endocrinology key points Flashcards
body systems
interact with external env - behaviour - nervous, reproductive regulate internal env - homeostasis - CV, respiratory, immune control other systems - nervous, endocrine
chemical communication
synapse
paracrine
endocrine
process at a chemical synapse
impulse arrives at terminal of pre-synaptic cell
transmitter released from storage vesicles
diffuses in synaptic cleft
binds to receptor on post-synaptic cell
alters post-synaptic cell
- excitatory/inhibitory
transmitter action terminated
drug actions on synapse
may enhance/suppress synapse
- synthesis/storage/release of tx
- action of tx on receptor
- 2nd messenger system
- inactivation of tx
autocrine
chemical acts on cell releasing it
nerve control
specific, localised, rapid, short duration
reflexes
sensory systems
salivary secretion
hormonal control
co-ordinated, body wide actions slow to act, but effect persists metabolism growth menstrual cycle
nerve and hormone combined control
bp
blood loss
thermoregulation
examples of 2nd messengers
G-proteins and cAMP
Ca2+
steroid hormones
can pass through membrane
change transcription in nucleus
peptide transmitters
1st messengers
act on receptor protein on membrane
hyperfunction
excess production and secretion
upregulation of receptors
hypofunction
reduced production and secretion
down regulation of receptors
receptors not functioning
posterior pituitary - how are hormones released?
hypothalamus
nerve axons
PP
released into circulation
which hormones are released from the posterior pituitary?
ADH
oxytocin
how are hormones released from anterior pituitary?
hypothalamus
releasing hormones travel along hypothalamic - pituitary portal vessels
AP target cells
hormones released
hormonal local feedback system
function of hypothalamic hormones
control release of AP hormones
hypothalamic hormones
corticotropin RH gonadotropin RH thyrotropin RH growth hormone RH prolactin RH somatostatin dopamine
which hormone inhibits GH?
somatostatin
which hormone inhibits prolactin?
dopamine
anterior pituitary hormones
adrenocorticotropic hormone follicle stimulating hormone luteinizing hormone thyroid stimulating hormone growth hormone prolactin
structure of adrenal gland
endocrine, neuronal and epithelial tissue
capsule
cortex
- zona glomerulosa - aldosterone
- zona fasiculata - cortisol
- zona retiuclaris - sex hormones- androgens, DHEA
medulla - modified sympathetic ganglion - epinephrine (acetylcholine chemical signal for secretion)
islets of langerhans
a cells glucagon
B cells insulin
d cells somatostatin
when is insulin released?
in response to increased blood glucose conc
acts to lower it
how does insulin work?
facilitates glucose entry into muscle cells and adipocytes
promotes formation of glycogen and triglycerides
facilitates protein synthesis
when is glucagon released?
in response to raised blood glucose conc
acts to raise
how does glucagon work?
glycogenolysis and gluconeogenesis in liver
lipolysis and ketone synthesis
somatostatin
functions as a local hormone, inhibiting insulin and glucagon secretion
effects seem to be separate from action of inhibiting GH release from AP
Addison’s disease
destruction of adrenal cortex tissue
- inadequate secretion
Cushing’s syndrome
excess cortisol
therapeutic corticosteroids
suppression of adrenal action
steroid adverse effects
what stimulates release from hypothalamus?
neurogenic and systemic forms of stress
how does cortisol feedback work?
it feeds back and inhibits its own release
negative feedback
aldosterone
enhances Na+ resorption and K+ loss
H2O retention
= indirectly increases bp
renin-angiotensin system
drugs which inhibit aldosterone action
ACE inhibitors
AT2 blockers
side effects of ACE inhibitors
cough
angio-oedema
oral lichenoid drug reactions
cortisol release pattern
circadian release - nocturnal peak
actions of cortisol
antagonist to insulin - maintains blood glucose levels
inhibits protein synthesis, increases proteolysis
inhibits immune response, anti-inflammatory
raises bp
inhibits bone synthesis
stimulates erythropoietin synthesis
ADH antagonist
inhibits reproductive function
Conns syndrome
excess aldosterone
salt and water retention and hypertension
adrenal tumour/hyperplasia
Cushing’s syndrome
excess cortisol
primary gland failure - adrenal hypofunction
AI gland destruction, infection, infarction
often Addisons
adrenal hypofunction - secondary pituitary failure
can’t make ACTH
compression from non-fct adenoma
sheehan’s syndrome
Sheehan’s syndrome
pituitary gland damaged during childbirth
haemorrhage - reduce bp - pituitary infarction
link between ACTH and MSH
both made from the same protein precursor
aMSH identical to part of ACTH
if make lots of ACTH causes melanocytes to make a lot more melanin - pigmentation
tx of hypopituitarism
ACTH - cortisol TSH - thyroxine GH - only give to children FSH and LH - depends on age - may give O/P ADH - ddAVP, desmopressin oxytocin - replace during birth prolactin - don't replace
cushing’s syndrome gender distribution
F 4:1 M
causes of cushings syndrome
cushings disease - form of CS caused by a fct pituitary adenoma (ACTH). 70% spontaneous cushings pts
adrenal adenoma
adrenal hyperplasia
ectopic ACTH production (lung tumours)
cushings disease
form of CS caused by a fct pituitary adenoma (ACTH). 70% spontaneous cushings pts
signs of cushings syndrome
centripetal obesity moon face hypertension thin skin purpura muscle weakness osteoporotic changes and fractures
symptoms of cushings syndrome
DM features
poor infection resistance - opportunistic infections
back pain and bone fractures
psychiatric disorders - depression, emotional lability, psychosis
hirsuitism
amenorrhoea, impotence, infertility
when can you get skin and mucosal pigmentation in Cushings?
only if high ACTH level - not a SE of steroid medicines
causes of Addisons
TB - worldwide
UK - 90% AI adrenalitis (organ-specific AI disease)
slow onset - months, gradual destruction
signs of Addisons
postural hypotension hyponatraemic (risk of seizures) hypoglycaemia and hyperkalaemic acidosis weight loss and lethargy hyperpigmentation (only in primary - keep making more ACTH to try and stimulate gland) vitiligo - AI destruction of melanocytes
symptoms of Addisons
weakness
anorexia
loss of body hair (F)
investigating Cushings syndrome
high 24hr urinary cortisol excretion
abnormal dexamethasone suppression tests - tumour
CRH tests - Cushings disease show rise in ACTH with CRH
investigating Addisons disease
high ACTH
negative synACTHen tests - no plasma cortisol rise in response to ACTH injection
diagnosing hyperfunction
pituitary adenoma, ectopic ACTH production - high ACTH, high cortisol
gland adenoma - low ACTH, high cortisol
diagnosing hypofunction
pituitary failure - low ACTH, low cortisol, synACTHen positive
gland destruction - high ACTH, low cortisol, synACTHen negative
Addison crisis
when levels of cortisol in body fall significantly
hypotension, hypovolaemic shock, hyponatraemia, vomiting, coma, hyperkalaemia
absence of mineralocorticoid and mineralocorticoid effects of glucocorticoid
treating an addison crisis
tx the problem/ppt event e.g. infection
fluid resuscitation
corticosteroids IV
correct hypoglycaemia
Addison’s disease treatment
hormone replacement
- hydrocortisone - cortisol
- fludrocortisone - aldosterone
doubling addison’s disease steroid dose
dose increased by physical/psychological stress and infection
if significant double oral cortisol dose during illness
steroid prophylaxis/cover in Addisons
when increased physiological requirement anticipated
- surgery, infection, physiological stress
1 day + tx day + 1 day = double dose
Addisons in pregnancy
double oral dose in labour for 24hrs, increase dose for few days
when in dentistry would you consider steroid dose increase for Addisons?
MOS
spreading dental/facial infection
NOT for simple dental extractions
Addisons vs steroid as a tx
Addisons - physiological replacement - tendency to hypotension steroids - supraphysiological - tendency to hypertension
what should you always ask re steroids?
steroid use in prev 6m
therapeutic steroids
hydrocortisone (cortisol equivalent 1) prednisolone (4) triamcinolone (5) dexamethasone (25) betamethasone (30)
adrenal suppression
stops adrenal gland being able to respond to ACTH
enhanced glucocorticoid and mineralocorticoid effects
therapeutic steroids adverse effects
hypertension T2 diabetes - if already have then harder to control osteoporosis increased infection risk peptic ulceration thinning of skin easy bruising cataracts and glaucoma hyperlipidaemia (atherosclerosis) increased cancer risk psychiatric disturbance - sleeping problems
causes of oral pigmentation
racial SMOKING melanotic macule drugs - OCP - minocycline - antimalarials - AZT (antiretroviral) pigmented naevus pregnancy chronic trauma melanoma - Addisons not most common reason for oral pigmentation
MEN
malignancy in 1 endocrine gland - v likely malignancy in another - develop from same tissue as an embryo
MEN2b - oral mucosal neuromas
pituitary tumours
functional adenomas - make hormone excess
non-fct adenomas - space occupying
fct adenomas <40yrs
prolactin or ACTH
amenorrhoea - Galctorrhoea or Cushings disease
fct adenomas >40yrs
GH
acromegaly
non-fct adenomas
mass effects visual field defects - pituitary gland under optic chiasma - tumour could compress optic nerve - lose peripheral vision other hormone deficiencies
tx of pituitary tumours
trans-sphenoidal surgery
insufficient GH
growth failure children
metabolic changes adults
- increased fat, reduced vitality
excess GH
gigantism or acromegaly
assessing GH levels
IGF-1 - shows resemblance to overnight peak GH level
acromegaly onset
insidious
peak 30-50years
benign pituitary tumour
acromegaly features
get bigger coarse features enlarged hands - carpal tunnel syndrome T2 diabetes - GH antagonistic to insulin CV disease visual field defects hyperprolactinaemia hypopituitarism
IO acromegaly features
enlarged tongue interdental spacing 'shrunk' dentures changes in occlusion reverse overbite - mandible keeps growing
thyrotoxicosis without hyperthyroidism
thyroid tablets to increase metabolism as quick fix diet pills
causes of hyperthyroidism
Graves disease - 70-80%, AI disease, diffuse goitre - autoABs match TSH receptor toxic multi-nodular goitre toxic adenoma pituitary tumour - rare (secondary)
what other organ is affected in Graves disease?
ophthalmopathy
- scleral injection
- proptosis
- periorbital oedema
- conjunctival oedema
effects of hyperthyroidism
increased metabolism
often bouts
symptoms of hyperthyroidism
hot and sweating weight loss palpitations muscle weakness irritable, manic, anxious diarrhoea
signs of hyperthyroidism
warm moist skin tachycardia and AF increased bp and HF tremor and hyperreflexia eyelid retraction and lid lag
causes of primary hypothyroidism
AI Hashimoto's thyroiditis (90%) idiopathic atrophy radioiodine tx (to treat hyper) thyroidectomy surgery iodine deficiency drugs - carbimazole, amiodarone, lithium congenital (can cause cretinism)
AI hashimoto’s thyroiditis
antibody targets gland - destruction goitre, hypothyroidism older women associations - FH of AI disease - Down Syndrome
causes of secondary hypothyroidism
hypothalamic/pituitary disease
rare
effects of hypothyroidism
reduced metabolism
v gradual onset
symptoms of hypothyroidism
tired cold intolerance weight gain constipation hoarse goitre (in Hashimotos - inflammation) angina 'slow', poor memory hair loss
signs of hypothyroidism
dry coarse skin bradycardia hyperlipidaemia psychiatric/confusion delayed reflexes myxoedema
investigating thyroid disease
blood: TSH, T3, T4
imaging: US (cysts), radioisotope scans (gland uptake)
tissue: FNA/biopsy, see what damage is
T3
triiodothyronine
T4
thyroxine
hormones in hyperthyroidism
Graves/adenoma: reduced TSH, increased T3 pituitary cause (rare): increased TSH, increased T3
hormones in hypothyroidism
gland failure: increased TSH, reduced T4 pituitary cause (rare): reduced TSH, reduced T4
tx of hyperthyroidism
carbimazole
B-blockers
radioiodine
surgery
tx of hypothyroidism
T4 tablets thyroxine
slow response - weeks
increase dose slowly (IHD risk - heard attack)
test 6m-1yr to check levels stable
thyroid enlargement
goitre - diffuse enlargement
solitary nodule enlargement - adenoma, carcinoma, cyst formation
thyroid cancer
usually thyroid swelling
be suspicious in children or elderly
papillary or follicular in young
undifferentiated in elderly
dental aspects of hyperthyroidism
pain anxiety and psychiatric problems
caution for tx until controlled
dental aspects of hypothyroidism
avoid sedatives if severe
DM
abnormality of glucose regulation
DI
abnormality of renal fct - lack of ADH
T1 DM
insulin deficiency
T2 DM
insulin resistance
symptoms of DM
polyuria
polydipsia
tiredness - can’t move glucose efficiently into cells
general features T1
younger thin ? FH ? FH of AI disease diabetic symptoms easily get ketosis
general features T2
older obese strong FH ?diabetic symptoms present with complications rarely get ketosis
diabetes diagnosis
RPG - >11.1mmol/L on 2 occasions diagnostic
GTT
- 75g load after fasting
- amount of time body spends in high blood sugar levels
- levels before test and 2hr plasma glucose
IGT
on way to becoming diabetic
need lifestyle changes
definition of T1 DM
immune mediated pancreatic B-cell destruction - autoantibodies
- hyperglycaemia
- ketoacidosis
T1 circulating ABs
GAD - glutamic acid decarboxylase
ICA - islet cell antibodies
IAA - insulin autoantibodies
aetiology of T1
genetic - HLA associated
env - low twin concordance
T1 child/adolescence onset
higher ICA, IAA, more severe decompensation
T1 adult onset
gradual onset, GAD, less weight loss and ketoacidosis, LADA
acute presentation T1
hyperglycaemia with diabetic symptoms
ketoacidosis - metabolic acidosis you get from dissolving fat in body
T2 onset
usually >40yrs, gradual onset often found by accident often retinal damage at diagnosis unusual infections, diabetic complications MODY possible
T2 FH
strong
T2 pathogenesis
poorly fct insulin receptors
- hypersecrete
- B-cell exhaustion
bit of insulin in background - don’t get ketoacidosis
T2 as a metabolic disorder
defect in insulin resistance
defect in insulin secretion
basal hepatic glucose output increased
insulin stimulated muscle glucose uptake reduced
effects of T2
IGT hyperinsulinaemia hypertension obesity (abdo distribution) dyslipidaemia procoagulant epithelial markers early and accelerated atherosclerosis
management of diabetes
education targets drugs, insulin nutrition exercise monitoring
importance of diabetic control
good control = less future complications
but pts often keep slightly higher blood sugar as they don’t like hypo
T2 management
weight loss diet restriction 'diet pills' - orlistat, sibutramine surgery - gastric bypass oral hypoglycaemic agents - insulin secretagogues - insulin sensitisers insulin
insulin secretagogues
increase pancreatic insulin secretion
small hypoglycaemia risk
sulphonylureas e.g. gliclazide, tolbutamide
insulin sensitisers
thiazolidinediones - rosiglitazone
biguanides - metformin
- enhances cell insulin sensitivity
- reduces hepatic gluconeogenesis
insulin regimes
basal-bolus
- long acting, give spikes when have food
- more injections, better control
split-mixed control
- fewer injections, poorer control
- insulin that lasts 12hrs and gives spikes
SC injection - gradually taken up into circulation
HbA1c aim
48mmol/mol
6.5%
hypoglycaemia
adrenaline sweating, tremor confusion coma warnings often get less as get older - nerve dysfct worse
what are chronic diabetic complications due to?
prolonged hyperglycaemia
chronic diabetic complications
CV risk - macrovascular disease
- atheroma, angina, MI, claudication, aneurysm
infection risk - microvascular disease
- poor wound healing
- impaired neutrophil phagocytosis
renal disease - microvascular
- atherosclerosis renal artery, glomeruli
eye disease
- cataracts
- maculopathy
- diabetic proliferative retinopathy
neuropathy - microvascular
- general sensation - hands and feet, ischaemia to
nerves, pain and numbness
- motor - weakness and wasting of muscles
- autonomic regulation - awareness of hypoglycaemia
lost, postural reflexes, bladder and bowel dysfct
what causes the microvascular disease?
don’t know
something to do with toxicity to endothelial cells
diabetes care in surgery
fasting problem in T1
higher risks of complications - heart attack and infection
metabolic changes
increased insulin requirement T1 (T2)
dental aspects of diabetes
food intake disruption
acute emergencies
complications
infection risk and poor wound healing
