Paraneoplastic Syndromes

PARANEOPLASTIC SYNDROMES

DR. JUAN CARLOS BECERRA MARTÍNEZ

CÁTEDRA DE MEDICINA INTERNA-MC3087

Tecnológico de MonterreyCampus Guadalajara

Paraneoplastic syndromes

Harrison’s 18th Edition.

Paraneoplastic syndromes is the term used to refer to the disorders that accompany benign or malignant tumors but are not directly related to mass effects or invasion.

Endocrine Paraneoplastic Syndromes

Harrison’s 18th Edition.

Treatment: Humoral Hypercalcemia of Malignancy

Harrison’s 18th Edition.

Removal of excess calcium in the diet, medications, or IV solutions.

Oral phosphorus (e.g., 250 mg Neutra-Phos 3–4 times daily) should be given until serum phosphorus is >1 mmol/L (>3 mg/dL).

Saline rehydration is used to dilute serum calcium and promote calciuresis.

Forced diuresis with furosemide or other loop diuretics

Bisphosphonates such as pamidronate (60–90 mg IV), zoledronate (4–8 mg IV), and etidronate (7.5 mg/kg per day PO for 3–7 consecutive days

Dialysis should be considered in severe hypercalcemia.

Calcitonin (2–8 U/kg SC every 6–12 h) should be considered when rapid correction of severe hypercalcemia is needed.

Endocrine Paraneoplastic Syndromes

Harrison’s 18th Edition.

Endocrine Paraneoplastic Syndromes

Harrison’s 18th Edition.

Ectopic Vasopressin: Tumor-Associated SIADH

Harrison’s 18th Edition.

Most patients with ectopic vasopressin production develop hyponatremia

The disorder should be corrected gradually unless mental status is altered or there is risk of seizures.

Fluid restriction to less than urine output,

Salt tablets and saline are not helpful unless volume depletion is also present.

Demeclocycline (150–300 mg orally three to four times daily) can be used to inhibit vasopressin action on the renal distal tubule, but its onset of action is relatively slow (1–2 weeks).

Conivaptan, a nonpeptide V2-receptor antagonist, can be administered either PO (20–120 mg bid) or IV (10–40 mg) and is particularly effective when used in combination with fluid restriction in euvolemic hyponatremia.

Severe hyponatremia (Na <115 meq/L) or mental status changes may require treatment with hypertonic (3%) or normal saline infusion together with furosemide to enhance free water clearance.

The rate of sodium correction should be slow (0.5–1 meq/L per h) to prevent pontine myelinolysis.

Ectopic Vasopressin: Tumor-Associated SIADH

Harrison’s 18th Edition.

Treatment: Cushing's Syndrome Caused by Ectopic ACTH Production

Harrison’s 18th Edition.

Depression or personality changes because of extreme cortisol excess.

Metabolic derangements, including diabetes mellitus and hypokalemia, can worsen fatigue.

Adrenalectomy is not practical for most of these patients but should be considered if the underlying tumor is not resectable and the prognosis is otherwise favorable (e.g., carcinoid).

Medical therapy with ketoconazole (300–600 mg PO bid), metyrapone (250–500 mg PO every 6 h), mitotane (3–6 g PO in four divided doses, tapered to maintain low cortisol production), or other agents that block steroid synthesis or action.

Endocrine Paraneoplastic Syndromes

Harrison’s 18th Edition.

Endocrine Paraneoplastic Syndromes

Harrison’s 18th Edition.

Hematologic Syndromes

Harrison’s 18th Edition.

Hematologic Syndromes

Harrison’s 18th Edition.

Treatment: Erythrocytosis Successful resection of the cancer Phlebotomy may control any symptoms

related to erythrocytosis

Harrison’s 18th Edition.

Treatment: Thrombocytosis IL-6, a candidate molecule for the etiology of paraneoplastic

thrombocytosis, stimulates the production of platelets in vitro and in vivo.

Another candidate molecule is thrombopoietin, a peptide hormone that stimulates megakaryocyte proliferation and platelet production.

Thrombocytosis is present in 40% of patients with lung and gastrointestinal cancers; 20% of patients with breast, endometrial, and ovarian cancers; and 10% of patients with lymphoma.

Paraneoplastic thrombocytosis does not require treatment.

Harrison’s 18th Edition.

Treatment: Eosinophilia Definitive treatment is directed at the

underlying malignancy: Symptoms resolve with the use of oral or inhaled

glucocorticoids.

Harrison’s 18th Edition.

Treatment: Thrombophlebitis Deep venous thrombosis and pulmonary

embolism are the most common thrombotic conditions in patients with cancer.

The coexistence of peripheral venous thrombosis with visceral carcinoma, particularly pancreatic cancer, is called Trousseau's syndrome.

Harrison’s 18th Edition.

Treatment: Thrombophlebitis IV unfractionated heparin or low-molecular-weight heparin

for at least 5 days, and warfarin should be started within 1 or 2 days.

The warfarin dose should be adjusted so that the international normalized ratio (INR) is 2–3.

Patients with proximal deep venous thrombosis and a relative contraindication to heparin anticoagulation (hemorrhagic brain metastases or pericardial effusion) should be considered for placement of a filter in the inferior vena cava (Greenfield filter) to prevent pulmonary embolism.

Harrison’s 18th Edition.

Treatment: Thrombophlebitis

Paraneoplastic Neurologic Syndromes

Harrison’s 18th Edition.

Lambert-Eaton Sx

Guillain Barre Sx

SMNS vs SMNI

Antibodies

Harrison’s 18th Edition.

Antibodies

Harrison’s 18th Edition.