disorders of calcium homeostasis part 1 W2

Question 1

clinical manifestations of hypercalcaemia - phrase to remember?

Answer 1

‘stones, bones, abdominal moans and psychic groans’

Question 2

hypercalcaemia clinical manifestations - general?

Answer 2

muscle weakness
central effects
renal effects
bone involvement
abdominal pain
ECG changes

Question 3

features of muscle weakness in hypercalcaemia?

Answer 3

striated and smooth muscle weakness
possible competition between calcium and sodium ions into cells

Question 4

central effects in hypercalcaemia?

Answer 4

anorexia
nausea
mood change
depression

Question 5

renal effects of hypercalcaemia?

Answer 5

impaired water concentration
renal stone formation

Question 6

features of bone involvement in hypercalcaemia?

Answer 6

depends on underlying cause and severity of hypercalcaemia

Question 7

what feature of the ECG changes in hypercalcaemia?

Answer 7

shortened QT interval

Question 8

what can factitious hypercalcaemia (non-pathological) be due to?

Answer 8

raised calcium due to high plasma (albumin) due to eg:
-venous stasis
-dehydration
-IV albumin

Question 9

primary hyperparathyroidism epidemiology

Answer 9

affects women:men in 3:2 ratio
age 50

Question 10

primary hyperparathyroidism - what is this caused by? what types?

Answer 10

caused by growth in parathyroid gland
90% solitary adenoma
also due to hyperplasia or rarely a carcinoma

Question 11

primary hyperparathyroidism?

Answer 11

autonomous and inappropriate overproduction of PTH leading to hypercalcaemia

Question 12

secondary hyperparathyroidism?

Answer 12

appropriate increase of PTH in response to hypocalcaemia

Question 13

tertiary hyperparathyroidism?

Answer 13

rare. when secondary overactive gland becomes so overactive it is completely autonomous even in absence of hypocalcaemia

Question 14

histology of primary hyperparathyroidism?

Answer 14

cell types more similar and homogenous

Question 15

radiology of hyperparathyroidism?

Answer 15

osteopenia - PTH activates osteoclasts, leading to increased bone resorption. loss of normal bone structure, weakness.
white dots in abdomen - renal stones

Question 16

diagnosis of primary hyperparathyroidism?

Answer 16

raised calcium with inappropriately increased PTH
phosphate and bicarbonate tend to be low in serum (increased renal excretion)
alkaline phosphatase normal or moderately increased in more severe disease
further investigations - parathyroid imaging scan

Question 17

treatment of primary hyperparathyroidism?

Answer 17

acutely - rehydration, drugs
surgical removal of pituitary adenoma
mild cases - repeat follow-up of serum calcium/PTH
if surgery is difficult - drugs to lower calcium levels

Question 18

drugs to treat hypercalcaemia?

Answer 18

bisphosphonates - inhibit osteoclasts (after rehydration)

furosemide - inhibits Ca reabsorption (after rehydration)
calcitonin - inhibits osteoclasts (short term management)
glucocorticoids - inhibit vit D -> calcitriol (can prolong calcitonin action)

Question 19

why does cancer often cause hypercalcaemia?

Answer 19

endocrine factors secreted by malignant cells acting on bone
metastatic tumour deposits in bone locally stimulating bone resorption via osteoclast activation

Question 20

which malignancies more likely to cause hypercalcaemia?

Answer 20

lung 35%
breast 25%

Question 21

endocrine factors in malignant hypercalcaemia?

Answer 21

PTHrP (PTH-related peptide)
secreted from solid tumours
similar structure to PTH and shares similar actions

Question 22

name for when PTHrP is responsible for hypercalcaemia?

Answer 22

humoral hypercalcaemia of malignancy

Question 23

features of malignant hypercalcaemia associated with bony metastases?

Answer 23

secretion of osteoclast activating cytokines or other factors into the bone micro-environment

Question 24

multiple myeloma and hypercalcaemia of malignancy?

Answer 24

cancer of plasma cells (normally produce antibodies). excess production of plasma cells which produce single clone of an antibody or immunoglobulin called a monoclonal protein. also produce cytokines that lead to hypercalcaemia of malignancy. diagnosis involves bone marrow biopsy.

Question 25

pepperpot skull?

Answer 25

well defined lesions due to local bone absorption due to presence of cancer.

Question 26

diagnosis of malignancy? biochemistry

Answer 26

raised Ca with suppressed PTH
phosphate tends to be high
alkaline phosphatase may be very high (liver/bone metastases)
often clear from previous history of malignant disease

Question 27

principals of treatment of malignant hypercalcaemia?

Answer 27

rehydrate the patient
if required, use drugs which lower serum calcium (bisphosphonate)
treat underlying malignancy (surgery/chemo)

Question 28

‘other’ causes of hypercalcaemia?

Answer 28

granulomatous disease
exogenous vit D excess
familial hypocalciuric hypercalcaemia
drugs
some endocrine diseases
immobilization

Question 29

drugs which cause hypercalcaemia?

Answer 29

Li, thiazide diuretics

Question 30

what is sarcoidosis? how does it cause hypercalcaemia?

Answer 30

granulomatous disease - causes granulomas (full of macrophages - also found in eg TB)
raised calcium, normal PTH
granulomas hydroxylase vit D (which drives high calcium)

Question 31

familial hypocalciuric hypercalcaemia (FHH)?

Answer 31

rare
reduced sensitivity of calcium sensing receptors in parathyroid glands. altered set point for PTH/Ca interaction.
PTH normal/slightly raised
plasma ionised calcium increased
urine calcium excretion low