Tumor lysis syndrome and hypercalcemia of malignancy
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Transcript of Tumor lysis syndrome and hypercalcemia of malignancy
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HYPERCALCEMIA & TUMOR LYSIS SYNDROME
Dr. Gaurav Kumar
PGT ; Radiotherapy
MCH
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Hypercalcemia: Calcium levels above normal physiological range i.e. 9-11 mg/dl.
Hypercalcemia
Symptomatic Asymptomatic
Mild (<12mg/dl) Severe (>12mg/dl)
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CAUSES OF HYPERCALCEMIA
1] PARATHYROID RELATED
A) PRIMARY HYPERPARATHYROIDISM(Renal Calcium Absorption <99%)
i. solitary adenomaii. Multiple endocrine neoplasia
B) LITHIUM THERAPY
C) FAMILIAL HYPOCALCIURIC HYPERCALCEMIA(Renal Calcium Absorption >99%)
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2] MALIGNANCY RELATED :
A) SOLID TUMORS WITH METASTASIS (BREAST)
B) SOLID TUMOR WITH HUMORAL MEDIATION OF HYPERCALCEMIA
C) HEMATOLOGIC MALIGNANCIES
3] VITAMIN D-RELATED :
A) VITAMIN D INTOXICATION
B) 1,25(OH)₂D , SARCOIDOSIS , OTHER GRANULOMATOUS DS.
C) IDIOPATHIC HYPERCALCEMIA OF INFANCY
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4] ASSOCIATED WITH HIGH BONE TURNOVER :
A) HYPERTHYROIDISM
B) IMMOBILISATION
C) THIAZIDES
D) VIT-A INTOXICATION
5] ASSOCIATED WITH RENAL FAILURE :
A) SECONDARY HYPERPARATHYROIDISM
B) ALUMINUM INTOXICATION
C) MILK ALKALI SYNDROME
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CLINICAL FEATURES :
Mild Hypercalcemia: (11-11.5 mg/dl)Trouble concentrating , Personality changes ,
depression , peptic ulcer disease , nephrolithiasis ,increased fracture risk
Severe Hypercalcemia : (>12 mg/dl)Lethargy , Stupor , Coma
GI symptoms like nausea , anorexia , constipation or pancreatitis
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Psychic Moans
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Malignancy Related Hypercalcemia:
.2nd Most common cause
. 20% cancer patient
.Common causes: lung Ca (squamous variety) , Renal
neoplasms , Metastatic Ca Breast , hematological malignancies
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DIAGNOSIS :
ALBUMIN CONC. IN BLOOD ( 50% calcium is bound
to albumin)IF NORMAL
PTH level
PTH + Calcium + phosphate PTH + Calcium
Primary Hyperparathyroidism Malignancy or
Granulomatous ds.
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Cont.
0.2 mg/dl is added to total Calciumfor every 1 gm /dl decrease in Albumin conc. and vice versa
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PHPTH vs Malignancy
PHPTH
• Healthy
• Asymptomatic
• Calcium ranging from high normal to less than 1 greater than the upper limit of normal
• PTH elevated
MALIGNANCY
• Usually obvious by the time of dx
• Sicker, symptomatic inpatients
• Calcium usually over 13
• Solid tumors, leukemias, MM
• PTH-rp, or elevated calcitriol
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MECHANISMS OF HYPERCALCEMIA IN MALIGNANCY
1] Tumor releases PTHrP (parathyroid related peptide)which acts on bones causing increased resorption and thus
increased blood calcium levels.E.g- Squamous cell cancer of lung, Renal neoplasms
2] Tumor may cause Bone Marrow invasion,BM reacts by producing Lymphokines and Cytokines (IL-2, TNF), which inturncauses local destruction of bones by OAF (osteoclast activating
factor).E.g- Multiple myeloma, leukemias
3] Increased 1,25(OH)₂D by Abnormal Lymphocytes,which causes increased renal & gastric reabsorption of Calcium.
E.g- Lymphomas
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HUMORAL HYPERCALCEMIA OF MALIGNANCY
PTH like factor
Activates PTH1R
Action as parathyroid hormone
Increased Calcium
Decreased PTH secretion
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TREATMENT
1] CONTROL OF MALIGNANCY(Since it is reversible cause of hypercalcemia)
2] REDUCE CALCIUM LEVELSMild Hypercalcemia- Hydration (0.9% N.S) enoughSevere Hypercalcemia- Can be managed by
i) Decrease Skeletal Releaseii) Decrease Intestinal Absorption
iii) Increase Renal Excreation
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A] DECREASE BONE RESORPTIONi) Bisphosphonates (onset of action 1-2 days)
ii) Calcitonin (within hours)iii) Mithramycin -seldom usediv) Gallium Nitrate-rarely used
v) Glucocorticoidsvi) Phosphate Therapy
B] INCREASED RENAL EXCRETIONi) Forced Diuresis (Hydration along with frusemide /
Ethacrynic Acid)ii) Glucocorticoids
iii) Calcitonin
C] DECREASE INTESTINAL ABSORPTIONi) Glucocorticoids
ii) Hydration
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TREATMENT ALGORYTHMRestore Normal Hydration
Isotonic Saline Infusion (upto 3-4 lits or more)
Frusemide (Twice daily 40mg)
Add Calcitonin within 24 hrs(2-8 U/kg) & Bisphosphonates (Zolendronate 4-8 mg/5 min infusion)
More aggressive hydration (6 lits or more) and frequent dosing of Frusemide for life threatening hyperCalcaemia.
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“painful bones, renal stones, abdominal groans, psychic moans, and neuropsychiatric overtones”
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TUMOR LYSIS SYNDROME
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TUMOR LYSIS SYNDROME is characterised by Hyperuricemia , Hyperkalemia ,
Hyperphosphatemia and Hypocalcaemia caused by the destruction of large number of
rapidly proliferating neoplastic cells.
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PATHOPHYSIOLOGYDestruction of large number of neoplastic cell
Release of cellular contents in blood
a) Increased serum uric acidb) Increased serum Phosphatesc) Increased serum Potassiumd) Decreased serum Calcium
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Increased Uric acid Increased Lactic acid
Acidosis
Dehydration
Uric acid precipitation in Tubules , Medulla , Collecting Ducts of kidney
Renal Failure
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HOW TO DIFFERENTIATE RENAL FAILURE DUE TO ACUTE
HYPERURICEMIA FROM OTHER CAUSES?
Urinary Uric Acid : Urinary CreatinineIf > 1 Acute HyperuricemiaIf < 1 Other Causes
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HYPERPHOSPHATEMIA
Phosphates binds to Serum Calcium
Calcium Phosphates
Deposits in Renal Tubule Decrease Serum Calcium
Renal Failure Hypocalcemia
Fatal Neuromuscular Irritation and Tetany
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HYPERKALEMIA
Increased Potassium in serum Renal Failure
Life Threatining Hyperkalemia
Ventricular Arrythmias & Sudden Death
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TYPES OF TLS :
1] THERAPEUTIC 2] SPONTANEOUS
i)DURING THERAPY SPONTANEOUS ii)AFTER THERAPY NECROSIS
(1-5 DAYS) WITHOUT TREATMENT
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COMMONLY ASSOCIATED MALIGNANCIES
i) Burkitt‘s Lymphomaii) ALL
iii)Other high Grade Lymphomas*Rarely with Solid Neoplasms and Chronic Leukemias
COMMONLY ASSOCIATED TREATMENT MODALITIES
i) GLUCOCORTICOIDSii) HORMONAL AGENTS e.g- Letrozole , Tamoxifen
iii) MONOCLONAL ANTIBODIES e.g – Rituximab , Gemtuzumabiii) CHEMOTHERAPEUTIC DRUGS
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MANAGEMENT OF TUMOR LYSIS i) Maintain Hydration (Normal or ½ normal saline)
3000 ml/m² per dayii) Keep Urine pH at 7.0 or greater (Sodium bicarbonate)
iii) Allopurinol at 300 mg/m²per day
24-48 hours
Serum Uric acid >8 mg/dl Serum Uric acid <8 mg/dlSerum creatinine >1.6 mg/dl Serum Creatinine <1.6 mg/dl
Correct treatable Renal Failure Start ChemotherapyStart Rasburicase 0.2 mg/kg i.v Bicarbonate OFF
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Cont.
IF
Serum K⁺ >6.0 meq/dl
Serum Uric Acid >10 mg/dl
Serum Creatinine >10 mg/dl
Serum phosphate >10 meq/dl
Symptomatic HypoCalcemia present
Hemodialysis
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Thank you