Calcium Part II

Question 1

List some symptoms of hypercalcaemia.

Answer 1

• Polyuria/polydipsia
• Bone pain
• Renal stones (flank pain, haematuria)
• Constipation
• Confusion, seizures, coma → NOTE: these tend to occur when calcium level >3 mmol/L

Bones, stones, abdominal groans, psychiatric moans

Question 2

What are the main causes of primary hyperparathyroidism?

Answer 2

• Parathyroid adenoma
• Parathyroid hyperplasia (associated with MEN1)
• Parathyroid carcinoma

Question 3

Outline the serum biochemistry features of primary hyperparathyroidism.

Answer 3

• High calcium
• Inappropriately raised PTH (could be within normal range but this is still inappropriate in hypercalcaemia)
• Low phosphate (phosphate trashing hormone)

Question 4

Outline the pathophysiology of familial benign hypercalcaemia.

Answer 4

A mutation in the calcium-sensing receptor (CaSR) leads to a reduced sensitivity for Ca, thereby maintaing PTH release (leads to mild hypercalcaemia)

Question 5

Why don’t patients with familial benign hypercalcaemia get kidney stones?

Answer 5

Mutated CaSR in kidney also increases renal calcium absorption, thereby reducing urine calcium

Familial hypocalcuric hypercalcaemia

Question 6

What are the three types of hypercalcaemia of malignancy?

Answer 6

• Humoral hypercalcaemia of malignancy (e.g. small cell lung cancer) → high calcium caused by PTHrP release
• Bone metastases (e.g. breast cancer) → high calcium caused by local bone osteolysis
• Haematological malignancy (e.g. myeloma) → high calcium caused by cytokines

Question 7

List some other non-PTH driven causes of hypercalcaemia.

Answer 7

• Sarcoidosis (sarcoid tissue expresses 1 alpha hydroxylase)
• Thyrotoxicosis (increases bone resorption)
• Hypoadrenalism (reduced renal Ca²⁺ transport)
• Thiazide diuretics (reduced renal Ca²⁺ transport)
• Excess vitamin D (e.g. sun beds)

Question 8

Outline the management of hypercalcaemia.

Answer 8

• Fluids, fluid and more fluids! (0.9% normal saline, 1L over 1 hour)
• Bisphosphonates but only if there is cancer (stops cancer from eating bone)
• Treat the underlying cause.

Question 9

List some symptoms and signs of hypocalcaemia

Answer 9

• Neuromuscular excitability (Chvostek’s sign, Trousseau’s sign) - seizures, muscle spasms and cramping
• Stridor (due to laryngeal spasm)

Question 10

Recall some differentials for hypocalcaemia when the PTH is high

Answer 10

This is an appropriate response to low calcium - SECONDARY HYPERPARATHYROIDISM

Could be due to:

1. Vit D deficiency (most common cause)
2. CKD (as low renal alpha-1-hydroxylase)
3. Pseudohypoparathyroidism (gene deficit –> PTH resistance)

Question 11

Recall some differentials for hypocalcaemia when the PTH is low

Answer 11

This is an inappropriate response (low calcium should cause high PTH)

Could be due to:

1. Surgical mishap during thyroidectomy
2. Autoimmune hypoparathyroidism (rare)
3. Di George syndrome (even rarer! Agenesis of parathyroids)
4. Magnesium deficiency - can be caused by OMEPRAZOLE