Thyroid Flashcards
What is the process called that concentrates iodide in the cell?
Iodide trapping
How does iodide get into thyroid cells?
Sodium-iodide symporter (NIS) which co-transports one iodide with two sodium ions
What ensures there is a concentration gradient for sodium in thyroid cells so iodide can be transported in?
Na/K ATPase which pumps sodium out of cell
Where is thyroglobulin produced and modified?
Produced in the RER and modified in the Golgi apparatus of follicular cells
What molecule on thyroglobulins does iodine combine with to form thyroid hormones?
Tyrosine
What needs to happen to iodide ion before it can bind to tyrosine and what promotes this?
Oxidation (removal of electrons) to iodine by peroxidase and hydrogen peroxide
When one molecule of iodine is bound to a tyrosin on thyroglobulin what is the product called?
Monoiodotyrosine (T1)
Where is thyroglobulin with iodine atoms attached stored?
Lumen of thyroid follicle and is called colloid
What is the process by which colloid re-enters follicular cells?
Pinocytosis
What cleaves T3 and T4 from thyroglobulin?
Digestive enzymes (e.g. proteases) released by lysosomes
What is the main plasma protein that T3 and T4 bind to?
Thyroxine-binding globulin.
The biologically active hormones are unbound
What is the long name of T3
Triiodothyronine
What is the long name of T4
(tetraiodothyronine) Thyroxine
Name 3 actions of TSH
1) Active uptake of iodine
2) Stimulates uptake of colloid
3) Induces growth of the thyroid gland
4) Stimulates other reactions involved in thyroid hormone synthesis
What is the most common cause of congenital hypothyroidism?
Absence of thyroid or ectopic thyroid
What is a treatment for hypothyroidism?
Thyroxine
What is the commonest non-iatrogenic cause of hypothyroidism in the UK and how does it cause hypothyroidism?
Hashimoto’s Disease.
Autoantibodies against thyroid peroxidase and/or thyroglobulin
What supplements can interfere with treatment of hypothyroidism?
Calcium and iron supplements
What is Graves’ disease?
Autoimmune thyroid disease that causes hyperthyroidism
What is more common in the UK hyper or hypo thyroidism and is it more common in men or women?
Hypothyroidism more common and both more common in women.
Why does hyperthyroidism cause fatigue?
The excitable effects of the hormone on synapses make it difficult to sleep
Name 4 methods of treatment of hyperthyroidism
1) Thionamides - e.g Carbimazole, propylthiouracil
2) Beta-blockers - to alleviate some symptoms
3) Radioactive iodine
4) Surgical removal
What is a goitre?
Swelling of the neck resulting from enlargement of thyroid gland
Anatomically, what level can the thyroid be found?
C5-T1
What kind of receptor does TSH bind to on the thyroid?
GPCR
What stimulates TSH secretion from the anterior pituitary gland?
Thyrotropin-releasing hormone (TRH) from the hypothalamus
List some symptoms of hyperthyroidism
- Excitability
- Intolerance to heat
- increased sweating
- weight loss
- diarrhoea
- muslce weakness
- nervousness or other psychic disorders
- extreme fatigue but inability to sleep
- tremor of hands
- exophthalmos
What is exophthalmos
protrusion of the eyeballs - symptom of hyperthyroidism
Normally, what feedback to T3 and T4 have on hypothalamus and anterior pituitary gland?
Negative feedback
List some symptoms of hypothyroidism
- fatigue and extreme somnolence
- extreme muscular sluggishness
- slowed HR
- decreased HR and BP
- sometimes increased body weight
- constipation
- mental sluggishness
- dry, scaly skin, depressed hair growth
What is the cause of endemic goiters and what is the pathophysoilogy?
Lack of iodine.
prevents production of T3 and T4
No hormone to inhibit TSH.
Large amounts of thyroglobulin colloid form and gland grows larger
Other than lack of iodine, what can cause goitres?
- Deficient iodide-trapping mechanism
- Deficient peroxidase system
- Deficient coupling of iodinated tyrosines
- Deficiency of deiodinase enzyme preventing recovery of iodine from iodinated tyrosines that are not coupled to form thyroid hormones
How does carbimazole work?
prevents thyroid peroxidase enzyme from coupling and iodinating tyrosine residues thus reducing formation of T3 and T4
What is the pathophysiology of Graves’ disease
Autoantibodies to TSH receptor so it’s constantly stimulated.
Increased TSH produced
What is endocrinology?
the study of glands and the hormones they produce
What is the difference between exocrine and endocrine cells?
Exocrine - secrete products externally or into lumen/duct.
Endocrine - secrete in blood stream
Using the HPA axis as an example, what occurs in primary adrenal insufficiency?
State how the levels of CRH, ACTH and cortisol will be affected.
Name an example where this happens
Problem with adrenal gland itself.
Don’t get negative feedback to pituitary and hypothalamus as normal.
Cortisol level = low
CRH = high
ACTH = high
Addison’s Disease - hyperpigmentation due to pituitary gland producing high levels of proopiomelanocortin which is a precursor for ACTH but also melanocyte-stimulating hormone
Using the HPA axis as an example, what occurs in secondary adrenal insufficiency?
State how the levels of CRH, ACTH and cortisol will be affected.
Pathology in pituitary gland.
ACTH = low
Cortisol level = low
CRH = high
Using the HPA axis as an example, what occurs in tertiary adrenal insufficiency?
State how the levels of CRH, ACTH and cortisol will be affected.
Pathology in hypothalamus.
CRH = low
ACTH = low
cortisol = low
What test is used to test how well a gland is functioning?
Dynamic function test
In dynamic function testing what do you do if you suspect
1) gland insufficiency
2) gland over-production
1) Stimulate gland
2) Suppress gland
How do levels of cortisol, ACTH and CRH differ in Cushing’s syndrome compared to cushing’s disease?
Cushing’s syndrome (tumour or adenoma in adrenal cortex) - increased cortisol, low ACTH and CRH
Cushing’s disease (pathology in pituitary) = High ACTH and cortisol but low CRH
If you had low levels of T4 but high levels of TSH and TRH what would be the diagnosis?
Primary hypothyroidism
Diagnose - Low levels of T4 and TSH but high TRH
Secondary hypothyroidisme
Low levels of T4, TSH adn TRH - Diagnosis?
Tertiary hypothyroidism
High levels of T4, low levels of TSH and TRH - Diagnosis?
Primary hyperthyroidism
High levels of T4 and TSH. low levels of TRH - Diagnosis?
Pituitary (secondary) hyperthyroidism
What effect does dopamine have on prolactin?
Inhibits it - hence why dopamine antagonists cause hyperprolactinemia
What is another name for vasopressin?
Anti-diuretic hormone
Name an example of a positive feedback?
Prolactin - baby sucking causes further release of prolactin
Oxytocin - stretching of neurons during childbirth produces more oxytocin which contracts uterus to aid in delivery
What two hormones are made in the hypothalamus then stored/released by the posterior pituitary?
ADH
Oxytocin
