Calcium Dysregulation

Question 1

Hormones that increase calcium and phosphate

Answer 1

Vitamin D - Synthesised in skin or intake via diet

Parathyroid hormone (PTH) (secreted by parathyroid glands)

Main regulators of calcium & phosphate homeostasis via actions on kidney, bone and gut

Question 2

Hormones that decrease calcium and phosphate

Answer 2

Calcitonin (secreted by thyroid parafollicular cells)

Can reduce calcium acutely, but no negative effect if parafollicular cells are removed eg thyroidectomy

Question 3

Vitamin D metabolism

Answer 3

Serum 25-OH vitamin D = good indicator of body vitamin D status

1,25(OH)2 vitamin D (calcitriol) - active form of vitamin D - regulates its own synthesis by decreasing transcription of 1 alpha hydroxylase

Question 4

Vitamin D pathway in body

Answer 4

UVB
7-dehydrocholesterol
Pre vitamin D3
Vitamin D3 - hydroxylated by 25-hydroxylase from liver - 25(OH) vitamin D
Hydroxylated again by 1 alpha hydroxylase from kidney - calcitriol formed

OR

Vitamin D2 from diet that goes through same process as D3

Question 5

Effects of calcitriol

Answer 5

Increased osteoblast activity in bones

↑ Ca2+ and PO43- reabsorption in kidneys

Increased calcium and phosphate absorption in gut

Net increase in calcium and phosphate

Question 6

Actions of parathyroid hormone (PTH)

Answer 6

↑ Ca2 resorption from bone

↑ Ca2+ absorption and ↑ PO43- absorption in gut

↑ Ca2+ reabsorption ↑ PO43- excretion (inhibit sodium phosphate cotransporter) ↑ 1-a-hydroxylase activityin kidneys - stimulate calcitriol synthesis - stimulate gut

Increased calcium but normal phosphate

Question 7

FGF23

Answer 7

Regulate serum phosphate

Inhibit sodium phosphate cotransporter to stop phosphate reabsorption in kidney

Inhibit calcitriol formation

Question 8

Hypocalcaemia

Answer 8

Sensitises excitable tissues; muscle cramps, tetany, tingling

Signs & symptoms
Paraesthesia (hands, mouth, feet , lips)
Convulsions
Arrhythmias
Tetany

Mnemonic - [CATs go numb]

Chvosteks’ sign – facial paresthesia
Trousseau’s sign – carpopedal spasm

Question 9

Causes of hypocalcaemia

Answer 9

Low PTH levels = hypoparathyroidism
Surgical – neck surgery
Auto-immune
Magnesium deficiency
Congenital (agenesis, rare)

Low vitamin D levels
Deficiency – diet, UV light, malabsorption, impaired production (renal failure)

Question 10

Hypercalcaemia

Answer 10

‘Stones, abdominal moans and psychic groans’
Reduced neuronal excitability – atonal muscles

Stones – renal effects
Nephrocalcinosis – kidney stones, renal colic

Abdominal moans - GI effects
Anorexia, nausea, dyspepsia, constipation, pancreatitis

Psychic groans - CNS effects
Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)

Question 11

Causes of hypercalcaemia

Answer 11

Primary hyperparathyroidism
Too much PTH
Usually due to a parathyroid gland adenoma
No negative feedback - high PTH, but high calcium

Malignancy
Bony metastases produce local factors to activate osteoclasts
Certain cancers (eg squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors

Vitamin D excess (rare)

Question 12

Relationship between PTH and calcium

Answer 12

Increased PTH - decreased calcium

Decreased PTH - increased calcium

Question 13

Primary Hyperparathyroidism

Answer 13

Parathyroid adenoma producing too much PTH
Calcium increases, but no negative feedback to PTH due to autonomous PTH secretion from parathyroid adenoma

High calcium
Low phosphate – increased renal phosphate excretion (inhibition of Na+/PO43- transporter in kidney)
High PTH (not suppressed by hypercalcaemia)

Question 14

Treatment of primary hyperparathyroidism

Answer 14

Parathyroidectomy is treatment of choice for primary hyperparathyroidism

Untreated hyperparathyroidism has risks of
Osteoporosis
Renal calculi (stones)
Psychological impact of hypercalcaemia – mental function, mood

Question 15

Secondary hyperparathyroidism

Answer 15

Secondary hyperparathyroidism is a normal physiological response to hypocalcaemia

Calcium will be low or low/normal

PTH will be high (hyperparathyroidism) secondary to the low calcium

This is different from primary hyperparathyroidism where calcium is high

Question 16

Causes of secondary hyperparathyroidism

Answer 16

Most common cause of secondary hyperparathyroidism is vitamin D deficiency

Commonly - diet, reduced sunlight

Less common, but important = renal failure – can’t make calcitriol in renal failure

Question 17

Treatment of secondary hyperparathyroidism

Answer 17

Vitamin D replacement
In patients with normal renal function
Give 25 hydroxy vitamin D

Patient converts this to 1,25 dihydroxy vitamin D via 1a hydroxylase
Ergocalciferol 25 hydroxy vitamin D2
Cholecalciferol 25 hydroxy vitamin D3

In patients with renal failure - inadequate 1a hydroxylation, so can’t activate 25 hydroxy vitamin D preparations
Give Alfacalcidol - 1a hydroxycholecalciferol

Question 18

Tertiary hyperparathyroidism

Answer 18

Tertiary hyperparathyroidism = rare

Occurs in chronic renal failure

Can’t make calcitriol

PTH increases (hyperparathyroidism)

Parathyroid glands enlarge (hyperplasia)

Autonomous PTH secretion causes hypercalcaemia

Treatment is parathyroidectomy

Question 19

Diagnostic approach to hypercalcaemia

Answer 19

When looking at a patient with hypercalcaemia, always look at the PTH!

Normal PTH response to hypercalcaemia is for PTH to fall
Hypercalcaemia due to malignancy
High calcium (hypercalcaemia)
Low/suppressed PTH

If patient with hypercalcaemia has raised PTH, the diagnosis is hyperparathyroidism
Primary hyperparathyroidism if renal function is normal (eg parathyroid adenoma)
Tertiary hyperparathyroidism (all 4 glands enlarged – hyperplastic) if chronic renal failure

Question 20

Diagnostic approach to vitamin D deficiency

Answer 20

Calcium will be low or low/normal

PTH will be high (hyperparathyroidism) secondary to the low calcium

Vitamin D is measured as 25 (OH) vitamin D

Calcitriol (1,25 dihydroxy vitamin D) is very difficult to measure

Question 21

Regulate phosphate

Answer 21

FGF23