Hypercalcemia is a common occurrence in the patients suffering from cancer. In some cancers, the severity of hypercalcemia is increased. Various mechanisms are proposed to show how hypercalcemia occurs in malignancy.
Is Hypercalcemia A Paraneoplastic Syndrome?
Hypercalcemia is one of the most common presentations seen in cancer patients. It has been estimated that almost 10-20% of patients with cancer experiences hypercalcemia5. Patients with renal cancer, lung cancer, and myeloma most commonly suffer from this condition. It is to be noted that not all the cases of hypercalcemia are related to malignancy. Various mechanisms are elucidated for hypercalcemia in malignancy. The first mechanism is through the increased effect of Parathyroid Hormone-related peptide. It increases the bone resorption and also increases the renal absorption of calcium leading to hypercalcemia. This mechanism holds true for at least 80% of all the malignancy-related hypercalcemia6.
In cancers such as breast cancer and multiple myeloma, the release of RANKL is increased which leads to increased bone resorption. Breast cancer cells also produce PTH related peptide without increasing the serum level of this peptide.
Another mechanism that is found to be important is the ectopic effect of alpha-hydroxylase that leads to increased serum calcium level. Hypercalcemia through this mechanism is found in some ovarian germ cell tumors.
Symptoms In Paraneoplastic Syndrome
Paraneoplastic syndrome is characterized by a group of symptoms that occurs because of the presence of cancerous cells. These symptoms occur not because of the growth of malignant cells or their metastasis rather the condition is believed to be caused because of the chemical and hormones secreted by these cells or the trigger within the immune system against these cells. The symptoms are not limited to the location of cancer rather the effects seen are widespread. Following are some of the symptoms associated with paraneoplastic syndrome:
Endocrinological Symptoms: Endocrine symptoms are mainly manifested through two different mechanisms. First, it increases the secretion of hormones in the cells that are already differentiated to produce the hormones in physiologically low levels. The excess secretion of these hormones causes a lot of symptoms in the patients, for instance, increased secretion of parathyroid hormone in parathyroid cancer. The second mechanism is through secretion of hormones by the cells which do not secrete hormone in normal conditions1. The symptoms related to the endocrine system include Cushing’s syndrome, hypoglycemia, hypercalcemia, and hyperaldosteronism.
Neurological Symptoms: Various neurological symptoms are experienced by the patient suffering from paraneoplastic syndrome. Cerebellar degeneration occurs in which area of the brain controlling the muscular function and balance gets damaged. Area controlling the emotions and behavior gets inflamed and the condition is known as limbic encephalitis. Other examples of the paraneoplastic syndrome of the nervous system include Opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome, Myasthenia gravis, Peripheral neuropathy, Neuromyotonia, Dysautonomia, Stiff person syndrome, and Encephalomyelitis2.
Hematological Symptoms: Various symptoms occur as a result of the paraneoplastic syndrome because of the release of chemicals and hormones. Some conditions are triggered because of the response to symptoms of cancer. Hypoxia may lead to increased erythropoietin production. Increase in the level of erythropoietin may also be due to its ectopic synthesis. Erythrocytosis is commonly found in the tumor near to liver, kidney, nervous system or thymus. Anemia may also occur because of the chronic hemorrhages from tumors with ulcers3.
Mucocutaneous Symptoms: These are characterized by the presence of various dermatoses occurring due to visceral malignancy. Mucocutaneous conditions due to paraneoplastic syndrome include pyoderma gangrenosum, Sweet’s syndrome, acquired generalized hypertrichosis, florid cutaneous papillomatosis, and acanthosis nigricans. The conditions may be of varied etiology, pathology, and morphology4.
General symptoms: The most common symptom of the paraneoplastic syndrome is fever which is caused due to the production of inflammatory mediators and endogenous pyrogens.
Not all the cases of hypercalcemia in cancer patients are linked to malignancy. The most common mechanism of hypercalcemia in these patients is the overactivity of Parathyroid Hormone-related peptide that increases bone resorption.