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Paraneoplastic  syndromes
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  • 1. PARANEOPLASTIC SYNDROMES Presentation BY DR Mohammad Shafi Moona
  • 2.  Paraneoplastic Syndromes: Paraneoplastic syndromes are a group of disorders associated with specific neoplsms that have signs and symptoms at sites distant from the primary tumor or its metastasis. The syndrome may be due to: Production of substances that directly or indirectly cause distant symptoms.
  • 3.  PS ARE DIVIDED IN TO 1) Endocrine PS. 2) Neurological PS. 3) Haematological PS.
  • 4.  1): Syndrome of inappropriate ADH( SIADH): Hyponaremia is the primary biochemical indicator of clinically inappropriate secretion of ADH. CAUSES : SCLC 15 %. Pancreatic Ca. Carcinoid tumors. Head & neck cancer. Chemotherapy induced transient hyponatremia
  • 5.  Presentation: Asymptomatic. Fatigue, anorexia, headache and mild altered mental status. Delirium , confusion & seizures.
  • 6.  Laboratory criteria for diagnosis: Hypnatremia Na<130 mEq/L. Normal serum albumin & glucose. Serum hypo osmolality <280 mOsm/kg. Urine osmolality >100 mOsm/Kg. Urinary sodium > 20 mEq/L. Non suppressed ADH.
  • 7.  Differential diagnosis: C.H.F. Nephrotic syndrome. Malignant ascites. Liver diseases.
  • 8.  Treatment: Fluid restriction to less than 1 litre/day if Na>125. Demeclocycline. Infusion of 3% saline at a rate of 0.1 ml/Kg/min for 24 hours. Frusemide. For long term treatment : Demeclocycline ( 1gm/day for 2 weeks). Fludrocortisone ( 0.1- 0.3mg twice daily). Lithium carbonate.
  • 9.  2) Cushings syndrome : Production of ACTH or ACTH like substances which lead to adrenal hyperplasia & hypercortisolism. CAUSES : SCLC, NSCLC, pancreatic, thymic and carcinoid tumors medullary carcinoma of thyroid, pheochromocytoma. Presentation : Muscle wasting . Weakness secondary to proximal myopathy. Hyperpigmentaton, hypertension, glucose intolerance. Abnormal fat distribution, hypokalaemic alkalosis.
  • 10.  Diagnosis : In primary adrenal hyperplasia ACTH plasma level will be low. In ACTH dependent cushing syndrome (ACTH high) In ectopic ACTH production (plasma ACTH & ACTH precursor levels are very high) 24 hour urinary cortisol. Low dose dexamethasone suppression test. High dose dexamethasone suppression test. Hpokalaemia & metabolic alkalosis . High plasma ACTH with no response to high dose dexamethasone suppression test.
  • 11.  TREATMENT: Surgery. Bilateral adrenalectomy ( occult ACTH production, severe muscle weakness, & uncontrolled hypertension). Use of octreotide, ketoconazole & metyrapone.
  • 12.  3): Hypercalcemia: Due to tumour production of parathyroid hormone related protein. CAUSES: Highest : multiple myeloma , Ca breast. Lowest : NSCLC ,colon prostate & SCLC.
  • 13.  Presentation: Nausea, polyuria, polydipsia, dehydration & cardiac arrhythmias. Differential diagnosis: Primary hyperparathyroidism (adenoma or hyperlasia of parathyroid glands)
  • 14.  Malignancy: a) Osteolytic hypercalcemia: Due to producton of interleukin 1( ca breast, NSCLC, myeloma & lymphoma). b) Humoral hypercalcemia of malignancy: secretion of PTH-related protein which act via PTH receptors (SCC of lung, head & neck cancer, ca bladder & ovarian carcinoma).
  • 15.  DIAGNOSIS : Serum ca>10.3 mg/dl or ionized ca>5.2 mg/dl. Serum chloride low. Hypercalciuria. High urinary phosphate. Low/undetectable plasma parathyroid hormone. TREATMENT: Saline hydration, biphosphonates.
  • 16.  4) Hypoglycemia: Non-insulinoma associated hypoglycemia or non-islet cell tumor hypoglycemia. Occuring in patients with tumors of mesenchymal origin(retroperitoneal, intrathoracic & intraperitoneal) & hepatoma. Secretion of insulin like growth factor . Plasma insulin level low. Management: Palliative or surgical .
  • 17.  5) Cerebellar degeneration: Seen in < 1% of patients. Causes: Ca breast , Small cell lung cancer , Ca ovary, endometrial & fallopian tube cancers . Pathogenesis: Anti Yo antibody directed agaanist purkinje cells & tumor cells with there shared antigen. Presentation: Visual loss, vertigo & truncal ataxia. Diagnosis: Immunofluorescent method.
  • 18.  Management: Steroid . I/V immunoglobulin. Plasmapheresis. Chemotherapy.
  • 19.  6) Lambert-Eaton myasthenic syndrome: Cause: Small cell lung cancer. Pathogenesis: Autoantibody that reacts with voltage-gated calcium channels of peripheral cholinergic nerve terminals and tumor cell membranes. Presentation: Proximal muscle weakness (pelvic girdle) Hyporeflexia, muscle tenderness . Autonomic dysfunction ( orthostatic hypotension, dry mouth). 30% of patients have dysphagia.
  • 20.  Diagnosis : EMG findings (muscle action potential that increase after brief exercise. Management:. Azathiopirine. Immunoglobulin. Plasma exchange
  • 21.  7)Erythrocytosis: 1) High erythropoietin production: RCC , Hepatoma, Cerebellar haemangioblastoma. Uterine fibroids , Adrenal tumors Phaechromocytoma . 2) Adrenal cortical tumors : Production of androgen hormones 3)Prosrtoglandin production by tumors: Treatment: Phlebotomy: Hematocrit > 55% in males > 50 in females.
  • 22.  8) Granulocytosis: WBC > 15000 Causes : Hodgkins disease. Solid tumors ( gastric, lung, pancreatic, brain & malignant melanoma). Mechanism: Production of growth factors including GCSF & GMCSF.
  • 23.