Download Thyroid gland

Hormones of the thyroid and
parathyroid gland
Romana Šlamberová, M.D. Ph.D.
Department of Normal, Pathological and
Clinical Physiology
Thyroid and Parathyroid glands
Thyroid gland

Produces hormones:





Thyroxine (T4)
Triiodothyronine (T3)
Calcitonin
other thyroid hormones, such as
rT3, T2, and T1. - build T4 and T3,
but it is possible that thay have
function of their own
Controlled by


The hypothalamus [Thyreotropinreleasing hormone - TRH] and pituitary
[Thyroid-stimulating hormone - TSH]
Level of calcium
Histology



Follicles - The thyroid is composed of spherical follicles that
selectively absorb iodide ions (I-) from the blood for production
of thyroid hormones.
 25% I- in the thyroid gland
 Inside the follicles = colloid (reservoir of materials for thyroid
hormone production)
 Colloid is rich in a protein called thyroglobulin.
Follicular cells - single layer of thyroid epithelial cells (secretes
T3 and T4).
 Inactive gland = cuboidal cells
 Active gland = columnar cells
Parafolicular cells (C-cells)
 Location - scattered among follicular cells
and in spaces between the spherical follicles
 secrete calcitonin
Synthesis and secretion




Once the iodide is in the cell, it must be transformed
into thyroid hormones and stored until it is needed.
To create the hormones, the iodide must be attached
to the tyrosine molecule (the tyrosine must be
"iodinated“).
The iodination requires four separate components in
close proximity:
 iodide
 hydrogen peroxide (H2O2)
 thyroid peroxidase (TPO, an enzyme)
 thyroglobulin (Tg)
When TSH activates the secretion, the hormones are
separated from the thyroglobulin and secreted into the
blood stream, where 99% combine with transport
proteins.
Synthesis and secretion




Thyroglobulin - synthesized in the rough endoplasmic reticulum and then
enter the colloid in the lumen of the thyroid follicle by exocytosis.
Sodium-iodide (Na/I) symporter pumps iodide (I-) into the cell
This iodide enters the follicular lumen from the cytoplasm by the
transporter pendrin
In the colloid, iodide (I-) is oxidized to iodine (I0) by an enzyme called
thyroid peroxidase.

Iodine (I0) is very reactive and
iodinates the thyroglobulin at
tyrosyl residues in its protein
chain

In conjugation, adjacent tyrosyl
residues are paired together.

The entire complex re-enters
the follicular cell by
endocytosis.

Proteolysis by various proteases
liberates thyroxine and
triiodothyronine molecules, which
enters the blood
Synthesis and secretion
Thyroxine (T4)




It consists of four atoms of iodine attached to a molecule of tyrosine.
secreted by the follicular cells of the thyroid gland
Thyroxine (T4) is 65% iodine by weight.
transported in blood




T4 accounts for up to 90% of the protein-bound iodine in the
blood.
T4 seems to function primarily as a storage form, being transformed
into T3 as needed to maintain proper body function.



99.95% bound to thyroxine-binding globulin (TBG)
0.05% bound to transthyretin and serum albumin.
Up to 80% of the T4 is converted to T3 by peripheral organs such as the
liver, kidney and spleen.
T3 is about ten times more active than T4.
Deiodination



process by which an iodide atom is removed in transforming T4 to T3.
It occurs throughout the body, including the thyroid, liver, pituitary,
brain, and other organs.
It is performed by enzymes containing selenium (important selenium in
diet).
T3, T4 - mechanism of action



Most body cells have receptors for thyroid hormones on the cell
membrane.
 the specific nuclear receptors, where they then regulate gene
expression.
Function:
 Regulation of oxygen use
 Regulation of basal metabolism rate
 Regulation of cellular metabolism
 Regulation of growth and development
 Stimulate the use of cellular oxygen to produce ATP
 Stimulate the synthesis of Na-K pumps
As the cells produce and use more ATP, more heat is given off, and
the body temperature rises.
Functions of T4 and T3





stimulate protein synthesis
increase the use of glucose and fatty acids for
ATP production
increase the decomposition of fats and
enhance cholesterol excretion (thus reducing
blood cholesterol levels)
affect the regulation of body fluids, vascular
resistance and blood pressure
accelerate body growth, particularly the
growth of nervous tissue
Thyroid hormone diseases

Iodine deficiency






Decrease in serum T4
Increase in serum TSH
Thyroid enlargement (goitre)
Decrease in the degree of iodination of Tg
Increase in T3/T4 ratio
Iodine excess



Inhibits iodide transport and hormone synthesis
Inhibits thyroid growth
Inhibits the function of thyroid hormones and
growth
Goitre (struma)





term that refers to an enlargement of the thyroid (thyromegaly)
Signs and symptoms
 associated with hypothyroidism or hyperthyroidism, can be inactive
Growth pattern
 Uninodular, Multinodular, Diffuse
Size
 Class I - palpation struma
 Class II - easily seen
 Class III - very large and is retrosternal (pressure results in compression
marks)
Causes
 Iodine deficiency
 Congenital hypothyroidism
 Hashimoto's thyroiditis or other thyroiditis
 Pituitary disease
 Graves' disease
 Thyroid cancer
 Thyroid hormone insensitivity
Hypothyroidism

Primary – deficiency of thyroid hormones





Hashimoto's thyroiditis
Cretinism
Secondary – deficiency of TSH from pituitary
gland
Tertiary – deficiency of TRH from hypothalamus
Main symptoms





Slowed speech and breaking voice
Dry puffy skin, especially on the face
Thinning of the outer third of the eyebrows (sign of
Hertoghe)
Abnormal menstrual cycles
Low basal body temperature
Hashimoto's thyroiditis




an autoimmune disease where the body's
own T-cells attack the cells of the thyroid
antibodies against thyroid peroxidase and/or
thyroglobulin cause gradual destruction of
follicles in the thyroid gland
Symptoms – Myxedema, weight gain,
depression, mania, fatigue, panic attacks,
bradycardia, high cholesterol, reactive
hypoglycemia, constipation, migraines,
memory loss, infertility and hair loss.
Treatment - thyroid hormone replacement
Myxedema

specific form of cutaneous and dermal edema


increased deposition of connective tissue components (like
glycosaminoglycans, hyaluronic acid, and other mucopolysaccharides)
in subcutaneous tissue
Symptoms:


fatigue, weight gain, depression, dry skin, and brittle hair
intolerance to cold, low blood pressure, shortness of breath, lethargy
and seizures
Cretinism



A condition of severely stunted physical and
mental growth due to untreated congenital
deficiency of thyroid hormones.
Reasons can be:
 endemic (deficiency of iodine)
 genetic
 sporadic (abnormal development of
thyroid gland)
Symptoms:
 reduced muscle tone and coordination
 cognitive impairment
 thickened skin and a protruding abdomen
Hyperthyroidism



Overactive tissue within the thyroid gland, resulting in
overproduction of T4 and T3.
Symptoms:
 Fast heart beat results in palpitations
 a fast nervous system in tremor and anxiety
symptoms
 a fast digestive system in weight loss and diarrhea
Diseases:
 Graves-Basedow disease
 Toxic thyroid adenoma – „hot“ adenoma
 Thyroiditis – inflammation
Graves-Basedow disease

caused by an
antibody-mediated
auto-immune
reaction

Symptoms:







Goiter
Exophthalmos
(swelling behind
the eyeball)
"orange-peel" skin
Fatigue
weight loss with
increased appetite
rapid heart beats
muscular weakness
CALCITONIN
Parafollicular cells of thyroid gland (C-cells)
peptide of 32 amino acids
stimulus for secretion – high plasma calcium
(food intake – gastrin, cholecystokinin,
glucagon)
Function – to DECREASE plasma calcium and
phosphates








inhibits osteolysis – decreases absorption of Ca2+, P
from bones
stimulates incorporation of Ca2+, P to bones
decreases absorption of Ca2+, P in kidneys
decreases the effect of PTH on bones – PTH antagonist
Parathyroid glands




Parathyroid hormone (PTH)
polypeptide of 84 amino acids
stimulus for secretion – low plasma
calcium
function – to INCREASE plasma
calcium




activation of osteoclasts – stimulates
absorption of Ca2+, P from bones
decreases excretion of Ca2+ by kidneys
increases excretion of P by kidneys
stimulates conversion of vitamin D to
calcitriol (vitamin D hormon) in kidneys
Changes in PTH plasma level
Hypoparathyroidism
 Muscle tetany (spasms)
 Convulsions
 Pain in the face, legs, and feet, abdominal pain
 Dry hair, dry skin
 Cataracts
Hyperparathyroidism
 Decalcification of bones
 Multiple fractures (Osteitis fibrosa cystica)
 Kidney stones
 Lack of energy, memory problems, depression
Relation - plasma Ca2+
concentration x hormones