Oncology based

1. HYPERCALCEMIA AND
HYPOCALCEMIA
CAUSES
SYMPTOMS
MANAGEMENT
PRESENTER: DR GOWTHAM MANIMARAN
MODERATOR : DR JYOTIKA JAIN

2. Introduction
Calcium is one of the most abundant minerals in the human body and it has many important
biologicalfunctions.
Functionsof calcium :
1. Musclecontraction
2. Neuromuscular / nerve conduction
3. Intracellular signalling
4. Bone formation
5. Coagulation
6. Enzyme regulation
7. Maintenance of plasma membrane stability

3. NORMAL DISTRIBUTION:
• A 70 kg person has approximately 1.2kg of calcium in the body, 99%
is stored as hydroxyapatite in bones.
• <1% (5-6 g) of this calcium is in the intracellular and extracellular
compartments.
• Only 1.3 g is located extracellularly.
• Total normal calcium concentration in the plasma is 8.9-10.1 mg/dL.
• 50% of plasma calcium is ionized ,the active form of calcium which is
clinically significant
• 40% is bound to proteins (90% to albumin), 10% circulates bound to
anions (eg, phosphate, carbonate, citrate, lactate, sulfate).

4. Calculation of calcium levels:
• Step1:Ensurethatthealterationinserumcalciumlevelsisnotduetoabnormal
albuminconcentration(sinceionizedformistheactiveformofcalcium)
• Directmeasurementof ionisedcalciumiseasilyinfluencedbycollection
methodsandotherartefacts,hencewe prefertomeasurecorrectedcalcium
fromtotalcalciumandalbumin.
Corrected calcium:
• For every 1-g/dL drop in serum albumin below 4 g/dL, measured serum calcium
decreasesby0.8 mg/dL.
• Correctedcalcium=MeasuredCa+[0.8x(4–measuredalbumin)]
(Calciuminmg/dl;albumining/dl)

5. Calcium Homeostasis
• Extracellular calcium concentration - (8.9-10.1 mg/dl)
• Feedback mechanisms that involve parathyroid hormone ,calcitonin and the active Vitamin
D metabolite (1,25 dihydroxyvitaminD)

7. I. HYPERCALCEMIA
• Causes :
1. Too much calcium enters the ECF.
2. There is insufficient calcium excretion from the kidney.
* ~ 90% are caused by malignancy or hyperparathyroidism.
MILD MODERATE CRISIS
TOTAL CALCIUM 10.5-11.9 mg/dl 12-13.9 mg/dl 14-16 mg/dl
IONISED CALCIUM 5.6-8 mg/dl 8-10 mg/dl 10-12 mg/dl

9. Causes of hypercalcemia:
I.Parathyroid-related
• Primary hyperparathyroidism –Adenoma , Multiple
endocrine neoplasia , Carcinoma
• Lithium therapy
• Familial hypocalciuric hypercalcemia
II.Malignancy-related
• Solid tumour with metastases (breast)
• Solid tumour with humoral mediation of hypercalcemia
(lung , kidney)
• Hematologic malignancies (multiple myeloma,
lymphoma, leukaemia)
III. Vitamin D-related
• Vitamin D Intoxication
• Increased 1,25(OH)2D; sarcoidosis and other
granulomatous diseasesimpaired metabolism due to 24-
hydroxylase deficiency
IV.Associated with high bone turnover
• Hyperthyroidism
• Immobilization
• Thiazides
• Vitamin A intoxication
• Fat necrosis
V.Associated with renal failure
• Severe secondary hyperparathyroidism
• Aluminium intoxication
• Milk-alkali syndrome

10. Clinical manifestations
• Mild hypercalcemia – asymptomatic.
- Recognized on routine calcium measurements.
- Vague neuropsychiatric symptoms – concentration deficit, personality changes,
or depression.
- Others : Peptic ulcer, nephrolithiasis, fracture risk.
• Severe hypercalcemia – Acutely  Lethargy, stupor, or coma, GI symptoms
(nausea, anorexia, constipation, or pancreatitis).
(decreases renal concentrating ability polyuria and polydipsia).
• Longstanding hyperparathyroidism bone pain/ pathologic fractures.
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• Hypercalcemia - significant ECG changes  bradycardia, AV block, short QT
interval
• Changes in serum calcium - monitored by following the QT interval.

11. Renal “stones”
Nephrolithiasis
Nephrogenic diabetes insipidus
Dehydration
Nephrocalcinosis
Skeleton “bones”
Bone pain
Arthritis
Osteoporosis
Osteitis fibrosa cystica in hyperparathyroidism
(subperiosteal resorption, bone cysts)
Gastrointestinal “abdominal
moans”
Nausea, vomiting, Anorexia,
weight loss ,Constipation
Abdominal pain , Pancreatitis
Peptic ulcer diseaseNeuromuscular “psychic groans”
Impaired concentration and memory Confusion,
stupor, coma
Lethargy and fatigue
Muscle weakness
Corneal calcification (band
keratopathy)
Cardiovascular
Hypertension
Shortened QT interval on E C G Cardiac arrhythmias
Vascular calcification

13. MALIGNANCY-RELATED HYPERCALCEMIA
• Hypercalcemia is the most common paraneoplastic syndrome, occurring in
10% to 30% of patients with advanced cancer
• Main mechanisms in cancer hypercalcemia
1. Bone mets-Local invasion and destruction of bone by tumor cells.(breast
cancer ,multiple myeloma)
2. Humoral hypercalcemia of malignancy is by PTHrP(PTH related peptide)
by a variety of carcinomas like squamous cell ca lung ,renal tumours
,breast
3. In some lymphomas- increased blood level of 1,25(OH)2D by the
abnormal lymphocytes.
4. Prostaglandins and interleukin 1 produced by various tumours enhances
bone resorption
5. Ectopic parathyroid hormone –very rare
Squamous cell tumors are most frequently associated with hypercalcemia, particularly tumors of the
lung, kidney, head and neck, and urogenital tract.

14. Investigations:
• Serum calcium(ionised ,total) , phosphorus(2.5 to 4.5mg/dl) and albumin
• Serum ALP
• Blood urea nitrogen and serum creatinine
• ECG
• PTH (10-65 pg/ml)
• PTHrP assay
• Bone scans
• Bone marrow biopsy
Treatment : (malignancy hypercalcemia)
• First to control of tumor; reduction of tumor mass usually corrects hypercalcemia.
• If a patient has severe hypercalcemia yet has a good chance for effective tumor therapy, treatment of the
hypercalcemia should be vigorous while awaiting the results of definitive therapy.
• If hypercalcemia occurs in the late stages of a tumor that is resistant to antitumor therapy, the treatment of
the hypercalcemia should be judicious as high calcium levels can have a mild sedating effect.

15. Management of Hypercalcemia
a.)Hydration and saline diuresis
Volume Restoration expansion and saline diuresis are most useful and
effective measures to correct hypercalcemia
0.9 % NaCl is infused to correct dehydration for volume expansion and
diuresis.(almost @ 200 to 300ml/hr and then tapered as required)hence
always use cautiously in HEART FAILURE AND ELDERLY patients to avoid
pulmonary oedema
Furosemide – Additive effect with 0.9 NS as it leads to forced Diuresis.
Precautions – fluid intake, output, blood levels of ca,k,mg every 8-12 hours

16. b.) BISPHOSPHONATES
MOA- Analogues of pyrophosphate with high affinity for increased bone turnover sites and inhibits osteoclysis
ZOLEDRONATE(4/8MG in 100 ml NS over 15 mins) is the most effective
PAMIDRONATE(60-90 mg in 500ML NS over 2-4 hours)
Doses may be repeated every 7 to 30 days
S.E –Osteonecrosis of jaw ,subtrochanteric #
c.) CALCITONIN
MOA-Inhibits bone resorption and increases urinary excretion
useful in acute crisis
DOSAGE-4IU/KG s.c 12hourly
Indications –diuresis , other drugs are contraindicated (RF , CHF)
S.E - tachyphylaxis
d.) DENOSUMAB
MOA-antibody that blocks RANK ligandand so reduces
osteoclast number and function
DOSAGE-120mg/s.c monthly
e.) HAEMODIALYSIS- Reserved for treatment of
patients with severe hypercalcemia and in CRF

17. • GLUCOCORTICOIDS
MOA- Causes decreased absorption and increases urinary excretion ,
decrease 1,25 OH dihydroxy vitamin production
Are effective in sarcoidosis,malignancy,vit d toxicity but not in primary
hyperparathyroidism
• SPECIFIC TREATMENT
Discontinue drugs responsible
Surgical treatment in primary
hyperparathyroidism
Specific treatment in cases of malignancy
and granulomatous conditions

19. II. HYPOCALCEMIA
A decrease in serum calcium
less than 8.5mg/dl or ionized
calcium less than 3-4.4mg/dl
is termed as Hypocalcemia.

20. Mechanisms of hypocalcemia in malignancy
1. Paraneoplastic syndrome leading to hypocalcemia –very rare
2. Osteoblastic bone mets
3. CA prostate , breast on hormonal agents because of rapid bone healing.
4. Calcitonin –by medullary carcinoma of thyroid
5. Magnesium deficiency( both PTH secretion and its action)
• Prolonged nasogastric drainage
• On TPN without any magnesium supplementation
• Cisplatin therapy induced renal tubular dysfunction –urinary loss
• Chronic alcoholism
• Chronic diarrhoea
• EGFR blocking antibodies: cetuximab and panitumumab
6. Therapy for hypercalcemia

21. TUMOUR LYSIS SYNDROME
• Tumor cell death with the release of intracellular
contents can lead to a constellation of metabolic
abnormalities is tumor lysis syndrome (TLS).
• it can occur spontaneously in rapidly proliferating
tumors, it occurs most frequently following
administration of cytotoxic chemotherapy to patients
with hematologic malignancies, with a large percentage
of proliferating, drug-sensitive cells . Ex: acute leukemias
,large bulky high-grade non-Hodgkin lymphomas [NHL],
especially Burkitt lymphoma
• TLS occurs a few hours to a few days after the initiation
of therapy.
• Cell death leads to the release of potassium, phosphate,
uric acid, and other purine metabolites overwhelming
the kidney’s capacity for clearance with resultant
hyperkalemia, hyperphosphatemia and secondary
hypocalcemia, and hyperuricemia
• Unchecked, TLS can progress to acute renal failure and
metabolic acidosis . Established TLS is associated with a
high morbidity and mortality.
Cairo Bishop classification system

22. • The best management for TLS is prevention.The preventive regimen
consists of ,
1. IV hydration- goal is urine output of 80 to100ml/hr/m2. Recommended fluids
are 5% dextrose/0.45% NS. In hyponatremic patients 0.9% NS .Furosemide can
be added .
2. Urinary alkalinisation- pH as high as 7 (uric acid crystals form only in acidic
environment)
3. Hypouricemic drugs
• Allopurinol-100mg/m2 every 8 hours
• Rasburicase-0.15 to 0.2mg/kg once daily for 5 days
• Febuxostat- safe in liver and renal disease

23. Clinical Manifestations
• Usually asymptomatic if mild /chronic
• Moderate to severe parasthesia(fingers,toes,circumoral
region).Clinically Chovstek’s sign , trousseau’s sign are seen
• Severe  seizures,carpopedal spasm,laryngospasm,prolongation of
QT interval
Carpopedal spasm Chovstek’s sign:

24. DIAGNOSTIC APPROACH
In addition to measuring serum calcium, it is useful to determine albumin, phosphorus, and magnesium levels.
• A suppressed (or “inappropriately low”) PTH level in the setting of hypocalcemia establishes absent or reduced PTH
secretion (hypoparathyroidism) as the cause of the hypocalcemia. Further history will often elicit the underlying
cause (i.e., parathyroid agenesis vs. destruction).
• By contrast, an elevated PTH level (secondary hyperparathyroidism) should direct attention to the vitamin D axis as
the cause of the hypocalcemia.
• Nutritional vitamin D deficiency is best assessed by obtaining serum 25-hydroxyvitamin D levels(20-100 ng/ml),
which reflect vitamin D stores. In the setting of renal insufficiency or suspected vitamin D resistance, serum
1,25(OH)2D levels are informative.

25. Management of Hypocalcemia
The approach to treatment depends on the severity of the hypocalcemia, the rapidity with
which it develops, and the accompanying complications (e.g., seizures, laryngospasm).
• Severe Acute, symptomatic hypocalcemia (S.ca<6mg/dl)-
a.) calcium gluconate 1gm diluted in 50 mL of 5% dextrose or 0.9% sodium chloride, given
intravenously over 10 to 20mins.
b.) followed by slow infusion of 11gm calcium gluconate in D5% /NS @50 ml/hr
c.)Magnesium sulphate 1gm IV every 8 hrs to 12 hrs if levels unknown or <1.5mg/dl
d.)Serum ca2+ levels every 2 hours
AVOID RINGER LACTATE WHEN INFUSING CALCIUM PREPARATIONS

26. • Moderate hypocalcemia: (6-8 mg/dl)
a.) calcium either oral or IV (1000mg of elemental iron daily)
b.) magnesium 1gm IV once/twice daily
c.) patients recovering from hypercalcemia are in risk
• Chronic hypocalcemia due to hypoparathyroidism is treated with calcium
supplements (1000–1500 mg/d elemental calcium in divided doses) and either
vitamin D2 or D3 (25,000–100,000 U daily) or calcitriol [1,25(OH)2D, 0.25–2
μg/day].
• Vitamin D deficiency, however, is best treated using vitamin D supplementation,
with the dose depending on the severity of the deficit and the underlying cause.

29. Management of Hypercalcemia
• Hydration and saline diuresis
• Bisphosphonates
• Calcitonin
• Denosumab
• Glucocorticoids
• Haemodialysis
Management of Hypocalcemia
• Calcium gluconate
• Magnesium sulphate
• Vit D supplementation

30. THANK YOU