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Flashcards in CSIM endocrinology Deck (128):
1

where are ca sensing receptors?
what kind of receptor?

parathyroid cells and renal tubules

G-protein coupled receptor

2

where are PTH receptors?

bone
renal tubule
duodenum (acts on vit. D absorption)

3

cells responsible for re-sorption?

osteoclasts- create pits in the bone

4

cells responsible for forming bone?

osteoblast

5

3 components of bone?

inert mineral (hydroxyapatite)
osteoid (type I collagen and chondroitin)
cellular (osteoblasts, osteoclasts and osteocytes)

6

symptoms of hypercalcaemia?

stone, bones, groans and moans

7

causes of primary hypercalcaemia?

85% benign solitary parathyroid adenoma

8

why OP in hyperparathyroidism?

PTH is pulling calcium from the bone and you wee it out

9

eye complication of primary hyperparathyroidism

corneal calcification

10

Mx of primary hyperparathyroidism?

conservative- if asymptomatic
calcimimetic drugs- calcium receptor agonists e.g. cinacalcet
surgical neck exploration if there are complications

11

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)

12

Tx for severe hypercalcaemia?

treat dehydration
IV bisphosphonates

13

most common cause of hypocalaemia

vit. D deficency

14

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)

15

e.g. of congenital parathyroid absence?

DiGeorge syndrome

16

biochem of hypoparathryroidism?

high phosphate (PTH is involved in the renal clearance of phosphate)
low calcaemium
low/ undetectable parathroid

17

3 most common breaks in OP?

NoF
wrist
vertebral collapse

18

define fragility fracture

fracture from a fall from standing or less

19

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

20

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

21

risk factors for fragility fracs?

smoking alcohol
low weight, tall
steroids
menopause

22

drug tx for OP

bisphosphonates
denosumab (anti-resorbative like bisphos.)
PTH injections

23

risk assessment tool for OP?

FRAX

24

how do children present with osteomalacia?

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