CSIM endocrinology Flashcards
1
Q
where are ca sensing receptors?
what kind of receptor?
A
parathyroid cells and renal tubules
G-protein coupled receptor
2
Q
where are PTH receptors?
A
bone
renal tubule
duodenum (acts on vit. D absorption)
3
Q
cells responsible for re-sorption?
A
osteoclasts- create pits in the bone
4
Q
cells responsible for forming bone?
A
osteoblast
5
Q
3 components of bone?
A
inert mineral (hydroxyapatite) osteoid (type I collagen and chondroitin) cellular (osteoblasts, osteoclasts and osteocytes)
6
Q
symptoms of hypercalcaemia?
A
stone, bones, groans and moans
7
Q
causes of primary hypercalcaemia?
A
85% benign solitary parathyroid adenoma
8
Q
why OP in hyperparathyroidism?
A
PTH is pulling calcium from the bone and you wee it out
9
Q
eye complication of primary hyperparathyroidism
A
corneal calcification
10
Q
Mx of primary hyperparathyroidism?
A
conservative- if asymptomatic
calcimimetic drugs- calcium receptor agonists e.g. cinacalcet
surgical neck exploration if there are complications
11
Q
most common cause of malignant hypercalcaemia
A
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)
12
Q
Tx for severe hypercalcaemia?
A
treat dehydration
IV bisphosphonates
13
Q
most common cause of hypocalaemia
A
vit. D deficency
14
Q
symptoms of hypocalc?
A
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)
15
Q
e.g. of congenital parathyroid absence?
A
DiGeorge syndrome
16
Q
biochem of hypoparathryroidism?
A
high phosphate (PTH is involved in the renal clearance of phosphate)
low calcaemium
low/ undetectable parathroid
17
Q
3 most common breaks in OP?
A
NoF
wrist
vertebral collapse
18
Q
define fragility fracture
A
fracture from a fall from standing or less
19
Q
two way sof defining OP?
A
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
20
Q
what is osteomalacia and what is the boichem?
A
low serum vit D
high PHT
high ALP
low Ca and phosphate
reduced mineral component to bone
21
Q
risk factors for fragility fracs?
A
smoking alcohol
low weight, tall
steroids
menopause
22
Q
drug tx for OP
A
bisphosphonates
denosumab (anti-resorbative like bisphos.)
PTH injections
23
Q
risk assessment tool for OP?
A
FRAX
24
Q
how do children present with osteomalacia?
A
knock knees and bow legs when they start to walk is the most common
25
symptoms of osteomalacia and rickets?
weakness, myalgia, bone pain, tetany
| in Rickets: bowing of the legs/ knock kees, craniotabes
26
x ray appearence of osteomalacia
Cupped epiphyses
Loosers zones- looks expanded
Rachitic rosary
27
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
28
hypothyroidism presentation
```
weight gain
muscle fatigue
cold intollerance
tired
change in bowel habit
```
29
hypothyroidism TFTs?
low fT4
| high TSH
30
clinical signs of hypothyroidism
```
mentally slow
proximal myopathy
bradycardia
dry skin
slow reflexes
```
31
presentation of hyperthyroidism
weight loss
tremor
heat intolerance
altered bowel habit
32
4 causes and most common cause of thyrotoxicosis?
GRAVES DISEASE (get extra-thyroid manifestations)
single toxic nodule
toxic multi nodular goitre
thyroiditis
33
TFTs in primary thyrotoxicosis?
high fT4
| low TSH
34
biochem of primary hyperparathyroidism
low phosphate
| high calcium
35
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
36
clinical features of primary adrenal failure including biochem?
```
addisons:
weight loss
pigmentation (ACTH increases melanocyte activity)
fatigue
malaise
postural hypotension
hyponatraemia and hyperkalaemia
```
37
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%
38
presentation of cushings
```
weight gain (central obesity, moon face)
proximal myopathy
hirsutism / acne
depression
thin skin / bruising
hypertension
OP
metabolic disturbance e.g. DM
```
39
how can cushings cause DM?
increase steroids leads to increase gluconeogenisis
40
4 causes of cushings ?
iatrogenic
ectopic (pancreas, small cell lung cancer)
pituitary tumour (cushings disease)
adrenal adenoma / carcinoma
41
what is Conns syndrome and what are the clinical features?
primary hyperaldosteronism
hypertension
hypOkalaemia
alkalosis ( increased activity of the H+ / Na+ pump )
42
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)
43
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.
44
why is there increased BP in cushings?
steroids acting on the aldosterone receptor making the kidneys retain Na and therefore water
45
what is alendromic acid used for?
OP
| it is a type of bisphosphonate
46
what is SIADH
syndrome of inappropriate ADH (vasopressin) secretion
| ADH draws in water without the solute so it is a cause of hyponaturaemia
47
how can PPIs cause electrolyte disturbance?
decrease magnesium
48
how does addisons cause hypovolaemia?
decreased mineralocorticoids ??
49
biochem definition of hyponatraemia?
<135mmol/L
50
symptoms of hyponatraemia
```
none
headache
n and v
muscle cramps
lethergy
```
51
signs of hyponatraemia
disorientation
confusion
seizure
52
examples of pseudohyponatraemia
hyperglycaemia
hypertriglycerideamia
these must be excluded first!!!!
53
what can cause sodium depletion?
diuretics
hypoadrenalism
nephropathy
loss through gut
54
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
55
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
56
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
57
where is ferritin stored?
liver
reticular endothelial system
bone marrow
58
how is iron involved in energy production?
oxidative phosphorylation in cytochromes
| Krebs cycle enzyme
59
how is iron involved in liver metabolism?
CYP450
60
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
61
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
62
3 ways our bodies can keep iron in haemolytic disease
1. haemoglobin binds to hepatoglobins to be reabsorbed by the liver
2. haem binds to haemopexin to be reabsorbed by the liver
3. haem is reabsorbed by the kidney
63
what is ferritin?
intracellular storage protein found mostly in the liver
64
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
65
how is iron transported?
rbc (but this is non-exchangable)
| transferrin- made in the liver
66
effect of increased iron on transferrin production?
decreased
| increased in deficiency
67
why is serum iron test not that useful? when is it useful?
most iron in stored in ferritin and transferrin
| useful in poisoning
68
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
69
95% of genetic haemochromotosis is caused by a defect in which gene?
HFE
70
pathophys of haemochromotosis?
decreased HFE-> decreased hepcidin -> increased duodenal iron absorption
71
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
72
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
```
73
5 ways of measuring iron overload?
```
transferrin
ferritin
MRI
liver biopsy
GENETIC TEST FOR HFE
```
74
Tx for haemochromotosis?
venesection- to deplete iron stores takes years
75
what is it that changes the colour of the skin in haemochromotosis?
bronze look
haemosiderin deposition
this has the effect of increasing melanocytes too
76
what conditions need to be excluded in any iron deficiency?
colon and gastric cancer
| coeliac
77
which hormones are released from the ant. pituitary?
```
Prolactin
ACTH
TSH
LH / FSH
Growth hormone
```
78
which hormones are released formt eh post. pituitary and what are their target organs?
oxytocin- brain, breast and uterus
| ADH- renal tubules
79
what is the most common cause of central hormone excess?
functioning benign pituitary adenoma
| ectopic is rare
80
what are the common mass effects of a benign pituitary adenoma?
nausea
headaches
bitemporal hemianopia
81
what effect does a pituitary adenoma have on hormone levels?
increase or decrease them
82
what is pituitary apoplexy and what are the symptoms?
infarction / haemorrhage of the pituitary
Acute Headache
Collapse
Visual loss, ophthalmoplegia
Death :(
83
in secondary hypoadrenalism what is deficient?
ACTH deficiency - > glucocorticoid deficiency
84
electrolyte disturbance in glucocorticoid deficiency?
low sodium, high potassium (also acidotic)
85
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
86
presentation of adrenal crisis? when?
circulatory collapse
missed medication
stress (illness etc.)
87
signs of adrenal crisis?
dehydration
postural drop
decreased GCS
88
Tx for adrenal crisis?
LIFE SAVING HYDROCORTISONE 100mg IM
| fluids
89
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
90
Mx for cushings disease if surgical resection of pituitary fails?
Steroidogenesis inhibitors- Metyrapone
| Bilateral adrenalectomy and pituitary radiotherapy
91
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 )
92
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)
93
hormone levels in primary gonadal failure?
low sex hormones
| high LH and FSH
94
2 examples of congenital gonadal failure?
Kleinfelters 47 XXY
| Turnes 45X
95
what two things increase prolactin levels?
oestrogen
| TRH from the hypothalamus (thyrotropin releasing hormone)
96
three physiological reasons for raised prolactin
stress
sex
pregnancy
97
three presenting features of hyperprolactinaemia in women
1. galactorrohoea v. common
2. infertility
- direct inhibition of gonadatropins
- inhibition of GnRH
3. menstrual inrregularity
98
features of hyperprolactinaemia in men
1. Galactorrhoea (uncommon)
2. Erectile dysfunction
3. Visual field defects
4. Headaches
5. Osteopenia / osteoporosis
99
Mx of hyperprolactinaemia
medical only: dopamine agonists
100
which hormones increase and decrease growth hormone?
increase: GHRH
decrease: insulin- like growth factor - 1 (ILF-1) and somatostatin
101
diagnosis of acromegaly
1. glucose tolerance test: GH should decrease with an oral glucose load
2. elevated ILF-1
3. often can see macroademomas on MRI
102
tx for acromegaly?
transsphenoidal surgery
| if failed: somatostatin analogues and pituitary radiotherapy
103
tx for diabetes insipidus?
desmopressin
104
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)
105
most common type of genetic error to cause MODY?
gulcokinase: roughly 1/3
causes an increased threshold for glucose stimulated insulin release
106
what does glucokinase do?
controls the secretion of insulin from beta- cells by phosphorylation of glucose
107
normal mx for glucokinase MODY?
conservative - dont tend to see microvasc. complications so dont use pharmacological intervention
108
presentation of glucokinase MODY?
normally incidental high fasting glucose
| asymptomatic
109
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
110
clinical presentation of transcription factor MODY?
presents around 20 -30
often diagnosed as type I
do get complications
autosomal dominant so strong family history
111
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
112
what extra pancreatic feature is present in HNF- 1 beta?
renal cysts
113
presentation of neonatal diabetes?
high glucose or DKA in first 6 months (RARE)
114
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
```
115
clinical features of insulin resistance?
high glucose with increasing doses of insulin
PCOS
Acanthosis nigricans - skin pigmentation
116
two genetic reasons for insulin resistance?
```
lipodystrophy syndrome (fat all stored high up- legs like Alan Sheerer)
insulin receptor defects
```
117
why do HIV patients get DM?
HAART
118
which systems does hypokalaemia effect?
kidney(directly nephrotoxic)
heart
endocrine (growth problems)
neuromuscular
119
clinical features of hyperkalaemia?
abnormal ecg
paraesthesia / weakness
increased insulin secretion
120
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
121
96% of K is where?
in the cells- mostly in the MUSCLE, liver and RBC
122
how do we get rid of K?
KIDNEYS and small intestine
123
alkalosis has what effect on K?
moves K into cells
| exchanged for H+
124
insulin has what effect on K?
drives it into cells
125
what 3 things drive K into the extra-cellular space?
```
alpha- adrenergic agonists
intense exercise (muscle damage)
acidosis
```
126
where in the kidney is most of the K absorbed?
PCT under passive reabsorption
127
which two substances cause K secretion into the distal tubule if in high concentrations?
potassium
aldosterone
also when alkalotic
128
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
```
