HYPERCALCAEMIA  - Presentation and Management

Hypercalcemia is an elevated serum calcium level above 11.0 mg/dl. This is the commonest serious metabolic disorder associated with malignancy, affecting 10-20% of cancer patients. Malignancies most commonly associated include lung, breast, head, neck, kidney, lymphoma and myeloma. It is caused by local osteolytic metastatic lesions, secretion of humoral factors that increase bone resorption and impaired renal calcium clearance.

PRESENTATION

        As symptoms and signs of hypercalcaemia involve many systems and are often non-specific, the diagnosis must be frequently considered in any oncology patient. Early symptoms include polydipsia, polyuria, dehydration, anorexia, constipation, lethargy, drowsiness or lethargy. Abdominal discomfort, nausea, vomiting, increased gastric acid secretion, constipation, bradycardia, muscle weakness or change in mental status can also be features.

MANAGEMENT

        Hypercalcaemia is a poor prognostic indicator in malignant disease and may indicate uncontrolled tumor progression and metastatis. Drugs which may aggravate hypercalcaemia should be discontinued. Initial therapy should include intensive rehydration for 12-24 hours with 4-6 liter of normal saline. A loop diuretic like furosemide 40-8- mg I.V. every 12 to 24 hrs should be considered in order to induce natriuresis (only after the patient has been rehydrated).

        Bisphophonates play an integral role in the management of hypercalcaemia. Commonly used bisphosphonates are pamidronate – 90 mg given as a 2 to 4 hour infusion and zoledronic acid – 4mg given as a 15-minute infusion.

        Corticosteroids, gallium nitrate, plicamycin and calcitonin may be used as second-line or adjunctive therapies. Of last resort is the use of haemodialysis in refractory hypercalcaemia. Certainly, treatment of the underlying malignancy also serves to improve hypercalcaemia.

 

SYNDROME OF INAPPROPRIATE SECRETION OF ANTIDIURETIC HORMONE

        SIADH is a paraneoplastic condition associated with malignancy (small cell lung cancer), CNS disease, pulmonary disease, or certain drugs(morphine, vincristine, cyclophosphamide, chlorpropamide, amitriptyline and fibrates). It is due to the production of arginine vasopressin by tumor cells. The syndrome of inappropriate ADH secretion affects 1-2% of cancer patients. The condidtion should be considered whenever a patient with malignancy presents with hyponatraemia.

PRESENTATION AND DIAGNOSIS

        Hyponatraemia is the commonest sign of SIADH. This may be asymptomatic or symptomatic, with patients experiencing symptoms such as lethargy, irritability, anorexia, depression, muscle cramps, weakness or behavioural change, in severe cases, seizures and even coma may occur. Being a diagnosis of exclusion, SIADH is diagnosed in a patient with normal fluid status and normal renal, adrenal and thyroid function, who meets the following criteria: (1)Hyponatraemia; (2)Hypernatraemic urine without diuretic therapy (urine sodium > 20 mEq/L); (3) Hypo-osmotic plasma (plasma osmolality <280 mOsm/kg); and Hyperosmotic urine.

MANAGEMENT

        The mainstay of management of SIADH is treatment of the underlying malignancy. Acute treatment for patients who are symptomatic and who have severe hyponatraemia includes fluid restriction (500 – 1000 ml daily), diuresis with loop diuretics, doxycycline and replacement of sodium and potassium lost in the urine. Correction of sodium levels should not exceed 10-12 mEq/L per day, to prevent the development of central pontine myelinolysis.

VENOUS THROMBOEMBOLISM

        The association between malignancy and increased risk of thrombosis was observed by Trosseau, and is attributable to various factors, including hypercoagulable states, chemotherapy, prolonged immobilisation, indwelling central catheters and greater incidence of surgical intervention.

        A hypercoagulable state in oncology patients can be contributed to by abnormal blood composition with increased levels of clotting factors and procoagulants. Patients undergoing chemotherapy have an increased risk of thrombosis due to endothelial cell damage, while patients with central venous catheters are more prone to upper limb thrombosis and thrombosis of the axillary and subclavian veins. Certain tumors have been associated with higher rates of thromboembolism, such as pancreatic tumors, lung tumors, and other mucinsecreting tumors.

PRESENTATION AND DIAGNOSIS

        In cancer patients presenting with a swollen extremity, venous thrombosis should be suspected and investigated promptly via an ultrasound Doppler of the limb. Pulmonary embolism should be suspected in patients who present with acute dyspnoea, pleuritic chest pain, haemoptysis, dizziness or syncope. Signs include tachycardia, tachypnoea, hypotension, raised jugular venous pressure, pleural rub or pleural effusion. ECG most commonly shows tachycardia, right bundle branch block, right ventricular strain pattern or the classical S1Q3T3 pattern. Chest X-ray may be normal or show oligaemia of the affected segment, a dilated pulmonary artery, linear atelectasis, small pleural effusions or a wedge- shaped opacity. Arterial blood gas analysis classically shows hypoxaemia and hypocarbia. Diagnostic modalities of choice include a spiral CT of the thorax, CT pulmonary angiogram or a ventilation/perfusion scan.

MANAGEMENT

        Prophylactic measures can be non-pharmacological or pharmacological, the former including pneumatic compression, elastic stockings, and inferior vena cava filters. However, in the cancer patient with VTE, treatment can be complicated with the risk of bleeding. Pharmacological anticoagulation is usually with unfractionated heparin or low molecular weight heparin (LMWH). The dose of unfractionated heparin is often titrated to achieve a partial thromboplastin time (PTT) of approximately 1.5 to 2 times control in most patients. Warfarin is usually commenced on day 1 or 2 of treatment, and doses are titrated to achieve an international normalized ratio (INR) of 2.0 to 3.0, while maintaining heparin for at least 3-5 days until warfarin dosage is titrated adequately. Generally, the dose of LMWH (e.g enoxaparin, fraxiparin) for therapy of proven VTE is 1mg/kg administered subcutaneously every 12 hours. It is also postulated that LMWH may be more effective in malignancy than both unfractionated heparin and warfarin due to its anti-inflammatory and antiangiogenic properties.

HYPERCALCAEMIA  - Presentation and Management