1
Q
what is the thyroid follicle important in terms of?
A
production of thyroid hormone
2
Q
what is stored in the colloid?
A
thyroid precursors
3
Q
what are key elements of thyroid hormones?
A
tyrosine and iondine
4
Q
what is T3?
A
active hormone
5
Q
what is most circulating T3 derived from?
A
T4 by deiodination
6
Q
what are thyroid homrones bound to?
A
thyroxine-binding globulin (TBG) and transthyretin (TTR)
7
Q
what is the process of thyroid hormone secretion?
A
hypothalamus releases thyrotrophin-releasing hormone which stimulates anterior pituitary to secrete thyroid stimulating hormone (TSH) which stimulates thyroid gland to secrete thyroid hormone
8
Q
what does negative feedback in the precursor glands result in?
A
increase of T3 and T4 would decrease TRH and TSH
9
Q
what is the hypothyroid state?
A
thyroid hormone secretion is subnormal (myxoedema)
10
Q
what is the euthroid state?
A
thyroid hormone secretion is normal
11
Q
what is the hyperthyroid state?
A
thyroid hormone secretion is excessive (thyrotoxicosis)
12
Q
what is the actions of TSH
A
- increases protein sythesis in follicular epithelial cells, increases DNA replication and cell division
- increases rough ER and cell machinery required for protein synthesis
13
Q
what will happen to the thyroid if it is exposed to greater TSH concentration?
A
hypertrophy - results in goitre (dysfunction of the gland in any state)
14
Q
what is the tissue action of thyroid hormones?
A
- increased basal metabolic rate
increased heat production
increased responsiveness to sympathetic output - permits normal growth and development
15
Q
what are actions of thyroid hormone on the nervous system?
A
permits normal growth and development
permits maintainence of normal activity
16
Q
what is iodine deficiency disease?
A
- cretinism is the most extreme case
- mental retardation
- reduction in physical growth
- deaf-mutism
17
Q
what can iodine deficiency be caused by?
A
inadeqaute dietary intake (150mcg/day)
maternal iodine deficinecy
18
Q
what are the ranges for TSH, free T4 and free T3 in a test result?
A
- TSH (0.27-4.2 mU/L)
- Free T4 (12-22 pmol/l)
- Free T3 (3.1-6.8pmol/l)
19
Q
what is the difference between primary and secondary hypothyroidism?
A
primary: thyroid gland itself is damaged and is unable to produce thyroid homrones (T3/T4 is low, TSH is high), can also be due to inadequate iodine intake
secondary: problem with the pituitary gland which fails to produce enough TSH resulting in low thyroid hormone levels
20
Q
what will the levels of TSH and T4 be in hyperthyroidism?
A
TSH: low
T4: high
21
Q
what are signs and symptoms of hypothyroidism?
A
cold intolerance
modest weight gain
bradycardia
tiredness for no reason
constipation
forgetfullness and personality changes
pale, dry coarse skin
puffiness of the face
22
Q
what is the aetiology of primary hypothyroidism?
A
- hasimotos thyroiditis
- most common cause
- autoimmune disease (antibodies to thyroid peroxidase)
- more prevalent in women
- can result in goitre
23
Q
when is the does of levothyroxine adjusted until?
A
until the TSH levels are mid-range
24
Q
what does of levothyroxine will pregnant women require?
A
50-100% of normal dose (requires monitoring)
25
what are adverse effects of levothyroxine?
hair loss
headache
sleep problems
nervousness
fever, hot flushes
pounding heart beat and fluttering in chest
appetite changes
26
what is liothyronine?
sythetic form of T3 - not supported by the royal collage of physicians
risks on bone (osteoporosis) and heart (arrhythmia)
5x as potent than levothyoxine , single dose reaches maximum effect in 24hrs
27
how long does it take for levothyroxine to reach maximum effect?
~10 days
28
what is a myoemdema coma?
- end result of untreated hypothyroidism
- progressive weakness leading to loss of conciousness
- extreme hypothermia
- areflexia (absense of reflexes), seizures and respiratory depression
29
what are precipitating factors of myoemdema coma?
illness
infection
trauma
drugs that suppress the CNS
exposure to cold
30
how does corticosteroids affect thyroid function?
can decrease basla production of TRH and TSH, decreasing thyroid hormone levels
31
how does lithium affect thyroid function?
inhibits the release of thyroid hormones and interferes with their peripheral deiodination
32
how does amiodarone affect thyroid function?
contains iodine and can cause both hypothyroidism and hyperthyroidism
33
how does cholestyrame affect thyroid function?
reduces the absoprtion of thyroxine
34
what are signs and symptoms of hypertyroidism?
heat intolerance
palpitations
weight loss
restlessness and nervousness
fatigue
increased sweating
frequent bowel movments
goitre may be present
35
what is graves disease
autoimmune disease caused by thyroid stimulating immunoglobulin
activates TSH receptor on thyroid follicular cells
increased secretion of thyroid hormones
36
what is treatment for hyperthyroidism ?
- surgery
- radioactive iodine (administered oraly and taken up in the thyroid gland - radiates cells responsible so lowers thyroid hormones)
37
what are antithyroid drugs?
thioamides (eg. carbimazole, propylthiouracil)
- accumulated by the thyroid
38
what is the mechanism of action of thioamides?
inhibit thyroid peroxidase (enzyme responsible for the iondination of tyrosine) and prevents hormone synthesis
propylthiouracil also inhinbits peripheral deiodination
39
what is the onset of thioamines?
slow usually 4-6 weeks
40
what might thioamides cause?
agranulocytosis (severe lowered white blood cells), thereby increasing the risk of infection
41
what are the different regions of the adrenal cortex?
zona glomerulosa
zona fasciculata
zona reticularis
42
what are mineralcorticoids, site and mechanism?
- primarly aldosterone
- zona glomerulosa
- Na+ reabsorption and K+ excretion in the kidneys
43
what are glucocorticoids , site and mechanism?
- primarily cortisol
- zona fasciculata
- regulates bodys response to stress
44
what are sex hormones , site and mechanism?
- primarily androgens eg. testosterone
- zona reticularis
- regulate reproductive function
45
what does the adrenal medulla secrete?
catecholamines
- adrenaline and noradrenaline
46
how is cortisol released from the adrenal cortex
stress response -> hypothalamus -> corticotrophin releasing hormone (CRH) secretion -> anterior pituitary -> adrenocorticotrophic hormone (ACTH) secretion-> adrenal cortex -> cortisol -> target cell response
47
what can you relate serum cortisol levels to?
circadian rhythm of the body
- at night the parasympathetic NS takes over and reduces cortisol
- anything that challenges the body will increase cortisol levels eg. getting up the morning
48
what are cellular actions of cortisol?
- increasing glucose levels
- maintain the normal responsiveness of blood vessels to vasoconstrictive stimuli
- effects on immune system, nervous system and kidneys
- pharmacological actions (anti-inflammatory, immunosuppressants) - drugs can minic or inhibit glucocorticoids
49
what is the effects of cortisol on target tissues in the body?
many tissues - decreases glucose uptake, decreases amino acid uptake
adipose tissue - increase lipolysis
muscle and other tissues - increases protein breakdown, decreases protein synthesis
liver - increases gluconeogenesis
50
what are the cellular actions of cortisol?
transactivation
transrepression (down regulation of nuclear transcription)
51
what is addisons disease?
- destruction or dysfunction of the entire adrenal cortex (occurs when 90% destroyed)
- affect both glucocortiod and mineralcortoid function
52
where is addisons disease most commonly seen
adults aged 30-50 years
53
what are symptoms of addisons disease?
- darkening areas of the skin
- extreme fatigue
- low blood pressure
- GI disturbance
- salt craving (sodium retention)
- low blood glucose
54
what is the aetiology of addisons disease?
- primary adrenal insufficiency (disease occurs in gland itself)
- infections (TB, HIV, syphillis)
- invasion (neoplastic, fibrosis, sarcoidosis)
- Haemorrhage (waterhouse-friderichsen syndrome)
55
what does addisons disease cause in the cortisol pathway?
- decreased secretion of cortisol (lack of negative feedback)
- increased secretion of corticotrophin releasing hormone and adrenocortitrophic hormone
56
what is the treatment of addisons disease?
- hydrocortisone (15-30mg)
- fludrocortisone (mineralcorticoid)
57
when might you reqiore an increase in glucocorticoid dose?
intercurrent illness (eg. infection)
58
what is secondary adrenal insufficiency?
- lack of ACH secretion from pituitary
- dont show hyperpigmnetation or cravings for salt
- can also by be due to glucocorticoid drug therapy
- can occur if glucocorticoid medication is stopped too abruptly
59
what is tertiary adrenal insufficiency?
lack of cortiocotrophin releasing hormone secretion from the hypothalamus
60
what is the treatment dor secondary adrenal insufficiency?
treatment for glucocorticoid eg. hydrocortisone but mineralcorticoid is unnecessary
61
what are therapeutic uses of glucocorticoid?
- replacement therapy
- acute inflammatory disease (eg. asthma)
- chronic inflammatory diease eg. renal, hepatic, GI disorders
- cancers
- transplantation
62
what is the effect of glucocorticoids?
suppress the hypothalamus and anterior pituitary
- see high levels of circulating cortiosl
63
what are examples of glucocorticoid drugs?
prednisolone
dexamethasone
hydrocortisone
beclomethasone
64
what courses of glucocortosteroids can be stopped abruptly?
short courses < 3 weeks
65
what should gradual withdrawal of glucocorticoids be considered with?
- those who have recieved >3 weeks treatment
- recieved repeat courses of treatment
- received >40mg prednisolone for > 1 week
66
what are symptoms of adrenal crisis?
- sudden, severe pain in lower back, abdomen or legs
- severe vomiting and diarrhoea
- dehydration
- low bp
-loss of consciousness
can result in death if not treated immediately
67
what is cushing syndrome ?
hypersecreton of cortisol
- can change body mass
- metabolic complications eg T2D
- hypertension
68
what is the aetiology of cushing syndrome?
- pituitary tumour leading to increased secretion of adrenocorticotrophic hormone
- adrenocortical tumours (benign or malignant)
- tumours external to hypothalamic-pituitary-adrenal axis
69
what is the classification of cushing syndrome?
ACTH dependant (pituitary)
- body is making too much ACTH
- due to pituitary tumour or ectopic tumour producing ACTH
ACTH independent (coming from gland itself)
- ACTH level is low
- adrenal glands are making too much cortisol due to adrenal tumour or adrenal hyperplasia
70
what is drug induced cushing syndrome?
- iatrogenic (drug-related or exogenous)
- glucocorticoid treatment
- if treatment is prolonged and the drug is potent cushings can occur
71
what are examples of drugs that can inhibit cytochrome P450 and prolong the action of glucocorticoids?
itraconazole
ritonavir
a number of antidepressants
72
what is the treatment of cushings syndrome?
- surgery (removal of the pituitary gland or adrenal glands)
- when drug induced: gradual withdrawal of causative drug with aim to discontinue
- mifeprisone (glucocorticoid receptor antagonist) - restoration of glucose tolerance and lowered blood pressure but doesnt reduce cortisol
- metyrapone requires dose titration and monitoring
73
what does the thyroid gland convert tyrosine to?
monoiodo and diidotyrosine
74
how is T4 converted to T3
T4 interacts with deiodinases to rip off the 5-dionase to for T3
75
why is log p of liothyronine lower than levothyroxine?
liothyronine has one less iodine which is lipophillic
76
what salt is hypothyroidism treatment given as and why?
sodium salt so it absorbes easier
77
what does carbimazole hydrolyse to?
mathimazole which inhibits thyroid peroxidases which convert tyrosine in to MIT and DIT
78
what does propylthiouracil inhibit?
- thyroid peroxidases
- also inhibits 5' deionase enzymes helping stop T3 biosynthesis
