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

Pancreas: Insulin & Glucagon

Physical activity 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 g 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

Systemic Deiodonase Balance: good for maintaining fine control

-Cortisol

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 protein-coding 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 -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

Slower heart rate, slower breathing, loss of appetite combined with weight gain

Loss of Thermogenic control Low body temp, cold intolerance

Cells that turn over quickly, like skin and hair, can’t be replaced fast enough Thin, brittle skin; hair loss In women: irregular menstrual cycle

Blunting of sympathetic (fight/flight) response 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

SummarryTable 335-5 Signs and Symptoms of Hypothyroidism (Descending Order of Frequency)

Symptoms  Tiredness, weakness  Dry skin  Feeling cold  Hair loss  Difficulty concentrating and poor memory  Constipation  Weight gain with poor appetite  Dyspnea  Hoarse voice  Menorrhagia (later oligomenorrhea or amenorrhea)  Paresthesia   Impaired hearing

Signs  Dry coarse skin; cool peripheral extremities  Puffy face, hands, and feet (myxedema)  Diffuse alopecia  Bradycardia  Peripheral edema  Delayed tendon reflex relaxation  Carpal tunnel syndrome  Serous cavity effusions

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 Fast heart rate, fast breathing, loss of weight despite

ravenous appetite Ketotic state Muscle weakness (remember, cata > ana)

Loss of Thermogenic control 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 Signsa

  Hyperactivity, irritability, dysphoria  Heat intolerance and sweating  Palpitations  Fatigue and weakness  Weight loss with increased appetite  Diarrhea  Polyuria  Oligomenorrhea, loss of libido

  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 Body produces antibodies that mimic TSH

Neoplastic / Hyperplasic Primary goiter (Multinodular Goiter) Thyroid adenoma, other active endocrine

adenoma Nutritional

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 g per day (150 g 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!