Equis ISSN 2398-2977

Endocrine: paraneoplastic syndromes

Contributor(s): Michel Levy, Tim Watson

Introduction

  • Paraneoplastic syndromes are clinical conditions from the non-metastatic systemic effects of various cancers.
  • The clinical signs and laboratorial findings are associated with the pathophysiological response of target organs to factors (hormones, cytokines, growth factors, antibodies) released by these tumors, but the effects occur remotely from the tumor.
  • The clinical signs can be endocrine, musculoskeletal, cardiovascular, cutaneous, hematological, gastrointestinal, renal or others.
  • The underlying mediators of paraneoplastic conditions are in most cases unknown.  
  • Well documented examples in the horse include hypercalcemia of malignancy   Blood: biochemistry - calcium  , hypoglycemia   Hypoglycemia  and erythrocytosis   Blood: erythrocyte count (RBC)  .

Pathogenesis

Etiology

  • The etiology of paraneoplastic syndromes is not always clear but they result from the production of hormones and cytokines by various tumors, which in turn have physiological effects in distant tissues.
  • Hypercalcemia of malignancy has been documented in horses with lymphoma, squamous cell carcinoma (prepuce, gastric), multiple myeloma, ameloblastoma and malignant mesenchymoma.
  • Lymphoma and squamous cell carcinomas are the most common causes of hypercalcemia.
  • These tumors induce hypercalcemia by secreting parathyroid hormone-related protein (PTHrP), which interacts with the receptor for parathyroid hormone (PTH).
  • In the kidney PTHrP increases calcium reabsorption and vitamin D synthesis; in bone, PTH increases osteoclast activity and bone resportion. The end result is hypercalcemia.
  • Hypoglycemia   Hypoglycemia   and seizures have been documented in horses with insulinomas.
  • Hypoglycemia   Hypoglycemia  has also been associated with hepatocellular carcinomas and renal cell carcinomas, and is believed to result from the production of insulin-like growth factors.
  • Polycythemia/increased red blood cell number/erythrocytosis   Blood: erythrocyte count (RBC)   has been linked to the production of erythropoietin and androgenic hormones in horses with renal cell tumors, lymphoma     and hepatic carcinomas.
  • This condition results from excessive production of erythropoietin   Endocrine: erythropoietin  , which increases red cell production. 
  • The etiology of hypertrophic osteopathy   Hypertrophic osteodystrophy  is unclear but the condition is usually linked to an intrathoracic disease, including primary and secondary lung tumors.
  • A neurovascular mechanism has been postulated.
  • Paraneoplastic pruritus has been documented in horses with lymphoma     but the underlying mechanism is unknown.
  • Cancer-associated cachexia is believed to result from inflammatory mediators and catabolic factors that induce an inefficient metabolism of lipids and carbohydrates, and increase protein catabolism.
  • Most weight loss in cancer results from body fat depletion.
  • Protein depletion has negative consequences for the immune system.
  • The ectopic production of other hormones (corticotropin, PTH, calcitonin, gastrin, adrenomedullin, and others), documented in humans and other species, has not been demonstrated in horses.
  • Anemia is a common manifestation of cancer. Several factors are involved in the development of anemia of malignancy and include:
    • Shortened erythrocyte half-life (destruction, immune-mediated anemia).
    • Insufficient bone marrow response (inflammatory cytokines, erythropoietin deficiency, aplastic anemia).
    • Decreased iron release from the reticulo-endothelial system (iron release is inhibited by cytokines).

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Swain J M, Pirie R S, Hudson N P et al (2005) Insulin-like growth factors and recurrent hypoglycemia associated with renal cell carcinoma in a horse. J Vet Intern Med 19 (4), 613-616 PubMed.
  • Baker J L, Aleman M & Madigan J (2001) Intermittent hypoglycemia in a horse with anaplastic carcinoma of the kidney. JAVMA 218, 235-237 PubMed.
  • Lennox T J, Wilson J H, Hayden D W et al (2000) Hepatoblastoma with erythrocytosis in a young female horses. JAVMA 216, 718-721 PubMed.
  • Ogilvie G K (1998) Paraneoplastic syndromes. Vet Clin North Am 14 (3), 439-449 PubMed.


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