PARANEOPLASTIC SYNDROMES Presentation BY DR Mohammad Shafi Moona
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.
PS ARE DIVIDED IN TO 1) Endocrine PS. 2) Neurological PS. 3) Haematological PS.
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
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.
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.
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.
TREATMENT: Surgery. Bilateral adrenalectomy ( occult ACTH production, severe muscle weakness, & uncontrolled hypertension). Use of octreotide, ketoconazole & metyrapone.
3): Hypercalcemia: Due to tumour production of parathyroid hormone related protein. CAUSES: Highest : multiple myeloma , Ca breast. Lowest : NSCLC ,colon prostate & SCLC.
Presentation: Nausea, polyuria, polydipsia, dehydration & cardiac arrhythmias. Differential diagnosis: Primary hyperparathyroidism (adenoma or hyperlasia of parathyroid glands)
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).
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 .
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.