The Thyroid Gland Flashcards
Where is the thyroid gland?
- shapes like a bow tie and situated where you would wear a bow tie
- Lies agaisnt and arounf front larynx and trachea
- Below thyroid cartilade (Adam’s apple)
- Isthmus extends from 2nd to 3rd rings of trachea -emergency thyroidectomy in gap between thyroid and cricoid cartilage.
What shape is the thyroid gland?
- 2 lobes joined by isthmus
- “Bow Tie” shape and location
- Parathyroid and thyroid are distinct glands. (can have anythignf rom 1-6 parathyroid glands but textbooks say 4)
How does the thyroid develop embryologicaly?
- Thyroid is first endocrine gland to develop
- ST 3-4 weeks gestation, thyroid gland appears as an epithelial proliferation in floor of larynx at base of the tounge and takes several weeks to migrate to its final position.
- First descends as diverticulum through thyroglossal duct and migrates downwards passing in front of hyoid bone
- During migration, it remians connected to the tongue by thyroglosseal duct which sibsequently degererates.
- Detached thyroid then continues to its final position over the following two weeks.
- Can get thyroid tissue higher up or thyroglosseal cysts if thyroid does not migrate properly.
- Pyramidal lobe of the thyroid gland can be a reminant of it travelling down.
Outline the histology of thyroid tissue
- Follicular cells arranged in spheres called thyroid follicles.
- Follicles filled with colloid, a deposit of thyroglobulin
- Colloid is “extracellular” even though it is inide follicle.
What is the difference bewteen the histology of the parathyroid gland and the thyroid gland?
Parathyroid:
- Principle cells (chielf cells produce parathyroid hormone essential for Ca2+ homeostasis
Thyoid:
- Thyroid follicular cells produce thyroid hormone
- Cilloid stores thyroglobulin,
- Thyroid parafollicular cells produce calcitonin
How are the thyroid hormones produced?
- They are produced by iodonating tyrosine residues which are part of the protein thyroglobilin.
- Follicular cells are producing this protein and exporting it into the colloid where they are iodinated.
- Iodinating can involve one iodine being added (monoiodotyrosine - MIT) or two (diiodotyrosine - DIT).
- In a coupling reaction, the two tyrosine residues can be joined together to produce T3 or T4.
- MIT + DIT = T3 / triiodothyronine
DIT + DIT = T4 Tetraiodothyronine (thyroxine)
Why does thyroglobulin do?
Thyroglobulin acts as a scaffold on which hormones are formed.
What are thyroid peroxidases?
These are membrane bound enzymes that regulate 3 separate reactions involving iodide
- Oxidation of Iodide to Iodine (reqires presence of H2O2)
- Addition of Iodine to tyrosine acceptor residues on the protein thyroglobulin
- Coupling of MIT or DIT to generate thyroid hormones within the thyroglobulin protein
How is dietary iodine absorbed and used?
- Dietary iodine is reduced to iodine before absorbtion principally in the small intestine
- Thyroid hormones and precursors are the only molecules in the human body that contain iodine
- Thyroid gland contains 90-95% of iodine in the body
- Iodide is taken up from blood by the thyroid epithelial cells, which have a sodium-iodine symporter or “iodine trap.”
- Essential in small intestine and follicular cells.
What are some good sources of iodine in our diet?
- Dairy products (not as much from milk anymore)
- Grains
- Meat
- Vegtables
- Eggs
- iodised salt (although table salt isn’t regularly iodinised)
How is thyroid hormone synthesised?
Where is T4 converted into T3?
- Most T4 is converted to T3 outside the thyoid
- 90% of thyroid hormone secreted form thyroid is T4
- Biological activity of T3 is 4 times that of T4
- Most T4 is converted to T3 in the liver and kidnets
- 80% of circulating T3 is derived fron T4
- T3 and T4 are transported in blood boudn to the protein thyroxine-binding globulin because they are lipid and not water soluble.
How is thyroid hormone secreting controlled?
Regulation of thyroid hormone secreting is via Negative feedback.
- Hypothalamus secrets TRH
- This stimulates anterior pituitary to release TSH
- This stimulates tyroid gland to produce thyroid hormone.
Generally, what effects does thyroid hormone have?
Thyroid hormone effects virtually every cell in the body and has two interconnected resonses:
- Effects on cellular differentiation (growth( development
- Effects on metabolic pathways
What is the structure of thyroid stimulating hormone (TSH)?
- Glycoprotein composed of 2 non-covamently bound sununits (a and B)
- The a sbunit is also present in FSH and LH (other anterior pituitary hormones).
- B subunit provided unique biological activity.
How does TSH work and what does it stimulate?
TSH can eithet stilulate Gas or Gaq. This then causes the usual signalling cascade from a GPCR (second messenger pathways).
This stimulates all the steps required to make thyroid hormone:
- Iodine uptake
- Iodine oxidation
- Thyroglobulin synthesis
- Thyroglobulin iodination
- Colloid pinicytosis into cell
- Proteolysis of thyroglobulin
- Cell metabolism and growth
What are the general actions of thyroid hormone?
- Increase in basal metabolic rate and hear production
- In most tissues (except brain, spleen and testis), thyroid hormones stimulate the metabolic rate by:
- Increasing the number an size of mitochondria
- Stimulating the synthesis of enzymes in the respiratory chain,
- In most tissues (except brain, spleen and testis), thyroid hormones stimulate the metabolic rate by:
- Stimulation of metabolic pathways
- Catabolic pathwyas are generally stimulated more than anabolic
- Lipid metabolism: Stimulates lipolysis and B-oxidation of fatty acits
- Carbohydrate metabolism: Stimulate insulin-dependant entry of glucose into cells (more GLUT4 receptors) and increase glconeogenesis and glycogenolysis.
- Catabolic pathwyas are generally stimulated more than anabolic
- Sympathomometic effects (miminc actions of sympathetic nervous system)
- Increases target cell response to catecholamines by increasing receptor number on target cells.
What are the tissue specific (CVS and nervous) effects of thyroid hormone?
Cardiovascular:
Increases the heart’s responsiveness to catecholamines
- Increase cardiac output
- Positive conotropy and positive inotropy
- Increase peripheral vasodilation to carry extra heat to body surface (to conpensate increased basal metabolic rate)
Nervous:
Essential for both development and adult function
- Increase myelination of nerves and development of neurones
Where are thyroid hormone receptors and how do they work?
- Member of the largefamily of nuclear receptors
- Function as hormone-activated transcription factors
- Act by modulatinf gene expression
- Thyroid hormone receptors bind DNA in the absence of hormone, usually leading to transcriptional repression.
- Hormone binding is associated with a conformational change in the receptor that causes it to function as a transciptional activator.
How do thyroid hormones bind to intracellular receptors?
- Thyroid hormone is lipid soluble and enters the cell through thyroid hormone transporters.
- Thyroid hormone receptor is pre-bound to specific DNA sequence on DNA called a hormone response elements (HRE) in promoter region of thyroid hormone regulated genes.
- Thyroid hormone enters nucleus and binds to thyroid hormone receptor on DNA. Binging relieves repression of gene transcroption and the gene is now expressed. This is because it changes the conformation.
- This then causes the production of mRNA to make new protein which mediate the effects thyroid hormone.
- Examples of thyroid hormone activated genes:
- PEPECK (gluconeogenesis)
- CA2+ATPase
- Na+, K+ ATPase
- Cytochrome oxidase
- 6-phosphogluconate dehydrogenase (pentose phosphate pathway)
6.
What range are the levels of thyroid hormones in the blood?
they are in picolomolar range -much smaller than glucose which is in the mM range.
What is a goitre?
Enlargment of the thyroid gland.
This may accompany either hypo- or hyperthyroidism (but not necessarily present in either)
Develops when the thyroid gland is overstimulated.
What are some causes of hypothyroidism?
- Failure of the thyroid gland
- TSH or TRH deficiency
- Inadequate dietary supply of iodine
- Radioactive iodine
- Autoimmunity - Hashimotos disease
- Post surgery - if inadequate thyroxine replacement.
- Congenital (from birth)
- Anti-thyoid drugs
What are the general symptoms of hypothyroidism?
- Obesity / weight gain
- Lethargy / tiredness
- Memory problems, depression, psychosis (myxoedema medness)
- Intolerance to cold
- Bradycardia
- Dry, flaky skin
- Puffy eyes, face, hands and skin
- Alopecia - particualry on outer 1/3 of eyebrow
- Symptoms of carpal tunnel syndrome
- Hoarse / croaky voice
- Constipation
- Menorrhagia
- Muscle weakness and cramps.
- Slow reflexes
- Low T3
- Low T4
- Elevated TSH
What is cretinism?
A hypothyroid condition in infants.
They present with:
- Dwarfed stature
- Mental deficiency
- Poor bone development
- Slow pulse
- Muscle weakness
- GI disturbances
What is myxedema?
A hypothyroid condition in adults.
Patients present with:
- Thick puffy skin -due to polysaccharides in the skin.
- Muscle weakness
- Slow speech
- Mental deterioration
- Intolerance to cold
What is Hashimito’s disease?
- Autoimmune disease resulting in destruction of thyroud follicles. Lead to hypothyroidism.
- Most common disease of the thyroid gland.
- 5 times more common in women than in men
- Goitre may or may not be present
- Plasma:
- Low T3
- Low T4
- Elevated TSH
- Treatment:
- Oral thyroid hormone
- T4 used since it has a longer half life
- Normally around 50-200ug/day in a single dose
What are some causes of hyperthyroidism?
- Autoimmune Graves’ disease
- Toxic multinodular goitre
- Solitary toxic adenoma
- Excessive T4 (or T3) therapy
- Drugs - amiodarone
- Thyroid carcinoma
- Extopic thyroid tissue
- Toxix multinodular goitre
What are some general symptoms of hyperthyroidism?
- Weight loss
- Irritability
- Hear intolerance, sweating, warm, vasodilated hands
- Tachycardia (noticeable heart beat) often irregular
- Fatigue, weakness
- Increased bowel movements -increased appetite
- Possible tremor of outstretched hands
- Hyper-reflexive
- breathlessness
- Loss of libido
- Sweating and temor
- Sometimes:
- Goitre
- Bulging eyes
What is graves’ disease?
- Autoimmine disease resulting in hyperthyroidism
- Caused by the production of thyroid stimulating immunoglobulin (TSI)
- TSI continuously stimulates thyroid secretion (outside normal negative feedback control)
- Causes symtoms of throtoxicosis and some additional unique symptoms:
- Exopthalmos (bulging eyes) - can get this alone.
- Pre-tibial myxoedema (confusiong because nothing to do with hypothyroidism / myoedema!)
- It only affects 5% of people with graves disease
What is a thyroid scintigraphy?
- Technetium-99m is used for isotope scanning of the thyroid with a gamma camera
- Most commonly used medical radioisotope (Although, Iodine is also used)
- Biological half time of about a day
- Radiation exposure is therefore low
- Also used for:
- Bone scan
- Myocardial perfusion imaging
- Brain imaging
What are the antithyroid drugs?
- Used to treat overactive thyroid (hyperthyroidism) e.g. Graves’ disease
- Block formation of thyroid hormone
- Carbimazome is the most commonly used in the UK
- Carbimazole is a pro-drug and is converted to methmazole in the body (key as it inhibits thyroid peroxidases).
- It prevents thyroid peroxidases from coupling and iodinating tyrosines in thyroglobulin.
- Takes 2-4 months for drug to have an effect as we have a store of thyroglobulin in the colloid
How do you examine a thyroid gland?
Stand behind and put the palms (which are the most flexible) around the neck.
It is not possible to feel a normal thyroid.
What is the pre-tracheal fascia?
The pre-tracheal fascia attaches the thyroid gland to the trachea and larynx.
Thus, the thyroid moves upwards on swallowing, an important diagnostic feature for lumps in the neck.
What is the most common modality used to examine the thyroid?
Ultrasound
What is a lingual thyroid and what effect can this have?
A lingual thyroid is a specific type of ectopic thyroid and results from the lack of normal caudal migration of the thyroid gland.
Most commonly get thyroid deposits at the base of the tongue but can be anywhere along the course of the thyroglosseal duct.
Can cause hypothyroidism because the thyroid releases extra TSH. This makes it get bigger.
Treat by giving thyroxine (T4) which lowers the levels of TSH and so makes the thyroid smaller.
What are thyroglossal duct cysts?
- Thyroglossal duct normallu dissappears but remanants of epithelium may remain and form a thyroglossal duct cyst.
- The cyst is usually near or within the body of the hyoid and forms a swelling in the anterior part of the neck.
- Always on the midline!
- The have a risk of infection because of static fluid.
- A thyroglossal cyst moves upwards on toungue protrusion (unlike the gland which moves up on swallowing).
What is metabolic thyroid disease and what is it usually due to?
Metabolic thyroid disease is an under or over functioning thyroid.
- 98% of metabolic throid (hyper or hypothyroidism) disease is due to a primary abnormality of the thyroid gland itself.
- This is becuase:
- It is EXTREMELY rare for a pituitary adenoma to produce TSH and lead to thyrotoxicosis
- Pituitary failure only VERY rarely presents with isolated hypothyroidism.
Why are the levels of TSH significant?
TSH levels can be used as a screening test for hyperthyroidism (TSH decrease) or hypothyroidism (TSH increase) as 98% of the time TSH levels are due to a thyroid malfunction.
TSH levels tell us what the patient’s own brain thinks of their thyroid gland flunction.
Raised TSH = hypothyroidism
Low TSH = Hyperthyroidism
What are the levels of TSH and free T4 in hypo and hyperthyroidism?
Hypothyroidism:
- TSH increased
- Free T4 decreased
Hyperthyroidism:
- TSH decreased
- Free T4 increased
There is a large range for both TSH and T4 because the levels of these hormones are constantly responding to the environment via negative feedback.
Where do autoimmine diseases commonly affect?
Autoimmine diseases commonly affects endocrine glands.
- Islets of langerhans - Type 1 diabetes
- Thyroid
- Hypothyroidsim (Hashimotos disease - caused by autoantibodies)
- Hyperthyroidism (Grave’s disease - eyes, thyroid and leg by circulating antibodies which mimic TSH)
- Adrenal glands - Addisons
- Autoimmine pituitary disease
- Autoimmune ovarian and testicular disease
Autoimmune disorders are more common in women - we don;t know why.
What different characteristics can a goitre have?
- Diffuse
- Multinodular (most common in uk)
- Single nodule
Prevelent in 7% of females and 1% of males in the UK. We are not sure why but, there is increasing evidence that it is to with the oestrogen:progesterone ratio.
When does a physiological goitre occur?
- Menarche (First period)
- Pregnancy
- Menopause
What are the most common causes of goitre?
-
Iodine deficiency (most common cause globally)
- Reduced thyroxine levels lead to increased TSH which leads to gneralised thyroid enlargement, usually nodular. Severe cases may become hypothyroid. 2.2 billion people are iodine deficient and 30% of the population live in iodine deficient areas (mainly mountainous
-
Multinodular goitre (Colloid goitre -By far most common in UK)
- Affects 5% of Western populations and seven ties commoner in women, Aetiology unknown, Normal thyroid function, although after many years a very small number may develop hyperthyroidism 0 toxic multinodular goitre.
What effect does iodine deficiency have on pregnant women / foetus?
If a mother is iodine deficient and hypothyroid then the foetus is also iodine deficient. This leads to a child with:
- Mental retardation
- Abnormal gait
- Deaf-mutism
- Short stature
- Goitre
- Hypothyroidism.
Children like this used to be called a “cretin”
What is a retrosternal multinodular goitre?
A multinodular goitre may enlarge inferiorly into the superior mediastinum to form a retrosternal goitre. This can cause tracheal conpression and needs to be fixed using surgery.
What are signs of hypothyroidism?
- May be no obvious signs
- Weight gain
- Dry skin, coarse brittle hair, loss of outer third of eyebrows
- Pallor “peaches and cream” face
- Coarse facial features and periorbital puffiness
- Bradycardia
- Hypoflexia with delayed relaxation
- Non pitting oedema - myxoedema. Due to deposition of mucopolysaccharides, particularly arounf eyes, hands and feet.
- Ascites or pericardial effusion (both uncommon)
What does Myxoedema mean?
- Non pitting oedema particularly around the eyes, hands and feet
- But, can also mean hypothyroid in general.
This can be a bit confusing!
What is Hashimoto’s disease?
This is an autoimmune destruction of the thyroid causing hypothyroidism.
10x commoner in women and 10% of women over the age of 30 have Hashimitos thyroiditis.
Antibodies to thyroglobulin and thyroid peroxidase are present in the blood.
Hashimotis disease may be associated in the early stages with a small, diffuse goitre (due to inflammation) or the thyroid may never enlarge amd shrink in size from the beginning of the disease.
How do you treat hypothyroidism?
Oral thyroxine - not distroyed by gastric acid
Adjust dose to normalise serum TSH.
What are symptoms of thyrotoxicosis?
(Hyperthyroidism is thyrotoxicosis due to over production of thyroxine by the thyroid gland)
- Overactivity, tiredness
- Nervousness, anxiety, insomnia
- Shaking, trembling
- Hear intolerance
- Increased sweating - warm, sweaty hands
- Palpitations, rarely angina
- Weight loss in spite of increased appetite
- Diarrhoea
- Amenorrea
- Proximal muscle weakness
What are some signs of thyrotoxicosis?
- Weight loss
- warm sweaty hands
- Fine hand tremor
- Tachicardia - AF
- Boudning pulse
- Proximal myopathy
- Lig lag (see scarea above iris)
- Staring eyes
What causes staring eyes and lig lag?
Levator palpebrae superioris muscle.
90% skeletal muscle and 10% smooth muscle.
The smooth muscle portion is supplied by the sumpathetic nervous system.
Over stimulation of the sympathetic portion leads to ‘staring eyes’ and lig lag.
What is toxic multinodular goitre?
- Not autoimmune. Therefore, no exopthalmos or pretibial myoedema
- Develops in a very small portion of patients with a multinodular goitre
What is a toxic adenoma?
A single adenoma develops in the thyroid and oroduced thyroxine autonomously.
How do we treat thyrotoxicosis?
Carbimazole. This prevents thyroid peroxidase from couplign and iodinating the tyrosine residies on thyroglobulin, thereby reducing the production of T4
Side effect is neutropenia - so can die from it.
Surgical excision of thyroid. Thyroidectomy
Ablative dose of radioactive iodine
What is a thyroid cancer?
- Less than 1% of all thyroid nodules are malignant
- Thyroid cancer accounts for less than 1% of all cancers in the UK
- Thyroid cancers do not cause a metabolic disturbance (either hypo / hyperthyroid)
- Presents as a thyroid nodule
- Prognosis is excellent - 97% cure rate
- The are well differentiated (so behave like thyroid tissue) -This means they can be killed with a large dose of iodine.
