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

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.

<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

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

Ninety percent of hypercalcaemia is due to primary hyperparathyroidism or malignancy

Causes

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

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

Assess for cognitive impairment

Fluid balance status

For underlying causes, including neck, respiratory, abdomen, breasts, lymph nodes

Look for shortened QT interval or other conduction abnormalities

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)

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

Zoledronic acid 4 mg over 15 min

If further treatment required after intravenous saline, consider intravenous bisphosphonates

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