THYROID

HORMONES
SHERWIN B. TORIANO, RMT,MSMT
 THYROID GLAND
• The thyroid gland, or simply the
thyroid, is an endocrine gland in the
neck, consisting of two lobes
connected by an isthmus. It is
found at the front of the neck,
below the Adam's apple. The
thyroid gland secretes thyroid
hormones, which primarily
influence the metabolic rate and
protein synthesis.
• The thyroid weighs 25 grams in adults,
with each lobe being about 5 cm long,
3 cm wide and 2 cm thick. The gland is
usually larger in women, and increases
in size in pregnancy.
• Typically four parathyroid glands, two
on each side, lie on each side between
the two layers of the capsule, at the
back of the thyroid lobes.
Microanatomy
There are three primary cells of the thyroid—
follicles, follicular cells, and parafollicular cells.
• Follicles
Thyroid follicles are small spherical groupings
of cells 0.02–0.9mm in diameter that play the
main role in thyroid function. They consist of
a rim that has a rich blood supply, nerve and
lymphatic presence, that surrounds a core of
colloid that consists mostly of thyroid
hormone precursor proteins called
thyroglobulin, an iodinated glycoprotein. colloid
parafollicular cells
• Follicular cells
The core of a follicle is surrounded by a single layer of follicular cells. When
stimulated by thyroid stimulating hormone (TSH), these secrete the thyroid
hormones T3 and T4. They transport and metabolize the thyroglobulin
contained in the colloid. Follicular cells vary in shape from flat to cuboid to
columnar, depending on how active they are.
• Parafollicular cells
They are scattered among follicular cells and in spaces between the spherical
follicles. These cells secrete calcitonin, and are also called C cells.
Thyroid hormones functions
The primary function of the thyroid is the production of the iodine-containing
thyroid hormones, triiodothyronine (T3) and thyroxine (T4) and the peptide
hormone Calcitonin. The thyroid hormones have a wide range of effects on the
human body. These include: Metabolic, Cardiovascular and Developmental

• Thyroid hormones regulates oxidative metabolism (↑ basal metabolic rate

and ↑O2 consumption), ↑ rates of anabolic and catabolic processes, ↑ growth
and development, ↑ systemic function.
• Enhanced metabolic activity increases the body’s demand for oxygen
consumption ↑ cardiac output, ↑ respiratory drive, and ↑ production of red
blood cells ( ↑ EPO), ↑ appetite, ↑ GI motility, and ↑ intestinal absorption.
• Heart: o Cardiac Hypertrophy: ↑ cardiac proteins and myocytes, ↓ collagen in
non-myocytes.
o Contractility: ↑ speed and force of systolic contraction, ↑ speed of
diastolic relaxation.
o Electrical Activity: ↑ rate of impulses, ↑ speed of conduction.
• Skeletal Muscle: o ↑ O2 consumption, ↑ blood flow, ↑ protein synthesis,
and ↑ contractility
• Bones: o Lack of development without T3
• Renal and Liver: o ↑ blood flow, ↑ clearance rates, ↑ vasoactive mediation sensitivity,
↑ protein synthesis
• Growth, Brain, and CNS: o critical for normal fetal and neonatal development,
regulates growth and function genes, effects mood and condition,
↑ GH and IGF secretion and ↑ tissue responsiveness.
Thyroid hormones Regulation
• The production of thyroxine (T4) and
thyronine (T3) is primarily regulated by
thyroid-stimulating hormone (TSH). TSH
release is stimulated by thyrotropin releasing
hormone (TRH), released in a pulsatile manner
from the hypothalamus.
• The thyroid hormones provide negative
feedback to the thyrotropes TSH and TRH:
when the thyroid hormones are high, TSH
production is suppressed. This negative
feedback also occurs when levels of TSH are
high, causing suppression of TRH production.
• The thyroid gland parafollicular cells produce
calcitonin in response to high blood calcium.
Calcitonin decreases the release of calcium
from bone, by decreasing the activity of
osteoclasts, cells which break down the bone.
• The effects of calcitonin are opposite those of
the parathyroid hormone (PTH) produced
in the parathyroid glands. However, calcitonin
seems far less essential than PTH, as calcium
metabolism remains clinically normal after
removal of the thyroid (thyroidectomy), but
not the parathyroid glands.
 THYROID HORMONES
Hormone synthesis
• The thyroid hormones are created from
thyroglobulin.
• Thyroglobulin is a protein within the
follicular space that is originally created
within the rough endoplasmic reticulum
of follicular cells and then transported
into the follicular space.
• Thyroglobulin contains 123 units of
tyrosine, which reacts with iodine within
the follicular space.
• Iodine is essential for the production
of the thyroid hormones.
• Iodine (I0) travels in the blood as
iodide (I−), which is taken up into the
follicular cells by a sodium-iodide
symporter, an ion channel on the cell
membrane.
• Iodide then travels from within the
cell into the follicular space, through
the action of pendrin, an iodide-
chloride antiporter.
• In the follicular space, iodide is
oxidized to iodine. The iodine is
attached to the active tyrosine units
in thyroglobulin by the enzyme
thyroid peroxidase. This forms the
precursors of thyroid hormones
monoiodotyrosine (MIT), and
diiodotyrosine (DIT).
• When the follicular cells are
stimulated by TSH, the follicular
cells reabsorb thyroglobulin from
the follicular space.
• The iodinated tyrosines are cleaved,
forming the thyroid hormones - T4,
T3, DIT, MIT, and traces of reverse
triiodothyronine. T3 and T4 are
released into the blood.
• The hormones secreted from the
gland are about 80–90% T4 and
about 10–20% T3.
• Deiodinase enzymes in peripheral
tissues remove the iodine from MIT
and DIT, convert T4 to T3, and RT3.
T4 is a major source of both RT3
(95%) and T3 (87%) in peripheral
tissues.
Hormone Structural Variants:
T4 and T3 is made up of a protein and iodine (in the form of iodide). Total
T4 and T3 refers to the total amount of circulating T4 and T3 which are
bound to proteins, which makes it inactive.

• T4 - 4 molecules of iodide, thyroxine. Fully iodinated.

The major secretory product.
• T3 - 3 molecules of iodide, triiodothyronine. Active circulating form
• rT3 (reverse T3) - lacks one iodine on its inner ring. Physiologically inert.
• Free T4 and Free T3, or FT4 and FT3 are the intracellularly active form of
thyroid hormones in the blood.
Secretion and Transport of Thyroid Hormones
• T4 and T3 are secreted from the thyroid gland at rates of 80-100 µgm/day
and 5µgm/day respectively.
• Majority of circulating T4 and T3 molecules are bound :
70% to thyroxine binding globulin or TBG (high affinity)
15-20% to albumin (low affinity)
10-15% to transthyretin (low affinity).
• Only the 0.03% of T4 and 0.3% of T3 traveling freely has hormonal activity.
Up to 85% of the T3 in blood is produced following conversion from T4 by
iodothyronine deiodinases in organs around the body.
• The tiny (FT3 and FT4) free or unbound fraction of T4 and T3 enter cells
and determines to a large extent the metabolic rate of many tissues.
• T3 and rT3 can be produced from T4 in peripheral tissues via deiodinases.
Most of the circulating pool of T3 (80%) is produced from T4. In contrast,
all T4 is produced by the thyroid.
• The body adjusts its metabolic rate downward by shunting T4 to reverse T3
(rT3) rather than to T3 during times of stress, illness and caloric
deprivation as a protective mechanism
 Thyroid diseases
Hyperthyroidism (thyrotoxicosis) – “tired from the neck-down”. Hyperthyroidism is
the excessive production of the thyroid hormones which is most commonly a result of:
1) Graves' disease
2) Toxic multi-nodular goitre
3) Thyroid storm (an endocrine emergency)
4) Toxic nodular struma (Plummer's disease)
5) Hashitoxicosis (transient hyperthyroidism that can occur in Hashimoto's thyroiditis)
6) Drug-induced excess of iodine (amiodarone and iodinated contrast imaging)
Hypothyroidism - “tired from the neck-up”. Hypothyroidism is a state in which
the body is not producing enough thyroid hormones, or is not able to respond
to/utilize existing thyroid hormones properly. The main categories are:

1)Thyroiditis: an inflammation of the 2)Iatrogenic hypothyroidism

thyroid
• Hashimoto's thyroiditis /
Hashimoto's disease
• Ord's thyroiditis
• Postpartum thyroiditis
• Riedel's thyroiditis (approximately
30% of cases lead to hypothyroidism)
• Postoperative hypothyroidism
• Medication- or radiation-induced
hypothyroidism
3)Thyroid hormone resistance
4)Euthyroid sick syndrome
5)Congenital hypothyroidism (a
deficiency of thyroid hormone
from birth, leading to cretinism)
Signs and Symptoms
Symptoms of hyperthyroidism are: Symptoms of hypothyroidism are:
•Difficulty sleeping (insomnia) •Tiredness
•Unexplained weight loss •Unexplained weight gain
•Tremors •Slow movement
•Fast heart rate (tachycardia) or palpitations •Muscle cramps
•Sensitivity to hot temperatures •Slow heart rate (bradycardia)
•Excessive sweating •Sensitivity to cold temperatures
•Diarrhea •Constipation
•Anxiety or irritability •Depressed mood
•Memory difficulty
Note: certain symptoms and physical changes can be seen in both hypothyroidism and
hyperthyroidism —fatigue, fine / thinning hair, menstrual cycle irregularities, muscle weakness
and aches (myalgia).
 Grave’s Disease (thyrotoxicosis - primary hyperthyroidism)
• Autoimmune hyperfunctionality of the thyroid gland (excessive stimulation
of the TSH receptors).
• Grave’s disease is more prevalent in women than men.
• TSH levels are ↓ (negative feedback from ↑T3/T4 levels).
• Over-stimulation of TSH receptors occurs via anti-TSH receptor antibodies
that stimulate uncontrollable activation of the thyroid that mimics the tropic
effects of TSH
- ↑ size and number of follicular cells
- ↑ vascularization of the enlarged thyroid is manifested by an audible bruit
 Hashimoto’s Thyroiditis (primary hypothyroidism)
• Hashimoto's thyroiditis is an autoimmune process that is characterized by
auto-antibodies against antigens derived from thyroid gland components,
generalized destruction of thyroid follicles and ↓ thyroid hormone
biosynthesis and secretion.
• Presents with complaints of feeling cold and fatigued. More prevalent in
women. A primary disease where the level of TSH produced from the
pituitary is high.
• Additionally, anti-TSH receptor antibodies that bind to the TSH receptors
block TSH stimulation of the thyroid gland. Net result is diminished
production of T3 and T4 from the thyroid gland.
Structural Abnormalities of the Thyroid
1) Goiter: an abnormal enlargement
of the thyroid gland
• Endemic goiter
• Diffuse goiter
• Multinodular goiter
• Lingual thyroid
• Thyroglossal duct cyst
2) Tumors/Cancer
• Thyroid adenoma (benign tumor)
• Thyroid cancer
• Lymphomas and metastasis from
elsewhere (rare)
 Goiter
• A goiter is an abnormally large
thyroid gland. A goiter develops
either because the whole gland is
swollen or the gland has multiple
growths or nodules on it.
• While some people with a goiter
have no symptoms, others may
have symptoms of an overactive
or underactive thyroid.
 What Causes a Goiter?
•Iodine deficiency — A goiter may be caused by inadequate iodine through in the
foods you eat.
•Graves' disease — This autoimmune disorder causes hyperthyroidism. Grave’s
disease causes the body to produce a thyroid-stimulating immunoglobulin
that mistakenly attacks the thyroid, causing it to overproduce thyroid hormones
and swell in size.
•Hashimoto's disease — another autoimmune disorder in which antibodies damage
thyroid cells. The pituitary gland stimulates the thyroid to produce more
hormones, causing the thyroid to swell.
•Thyroid nodules — are overgrowths of tissue that overproduce thyroid hormone.
•Thyroiditis — an inflammation of the cells in the thyroid.
•Thyroid cancer — malignant or cancerous cells may grow in the nodules of the thyroid.
 Laboratory Tests
Thyroid function tests and Interpretation
• Thyroid function tests include a battery of blood tests including the
measurement of the thyroid hormones T3 and T4, as well as the
measurement of TSH. They may reveal hyperthyroidism, hypothyroidism,
or subclinical hyperthyroidism (normal T3 and T4 with a low TSH).
TSH
• The most useful marker of thyroid gland function is serum TSH levels. TSH
levels are determined by a classic negative feedback system in which high
levels of T3 and T4 suppress the production of TSH, and low levels of T3
and T4 increase the production of TSH. TSH levels are often used by doctors
as a screening test.
• Elevated TSH levels can signify inadequate thyroid hormone production
(hypothyroidism). Suppressed TSH levels point to excessive thyroid hormone
production (hyperthyroidism).
Free T3 and Free T4
• Only a small fraction of the circulating thyroid hormones are unbound or free,
and thus biologically active. T3 and T4 levels can be measured as free T3 and
T4, or total T3 and T4, which takes into consideration the free hormones in
addition to the protein-bound hormones. Free T3 and T4 measurements are
important because certain drugs and illnesses can affect the concentrations of
transport proteins, resulting in differing total and free thyroid hormone levels.
Clinical Interpretation

What are Normal TSH, T4 and T3 Levels

The normal range for T4 and T3 will vary depending on the lab analyzing the
sample. Test results need to be compared to the reference range of that specific lab.
Normal ranges for adults generally fall between these values:
Total T4 - 5.0 - 12 μg/dL
Total T3 - 80 - 190 ng/dL
Free T4 - 1.0 - 3.0 ng/dL
Free T3 - 0.25 - 0.65 ng/dL
TSH - 0.27 - 4.20 uIU/mL
High T4 and T3 Levels and What This Means?

High circulating levels of T4 typically indicate hyperthyroidism. This is also known

as Graves’ disease. Hyperthyroidism is usually diagnosed when we see:
T4 High
Total or FT3 High
TSH Low
Summary: High T4 and T3 levels usually indicate hyperthyroidism in the context
of low TSH.
Low T4 and T3 levels and What This Means?

Low levels of T4 (with high TSH) indicates hypothyroidism.

Primary Hypothyroidism
It’s the most common type of hypothyroidism.
TSH levels increase as the body tries to increase production of T4 and T3.
However, T4 levels remain low because the thyroid gland is not functioning
properly. Primary hypothyroidism is typically diagnosed when we see:
FT4 Low
Total or FT3 Normal or Low
TSH High
Secondary Hypothyroid
This is rare and occurs when the pituitary (or hypothalamus) malfunctions and
not enough TSH is secreted. In this case, the thyroid gland is functioning
properly but does not receive enough TSH to signal the production of T4 and
T3. Secondary hypothyroidism is typically diagnosed when we see:
FT4 Low
Total or FT3 Normal or Low
TSH Normal or Low
Summary: Low T4 and T3 levels alongside elevated TSH can indicate
hypothyroidism (malfunctioning thyroid gland).
Can T4 and T3 Be Normal When TSH Is Elevated?

The simple answer is yes. This is known as subclinical hypothyroidism.

Although TSH is elevated, the thyroid is still able to produce enough T4 and T3
to meet demand. Therefore, hypothyroid symptoms are not present. If TSH
levels are significantly raised (above 10 uIU/mL) medication may be prescribed.

Summary: Subclinical hypothyroidism occurs when TSH levels are high but T4
and T3 are normal. Usually there are no symptoms.
Treatment:
• Hyperthyroidism: aimed at ↓ overproduction of thyroid hormones with
drugs that inhibit thyroid hormone synthesis (propylthiouracil) and/or
drugs that inhibit peripheral effects of thyroid hormones (adrenergic
blocking agents). Surgery or radioactive iodine ( I131 - destroys part of
the tissue), may be used to ↓ excessive thyroid hormone production.
• Hypothyroidism: requires hormone replacement therapy (T4)
THANK YOU VERY MUCH