SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute hypercalcaemia in adult patients

Abstract

Introduction Under physiological conditions, serum calcium concentration is tightly regulated. Abnormalities of parathyroid function, bone resorption, renal calcium reabsorption or dihydroxylation of vitamin D may cause regulatory mechanisms to fail and serum calcium to rise. Serum calcium is bound to albumin, and measurements should be adjusted for serum albumin. This guideline aims to take the non-specialist through the initial phase of assessment and management. Severity of hypercalcaemia <3.0 mmol/L: often asymptomatic and does not usually require urgent correction 3.0–3.5 mmol/L: may be well tolerated if it has risen slowly, but may be symptomatic and prompt treatment is usually indicated >3.5 mmol/L: requires urgent correction due to the risk of dysrhythmia and coma Clinical features of hypercalcaemia Polyuria and thirst Anorexia, nausea and constipation Mood disturbance, cognitive dysfunction, confusion and coma Renal impairment Shortened QT interval and dysrhythmias Nephrolithiasis, nephrocalcinosis Pancreatitis Peptic ulceration Hypertension, cardiomyopathy Muscle weakness Band keratopathy Causes Ninety percent of hypercalcaemia is due to primary hyperparathyroidism or malignancy Less common causes include Thiazide diuretics Familial hypocalciuric hypercalcaemia Non-malignant granulomatous disease Thyrotoxicosis Tertiary hyperparathyroidism Hypervitaminosis D Rhabdomyolysis Lithium Immobilisation Adrenal insufficiency Milk-alkali syndrome Hypervitaminosis A Theophylline toxicity Phaeochromocytoma Investigation History Symptoms of hypercalcaemia and duration Symptoms of underlying causes, e.g. weight loss, night sweats, cough Family history Drugs including supplements and over-the-counter preparations Examination Assess for cognitive impairment Fluid balance status For underlying causes, including neck, respiratory, abdomen, breasts, lymph nodes ECG Look for shortened QT interval or other conduction abnormalities Bloods Calcium adjusted for albumin Phosphate PTH Urea and electrolytes High calcium and high PTH = primary or tertiary hyperparathyroidism* High calcium and low PTH = malignancy or other less common causes (*Familial hypocalciuric hypercalcaemia may be misdiagnosed as primary hyperparathyroidism due to hypercalcaemia with inappropriately normal or raised PTH. However, the hypercalcaemia is not usually severe and it is less likely to present as an emergency) Management Rehydration Intravenous 0.9% saline 4–6 L in 24 h Monitor for fluid overload if renal impairment or elderly Loop diuretics rarely used and only if fluid overload develops; not effective for reducing serum calcium May need to consider dialysis if severe renal failure If further treatment required after intravenous saline, consider intravenous bisphosphonates Zoledronic acid 4 mg over 15 min OR Pamidronate 30–90 mg (depending on severity of hypercalcaemia) at 20 mg/h OR Ibandronic acid 2–4 mg Give more slowly and consider dose reduction in renal impairment Monitor serum calcium response: will reach nadir at 2–4 days Can cause hypocalcaemia if vitamin D deficiency or suppressed PTH Second-line treatments Glucocorticoids (inhibit 1,25OHD production) In lymphoma, other granulomatous diseases or 25OHD poisoning Prednisolone 40 mg daily Usually effective in 2–4 days Calcimimetics, denosumab, calcitonin Under specialist supervision Can be considered if poor response to other measures Parathyroidectomy Can be considered in acute presentation of primary hyperparathyroidism if severe hypercalcaemia and poor response to other measures