Description
This oncology presentation provides a detailed overview of hypercalcemia as a common paraneoplastic syndrome, focusing on its etiology, pathophysiology, clinical presentation, and management. The material explains the regulation of calcium homeostasis by PTH and vitamin D, and outlines the primary mechanisms by which malignancies cause hypercalcemia: humoral hypercalcemia mediated by PTHrP (accounting for 80% of cases), local osteolytic hypercalcemia from bone metastases (notably in breast cancer and multiple myeloma), ectopic 1-alpha-hydroxylase activity (seen in lymphomas), and ectopic PTH production. Clinical manifestations across neurological, renal, gastrointestinal, and cardiovascular systems are highlighted, alongside key investigations such as serum calcium, PTH/PTHrP levels, and ECG. Treatment strategies range from intravenous hydration and bisphosphonates (e.g., zoledronic acid) to calcitonin, denosumab, and corticosteroids. This resource is essential for medical students, oncology trainees, and practitioners in Zambia, offering structured, exam-focused content for understanding and managing hypercalcemia in cancer patients within a tertiary medical education setting. Download these comprehensive notes for thorough preparation and clinical application.
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HYPERCALCEMIA OF MALIGNANCY OBJECTIVES Introduction Etiology Clinical presentation Investigation Treatmemt Calcium is an essential element that participates in various biochemical reactions, including muscle contractions, coagulation and bone development amoung others Calcium is absorbed predominantly in the small intestines, and it is necessary to note that only 10-20% of ingested calcium is absorbrd, and the rest excreted with the stool. Calcium in the body is present in two major compartments: Bone, where it is stored as hydroxyapatite salt and in plasma Normal range: 2.2-2.6 mmol/L INTRODUCTION Several hormone systems regulate calcium absorption and metabolism. Drop in calcium levels below 10mg/dl stimulates the release of PTH. PTH activates the 1 –alpha-hydroylase enzyme located in the renal proximal tubles, which in turn converts 25-hydroxyvitamin D into the more active 1,25-dihydroxyvitamin D. PTH also stimulates calcium reabsorption in the distal part of the nephron PTH also leads to calcium mobilization from the bone with the help of 1,25-dihydroxyvitamin D. Humoral hypercalcemia- PTHrP mediated Local osteolytic hypercalcemia 1,25-dihydroxyvitamid D mediated hyperparathyroidism ETIOLOGY AND PATHOBIOLOGY The major mechanism, accounting for approximately 80% of malignancy –related hypercalcemia, is mediated by production of PTHrP. (humoral hypercalcemia) It is important to note that PTHrP is normally produced and secreted by various cells, and normal breast cells in particular Both PTH and PTHrP act on the same receptors and their effects overlap Squamous cell cancers, urinary tract cancers, breast cancer, nonHodgkin’s lymphoma, account for majority of malignancies leading to hypercalcemia via PTHrP Aetiology The second mechanism by which malignancies cause hypercalcemia includes osteolytic metastases and excessive calcium release from bone accounting for 20% approx of malignancy related hypercalceamia Breast cancer and multiple myeloma account for vast majority of the osteolytic hypercalceamia Metastatic breast cancer cells may produce PTHrP locally, which may lead in the elevation of calcium levels, this further stimulates local PTHrP generating a vicious cycle The third mechanism includes ectopic activity of 1-alpha-hydroxylase, which is common in lymphomas and in some ovarian germ cell tumors The fourth mechanism by which cancer can lead hypercalceamia includes ectopic production of PTH, which can also be due to parathyroid carcinama CLINICAL PRESANTATION OF HYPERCALCEAMIA Neuropsychiatric Anxiety Mood changes Decreased cognitive functions 2.Renal manifestation. Polyuria Nephrolithiasis Chronic renal failure 3.Gastrointestinal manifestations Anorexia Constipation Nausia and vomiting 4.CVS manifestations Shortened QT interval ST segment elevation Ventricular arrhthmias Investigations FBC Serum total calcium PTH and PTHrP levels LFTs ECG TREATMENT The management of hypercalcemia is based on presence of characteristic symptomatology and severity of calcium elevation. The treatment options include: IV hydration Calcitonin Bisphosphonates eg zoledronic acid, ibadronate, pamidronate Denosumab Gallium nitrate Prednisolone hemodialysis
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