Physiology of Hypercalcaemia

Question 1

• What is the major target of calcitonin?

Answer 1

Bone where it inhibits osteoclastic bone resorption

Question 2

• What is PTHrp?

Answer 2

PTH related protein – identical biological activity as PTH, produced by cartilage, bone, muscle, epithelium, CNS & specific tumours

Question 3

• What are the mechanisms of hypercalcaemia?

Answer 3

Increased PTH, production of PTHrp, increased vitamin D3, decreased urinary excretion of Ca

Question 4

• What levels could be measured to diagnose hypercalcaemia?

Answer 4

Total Ca, ionised Ca, PTH assay, PTHrp assay

Question 5

• What are the possible differential diagnoses?

Answer 5

PTH – primary or secondary (renal) hyperparathyroidism
PTHrp – humoral hypercalcaemia of malignancy or tumour
Vitamin D – vitamin D toxicosis
Renal – reduced calcium excretion
Other – hypoadrenocorticism or idiopathic hypercalcaemia

Question 6

• What is one of the most important effects of hypercalcaemia?

Answer 6

Inhibition of ADH, leads to an inability to concentrate urine

Question 7

• If primary hyperparathyroidism is the cause, what laboratory abnormalities will be seen?

Answer 7

Hypercalcaemia, hypophosphataemia (may be normal), PTHrp decreased to zero, normal or increased PTH – diagnose by simultaneous iCa2+ and PTH concentrations & ultrasound neck for enlarged parathyroid gland

Question 8

• What is secondary renal hyperparathyroidism a consequence of?

Answer 8

Chronic renal failure, impaired GFR

Question 9

• Why is fibrous osteodystrophia (rubber jaw) a result of secondary hyperparathyroidism?

Answer 9

Increased fast and slow retrieval of Ca from bone, excessive amounts of fibrous tissue laid down in an attempt to consolidate the weakened lamellar bone

Question 10

• What laboratory abnormalities will be seen with secondary hyperparathyroidism?

Answer 10

Hyperphosphataemia, hypercalcaemia, PTH normal to increased, low vitamin D3, normal PTHrp

Question 11

• What laboratory abnormalities will be seen if PTHrp is causing hypercalcaemia?

Answer 11

Hypercalcaemia, hypophosphataemia, elevated PTHrp, normal or low PTH

Question 12

• How does vitamin D toxicity affect calcium and phosphorus?

Answer 12

Increased calcium and phosphorus absorption from the kidneys, decreased calcium and phosphorus excretion by the kidneys

Question 13

• What causes soft tissue mineralization?

Answer 13

Increased Ca x P product