Lecture 17: Thyroid Flashcards
What is the function of the thyorid?
- Normal growth and development (In the first few weeks, the fetus is dependent on the maternal thyroid).
- Maintains metabolic activity and oxygen requirements esp brain
- Regulate lipid and carbohydrate metabolism and thus body weight
- Control of thryoid hormone is by the hypothalamic/pit axis
- Disorders in thyroid function are common.
Describe the embryology of the thyroid
Come from the back of the tongue.
At week 12-20 it is functional but independent in week 20-26 weeks
What is the word for a disorder where the thyroid failed to migrate
Lingual thyroid
Lingual thyroid is an abnormal mass of ectopic thyroid tissue seen in base of tongue caused due to embryological aberrancy in development of thyroid gland.
What are some abnormalities in thyroid embyrology?
Failure to migrate (lingual thyorid)
Remnants (thyroglossal cysts- move up on tongue protrusion)
Describe the clinical antomy of the thyroid
- Deep to sterno-hyoid muscle
- Posterior is recurrent laryngeal nerve and tracheal cartilage ring 2 and 3 (have to be careful in surgeries)
- Left is oesophagus
Describe the blood and nerve supply of the thyroid
Blood supply: S_uperior thyroid artery (_external carotid) and inf thyroid artery (subclavian)
Nervous supply: ANS innervation
Where is the thyroid hormone stored? (at a protein level)
In Colloid, attached to Thyroglobulin, which is produced by thyroid follicular cells
If someone has thyroiditis (over active thyroid), what would you observe?
Pain etc. But can measure the thyroglobulin- should be elevated
What does elevated thyroglobulin suggest?
- Thyroiditis
- Differentiated throid cancer and Goitre
- Factitious thyrotoxicosis (intermittent outbreaks- if the thyroid of the cow is processed int the hamburger)
What do Parafocclicular cells secrete?
Cells produce calcitonin (not sure what this does)
Indicative of Mellullary thyroid cancer
What is the Colloid?
The follicles are lined with follicular cells and are filled with a fluid known as colloid that c_ontains the prohormone thyroglobulin._
The follicular cells contain the enzymes needed to synthesize thyroglobulin, as well as the enzymes needed to release thyroid hormone from thyroglobulin.
What is increased calcitonin indicative of?
Medullary thyroid cancer
What do Parafocclicular cells secrete?
Cells produce calcitonin (not sure what this does)
What is increased calcitonin indicative of?
Medullary thyroid cancer
How much iodine dietary iodine do we need?
- Need min 150microgram iodide/daily
- Iodide content of NZ soil is low- due to dairy industry
- Many dietary sources of iodide e.g. salt, fish, bread
- Active transport of two Na+ ions results in the entry of one I- molecule against its concentration gradient
- Thyroid gland contains ~8000 mg iodide
What does iodine deficiency lead to?
Compensatory enlargement of thyroid (endemic goitre)
If in pregnancy, low maternal iodine-> fetal throid levels are low, and it can cause irreversible damage to the developing CNS: Cretinism
Describe Iodide in thyroid hormone synthesis
Iodide trapping
- Iodide is trapped by a sodium-iodide symporter (NIS)
- Active transport of two Na+ ions results in the entry of one I- molecule against its concentration gradient
- Thyroid gland contains ~8000 mg iodide
Where are large concentrations of the sodium-iodine symporters found?
- Breast (high-especially in pregnant women)
- Gastric mucosa
- Ciliary body eye
- Salivary glands
- Differentiated thyroid cancer cells
Describe the t4 and t3 production and release
a) Dietary iodine goes into cell (follicle?) via symporter
b) Oxidised by thyroid perioxidase and allows the iodine to go into the colloid
- If someone has a problem with their thyroid (under or overactive), we can measure thyroid peroxidase antibodies
c) Thyroid cells combine iodine and the amino acid tyrosine to make T3 and T4 and are attached onto the thyroglobulin in the colloid
d) When you need the thyroid hormone, it is endocytosed into the cell.
e) It is released from the thyroglobulin and T3/T4 are released into the blood stream- protease peitidase
f) Recycle iodine (deiodinase)
-If someone has a problem with their thyroid (under or overactive), we can measure ________ antibodies
-If someone has a problem with their thyroid (under or overactive), we can measure thyorid peroxidase antibodies (involved in getting iodine into the thyroid colloid)
What are some clinical points around iodine supplements?
-
Iodine supplements can make the thyroid overactive.
* e.g. amiodarone- Can result in Thyroiditis and thyrotoxicosis
-
Iodine supplements can make the thyroid overactive.
Describe the Pendred syndrome
Pendrin is a chloride transporter. High levels of pendrin expression have been identified in the inner ear and thyroid. In the thyroid, pendrin mediates a component of the efflux of iodide across the apical membrane of the thyrocyte, which is critical for the formation of thyroidhormone.
In pendred syndrome (deafness and hypothyroid)
Describe the storage and release of thyroid hormone
- Large store of thyroid hormone (T4/T3) incorporated into Tg (~50 day supply) (so if someone suddenly goes on a low-iodine diet, it won’t affect their thyroid hormone for a while)
- Thyroid hormone release involves endocytosis of Thyroglobulin (colloid) from follicular space
•Endosomes fuse with lysosomes
•Degradation of Tg -> T4 (80%) or T3 then released
What is TSH?
What is it’s clinical significance in pregnancy and some tumours
Thyroid stimulating hormone
Alpha subunit of LH, FSH, TSH, HCG the same
Clinical importance: In pregnancy and in rare conditions - tumours that produce HCG, the thyroid can be stimulated because the _alpha subinit of HCG has some affinity to the thyroid receptor_s. (The thyroid thinks TSH is coming in when in fact, it’s HCG).
If you stimulate the thyroid by HCG, the thyroid will respond by increasing T4 and T3 production. The pituitary will sense that there’s more T3 than normal and turn off TSH production.
Describe the TSH level in pregnant women
Alpha subunit of LH, FSH, TSH (thyroid stimulating hormone), HCG are all the same
Clinical point: In pregnancy and in rare conditions, the thyroid can be stimulated by HCG levels being high.
Thyroid can be tricked into thinking TSH has come in instead of HCG. Thyroid will i_ncrease T3 and T4 production (slightly)_
The brain will think the T3 has been increased, it’ll s_witch off TSH._ (so the TSH will decrease)
In pregnant people, T3 and T4 will be higher and TSH will be slightly lower
What does T3 ad T4 do?
T3: Target tissues T4: prduce more T3 - negatively feedback to hypothalamus and pituitary
What are some ‘abnormal’ TSH, T4 balance situations (4)
1) Low TSH, high T4
2) Normal TSH, low T4 (the patient is really sick or have a pituitary problem) (secondary hypothyoridsim)
3) High TSH, low T4 (primary hypothyroidism)
4) High TSH, high T4 (Rare)
What are the effects of TSH on thyroid (5)
All aspects of thyroid hormone synthesis
1) increase _iodide i_nto follicular lumen
2) Increases blow flow (Particularly in Graves disease- antibodies to TSH receptor so the thyroid think’s there is TSH when there isn’t))
3) Increase Tg, TPO and H2O2
4) Increases endocytosis and degradation of Tg
5) Increased release of T4
What are some ‘abnormal’ TSH, T4 balance situiatrion
Low TSH, high T4 (thyrotoxicosis)
Normal TSH, low T4 (the patient is really sick or have a pituitary problem) (secondary hypothyoridsim)
High TSH, low T4 (primary hypothyroidism)
High TSH, high T4 (Rare)
What are some ‘abnormal’ TSH, T4 balance situiatrion
Low TSH, high T4 (thyrotoxicosis)
Normal TSH, low T4 (the patient is really sick or have a pituitary problem) (secondary hypothyoridsim)
High TSH, low T4 (primary hypothyroidism)
High TSH, high T4 (Rare)
_____ is the main thyorid hormone in plasma/blood
T4 is the main thyorid hormone in plasma/blood
Describe Thyrotoxicosis + Signs and Symptoms
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormone by the thyroid gland.
Low TSH, high T4 and T3 (typical blood test)
Symptoms
1) Nervousness, and increased sweating
2) Weight loss (despite large calorie consumption)
3) Heat sensitivity -
4) Tachycardia (and palpatations)
5) Weakness
Signs
1) Bruit over thyroid, tachycardia
2) Goitre
3) Skin changes
4) Tremor
5) Eye changes [upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and bulgingeyes (exopthalmos)]
What is Low TSH, high T4 and T3 indicative of?
Thyrotoxicosis
What is goitre?
A goitre or goiter is a swelling in the neck resulting from an enlarged thyroid gland.
What are some causes of thyrotoxicosis? (5)
1) Graves disease: autoimmune production of an antibody that sitmualtes TSH receptor (the thyroid thinks TSH is present- overactivty)
2) Multinodular goitre: Hyperfunctioning regions of thyroid gland, not suppressed by circulating thyroid hormone
3) Drugs-amiodarone, iodine thyroxine
4) Toxic Nodule
5) Thyroiditis
Describe a disease that can cause Primary Hypothyroidism
High TSH, low T4, (+ve TPO antibodies)
Hashimoto’s disease
Hashimoto’s disease is a condition in which your immune system attacks your thyroid,
- Adult onset slow
- Can affect all organ systems
- Decrease in energy metabolism -low basal metabolic rate ± slightly low body temperature
- Decreased protein synthesis
Describe the Signs of Thyrotoxicosis
Low TSH, high T4 and T3 (typical blood test)
1) Bruit over thyroid, tachycardia
2) Goitre
3) Skin changes
4) Tremor
5) Eye signs (
Describe Hashimoto’s Disease
Inflammation from Hashimoto’s disease, also known as chronic lymphocytic thyroiditis, often leads to an underactive thyroid gland (hypothyroidism). Hashimoto’s disease is the most common cause of hypothyroidis
Describe thyroid eye disease
You get some autoimmune activity in the eye- produce glycosaminoglycans which infiltrates the fat in the eyes.
This pushes the eye forward, so we see retraction.
The eye eventually becomes v_ery red_ and inflamed.
Control of thryoid hormone is by the _____-
Control of thryoid hormone is by the hypothalamic/pit axis
Superior thyroid artery comes from_______ and inf thyroid artery comes from ________
Superior thyroid artery (external carotid) and inf thyroid artery (subclavian)
What is the clinical significance of thyroglobulin?
- It circulates in our system in small amounts in normal individuals
- If someone has an overactive throid (e.g. thyroditis, diffeentiated thyroid cancer and goitre, factitious thryotoxicosis), you can measure the thyroglobulin and it should be elevated.
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What are the symptoms of Thyrotoxicosis? (5)
Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism.
Low TSH, high T4 and T3 (typical blood test)
Present with:
1) Nervousness, and i_ncreased sweating_ (can show significant psychotic symptoms)
2) Weight loss (despite large calorie consumption)
3) Heat sensitivity - vasodilation
4) Tachycardia (and palpatations)
5) Weakness
Thyroid hormone synthesis requires ______
Iodide trapping
- Iodide is trapped by a sodium-iodide symporter (NIS)
- Active transport of two Na+ ions results in the entry of one I- molecule against its concentration gradient
what happens if the mother has iodine deficiency during pregnancy?
Low iodine -> the fetal throid levels are low,
it can cause irreversible damage to the developing CNS: Cretinism
What is thyroid colloid?
The follicles are made up of a central cavity filled with a sticky fluid called colloid.
Surrounded by a wall of epithelial follicle cells, the colloid is the center of thyroid hormone production, and that production is dependent on the hormones’ essential and unique component: iodine.
What is the role of iodide in producing thyroid hormone
The function of the thyroid gland is to take iodine, found in many foods, and convert it into thyroid hormones:thyroxine (T4) and triiodothyronine (T3).
Thyroid cells are the only cells in the body which can absorb iodine.
These cells combine iodine and the amino acid tyrosine to make T3 and T4. T3 and T4 are then released into the blood stream and are transported throughout the body where they control metabolism (conversion of oxygen and calories to energy).
Oxidation of I- is catalysed by _____
Thyroid perioxidase
What happens after a thyrodectomy?
- The patients are no longer producing T4
- But their T3 will also be absent
- So you need to give them enough thyroid hormone so they can make their T3 levels slightly higher than their pre-op because their thyroid is absent and cannot manufactor T3
Describe the Hypothalamic-Pituitary-Thyroid axis
- The hypothalamus releases TRH
- The pituitary releases TSH
- Thyroid gland releases T4 and T3(20%)
- T3 acts on different target tissues (e.g. heart, liver, bone, CNS)
- T4 and T3 go back and inhibit the release of TRH and TSH (negative feedback)
What is grave’s disease?
Also known as toxic diffuse goiter,
Graves’ disease is an immune system disorder that results in the overproduction of thyroid hormones (hyperthyroidism).
The disorder results from an antibody, called thyroid-stimulating immunoglobulin (TSI), that has a similar effect to thyroid stimulating hormone (TSH).[1]
These TSI antibodies cause the thyroid gland to produce excess thyroid hormone
After thyroidectomy, to maintain pre-op T3, need enough _____to ________
After thyroidectomy, to maintain pre-op T3, need enough Thyroxine (T4) to suppress TSH slightly
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