Transcript ENDOCRINE.Thyroid

Physiology of the
Thyroid gland.
Thyroid Gland
Introduction.







Thyroid gland maintains levels of metabolism in
tissues.
Thyroid hormones stimulate oxygen consumption in
most cells of the body.
Regulates lipid and CHO metabolism.
Necessary for normal growth and maturation.
Absence causes mental and physical slowing.
Excess causes body wasting nervousness
tachycardia and tremors.
Controlled by Thyroid stimulating hormones(TSH)
Anatomic considerations









Thyroid tissue is present in all vertebrates
Originates from evagination of the floor of the pharynx and
thyroglossal duct marking the path of the thyroid from tongue to
neck.
2 lobes connected by isthmus
Sometimes pyramidal lobe arising from the isthmus.
Well vascularised
Multiple follicles
Follicle surrounded by cells filled with colloids
When inactive, colloid is abundant and follicle large.
When active follicles are small.
Formation and secretion of
thyroid hormones.





The principal hormones secreted by thyroid gland
are Thyroxine(T4) and triiodothyronine(T3)
T3 is also formed in the peripheral tissue by
deiodination of T4
Both hormones are iodine-containing amino acids.
T3 is more active than T4
Calcitonin is also produced by thyroid in
response to increased calcium levels.
Structure of thyroid hormones
Thyroglobulin.





T3 and T4 are synthesized in the colloid by
iodination
The hormones are bound to thyroglobulin within the
thyroid cells
Thyroglobulin is also synthesized in the thyroid cells
The hormones remain bound to thyroglobulin until
secreted
When secreted, the colloids is ingested by thyroid
cells, peptide bonds are hydrolyzed and free T3 and
T4 are discharged into the system
Iodine Metabolism



Iodine is the raw material for thyroid hormone
synthesis.
Ingested iodine is converted to iodide and
then absorbed
The principal organs that take up the iodide
are the thyroid which uses it to make thyroid
hormones and the kidneys which excrete it in
the urine.
Iodide trapping




Thyroid concentrates iodide by actively
transporting it from circulation to the colloid
The transport mechanism is called “iodide
trapping” mechanism or the “iodide pump”
The pump is an example of a secondary
active transport system
In the gland, iodide is oxidized and bound to
tyrosine.
Thyroid Hormone synthesis





In the thyroid, iodide is oxidized to iodine and bound
within secs to tyrosine attached to thyroglobulin
The enzyme responsible for the oxidation and
binding of iodide is Thyroid peroxidase
Monoiodotyrosine (MIT) is next iodinated to
Diiodotyrosine(DIT)
2 DIT molecules undergo oxidative condensation to
form Thyroxine(T4)
T3 is probably formed by condensation of MIT and
DIT.
Iodide trapping
Transport and metabolism of
Thyroid Hormones








Large amounts of T3 and T4 are bound to plasma proteins.
The unbound T3 and T4 are the physiologically active forms of
the hormones.
Free T3 and T4 inhibit the secretion of TSH.
The plasma proteins that bind thyroid hormones are
albumin,transthyretin and thyroxin-binding globulin(TBG)
Most of the circulating T4 is bound to TBG
T3 is bound to albumin
TBG levels are increased in estrogen-treated patients and
pregnant women
TBG levels are reduced by glucocorticoids and androgens.
Regulation of thyroid hormone
secretion.
Effects of Thyroid hormones







Majority of action of thyroid hormones are secondary
to stimulation of oxygen consumption.
Regulates lipid metabolism
↑ absorption of CHO from the intestine
↑ mentation and concentration
↑ sensitivity of heart to chronotropic(heartbeat) and
inotropic (muscle contractions) effects of
catecholamine.
↓ circulating cholesterol levels.
Essential for normal growth and skeletal maturation.
Thyroid diseases
Hypothyroidism—caused by
 Hashimoto’s Thyroiditis
 Ord’s thyroiditis
 Post operative Hypothyroidism
 Congenital hypothyroidism(cretinism)
Hyperthyroidism---caused by
 Grave’s Disease
Thyroid diseases (ctd)

Anatomical –Goitre-Endemic
-Diffuse
-Multinodular
Clinical correlates.
Signs and symptoms of hypo or hyper thyroidism
are consequences of effect of thyroid hormones.
Hypothyroidism Syndrome of hypothyroidism is called myxedema.
 Term also used to describe skin changes in
hypothyroidism.
 May be end result of secondary pituitary failure
(pituitary hypothyroidism)
 May be due to hypothalamic failure( hypothalamic
hypothyroidism)
 May be due to thyroid disorder.

Cretinism
Children with hypothyroidism from birth are called
cretins
 They have reduced growth and mentally retarded.
 Potbellies
 Enlarged protruding tongue
CausesMaternal iodine deficiency
Fetal thyroid dysgenesis
Inborn errors of thyroid synthesis
Maternal antibodies that cross placenta
Fetal hypo pituitary hypothyroidism

cretinism
Hashimoto’s thyroiditis
Autoimmune disease where antibodies attack
thyroid cells.
 Females>males
 Atrophic (degeneration) form is known as Ord’s
thyroiditis
Causes :
 Genetic
 Chromosomal disorders
associated:Turners,klinfelter’s and Down’s
syndrome
 Presentation: hypothyroidism and goiter

Hyperthyroidism signs and
symptoms.









Nervousness
Wt loss
Hyperphagia
Heat intolerance
Increased pulse pressure
Fine tremors on outstretched fingers
Warm soft skin
Sweating
Increased BMR
Graves disease









Most common cause of hyperthyroidism
Also known as exophthalmic goiter
Thyroid is diffusely enlarged
Protrusion of the eyeballs
Autoimmune disorder
Circulating antibodies formed against TSH receptors
which activate the receptors and make gland
hyperactive.
4 types of antibodies-TSH stimulating,TSHblocking,Tg antibody,Tpo antibody
↑ T3 ,T4 levels
Inhibition of the TSH
Grave’s disease
Presentation:
 Palpitation
 Tachycardia
 ↑ BP
 ↑ sweating
 Tremors
 ↑ appetite
 Wt loss
 Protruding eyeballs
Graves Disease.
Iodine deficiency



When dietary intake drops,thyroid hormones
synthesis is inadequate and secretion is
reduced.
TSH is increased and thyroid hypertrophies
producing an iodine deficiency Goiter.
Endemic goiter-mountainous areas..
Thyroid response to low intake of iodine.
In most cases if iodine is deficient in the diet but not absent, the individual will
remain euthyroid (normal fxn thyroid) but will develop a goiter.


This is called Endemic goitre.
The enlarged gland may make maximum use of the iodine available and may be
able to just maintain normality but at the expense of a large goitre, hence the
description endemic goitre.
Prevention: supplementation of iodine, which can be added to a staple food
such as flour or salt.
Iodine deficiency.
Goiter..
Radioactive Iodine uptake.






Iodine uptake is an index of thyroid function
Uptake can be measured by using tracer doses of
radioactive isotopes of iodine that have no effect on
thyroid gland.
Tracer is administered orally
Gamma ray counter placed over the neck
Large amount of radioactive iodine destroys the
thyroid tissue.
Radioiodine therapy is useful in some cases of
thyroid cancer although can cause radiation
carcinogenesis.
Radioactive iodine scan.
Pathological Changes in Thyroid Hormone Secretion
T4
1. *Primary hypothyroidism
2. Pituitary hypothyroidism
(secondary)
3. Hypothalamic hypothyroidism
(tertiary)
4 Pituitary hyperthyroidism
(secondary)
5 . Grave’s disease (autoimmune
)
TSH
TRH