Severe hypercalcaemia (calcium >3.5 mmol/l) in the absence of significant renal disease usually is caused by malignancy, primary hyperparathyroidism or MAS.6
As malignancy and hyperparathyroidism could be ruled out MAS remained the most probable cause of hypercalcaemia in our case.
Development of MAS usually begins with hypercalcaemia by high calcium carbonate supplementation. Hypercalcaemia produces a decrease in glomerular filtration due to increased sodium and water excretion,7
and by direct glomerular vasoconstriction.8
The combined effects of increased alkali intake, a fall in glomerular filtration rate (GFR) and hypercalcaemia then lead to metabolic alkalosis. The alkalosis further enhances the hypercalcaemia by decreasing calcium excretion in the distal nephron.9
Vomiting, diuretics, and the natriuretic effects of hypercalcaemia further aggravate hypercalcaemia and alkalosis.
Our patient was treated for several years with calcium carbonate containing supplementation for osteoporosis and thiazide diuretics but her calcium level in the past remained in a high-normal range (total calcium 2.54 mmol/l) until 6 months before admission. Metabolic alkalosis was induced by: (i) calcium carbonate supplementation, (ii) volume contraction due to vomiting, thiazide diuretics and hypercalcaemia, and (iii) acid loss by vomiting. High bicarbonate levels persisted during the follow-up despite discontinuation of calcium carbonate and thiazide diuretics and vigorous volume substitution. The condition with chronic compensatory elevation of bicarbonate due to hypoventilation in normal circumstances does not lead to MAS. But given the patient's known condition with several risk factors for the development of MAS (calcium carbonate containing supplementation, thiazide diuretics and immobilisation), the morphine overdose induced vomiting with further volume contraction aggravated hypoventilation and increased compensatory renal bicarbonate generation, which finally led to MAS. How much the different factors contributed to the development of MAS in this case is unclear. As in the original and the modern version of the syndrome, ingested carbonate was probably the main source of bicarbonate. However, compensatory generation of bicarbonate due to aggravation of hypoventilation may contribute to the metabolic alkalosis and is probably not negligible.
- MAS should always be considered in patients with severe hypercalcaemia.
- Today's polymedication in the elderly with calcium carbonate containing supplementation for osteoporosis, thiazide diuretics, calcium carbonate containing antacids and reduced capacity to handle calcium (impaired GFR, reduced bone uptake of calcium) exposes them to a higher risk for MAS.
- Chronic hypoventilation associated with compensatory high bicarbonate levels seems to be another risk factor that should be taken into account.