Transcript The Thyroid Gland

The Thyroid Gland
Learning Objectives


Be able to answer “What is the thyroid gland?”
Understand the form and function of Thyroid
hormone




Understand the importance of Iodine
Become familiar with thyroid regulatory
mechanisms
Understand the role of the thyroid in maintaining
metabolic balance
Get a feeling for how thyroid dysfunction could
affect a patient.
Hormones Regulate Energy Useage

Where does energy go in the body?

Digestion & Absorption


Physical activity


Pancreas: Insulin & Glucagon
Adrenal Glands: Adrenaline, Cortisol
Basal Metabolism

Thyroid: Thyroxine
Basal Metabolism

Energy required just to stay alive



Maintain cellular respiration
Allow vital organs to function
Influences on basal metabolism




Lean Body Mass
Age
Growth requirements
Thyroid Hormone
Meet the Thyroid

The Thyroid is a large, bi-lobed gland,
positioned in the neck.

20-60 grams in an adult

You can feel your thyroid: place a finger to
either side of the neck, below the thyroid
cartilage (the “Adam’s Apple”), and swallow.
The spongy, soft tissue you can feel move
beneath the skin is your thyroid gland
Where does it come from?



In the human embryo, tissue
that becomes the thyroid starts
in the same place as the
tongue.
It then migrates distally as fetal
development continues,
ultimately reaching its adult
position.
Rare but interesting result:
misplaced thyroid tissue may
occur along the path that the
thyroid travels, called the
Thyroglossal Duct. Important
in ruling out thyroid cancer.
Quick Histo Review
What does it do?


Produces and releases Thyroxine (T4),
the thyroid hormone.
Allows for maintenance of basal
metabolic rate
Thyroid
Metabolically
active cells
Who needs a thyroid?



Everyone!
In infants, a lack of thyroid hormone
will quickly lead to permanent
developmental impairments.
In adults, lack of thyroid hormone is
not as devastating, but still causes
significant problems if untreated.
Thyroid Hormone



Thyroid hormone is the main product
of the thyroid gland
It is produced by action of the follicular
cells
It is synthesized extracellularly from
protein, called colloid, stored in the
follicles.
So, what IS thyroid Hormone?

Thyroxine, or T4, Starts its life as
Tyrosine residues in a protein called
Thyroglobulin, the main component
of Colloid.
So, what IS thyroid Hormone?

Enzymes in the thyroid add Iodine to
the Tyrosine residues, forming
Diiodotyrosine
So, what IS thyroid Hormone?

Two of these residues are then joined
together to form Thyroxine, or T4.
What’s the only part of that
you need to care about?

Iodine! The thyroid needs a lot of it! Or at
least 80 mg per day.


Despite the gland being ~0.05% of the body
weight, 30% of the body’s iodine is in the thyroid
Why might this be significant?



A lack of iodine will affect the thyroid first
Too much iodine will affect the thyroid first
Radioactive iodine will concentrate in the
thyroid, which is exploited in medicine.


Low doses: imaging
High doses: destroy the thyroid
So we’ve made T4, what now?




T4 is actually not very potent
In order to be maximally effective, one Iodine has to
be removed to form Triiodothyronine, or T3
This conversion occurs systemically, by the action
of deiodonase I and II
A third deiodonase
produces reverse T3,
which is inactive
What? Why?!

It’s all about regulation


T4 has low activity, is present in high
concentration, is cleared slowly,and is
heavily protein bound. It provides a
reservoir for the rapid production of T3.
T3 has high activity, is present in low
concentration, is cleared quickly, and
is slightly less protein bound. This
allows the body to quickly eliminate T3 if
it’s had enough.
Thyroid function is under two
regulatory systems
The Hypothalamus-Pituitary-Thyroid Axis: good for
long-term maintenance

TRH
-
+
TSH
-
+
T4,T3
Thyroid function is under two
regulatory systems

Cortisol
Systemic Deiodonase Balance: good
for maintaining fine control
-
Other regulating factors

Release of TRH and activity of
Deiodonase II are also under
thermogenic control.
+
TSH, DI II
T4,T3
How do T4&T3 work?


Unbound T4 and T3 enter cells by an uncertain
mechanism – evidence of both diffusion and
transporter-mediated cell entry.
Once inside, the hormones bind to Thyroid
Response elements



TREs associate with DNA and other proteins to form
regulatory complexes.
If the TRE is binding hormone, then it forms a gene
promotor complex
If the TRE is not binding hormone, it forms a gene
supressor complex
How do T4&T3 work?

Therefore, thyroid hormone both:


Promotes the transcription of some genes
Prevents the suppression of other genes
Get to how this affects
metabolism already!!

OK! OK! Calm Down! Gene products
promoted by hormone-bound TREs include:



Increased transcription of RNA Polymerase I:
this leads to inceased production of ALL proteincoding mRNAs.
Protease concentrations and activities also
increase: this leads to faster degredation of all
cellular proteins.
In a hypertyroid state, the catabolic effect
exceeds the anabolic effect
More Effects

Synthesis and activity of b-adrenergic
receptors increase



Increases sensitivity of body to
Epinephrine and Norepinepherine
Especially true in heart
Leads to increased stroke volume and
speed
More effects

OF SPECIAL NOTE IN
INFANTS!



Thyroid hormone is VITAL
to the proper development
of the nervous system
Induces myelination, axon
growth, neurotransmitter
production.
Infants with uncorrected
hypothyroidism develop a
syndrome of dwarfism and
mental disability (previously
termed ‘cretinism’).
So, knowing the effects…

What would happen if there’s too LITTLE Thyroid
hormone?

Less protein turnover = less need for energy, O2


Loss of Thermogenic control



Thin, brittle skin; hair loss
In women: irregular menstrual cycle
Blunting of sympathetic (fight/flight) response



Low body temp, cold intolerance
Cells that turn over quickly, like skin and hair, can’t be
replaced fast enough


Slower heart rate, slower breathing, loss of appetite
combined with weight gain
Fatigue, exercise intolerance
Weak pulse, slow maximum heart rate
Nervous system involvement



Poor memory, inability to concentrate
Parasthesia, i.e. “pins and needles”
Loss of hearing
Summarry
Table 335-5 Signs and Symptoms of Hypothyroidism (Descending Order of
Frequency)
Symptoms
Signs
Tiredness, weakness
Dry coarse skin; cool peripheral
Dry skin
extremities
Feeling cold
Puffy face, hands, and feet
Hair loss
(myxedema)
Difficulty concentrating and poor memory
Diffuse alopecia
Constipation
Bradycardia
Weight gain with poor appetite
Peripheral edema
Dyspnea
Delayed tendon reflex relaxation
Hoarse voice
Carpal tunnel syndrome
Menorrhagia (later oligomenorrhea or
Serous cavity effusions
amenorrhea)
Paresthesia
Impaired hearing
Major causes?

Congenital




Thyroid agenesis
Failure to produce any of the hormones
necessary to ultimately make T3
Mutations in thyroid-binding proteins, thyroid
response elements, or transporters.
Acquired




Autoimmune: body attacks own thyroid
Infective: virus attacks thyroid
Nutritional: Iodine deficiency
Drug induced
How about Hyperthyroidism?

Protein turnover is too rapid, high O2 and metabolic
demands




Loss of Thermogenic control


Fast heart rate, fast breathing, loss of weight despite
ravenous appetite
Ketotic state
Muscle weakness (remember, cata > ana)
Always generating too much heat; heat intolerance,
disproportionate sweating
Exaggerated Sympathetic response



Hyperactivity, Irritability
Bounding pulse, tachycardia, palpitations
Tremor
Table 335-7 Signs and Symptoms of Thyrotoxicosis (Descending Order of Frequency)
Symptoms
Hyperactivity, irritability, dysphoria
Heat intolerance and sweating
Palpitations
Fatigue and weakness
Weight loss with increased
appetite
Diarrhea
Polyuria
Oligomenorrhea, loss of libido
Signsa
Tachycardia; atrial fibrillation in the elderly
Tremor
Goiter
Warm, moist skin
Muscle weakness, proximal myopathy
Lid retraction or lag
Gynecomastia
Causes

Autoimmune: Grave’s Disease


Neoplastic / Hyperplasic



Primary goiter (Multinodular Goiter)
Thyroid adenoma, other active endocrine
adenoma
Nutritional



Body produces antibodies that mimic TSH
Too much iodine
Consuming thyroid tissue as supplement
Drug induced
Anyone still paying attention?
Or are you all just feeling dragged along?
VISUAL METAPHOR TIME!

With the right amount of thyroid hormone:
If there’s too little…
If there’s too much…
Compare to too much HGH
Revisiting the LOs

What is the Thyroid Gland?


A large, bi-lobed gland in the neck
The endocrine gland in charge of
maintaining basal metabolism
Revisiting the LOs

Thyroid hormone




You need iodine to make it
Acts on all metabolically active tissue
Stimulates protein synthesis and turnover
Iodine


Need 80 mg per day (150 mg oral intake)
Radioiodine can be used in thyroid
medicine
LOs, cont.

Thyroid regulation:

H-P-T axis for slow regulation


Classic negative feedback setup
Systemic Deiodonase activity for fast
LOs, cont.

Effects of thyroid abnormality


Hypothyroid: weight gain, loss of energy,
cold intolerance, PERMANENT neural
damage in infants.
Hyperthyroid: weight loss, hyperactivity,
tachycardia, heat intolerance, muscle
wasting
Aaaaaand…we’re done!