CSIM endocrinology Flashcards
where are ca sensing receptors?
what kind of receptor?
parathyroid cells and renal tubules
G-protein coupled receptor
where are PTH receptors?
bone
renal tubule
duodenum (acts on vit. D absorption)
cells responsible for re-sorption?
osteoclasts- create pits in the bone
cells responsible for forming bone?
osteoblast
3 components of bone?
inert mineral (hydroxyapatite) osteoid (type I collagen and chondroitin) cellular (osteoblasts, osteoclasts and osteocytes)
symptoms of hypercalcaemia?
stone, bones, groans and moans
causes of primary hypercalcaemia?
85% benign solitary parathyroid adenoma
why OP in hyperparathyroidism?
PTH is pulling calcium from the bone and you wee it out
eye complication of primary hyperparathyroidism
corneal calcification
Mx of primary hyperparathyroidism?
conservative- if asymptomatic
calcimimetic drugs- calcium receptor agonists e.g. cinacalcet
surgical neck exploration if there are complications
most common cause of malignant hypercalcaemia
humoral hypercalcaemia of malignancy- PTHrP (80%)
this is a squamous cell carcinoma mostly in the breast or head / neck that releases PTH releasing protein
will see suppressed PTH
not at risk of pathological fracture
(other 20% is boney erosion)
Tx for severe hypercalcaemia?
treat dehydration
IV bisphosphonates
most common cause of hypocalaemia
vit. D deficency
symptoms of hypocalc?
leg cramps and twitching paraesthesia of mouth and fungers stridor caropedal spasm SEIZURES when very low
(Chvostek’s Sign- tap paraotid gland to look for muscle excitation)
e.g. of congenital parathyroid absence?
DiGeorge syndrome
biochem of hypoparathryroidism?
high phosphate (PTH is involved in the renal clearance of phosphate)
low calcaemium
low/ undetectable parathroid
3 most common breaks in OP?
NoF
wrist
vertebral collapse
define fragility fracture
fracture from a fall from standing or less
two way sof defining OP?
clinically- presence of a low impact fracture
radiographically- presence of low bone mineral density
the composition of bone is the same as normal bone but there is less of it (more holes) and this is filled by marrow
what is osteomalacia and what is the boichem?
low serum vit D
high PHT
high ALP
low Ca and phosphate
reduced mineral component to bone
risk factors for fragility fracs?
smoking alcohol
low weight, tall
steroids
menopause
drug tx for OP
bisphosphonates
denosumab (anti-resorbative like bisphos.)
PTH injections
risk assessment tool for OP?
FRAX
how do children present with osteomalacia?
knock knees and bow legs when they start to walk is the most common
symptoms of osteomalacia and rickets?
weakness, myalgia, bone pain, tetany
in Rickets: bowing of the legs/ knock kees, craniotabes
x ray appearence of osteomalacia
Cupped epiphyses
Loosers zones- looks expanded
Rachitic rosary
where are there PTH receptors and what is the action of each site?
gut- to absorb more vit. D
renal tubule- to block resorption of phosphate and increase Ca resorption
bone- to increase osteoclast activity and decrease osteoblast activity thereby INCREASING serum Ca
hypothyroidism presentation
weight gain muscle fatigue cold intollerance tired change in bowel habit
hypothyroidism TFTs?
low fT4
high TSH
clinical signs of hypothyroidism
mentally slow proximal myopathy bradycardia dry skin slow reflexes
presentation of hyperthyroidism
weight loss
tremor
heat intolerance
altered bowel habit
4 causes and most common cause of thyrotoxicosis?
GRAVES DISEASE (get extra-thyroid manifestations)
single toxic nodule
toxic multi nodular goitre
thyroiditis
TFTs in primary thyrotoxicosis?
high fT4
low TSH
biochem of primary hyperparathyroidism
low phosphate
high calcium
biochem of osteomalacia / rickets?
low calcium leads to…
low phosphate as your kidneys excrete it in an attempt to retain Ca
high PTH due to low calcium
clinical features of primary adrenal failure including biochem?
addisons: weight loss pigmentation (ACTH increases melanocyte activity) fatigue malaise postural hypotension hyponatraemia and hyperkalaemia
how is addisons diagnosed?
sub-optimal plasma cortisol response to synactin (ACTH)
in normal people the baseline cortisol will double
in addisons a low baseline will rise no more than 25%
presentation of cushings
weight gain (central obesity, moon face) proximal myopathy hirsutism / acne depression thin skin / bruising hypertension OP metabolic disturbance e.g. DM
how can cushings cause DM?
increase steroids leads to increase gluconeogenisis
4 causes of cushings ?
iatrogenic
ectopic (pancreas, small cell lung cancer)
pituitary tumour (cushings disease)
adrenal adenoma / carcinoma
what is Conns syndrome and what are the clinical features?
primary hyperaldosteronism
hypertension
hypOkalaemia
alkalosis ( increased activity of the H+ / Na+ pump )
how is cushings confirmed?
dexamethosome suppression test
if no change in cortisol on low dose or high dose- cushings syndrome
if no change on low dose but change on high dose- cushings disease
(a normal result is an increase in cortisol on a low dose)
what must always be given when giving K and why?
glucose to prevent hypos
an increase in K will stimulate insulin release to try to drive the K into the cells.
why is there increased BP in cushings?
steroids acting on the aldosterone receptor making the kidneys retain Na and therefore water
what is alendromic acid used for?
OP
it is a type of bisphosphonate
what is SIADH
syndrome of inappropriate ADH (vasopressin) secretion
ADH draws in water without the solute so it is a cause of hyponaturaemia
how can PPIs cause electrolyte disturbance?
decrease magnesium
how does addisons cause hypovolaemia?
decreased mineralocorticoids ??
biochem definition of hyponatraemia?
<135mmol/L
symptoms of hyponatraemia
none headache n and v muscle cramps lethergy
signs of hyponatraemia
disorientation
confusion
seizure
examples of pseudohyponatraemia
hyperglycaemia
hypertriglycerideamia
these must be excluded first!!!!
what can cause sodium depletion?
diuretics
hypoadrenalism
nephropathy
loss through gut
if we cant measure ADH, how do we diagnose SIADH?
hyponatraemia
concentrated urine vol. of na
high urine osmol
absence of cofounders:
hypotension
oedema
adrenal failure
how does the body adapt to hyponatraemia to prevent cerebral oedema?
water will go into brain and make it swell
rapid adaptation: inorganic osmolyte loss to reduce water
slow adaptation: organic osmolyte loss
Tx for severe and not severe symptoms of hyponatraemia
severe: immediate hypertonic saline
not severe: do urine osmolality and if high then give hypertonic saline
where is ferritin stored?
liver
reticular endothelial system
bone marrow
how is iron involved in energy production?
oxidative phosphorylation in cytochromes
Krebs cycle enzyme
how is iron involved in liver metabolism?
CYP450
how is iron excreted?
desquamation (scraping off- from the latin word which means scraping scales off fish) of GI tract enterocytes
a small amount from menstrual loss
roughly 1-2 mg/day
which hormone is the key regulator of iron? where is it made?
hepcidin- when released it stops iron leaving the enterocyte so is lost through desquamation
hepatocytes
3 ways our bodies can keep iron in haemolytic disease
- haemoglobin binds to hepatoglobins to be reabsorbed by the liver
- haem binds to haemopexin to be reabsorbed by the liver
- haem is reabsorbed by the kidney
what is ferritin?
intracellular storage protein found mostly in the liver
when will ferritin be high?
IRON EXCESS is most obvious but also... acute phase response in inflammation tissue release high BMI post menopause
a low ferritin always means iron deficiency but normal ferritin doesn’t rule it out due to these other causes
how is iron transported?
rbc (but this is non-exchangable)
transferrin- made in the liver
effect of increased iron on transferrin production?
decreased
increased in deficiency
why is serum iron test not that useful? when is it useful?
most iron in stored in ferritin and transferrin
useful in poisoning
what test is done to determine a persons iron stores?
transferrin saturation: % of transferrin binding sites that are filled with iron.
in iron overload the amount of transferrin goes DOWN so the saturation goes UP e.g. in haemochromotosis
95% of genetic haemochromotosis is caused by a defect in which gene?
HFE
pathophys of haemochromotosis?
decreased HFE-> decreased hepcidin -> increased duodenal iron absorption
why is the penetrance of genetic haemochromotosis lower in women?
they are loosing a bit of iron though menstruation
penetrance is low in general though
which cells are most vulnerable to iron overload from haemochromotosis?
the ones with the most iron channels: pancreatic beta cells - diabetes M hepatocytes - liver disease (they become fibrotic) articular surfaces - arthritis cardiac muscle- cardiomyopathy pituitary gonadotrophs - hypogonadism
5 ways of measuring iron overload?
transferrin ferritin MRI liver biopsy GENETIC TEST FOR HFE
Tx for haemochromotosis?
venesection- to deplete iron stores takes years
what is it that changes the colour of the skin in haemochromotosis?
bronze look
haemosiderin deposition
this has the effect of increasing melanocytes too
what conditions need to be excluded in any iron deficiency?
colon and gastric cancer
coeliac
which hormones are released from the ant. pituitary?
Prolactin ACTH TSH LH / FSH Growth hormone
which hormones are released formt eh post. pituitary and what are their target organs?
oxytocin- brain, breast and uterus
ADH- renal tubules
what is the most common cause of central hormone excess?
functioning benign pituitary adenoma
ectopic is rare
what are the common mass effects of a benign pituitary adenoma?
nausea
headaches
bitemporal hemianopia
what effect does a pituitary adenoma have on hormone levels?
increase or decrease them
what is pituitary apoplexy and what are the symptoms?
infarction / haemorrhage of the pituitary
Acute Headache
Collapse
Visual loss, ophthalmoplegia
Death :(
in secondary hypoadrenalism what is deficient?
ACTH deficiency - > glucocorticoid deficiency
electrolyte disturbance in glucocorticoid deficiency?
low sodium, high potassium (also acidotic)
clinically what is the difference between primary and secondary adrenal insufficiency?
Tx?
primary
- get skin pigmentation (increased ACTH)
- get salt cravings due to mineralocorticoid deficiency
primary have to replace both corticoids with hydrocortisone and fludrocortisone
secondary only hydrocortisone
presentation of adrenal crisis? when?
circulatory collapse
missed medication
stress (illness etc.)
signs of adrenal crisis?
dehydration
postural drop
decreased GCS
Tx for adrenal crisis?
LIFE SAVING HYDROCORTISONE 100mg IM
fluids
3 causes of cushings syndrome and their hormone levels?
ACTH cortisol
ectopic secreting tumour very high high
adrenal adenoma very low high
drugs very low variable
Mx for cushings disease if surgical resection of pituitary fails?
Steroidogenesis inhibitors- Metyrapone
Bilateral adrenalectomy and pituitary radiotherapy
TFTs in primary and secondary hypOthyroidism
primary - low fT3/ fT4 and high TSH
secondary - low fT3 / fT4 and low or inappropriately normal TSH
(fT3 can be normal in both )
Tx for hypothyroidism is levothyroxine in both primary and secondary but what is used to guide the mx
primary- get TSH in middle of reference range
secondary- cant use TSH so use fT4 (upper end of normal)
hormone levels in primary gonadal failure?
low sex hormones
high LH and FSH
2 examples of congenital gonadal failure?
Kleinfelters 47 XXY
Turnes 45X
what two things increase prolactin levels?
oestrogen
TRH from the hypothalamus (thyrotropin releasing hormone)
three physiological reasons for raised prolactin
stress
sex
pregnancy
three presenting features of hyperprolactinaemia in women
- galactorrohoea v. common
- infertility
- direct inhibition of gonadatropins
- inhibition of GnRH - menstrual inrregularity
features of hyperprolactinaemia in men
- Galactorrhoea (uncommon)
- Erectile dysfunction
- Visual field defects
- Headaches
- Osteopenia / osteoporosis
Mx of hyperprolactinaemia
medical only: dopamine agonists
which hormones increase and decrease growth hormone?
increase: GHRH
decrease: insulin- like growth factor - 1 (ILF-1) and somatostatin
diagnosis of acromegaly
- glucose tolerance test: GH should decrease with an oral glucose load
- elevated ILF-1
- often can see macroademomas on MRI
tx for acromegaly?
transsphenoidal surgery
if failed: somatostatin analogues and pituitary radiotherapy
tx for diabetes insipidus?
desmopressin
what clinical things would make you think of maturity onset diabetes of the young (MODY ) rather than the normal DM?
if you think type I - still have endogenous insulin secretion 3 yrs after diagnosis
if you think type II - absence of metabolic syndrome (fit, healthy)
most common type of genetic error to cause MODY?
gulcokinase: roughly 1/3
causes an increased threshold for glucose stimulated insulin release
what does glucokinase do?
controls the secretion of insulin from beta- cells by phosphorylation of glucose
normal mx for glucokinase MODY?
conservative - dont tend to see microvasc. complications so dont use pharmacological intervention
presentation of glucokinase MODY?
normally incidental high fasting glucose
asymptomatic
which are the 3 key genes involved in beta cell development and transcription factor MODY?
HNF- 1 alpha (MOST COMMON)
HNF- 1 beta
HNF- 4 alpha
clinical presentation of transcription factor MODY?
presents around 20 -30
often diagnosed as type I
do get complications
autosomal dominant so strong family history
which drug to use in transcription factor MODY?
sulphonylurea to stimulate insulin production (very sensitive to this)
dont need insulin
APART FROM HNF-1 beta which DOES
what extra pancreatic feature is present in HNF- 1 beta?
renal cysts
presentation of neonatal diabetes?
high glucose or DKA in first 6 months (RARE)
which syndromes can cause diabetes?
Downs - auto-immune Prada- Willi's - due to food cravings Turners - auto-immune Wolfram (DIDMOAD = diabetes insipidus, diabetes mellitis, optic atrophy and deafness) Kleinfelters - insulin resistance Myotonic dystrophy - insulin resistance
clinical features of insulin resistance?
high glucose with increasing doses of insulin
PCOS
Acanthosis nigricans - skin pigmentation
two genetic reasons for insulin resistance?
lipodystrophy syndrome (fat all stored high up- legs like Alan Sheerer) insulin receptor defects
why do HIV patients get DM?
HAART
which systems does hypokalaemia effect?
kidney(directly nephrotoxic)
heart
endocrine (growth problems)
neuromuscular
clinical features of hyperkalaemia?
abnormal ecg
paraesthesia / weakness
increased insulin secretion
ecg changes in hyper and hypokalaemia?
hyper - tenting of t wave then widening of the QRS
hypo - widening complex, prolonged QT and the formation of a U wave
96% of K is where?
in the cells- mostly in the MUSCLE, liver and RBC
how do we get rid of K?
KIDNEYS and small intestine
alkalosis has what effect on K?
moves K into cells
exchanged for H+
insulin has what effect on K?
drives it into cells
what 3 things drive K into the extra-cellular space?
alpha- adrenergic agonists intense exercise (muscle damage) acidosis
where in the kidney is most of the K absorbed?
PCT under passive reabsorption
which two substances cause K secretion into the distal tubule if in high concentrations?
potassium
aldosterone
also when alkalotic
5 things found on investigations in Conn’s syndrome? (primary hyperaldosteronism)
high Na low K alkalosis (aldosterone also acts on a na - h+ exchange) reduced urine output (hypertension) high urine aldosterone
