Paraneoplastic Syndromes – Part 1 of 2
Internal Medicine Clinical Update: Paraneoplastic Syndromes, Part 1 of 2
Kevin Finora DVM, Diplomate ACVIM
(Oncology and Small Animal Internal Medicine)
Paraneoplastic syndromes (PNS) are cancer related alterations in body structure or function occurring at sites distant to the primary cancer. In addition to patient factors, tumour biology and appropriate treatment options, PNS are factors to be considered in cancer treatment.
The causes of PNS are varied but can result in medical conditions requiring attention prior to, or concurrent with, the treatment of the inciting cancer. In some cases the PNS may be first indication of the presence of cancer. The malignant neoplasia is only discovered as a result of the investigation into what turns out to be a PNS. Once the underlying cancer, the actual cause of the PNS, has been addressed, the PNS typically resolves. Interestingly, the PNS will often return in advance of the clinical signs of cancer recurrence. Therefore, the PNS can function as a sentinel for disease. There are many PNS. However, one of the most common is hypercalcemia. This month I will discuss the commonly seen Hypercalcemia of Malignancy and next month I will continue with the discussion of hypoglycemia and other less common PNS.
Hypercalcemia of malignancy is associated, in dogs, with many common tumours such as lymphoma (LSA), anal sac apocrine gland adenocarcinoma (ACA), and multiple myeloma (MM). The cause of hypercalcemia is not uniform with all cancers. Hypercalcemia of malignancy is seen in about 25% of dogs with LSA, 25% of dogs with ACA and 20% of dogs with MM.
The cause of hypercalcemia in both LSA and ACA is the tumour-associated production of the parathyroid hormone related peptide (PTHrp). This peptide differs by only a few amino acids from the parathyroid hormone (PTH). The body is unable to distinguish between PTH and PTHrp and therefore physiologic processes stimulated by PTH are also induced by PTHrp. Circulating PTHrp will therefore cause increased absorption of calcium in the kidneys and from the GI tract, increased mobilization of calcium from bone and increased renal excretion of phosphorous. The result will be a patient who is hypercalcemic with the associated physiologic and clinical complications (PU/PD, renal failure, CNS deficiency).
In multiple myeloma there is over production of the molecule known as the osteoclast-activating factor. This factor will up regulate the function of osteoclasts, the cells responsible for the mobilization of calcium from bone. The result of increased osteoclast activity is an elevation in circulating calcium levels. Other mechanisms of hypercalcemia in MM are direct extension of the tumour into bone and renal failure associated with direct tumour action or the development of glomerular nephritis.
For all cancers, calcium itself can be damaging to the proximal convoluted tubule in the glomerulus, resulting in renal failure associated hypercalcemia, a vicious cycle.
In some cases, hypercalcemia is severe and must be addressed prior to, or while, instituting treatment for the underlying cancer. Initial treatments for hypercalcemia include IV fluid diuresis with 0.9% NaCl and administration of calcitonin. Other treatments may include the use of furosemide or the use of prednisone. Furosemide should be used with caution and never given to a dehydrated patient. Prednisone should never be given to a patient suspected of having cancer but for whom a diagnosis has yet to be made. Prednisone can cause a short-term remission of certain cancers, such as LSA and MM, often making a diagnosis elusive while the prednisone is still on board. Once hypercalcemia has been addressed in the short term, long-term control is most often achieved with treatment and management of the underlying cancer. As previously mentioned, the return of a PNS is often the first indication the cancer has come out of remission.
Dr. Kevin Finora is a Board Certified Oncologist and Small Animal Internist who is part of the Healthcare Team at the Central Toronto Veterinary Referral Clinic. He is available for referrals and consultations Monday to Thursday (including Monday and Tuesday evenings). Please contact him with any oncology questions or concerns.