Week 7 - Thyroid Flashcards
What hormones does the thyroid produce?
Where are these hormones produced?
T3 and T4
Calcitonin
By follicular cells and parafollicular cells
What is the parathyroid composed of?
What is secreted here?
4 parathyroid glands on posterior thyroid
Can be up to 8 glands
Secrete parathyroid hormone
What are the roles of parathyroid hormones?
- Calcium homeostasis
- Raise serum calcium
- Stimulate osteoclast reabsorption of bone
- Increase calcium reabsorption in kidney
- Increase calcium uptake in gut
What are pathology related to thyroid gland?
- Hyperplasia (from overstimulation of gland producing TSH)
- Grave’s disease
- Tumour nodules
- Thyroid cancer
- Goitre
What are pathology related to parathyroid gland?
- Hyperparathyroidism
- Primary = tumour
- Secondary = kidney failure
What are T3 and T4?
What is their role?
Iodine-containing low molecular weight hormones
- Regulate BMR and growth maturation
- Secretion regulted by TSH from anterior pituitary
What is calcitonin?
What is its role?
Polypeptide hormone
- Lowers blood calcium
- PTH antagonist
- Produced by parafollicular cells
- Contain neuroendocrine granules
What is required for thyroid hormone synthesis?
What catalyses this process?
- Source of iodine
- Source of tyrosine residues
- Thyroglobulin for site of synthesis
Thyroid peroxidase
What are the actions of thyroid hormones?
- Increase body metabolism
- carb, protein, and fat metabolism
- O2 consumption and heat production
- Stimulate growth and development
- Synergistic with actions of SNS / catecholamines
What happens during the process of iodination of tyrosine residues on thyroglobulin?
- Tyrosine iodinated at 3’ ring –> MIT formed
- Tyrosine iodinated at 3’ and 5’ ring –> DIT formed
- DIT + DIT = T4
- MIT + DIT = T3
- DIT + MIT = reverse T3 = biologically inactive
What is the role of reverse T3?
Anatgonist at T3 receptors
What happens to T3,T4, and TSH levels in primary and secondary hypothyroidism and in lack of dietary iodine?
Primary = - T3 and T4, + TSH
Secondary = - T3 and T4, - TSH
Lack of iodine = - T3 and T4, + TSH
What happens to T3, T4, and TSH levels in primary and secondary hyperthyroidism, and hyper-secreting thyroid tumour?
Primary = + T3 and T4, - TSH
Secondary = + T3 and T4, + TSH
Tumour = + T3 and T4, - TSH
What are the main, primary, and secondary causes of hypothyroidism?
- Autoimmunity
- Lack of dietary iodine
- Drug-induced
- Thyroid hormone resistance
Primary = failure of thyroid gland
Secondary = anterior pituitary failure
What are the main causes of hyperthyroidism?
- Hyper-secreting thyroid tumour
- Latrogenic causes
- Grave’s disease
- Abnormal TSI
What are the symptoms of hypothyroidism?
- Weight gain
- Dry skin
- Hoarse voice
- Menstrual changes
- Cold intolerance
- Constipation
- Low HR/BR
- Depression, confusion, poor memory
- Myoxoedema (puffy appearance)
- Reduced BMR
What is cretinism?
Neonate
Dwarfism and mental retardation
Every newborn tested for TSH and T4
How can you treat hypothyroidism?
What are some issues though?
- Synthetic thyroid hormones
- Levothyroxine (T4)
- drug of choice, can worsen angina
- Liothyronine (T3)
- rapid onset can induce heart failure, used in severe hypothyroid state
What are the symptoms of hyperthyroidism?
- Weight loss
- Sweating
- Heat intolerance
- Palpitations
- Tremor
- Nervousness
- Diarrhoea
- Goitre and exopthalmos
How do you diagnose hyperthyroidism?
- Thyroid function test
- If Grave’s suspected, test for thyroid-stimulating antibodies
- Perform thyroid uptake test for thyroid tumours
How can you treat hyperthyroidism?
- Anti-thyroid drugs
- Thionamides - carbimazole + PTU
- Radioiodine
- Surgery
How do anti-thyroid drugs work?
- Decrease production of thyroid hormones by inhibitng iodination and coupling processes
- Blockage of T4 to T3 deiodination
- Non-selective beta blockers reduce actions of catecholamines
- 12-18 month restoration
When is radioiodine used?
- Used in older patients with nodular goitres and hyperthyroidism
- Used when thyroxicosis recurs after anti-thyroid drug therapy
- 2-4- max effect
How does + adipose tissue cause increase in CVD?
Adipose tissue secretes cytokines and inflammatory factors
What genetic factor can lead to obesity?
- POMC mutation
- Reduction in leptin
- Reduction in appetite suppression
- copies of FTO gene = + weight gain
- FTO controls neural regulation of appetite
What medications are used to treat obesity?
Orlistat - intestinal lipase inhibitor
Saxenda - GLP-1 analogue
What is the role of the arcuate and paraventricular nucleus?
Arcuate:
- NPY, AgRp and POMC, CART neurotransmitter release
- Stimulation or inhibition of food intake
- Reward circuit stimulated
Paraventricular:
- Involved in stimulation / inhibition of reward centre
What hormones are released upon gastric distention?
What is their role?
- CCK
- GLP-1
- Oxytonmodulin
- Peptide YY
- Apolipoprotein A-IV
- Enterostatin
All inhibit food intake
What is leptin and its role?
- Peptide hormone secreted from adipose
- food intake = - leptin
- food = + leptin = appetite suppression
- Production correlates with amount of adipose tissue
What is ghrelin and how does it act?
- Produced from GIT
- Secretion when food anticipated
- Acts centrally at ARC or brain stem to stimulate food intake
- Acts via NPY and AgRP
- ghrelin at certain times of day
What is PYY and how does it work?
- Secreted from distal GIT dependent on nutrient intake
- Stimulated by CCK, gastric acid, and bile
- Inhibits food intake
- PYY1-36 = cleaved to PYY3-36
- Acts at NPY Y2 receptor
- Inhibits release of NPY = less food intake
- PYY stays elevated for 12 hours post-meal
Which reward centres are stimulated upon food intake?
What is bupropion and how does it work?
Opioid receptors, Cannabinoid receptors, Dopamine
Bupropion = dopamine reuptake inhibitor
- dopamine in synapse
- Prolonged activation of dopamine receptor
How does orlistat work and how do you take?
Side effects?
Dosing?
- Inhibits gastric and pancreatic lipase
- Take before each meal
- Combine with low-fat diet
- Only give when obese or + risk factors
- SE = steatorrhea, fat soluble vitamin deifciency
- Dosing = 120mg at meal time, 360mg max.
How does saxenda work and what are problems with it?
- Glucagon-like peptide receptor agonist
- Subcutaneous injection
- Appetite suppression from + POMC/CART secretion
- Suppresses dopamin signalling
- Problems = + expensive and + similar to orlistat
