Hypercalcaemia background

Guideline Background

Hypercalcaemia (HM) is defined as: “A corrected plasma calcium concentration above the upper limit of normal”

Calcium ions are involved in neuromuscular transmission and cell function. Serum calcium is tightly controlled between 2.15 – 2.6mmol/l (HEFT reference range). The majority is protein bound, with the active ionised portion available for metabolic function. In cancer patients blood proteins are frequently low and hypercalcaemia will be missed without the serum level being corrected for concomitant hypoalbuminaemia.

Most labs quote the corrected calcium, where this is not available the following formula may be used:

Measured serum calcium mmol/l + 0.02 x (40 –[albumin g/l]) = corrected calcium mmol/l

HM has a prevalence of up to 20-30% in cancer patients, with squamous cell lung cancer, breast cancer, and myeloma being the most common (see table below).

Common

Lung – squamous cell
Breast
Myeloma
Head and neck
Kidney
Cervix
Lymphoma

Uncommon

Lung – small cell
Large bowel
Stomach
Prostate



HM can complicate any cancer type but is less common with adenocarcinomas and small cell lung cancer. Other causes of hypercalcaemia should be considered as Primary Hyperparathyroidism (PHPT) and cancer coexist in 15%. Particularly in colon and breast cancer, associated with MEN type 1 and lymphoma. Rarely ionising radiation may cause hyperparathyroidism.

There are generally two main mechanisms of HM. The majority of cases are caused by secretion of a humoral substance, usually PTH related protein (PTHrP), directly by the cancer cells. This results in hypercalcaemia in patients even without bone metastases. Only approximately 20% cases are caused by excessive bone metastatic disease. Therefore, the diagnosis of hypercalcaemia should be considered in all cancer patients including those without bone metastases.

It is important to differentiate hypercalcaemia of malignancy from a benign hypercalcaemia in a patient with cancer.

The prognosis of hypercalcaemia in a cancer patient with coexistent hyperparathyroidism is years, but a true HM has a median survival of 2 months. Treatment resistant hypercalcaemia is associated with a very poor prognosis. The appropriateness of treatment should always be considered, with involvement of Oncology or Specialist Palliative Care teams as needed. Good communication with the patient and family is essential. Involvement of the Specialist Palliative Care Team will help support the patient, family and responsible medical team.

There are many other causes of hypercalcaemia and if the patient is not known to have active malignant disease, they should be investigated for underlying disease. Investigations should include Full Blood Count, Urea and Electrolytes, Glucose, ESR, Liver Function Tests, Thyroid Function Tests, plasma Cortisol, Synacthen test, Vitamin D level, Parathyroid Hormone (PTH) level and myeloma screen. Oral calcium therapy, thiazide diuretics, vitamins A and D promote hypercalcaemia and should be stopped.

Presentation

Symptoms are determined mainly by the speed of rising calcium, not its actual level. The classic presentation of ‘Stones, Bones, Abdominal Groans and Psychic Moans’ describes the patient with a slowly rising calcium. The presentation of a patient with a rapid rise in serum calcium is more acute as homeostatic mechanisms attempt to excrete calcium causing polyuria and loss of sodium, potassium and magnesium in the proximal renal tubule. Loss of concentrating ability by the nephron leads to worsening dehydration. Further direct damage to the renal tubule itself is possible when the serum calcium exceeds 3mmol/l.

Patients usually complain of anorexia, nausea, vomiting, constipation, thirst and mental changes early in the course of the HM, leading on to a presentation with dehydration, renal insufficiency, obtundation, twitching, fitting, coma, and cardiac arrest, as the calcium rises above 4mmol/l. Severity of symptoms does not always correlate with degree of hypercalcaemia.

Mild symptoms

Fatigue / Lethargy
Weakness
Thirst
Cognitive dysfunction
Anorexia, nausea,
Constipation
Pain more difficult to control

Moderate symptoms

Polyuria
Dehydration
Renal failure
Nausea and vomiting
Drowsiness
Mental dullness, confusion
Worsening of pain

Severe symptoms

Patient incapacitated
Delirium
Coma
Fits
Myoclonus
Cardiac arrest due to arrhythmia

Despite the acute presentation and poor prognosis, treatment is often rapidly effective and worth it as good symptom control is frequently achievable. HM is a rare instance where one can misdiagnose dying in a patient with an advanced malignancy.

Disclaimer (SPAGG - Rewrite)

This Guide is intended for use by healthcare professionals and the expectation is that they will use clinical judgement, medical, and nursing knowledge in applying the general principles and recommendations contained within. They are not meant to replace the many available texts on the subject of palliative care.

Some of the management strategies describe the use of drugs outside their licensed indications. They are, however, established and accepted good practice. Please refer to the current BNF for further guidance.

While WMPCPS takes every care to compile accurate information , we cannot guarantee its correctness and completeness and it is subject to change. We do not accept responsibility for any loss, damage or expense resulting from the use of this information.