

Answer 2

• One of the largest glands
• Located below the larynx on each side of it and anterior to it
• 15-20 grams
• It produces two major hormones (Thyroxine “T4”, Triiodothyronine “T3”)
• It is mainly regulated by the TSH

Question 3

What are the hormones produced by the thyroid gland?

Answer 3

1) Thyroxine (T4 “the storage, it forms 93% of the thyroid hormone”)

• Binds better to plasma protein compared to T3

2) Triiodothyronine (T3)

• T4 are converted to T3 via 5’-iodinase once they reach the tissues
• T3 is more potent biologically compared to T4
• T3 has a shorter life-span than T4

3) Calcitonin (from the parafollicular cells important in calcium absorption into the bone)

4) Reverse rT3 (biologically not active)

• It indicates the conversion of the hormone

Question 4

Which part of the thyroid gland releases the calcitonin?

Answer 4

The parafollicular cells

Question 5

What is the major constituent of the thyroid gland?

Answer 5

The glycoprotein thyroglobin (stores the hormone)

Question 6

Which part of the thyroid gland is filled with secretory substance?

Answer 6

The colloid

Question 7

Describe the process of thyroid hormone conversion

Answer 7

1) Tetra-iodothyronine (thyroxine “T4)

2) Once it reaches the tissue, 5’-iodinase will de-ionate them, forming Tri-iodothyronine (T3)

3) Tri-iodothyronine (T3) will then trigger cellular effects, gene transcription and translation, cellular metabolism

Question 8

How is the thyroid hormone transported into the tissues?

Answer 8

• They bound to plasma proteins “99% is bound” (T4 binds better), like the Thyroxine binding globulin, thyroxine-binding prealbumin, and albumin
• T3 & T4 are both released slowly into the circulation as their is a high affinity for them, where half of T4 is released every 6-days, while half of T3 is released every day (due to lower affinity)
• In the target cells, the thyroid hormone has intracellular receptors, they will then be stored and slowly used over days/weeks
• FYI: Thyroid hormone has a slow onset and a long duration of action

Question 9

What is the onset and duration of action of the thyroid hormone?

Answer 9

The action of T4 (thyroxine) are longer and takes more time to appear, and stays in its active form for 6-8 weeks, it reaches the peak activity in 10-12 days, while T3 are four times faster, with a shorter latent period (10-12 hours) and a maximum cellular activity in 2-3 days

Question 10

What are the different actions of the thyroid hormone (1)?

Answer 10

• Only the free hormone is active (T3 binds to the nuclear receptor with a greater affinity than T4):
• 6B’s

1) Brain maturation

2) Bone growth

3) B-adrenergic effects (Increases B1 receptors in the heart, increasing the CO, HR, SV, Contractility)

4) Increases the BASAL metabolic rate

5) Increases Blood sugar (by glycogenolysis and gluconeogenesis)

6) Breaks down lipids (lipolysis)

Question 11

What are the functions of the thyroid hormone (2)?

Answer 11

1) Growth in young people

2) CNS development (synaptogenesis), increases the mental processes and it increases the activity of the endocrine gland

3) CVS it increases the:

• HR
• CO
• Tissue blood flow
• Respiration

4) Metabolism, it increases the:

• Mitochondria (it increases their number and activity)
• Na+-K+-atpase (incease in ion transport = utilizing more energy = increased heat = Increased BMR)
• O2 consumption
• Glucose absorption
• Gluconeogenesis
• Glycogenolysis
• Lipolysis
• Protein synthesis then protein break down
• Basal Metabolic Rate (rate of food utilization)
• It produces these effects by synthesizing new proteins from the binding of T3 to the thyroid hormone receptor in the nucleus

Question 12

What is the effect of the thyroid hormone on the CVS?

Answer 12

1) Increases cardiac output

• Due to the vasodilation from the increases metabolic end products

2) Increased Heart rate

• It might be due to the direct effect of the thyroid hormone on the excitability of the heart

3) It increases the heart strength initially due to the anabolism of protein initially (increasing the enzymatic activity) and then if it continuous to rise it decreases the strength of the heart due to protein catabolism, which might lead to death if the patient reaches toxic level from thyrotoxicotic

Question 13

What is the effect of thyroid hormone on respiration?

Answer 13

Increased metabolism will increase in the utilization of CO2 which will increase in respiratory rate (tachypnea)

Question 14

What is the effect of the thyroid hormone on the GI motility?

Answer 14

It increases the rate of secretion of the digestive juices and motility

• Hyperthyroidism leads to diarrhea
• hypothyroidism leads to constipation

Question 15

What is the effects of the thyroid hormone on the CNS?

Answer 15

It increases the speed of thinking

• In Hyperthyroidism nervousness, anxiety, and extreme worry
• Hypopituitarism will decrease the seed of thinking

Question 16

What is the effect of the thyroid hormone on the reaction time?

Answer 16

In hyperthyroidism the reaction time decreases while the opposite occur in hypo

Question 17

What is the effect of the thyroid hormone on the muscles?

Answer 17

↑ muscle contraction – hyperthyroidism leads to tremors, & Muscle weakness (thyrotoxic myopathy).

• The muscle weakness may be due in part to increased protein catabolism.
• Hypothyroidism causes sluggishness in muscles, also associated with muscle weakness, cramps, and stiffness.

Question 18

What is the effect of the thyroid hormone on sleeping?

Answer 18

1) Hyperthyroidism leads to tiredness due to decreased sleep as the person can’t stop being nervous

2) Hypothyroidism leads to increased hours of sleeping

Question 19

What is the effect of thyroid hormone on muscle tremors?

Answer 19

There is fine tremors in hyperthyroidism due to the increased reactional activity of the neuronal synapses

Question 20

What is the effect of the thyroid hormone on the body weight?

Answer 20

1) Hyperthyroidism: Decreased weight

2) Hypothyroidism: Increased body weight

3) Thyroid hormone also increases the appetite, which might counterbalance the change in the metabolic rate

Question 21

What is the function of the thyroid gland at the liver?

Answer 21

It increases the rate of glucose metabolism and insulin secretion

Question 22

What is the effect of the thyroid hormone on the adrenal glands?

Answer 22

It increases the secretion of glucocorticoid (cortisol)

Question 23

What is the sexual function of the thyroid gland?

Answer 23

• Males:

1) Hyperthyroidism causes impotence

2) Hypothyroidism causes loss of libido

• Females:

1) Hyperthyroidism causes oligomenorrhea

2) Hypothyroidism causes loss of libido, irregular periods

Question 24

What is the action of the thyroid hormone on the growth?

Answer 24

• Essential for normal growth and skeletal maturation
• Hypothyroidism delays the bone growth and epiphyseal closure, it also depresses the secretion of GH

Question 25

What are the effects of the thyroid hormone on development?

Answer 25

- Thyroid hormone is critical for skeletal and muscular development, in cases of hypothyroidism the rate of growth is slowed a lot, however in hyperthyroidism excessive skeletal growth occurs - It is also responsible for a normal brain development and regulates (synaptogenesis, neural integration, myelination and cell migration) - If the thyroid hormone is not produced sufficiently the brain is retarded, and a child without a thyroid gland will be mentally deficient through life

Question 26

What regulates the release of the thyroid hormone

Answer 26

- Stimulators 1) TRH from the hypothalamus synthesized in the periventricular which are transported by the hypothalamo-hypophyseal portal system, TRH will then bind to a PLC second messenger 2) TSH (thyrotropin) from the thyrotrope - Inhibitors 1) T3 & T4 have a negative feed-bk inhibition at both level thyrotrope and hypothalamus

Question 27

What is the mechanism of action of the TSH by which it secretes the thyroid hormone?

Answer 27

- It works through the adenylate cyclase cyclic AMP cycle: 1) It increases the proteolysis of thyroglobulin 2) It increases the activity of the iodide pump 3) It increases the iodination of tyrosine 4) It increases the size and activity of the thyroid cells 5) It increases the number of thyroid cells - By stimulating the thyroid gland frequently the TSH can induce goiter

Question 28

What are the primary causes hypothyroidism?

Answer 28

1) Destruction of the gland (chronic autoimmune thyroititis) 2) Idiopathic atrophy of gland 3) Surgical removal of the thyroid 4) Irradiation of the gland 5) Endemic colloid goiter 6) Idiopathic colloid goiter

Question 29

What is the secondary cause of hypothyroidism?

Answer 29

- Due to the destruction of the hypothalamus or the pituitary 1) Crentinism (in Children) 2) Thyroiditis/Myxedema (in Adults)

Question 30

What is cretinism?

Answer 30

- Extreme hypothyroidism in fetal life, childhood, or infancy

Question 31

What are the causes of cretinsim?

Answer 31

1) Untreated congenital deficiency of thyroid hormone 2) Congenital lack of thyroid gland 3) Lack of iodine in diet

Question 32

What is the clinical presentation of cretinism?

Answer 32

1) Enlarged tongue (it will obstruct the swallowing and breathing) 2) Intolerance to cold 3) Decreased BMR 4) Accumulation of myxedematous tissue under the skin and mucous membrane 5) Swollen eyelid 6) Failure of body growth, and the skeletal growth is more inhibited compared to soft tissues 7) Mental retardation (hallmark to differentiate between GHD and cretinism) 8) Depressed nose 9) Dry hair 10) thick fat pad on the supraclavicular region - All symptoms are reversible with replacement therapy except mental retardation, unless it is treated within few weeks after birth

Question 33

What is Myxedema?

Answer 33

Almost a total lack of the thyroid hormone function

Question 34

What are the causes of Myxedema?

Answer 34

1) Thyroiditis 2) Endemic colloid goiter 3) Idiopathic colloid goiter 4) Destruction of the thyroid gland by irradiation 5) Surgical removal of the thyroid gland

Question 35

What is the clinical presentation of myxedema?

Answer 35

1) Decreased basal metabolic rate (40% weight gain despite low calorie intake) 2) Cold intolerance 3) Bagginess under eyes 4) Thickened skin & facia, with periorbital edema 5) Atherosclerosis (due to high cholesterol level as there is little cholesterol degradation) 6) Impaired memory, mental sluggishness & confusion, slow speech, prolonged reflex time 7) Muscle aches and weakness 8) Chronic constipation 9) Goiter 10) Slow heart rate and low CO

Question 36

What is graves diseases?

Answer 36

- The most common thyroid disorder - It is an autoimmune disease disease, stimulating the thyroid via immunoglobulins (TSIs) which are formed against TSH receptor - The effects of TSI are way longer than TSH (12H compared to 1H), and thus plasma levels of TSH are suppressed - TSI occupy same TSH receptors and for longer time so we’ll increase T3 and T4 production for longer time - It occurs in females more by 4 times - They will have a goiter despite low TSH (Thyroid hormone level : normal or high, TSH : low , TSI : high)

Question 37

What des the thyroid stimulating immunoglobulin do?

Answer 37

- It will go to the TSH receptor and stimulate the thyroid gland, resulting in hyperthyroidism (and their effects are way longer than those of TSH) - The increases amount of the thyroid hormone will inhibit the hypothalamus and the release of TSH from the thyrotropes

Question 38

What is the clinical presentation of Graves disease?

Answer 38

1) Increased sweating due to the thermogenic effect of the thyroid hormone 2) Exophthalmos (protrusion of the eyeballs due to the edematous swelling and deposition of the mucopolysaccharides in the retro-orbital tissues, leading to a degenerative change in the extraocular muscles), this will lead to the incomplete closure of the eye lids which might lead to dryness of the cornea 3) Polyphagia & diarrhea 4) extreme fatigue due to exhaustion 5) Tachycardia and arrhythmias 6) Nervousness 7) Hypocholesterolemia 8) Fine tremors of outstretched fingers

Question 39

When do we have a goiter?

Answer 39

- Due to increased stimulation of the gland (Whenever we have high TSH we will have goitre) 1) In graves disease 2) When hypothyroidism is caused by thyroid gland failure or lack of iodine (thyroid hormone is low -- little negative-feedback inhibition of the anterior pituitary and hypothalamus -- TSH elevated – acts on thyroid -- increase size and number of follicular cells -- increase their secretion, lack of iodine -- no amount of TSH will be able to induce secretion of T3 and T4 -- TSH can promote hypertrophy – goiter -- even the gland is still underproducing) 3) When there is excess TSH secretion resulting from a hypothalamic or anterior pituitary defect - Tumors of the thyroid does not cause goiter