THYROID

HORMONES
LEARNING OBJECTIVES
▪ At the end of this lecture, you should be able to:
▪ Identify the steps in the biosynthesis, storage, and secretion of thyroid hormones
and their regulation.
▪ Describe factors that control the synthesis, storage, and release of thyroid
hormones.
▪ Explain the importance of thyroid hormone binding in blood on free and total
thyroid hormone levels.
▪ Describe the actions of thyroid hormones on development and metabolism.
▪ Understand the causes and consequences of a) over-secretion and b)
under-secretion of thyroid hormones.
THYROID GLAND
▪ immediately below the larynx on each
side of and anterior to the trachea
▪ one of the largest endocrine glands
▪ 15 to 20 grams
▪ thyroxine and triiodothyronine (T3, T4).
calcitonin
▪ secretion is controlled primarily by
thyroid stimulating hormone (TSH)
SYNTHESIS AND SECRETION
▪ 93% T4, 7% T3 (4x more potent)
▪ T4 conversion in tissues
▪ T3:
▪ Short half life
▪ Smaller quantities
PHYSIOLOGICAL ANATOMY
▪ Follicles
▪ Colloid
▪ Cuboidal epithelial cells
▪ Thyroglobulin
▪ blood flow about 5x the weight
of the gland each minute
▪ C cells that secrete calcitonin
SYNTHESIS OF THYROID
HORMONE
▪ Iodide transport
▪ Thyroglobulin synthesis
▪ Oxidation of I– to I°
▪ Iodination
▪ Coupling
▪ Storage of thyroid hormones
IODIDE TRANSPORT
▪ 50 milligrams/year or 1 mg/week
▪ common table salt- iodized with about 1 part sodium
iodide to every 100,000 parts sodium chloride
▪ Iodine uptake via a sodium/potassium pump powered
sodium/iodide symporter on the basal membrane (NIS)
▪ Blocked by: perchlorate and thiocyanate (compete with I)
▪ I¯ is transported into the lumen by an anion exchanger
called pendrin
THYROGLOBULIN SYNTHESIS
▪ high molecular weight protein (>300,000 daltons)
▪ synthesized in ribosomes, glycosylated in the
endoplasmic reticulum, packaged into vesicles in the
Golgi apparatus
▪ thyroglobubin then enters the lumen via exocytosis
OXIDATION OF I– TO I°
▪ thyroperoxidase (TPO)
▪ located at the apical border of the follicle cell, catalyzes
oxidation
▪ catalyzes iodination and coupling
IODINATION
▪ (<20%) of thyroglobulin
tyrosine residues are
iodinated
▪ Peroxidase
▪ Initial products: mono- and
diiodotyrosine (MIT and
DIT)
COUPLING
▪ Peroxidase also promotes the coupling of iodinated
tyrosine in the thyroglobulin Molecule
▪ two DITs couple, tetraiodothyronine (T4)
▪ one DIT and one MIT combine, triiodothyronine (T3)
▪ When iodine is abundant, mainly T4 is formed
▪ odine becomes scarce, the production of T3 increases
STORAGE OF THYROID
HORMONES
▪ stored as iodinated thyroglobulin in the follicular colloid
to last the body for 2–3 months
SECRETION OF THYROID
HORMONE
▪ Pinocytosis: Pieces of the
follicular colloid are taken
back into the follicle by
endocytosis.
▪ Fusion: The endocytosed
material fuses with lysosomes,
which transport it toward the
basal surface of the cell.
SECRETION OF THYROID
HORMONE
▪ Proteolysis of thyroglobulin:
Within the lysosomes, the
thyroglobulin is broken into
free amino acids, some of
which are T4, T3, DIT, and
MIT.
SECRETION OF THYROID
HORMONE
▪ Secretion: T4 and T3 are
secreted into the blood, with
the T4:T3 ratio being as high
as 20:1. The thyroid has the
same 5’-mono-deiodinase
found in many peripheral
tissues and in an
iodine-deficient state more
of the hormone can be
released as T3.
SECRETION OF THYROID
HORMONE
▪ Deiodination: A microsomal
deiodinase removes the
iodine from iodinated
tyrosines (DIT and MIT) but
not from the iodinated
thyronines (T3 and T4)
▪ iodine is then available for
resynthesis of hormone
TRANSPORT OF THYROID
HORMONES IN BLOOD
▪ T3 & t4 are bound to plasma proteins
▪ combine mainly with thyroxine-binding globulin and
much less so with thyroxine-binding prealbumin and
albumin.
▪ T4 half-life = 6 days
▪ T3 half-life = 1 day
▪ Thyroxine and triiodothyronine are released slowly to
tissue cells
SEATWORK
▪Identify the different substances that
would inhibit the different steps in
thyroid hormone synthesis.
PHYSIOLOGICAL
FUNCTIONS
OF THE THYROID
HORMONES
CONTROL OF THYROID
HORMONE SECRETION
▪ TRH provides a constant and
necessary
▪ absence of TRH - secretion of
TSH (and T4) decreases to
very low levels
▪ TSH targets the thyroid
CONTROL OF THYROID
HORMONE SECRETION
▪ Negative feedback of thyroid
hormones is exerted mainly at
the level of the anterior
pituitary gland.
▪ T4 that is responsible for most
of the negative feedback.
CONTROL OF THYROID
HORMONE SECRETION
▪ within the thyrotrophs the T4
is converted to T3 before it
acts to reduce the sensitivity
of the thyrotroph to TRH
CONTROL OF THYROID
HORMONE SECRETION
▪ As long as circulating free T4 remains normal, changes in
circulating T3 have minimal effects on TSH secretion.
▪ TSH secretion increases if there is a significant drop in
circulating free T4, even in the presence of an increase in
circulating T3.
ANTITHYROID SUBSTANCES
▪ best known antithyroid drugs:
▪ Thiocyanate
▪ propylthiouracil
▪ high concentrations of inorganic iodides
DISEASES OF THE
THYROID
HYPERTHYROIDISM
▪ Toxic Goiter
▪ Thyrotoxicosis
▪ Graves’ Disease

▪ thyroid gland is increased to 2x – 3x normal size

▪ tremendous hyperplasia and infolding of the follicular cell
lining into the follicles,
▪ number of cells is increased greatly
GRAVE’S DISEASE
▪ most common form of
hyperthyroidism
▪ autoimmune disease
▪ Antibodies called
thyroid-stimulating
immunoglobulins (TSIs)
▪ Form against the TSH receptor in
the thyroid gland
SYMPTOMS OF
HYPERTHYROIDISM
▪ (1) a high state of excitability
▪ (2) intolerance to heat
▪ (3) increased sweating
▪ (4) mild to extreme weight loss (sometimes as much as 100 pounds)
▪ (5) varying degrees of diarrhea
▪ (6) muscle weakness
▪ (7) nervousness or other psychic disorders
▪ (8) extreme fatigue but inability to sleep
▪ (9) tremor of the hands
HYPOTHYROIDISM
▪ often initiated by autoimmunity against the thyroid gland
(Hashimoto’s disease)
▪ autoimmunity destroys the gland rather than stimulates it
▪ thyroid glands of most of these patients first demonstrate
autoimmune “thyroiditis”
▪ progressive deterioration and finally fibrosis of the gland, with
resultant diminished or absent secretion of thyroid hormone
MYXEDEMA
▪ develops in persons who have
almost total lack of thyroid
hormone function
▪ greatly increased quantities of
hyaluronic acid and chondroitin
sulfate bound with protein form
excessive tissue gel in the
interstitial spaces, which causes
the total quantity of interstitial
fluid to increase
CRETENISM
▪ extreme hypothyroidism during fetal
life, infancy, or childhood
▪ failure of body growth and by mental
Retardation
▪ results from congenital lack of a
thyroid gland (congenital cretinism),
from failure of the thyroid gland to
produce thyroid hormone because of
a genetic defect of the gland, or from a
lack of iodine in the diet (endemic
cretinism)