thyroid gland and thyroid gland dysfunction Flashcards
what does the thyroid gland consist of?
numerous spheres each of which form a follicle.
what do the walls of follicles consist of?
single layer of cuboidal cells
what makes up the centre of the lumen?
colloid made up of protein called thyroglobulin
what are some of the amino acids in thyroglobulin?
they have some thyroid hormones such as thyroxine and triiodothyronine
what secretes calcitonine?
parafollicular or C-cells
what is calcitonine involved in?
calcium balance
what are the thyroid hormones?
- Thyroxine or T4 or tetraiodothyronine
- Triiodothyronine or T3
3,5,3’-Triiodothyronine
what is the first major step in the synthesis of thyroid hormones?
uptake of iodide ion by the thyroid gland
what is the second major step in the synthesis of thyroid hormones?
Oxidation of iodide and the iodination of tyrosyl groups of thyroglobulin
what is the third major step in the synthesis of thyroid hormones?
Coupling of iodotyrosyl residues by ether linkage to generate iodothyronine
what is the fourth major step in the synthesis of thyroid hormones?
Proteolysis of thyroglobulin and the release of thyroxine (T4) and T3
what is the normal daily intake of iodine?
150 µg
how is iodine absorbed?
Iodine is absorbed from the GI tract and reaches the circulation in the form of iodide.
how is iodide transported?
Thyroid gland efficiently and actively transports the ion.
what stimulates the transport mechanism of iodine?
thyroid-stimulating hormone (TSH or thyrotropin)
what is another mechanism the thyroid gland has?
The gland also have a mechanism (independent of TSH) to regulate the iodide uptake which depends on the iodine concentration in the blood
how are thyroid hormones transported in the blood?
highly bound to plasma protein
what are the 3 plasma proteins associated with thyroid hormone transport?
- Thyroxine-binding globulin (TBG)
- Thyroxine binding prealbumin (TBPA)
- Albumin
why is protein binding good for the thyroid hormone?
High protein binding protect thyroid hormone from metabolism and excretion
where is thyroxine converted to T3?
liver
what % of thyroid secretions are
triiodothyronine (T3).
what is the main biologically active level at the cellular level?
T3
what do most peripheral targets use?
Most peripheral target tissues utilize T3 derived from the blood supply.
where is 80% of circulating T3 derived from?
from the circulating T4.
what happens under normal condition to T4?
Under normal conditions about 41% of T4 is converted to T3 about 38% to reverseT3 and 21 % via other pathways such as conjugation
what is the half life of thyroxine?
6-7 days
what is the half life of triiodothyronine?
1 day
what happens to the half life of thyroid hormones in hyperthyroidism?
reduced protein binding causes a decrease in the half-life
what happens to the half life of thyroid hormones in hypothyroidism?
increases binding resulting in an increase in the half-life
what is the mechanism of action for thyroid hormones?
Thyroid hormone produces most of its effects through control of DNA transcription and ultimately, protein synthesis.
what are the physiological actions of thyroid hormones?
Virtually every body tissue is affected either directly or indirectly
Primary determinant of the body’s overall metabolic rate
Essential for normal growth and development
what are the effects of thyroid hormones?
Calorigenic effects
Effects on intermediary metabolism
Effects on cardiovascular system
Effects on growth and development
what are the calorigenic effects of thyroid hormones?
Increases body’s overall basal metabolic rate.
Increases bodies O2 consumption (heart, skeletal muscle, liver and kidney plays the major role) and leads to increased heat production
The action of thyroid hormones is sluggish
what are the effects of thyroid hormones on intermediary metabolism?
Thyroid hormone modulates the rate of many specific reactions involved in fuel metabolism. It also modulate the actions of other hormones such as insulin, glucagon, glucocorticoids and catecholamines
what are the effects of thyroid hormones on carbohydrate metabolism?
Stimulate almost all aspect of carbohydrate metabolism
what are the effects of thyroid hormones on fat metabolism?
Essentially all aspect of fat metabolism is also enhanced by thyroid hormone
Thyroid hormone increases the cholesterol secretion in bile. Increased thyroid hormone decreases the quantity of cholesterol in the plasma
what are the effects of thyroid hormones on mucopolysaccharide metabolism?
Thyroid hormones affect both synthesis and degradation of hyaluronic acid (HA) in connective tissues
what are the main effects of thyroid hormones on cardiovascular system?
Increased cardiac function
Increased heart rate
Increased force of contraction
Decreased peripheral resistance
how is decreased peripheral resistance caused?
Resulting from increased myocardial gene expression and increased number of β-adrenergic receptors.
what are the effects of thyroid hormones on growth and development?
Essential for normal growth and development of all tissues including the brain.
It also plays a permissive role for the growth hormone. The hormone is essential for the normal growth in children.
what is the main important function of thyroid hormone?
to promote growth and development of the brain during first few years of postnatal life.
what is the speed of onset for hypothyroidism?
gradual onset
what is the speed of onset for hyperthyroidism (thyrotoxicosis)?
develops acutely
what is goitre?
Goitre is the name given to any enlargement of the thyroid gland
what does goitre result from?
It results from the excessive stimulation of thyroid by either TSH or Thyroid Receptor Antibodies (also called Thyroid Stimulating Immunoglobulin) resulting in hypertrophy and hyperplasia.
what is goitre associated with?
Hypothyroidism,
Hyperthyroidism or
Normal thyroid function (Euthyroidism)
is a goitre present in all cases of thyroid dysfunctions?
not present in all cases of hypothyroidism or hyperthyroidism
what are the primary causes of hypothyroidism?
congenital, acquired, drug induced, iodine deficiency
what are the secondary causes of hypothyroidism?
Hypothalamic and pituitary diseases
TSH deficiency
what is an example of an acquired cause of hypothyroidism?
Hashimoto’s thyroiditis (an autoimmune disorder and the most common cause of hypothyroidism in western countries)
what are the most common drugs that cause hypothyroidism?
Amiodarone and Lithium
what is cretinism?
Arrested physical and mental development due to congenital lack of thyroid secretion
what are features of cretinism?
- Dwarfed with short extremities
- Mentally retarded
- Inactive, uncomplaining and listless
- The face is puffy and expressionless
- Enlarged tongue
- Dry and cool skin with a yellowish hue
- Slow heart rate
- Constipation is frequent
what is the most common cause of hyperthyroidism?
Graves disease
what is Graves’ Disease?
An autoimmune disorder and develop due to the presence of thyroid stimulating antibodies (thyroid receptor antibodies) that react with TSH receptors in the thyroid gland in the same manner as TSH
what are other causes of hyperthyroidism?
- Toxic multinodular goitre
- Solitary toxic nodules
- Amiodarone-induced thyrotoxicosis
- Thyroiditis
what is toxic multinodular goitre?
Multiple over active thyroid nodules
what is solitary toxic nodules?
Single over active thyroid nodule
what is the treatment of hypothyroidism?
Replacement therapy with synthetic thyroid hormones, unless due to iodine deficiency which is treated with iodide
what are the available drugs for hypothyroidism treatment?
Levothyroxine (The drug of choice)
L-Triiodothyronine (liothyronine)
what are the characteristics of Levothyroxine?
Orally active
Cheap
Takes long time to achieve steady state and dose adjustment is made only after 3-4 weeks
what are the characteristics of L-Triiodothyronine?
Can be given orally or IV
Quicker action but only advantageous in severe hypothyroid cases, but may cause wide fluctuation in plasma concentration between doses
what are the 3 main treatments of Thyrotoxicosis?
- antithyroid drugs
- radioactive iodine
- surgery
what are examples of antithyroid drugs?
Carbimazole and Propylthiouracil
Beta adrenoceptor antagonists
Iodine
which of the antithyroid drugs inhibit thyroid hormone synthesis?
Carbimazole and propylthiouracil
what is carbimazole converted to?
active compound methimazole
what does iodine do in terms of antithyroid drug?
Iodine blocks release of thyroid hormone and reduce vascularity of thyroid gland
what does propylthiouracil inhibit?
- thyroid hormone synthesis
- peripheral conversion of T4 to T3
how do beta adrenoreceptor antagonists function?
Beta adrenoceptor antagonists functionally antagonise the target organ effects of thyroid hormones.
what is the gradual dose titration anti drug regimen?
Initial dose of 15-40 mg carbimazole daily, after 4-8 weeks dose is progressively reduced to 5-15 mg daily. The therapy usually last for 12-18 months.
About 50% of patients relapse, usually within next 2 years.
what is the block and replace regimen?
With this regimen a full dose of antithyroid drugs (40-60 mg) is given to suppress thyroid completely while replacing thyroid activity with T4 (50-150 µg). The therapy is again given for 18 months. This regimen is claimed to have lower incidence of relapse. Not suitable during pregnancy
what can be done if carbimazole is not tolerated?
propylthiouracil can be used at 10 times carbimazole dose
when can surgery be done?
Surgery should only be performed in patients who have been rendered euthyroid
what happens to antithyroid drugs in preparation for surgery?
Antithyroid drugs are stopped 10-14 days before surgery and Lugol’s iodine is given which reduce vascularity of the gland
what does radioactive iodine do to the gland?
odine 131 accumulates in the gland and destroys the gland by local radiation
what must be determined before radioiodine therapy?
Patient must be rendered euthyroid before the therapy.
Antithyroid drugs are stopped about 5 days before radioiodine
why can’t carbimazole be taken for 2-3 days after radioiodine therapy?
because it will prevent radioiodine uptake by the gland. Beta-blocker may be used in this period.
