Immobility-induced hypercalcaemia is a diagnosis of exclusion for non-PTH mediated hypercalcaemia. The proposed pathophysiology underlying this is uncoupling of bone turnover, with greater deceleration in bone formation and increased resorption.
A 49-year-old Caucasian male with background of splenectomy presented with abdominal pain, purpuric rash and renal impairment secondary to streptococcus septicaemia. He developed purpura fulminans with ischaemic auto-amputation of his limbs. During ICU admission, he was intubated, required nasogastric feeding for two weeks and had a prolonged delirium. His serum calcium rose from normal to 3.12mmol/L at 7 weeks with suppressed PTH of 0.3pmol/L. His confusion and renal function had improved after a short period of intermittent haemodiafiltration. There was no history of malignancy and he was on no predisposing medications.
On examination, he appeared euvolaemic and haemodynamically stable. He was neurologically intact. He had bilateral below knee and hand amputations. Although he was moved passively, he remained bedbound. He had no lymphadenopathy or focal bony tenderness.
Results included PTH 0.6pmol/L(1.3-7.6), 25-hydroxyvitamin-D 35nmol/L(>50nmol/L), 1,25-hydroxyvitamin-D 19(60-200), electrophoresis showed a polyclonal inflammatory response, serum ACE level 41U/L(30-55), spot calcium:creat was 0.8mmol/mol cr(0-0.4), PTHrP <0.2pmol/L, TSH 4.5mIU/L(0.27-4.2), fT4 16pmol/L(12-25), morning cortisol 230nmol/L, ACTH 12.9pmol/L(<10), urine DPD/Cr 41.1(2.3-5.4). Chest imaging did not reveal hilar lymphadenopathy. Bone scan showed no osteoblastic deposits.
A provisional diagnosis of immobility-related hypercalcaemia was made. He was given 30mg pamidronate resulting in normalisation of calcium for 81 days. He developed recurrent hypercalcaemia to 2.9mmol/L and bone turnover markers were markedly elevated: P1NP 1100ug/L, CTX 3094ng/L(100-600). 4mg zoledronic acid was then given which resulted in normalisation of serum calcium.
Non-PTH mediated hypercalcaemia due to immobility presents with hypercalciuria and trabecular bone loss due to reduced osteoblast activity. Inflammation and acidity can predispose to increased bone resorption. Fluid and bisphosphonates are common treatments with remobilisation. Denosumab and PTH are potential alternatives.