Hypercalcaemia



Diagnostic tests for hyperparathyroidism vs FBHH

Christensen suggest using CCCR, followed by genetic testing for CaSR mutations if non-diagnostic. A result >0.02 (20 as calculated here) reliably excludes FBHH. A result <0.02 encompasses 98% of FBHH cases and 35% of PHPT cases. NB genetic testing is itself only about 70% sensitive.

Vitamin D deficiency should be treated before measuring urine calcium. Vitamin D deficiency is common in primary hyperparathyroidism due to increased hepatic degradation. Deficiency will lower urine calcium excretion and may result in false diagnosis of FBHH.

Test Threshold Result below: sensitivity for FBHH (%) Result above: sensitivity for PHPT (%)
To convert PTH from pmol/L to ng/L, multiply by 9.5. Calcium:creatinine clearance ratio = urine Ca/urine creat x serum creat/serum Ca, on blood sample and random or 24-hr urine specimen.
PTH (pmol/L) 2.5 32 99
3.0 49 95
8.5 95 49
9.1 99 44
24-hr urine Ca (mmol) 1.1 15 99
2.3 47 95
6.5 95 71
9.0 99 49
Ca:creatinine clearance ratio 2.5 17 99
6 57 95
10 81 88
13 95 79
17 99 63
CaE (µmol/L GF) 6 15 99
14 62 95
27 95 84
34 99 70
Calculate CaE
Requires second-void urine sample
Urine calcium (mmol/l)
Urine creatinine (mmol/l)
Serum creatinine (µmol/l)
Calcium:creatinine clearance ratio
On spot or 24-hr urine specimen
Urine calcium (mmol/l)
Urine creatinine (mmol/l)
Serum creatinine (µmol/l)
Serum calcium (mmol/l)

PTH is elevated in vitamin D deficiency

See Thomas, NEJM 1998 338 777. Vitamin D and PTH

Other causes of hypercalcaemia

  • Malignancy - osteolytic, or production of PTH-related protein
  • Granulomatous disorders - calcitriol in macrophages
  • Iatrogenic - thiazides, lithium, theophylline
  • Calcium intake - milk, antacids
  • Endocrinopathies - hyperthyroidism, hypoadrenalism, phaeochromocytoma
  • Familial benign hypocalciuric hypercalcaemia
  • Tertiary hyperparathyroidism - after renal transplant or initiation of dialysis
  • Paget's disease

NB lithium causes an FHH-like syndrome by interfering with G-protein coupled calcium receptor. Also hypothyroidism by interfering with TSH receptor in same way.


Criteria for parathyroidectomy

From JCEM 2009: 94; 335

Measurement Criterion
Serum calcium >= 0.25 mmol/l above normal
Bone mineral density T-score <-2.5
Radiographic vertebral fracture
Age <50
Creatinine clearance <60 ml/min
Urine calcium >10mmol per d
Renal stones Image routinely
Diagram showing typical calcium flux from gut, bone, kidney

To convert mg into mmol, divide by 40, i.e. typical daily intake is 25 mmol, of which about 4 mmol absorbed and renally excreted.