Title: HYPERCALCEMIA
1HYPERCALCEMIA
- Dr R V S N Sarma., M.D., M.Sc.,
- Consultant Physician and Chest Specialist
visit www.drsarma.in
2Hypercalcemia
- Commonly encountered in Practice
- Diagnosis often is made incidentally
- The most common causes are primary
hyperparathyroidism and malignancy - Diagnostic work-up includes measurement of serum
calcium, intact parathyroid hormone (I-PTH), h/o
any medications - Hypercalcemic crisis is a life-threatening
emergency
3Important Issues
- Most often asymptomatic Incidental Dx
- Mild Hypercalcemia is asymptomatic
- Most important cause is hyper parathyroid
- DD is needed to decide the treatment
- Optimal step by step evaluation is a must.
4Physiology of Calcium
- 98 of the body calcium is in the skeleton
- Only 2 is circulation and only half of this is
free calcium (ionized Ca) - This only is physiologically active
- The reminder 1 is bound to proteins
- Direct measurement of free Calcium ??
5Calcium Homeostasis
6Calcium Homeostasis
7Calcium Metabolism
(1,000 mg/day)
8How They control Ca Levels
Hormone Effect Bone Gut Kidney
PTH ? Ca ? Po4 Increases Osteoclasts Indirect via Vit. D Ca reab Po4 exr.
Vitamin D3 ? Ca ? Po4 No direct action ? Ca ? Po4 absorption No direct effect
Calcitonin ? Ca ? Po4 Inhibits Osteoclasts No direct effect Ca Po4 excretion
9Corrected Serum Calcium
- Corrected total calcium (mg)
- (Measured total calcium mg)
- (4.4 - measured albumin g) x 0.8
- Example
- 12.0 (4.4 2.4) x 0.8
- 12.0 (2 x 0.8) 12.0 1.6 13.6 mg
10Vitamin D Metabolism
Supplements Vitamin D 2
Calcitriol (Active)
11Formation of Calcitriol
12Calcium Homeostasis
13Hypercalcemia Grading
14Hypercalcemia
15Causes of Hypercalcemia
16The Two Important Causes
- More than 90 percent of hypercalcemia cases are
- Primary hyperparathyroidism and malignancy
- These conditions must be differentiated early
- to provide optimal treatment accurate
prognosis - Humoral hypercalcemia of malignancy implies a
very limited life expectancy only a matter of
weeks - Primary hyperparathyroidism has a benign course.
17Parathyroid hormone-related
- Primary hyperparathyroidism
- Sporadic, familial, associated with
- Multiple Endocrine Neoplasia (MEN I or II)
- Tertiary hyperparathyroidism
- Associated with chronic renal failure
- PTH ? due to Vitamin D deficiency
18Vitamin D-related
- Vitamin D intoxication
- Iatrogenic Vitamin D injections
- Usually 25-hydroxyvitamin D2 in
- over-the-counter supplements
- Granulomatous disease
- Sarcoidosis, Berylliosis, Tuberculosis
- Hodgkins lymphoma
19Malignancy
- Humoral hypercalcemia of malignancy (mediated by
PTHrP) common cause - Solid tumors, especially lung, head and neck
squamous cancers - Renal Cell Carcinoma (RCC)
- Local osteolysis (mediated by cytokines)
- Multiple Myeloma
- Breast cancer
20Medications
- Thiazide diuretics (usually mild) - common
- Lithium for depressive illnesses
- Milk-alkali syndrome (calcium antacids)
- Vitamin A intoxication (including
- analogs used to treat acne)
21Endocrine Diseases
- Hyperthyroidism
- Adrenal insufficiency
- Acromegaly
- Pheochromocytoma
22Genetic and Other disorders
- Familial hypocalciuric hypercalcemia (FHH)
- mutated calcium-sensing receptor gene
- Immobilization, with high bone turnover (e.g.,
Pagets disease, bedridden child) - Recovery phase of Rhabdomyolysis
23Hypercalcemia - Clinical
24Clinical Features
- Renal stones
- Nephrolithiasis
- Nephrogenic Diabetes Insipidus
- Dehydration
- Nephrocalcinosis
25Clinical Features
- Skeleton bones
- Bone pains
- Arthritis
- Osteoporosis
- Osteitis fibrosa cystica in HPTH
-
26Clinical Features
- Abdominal Moans
- Nausea, vomiting
- Severe anorexia, weight loss
- Constipation (not relieved by Rx.)
- Abdominal pain (vague and diffuse)
- Pancreatitis
- Peptic ulcer disease
27Clinical Features
- Psychological Groans
- Impaired concentration
- Impaired memory, Depression
- Confusion, stupor, coma
- Lethargy and severe fatigue
- Extreme muscle weakness
- Corneal calcification (band keratopathy)
28Clinical Features contd
- Cardiovascular
- Hypertension, Increased risk of CHD
- ECG changes of shortened QT interval, PR
prolonged, QRS widened, ST ?, Bradycardia - Cardiac arrhythmias Vascular calcification
- Others
- Itching (Generalized Pruritus)
- Keratitis, conjunctivitis
29Algorithmic Approach
Normal calcium
Hypocalcemia
30Algorithmic Approach
31Algorithmic Approach
Endocrine
32Serum Ca and I-PTH
33Hyperparathyroidism
- Increased screening for serum Ca and
- Wider availability of I-PTH assay
- 80 of cases single parathyroid adenoma
- Usually benign adenoma or hyperplasia
- Rarely parathyroid cancer
- High PTH in the setting of hypercalcemia
- Slowly progressive Sestamibi N-scan
- 25 require surgery RLN paralysis
34Sestamibi Nuclear Scan
64 yrs male - hyper parathyroid storm with a
serum calcium level of 16.4 mg
35Criteria for Surgery
- Serum calcium level gt 12 mg at any time
- Episodes of hyper parathyroid crisis
- Marked hypercalciuria (urinary Ca gt 400 mg
/day) - Nephrolithiasis Impaired renal function
- Osteitis fibrosa cystica Thinning of cortical
bone - Reduced bone density by DEXA scan (Z score lt 2)
- Classic neuromuscular symptoms, Proximal muscle
weakness and atrophy, Hyper reflexia and ataxia - Age younger than 50 years
36Vitamin D Related
- 25 OH - Vitamin D2 is the supplemental Vit D
- Level of 25 OH Vitamin D3 is to be measured
- Macrophages in the granulomas, lymphomas
- cause extra renal conversion of 25 OH form to
the1,25 hydroxy derivative the active Calcitriol - PTH levels are suppressed Calcitriol levels ?
- Stop the offending use of Vitamin D
- Glucocorticoids for over one month or more
- Manage hypercalcemia vigorously
37Hypercalcemia of Malignancy
- Most commonly mediated by systemic PTHrP
- Humoral Hypercalcemia of malignancy
- PTHrP mimics the bone renal effects of PTH
- Normal Calcitriol and suppressed PTH levels
- Excessive bone lysis due to primary or bone
secondaries can cause hypercalcemia - MM and metastatic Br Ca present in this way.
- In Osteolytic hypercalcemia, SAP is markedly ?
- Hodgkins lymphoma ? production of Calcitriol
38Medications and Hypercalcemia
- Thiazide diuretics increase renal calcium
- resorption and cause mild hypercalcemia
- Resolves after discontinuing the drug
- Thiazide unmasks hyperparathyroidism
- Milkalkali syndrome Ca Antacids
- Lithium ? the set point for PTH ?
- Excess Vitamin A - ? bone resorption and
- causes hypercalcemia.
39Other Causes of Hypercalcemia
- FHH Familial Hypocalciuric Hypercalcemia
- AD 100 penetrance Ca-R gene mutation
- Moderate hypercalcemia with normal/ ? PTH
- 24 hour urinary calcium is very low
- No benefit from parathyroidectomy
- High bone turnover in Pagets disease or
prolonged immobilization - Recovery phase of Rhabdomyolysis
40Treatment
- Ca lt12 but gt 10.3 mg no appreciable clinical
benefit they need evaluation - Any patient with Serum Ca gt 12 mg should be
aggressively treated - Ca gt 14 mg is Hypercalcemic crisis
- Always correct the Ca value for Sr Albumin
41The Four Rx Modalities
42Hydration and Diuresis
- Vigorous I.V. Nacl Diuresis N Saline
- Adequate hydration urine out put must be
maintained 200 ml/hour 5 L /day - The safest and most effective treatment of
Hypercalcemic crisis is saline rehydration - Once the urine out put is maintained give I.V.
Furosemide a loop diuretic in low doses of 10
to 20 mg - ERT - might be beneficial in PMW new RCT
43Calcitonin
- In severe hypercalcemia refractory to saline
diuresis - Calcitonin (Zycalcit, Miacalcin) 6 -8 U/kg IM/SC
(400 i.u) given every six hours. - This treatment has a rapid onset but short
duration of effect - Patients develop tolerance to the
calcium-lowering effect of Calcitonin.
44Bisphosphonates
- Zoledronic acid (Zometa) - 4 mg IV diluted in 100
ml of N Saline - over at least 15 once a M - Pamindronate (Pamidria) - 60 mg IV infusion over
4 h initial repeated after a month - Etidronate (Didronel) - 7.5 mg/kg IV over 4 h
daily for 3-7 d dilute in at least 250 ml of
sterile N Saline - They inhibit bone resorption, inhibit the
Osteoclastic activity.
45Other Rx Options
- Dialysis for refractory Hypercalcemic crisis
- Parathyroidectomy for adenomas
- Rx. of the underlying cause Eliminate drugs
- Plicamycin (Mithracin) 25 mcg/kg/d IV for 4 d
- Gallium nitrate (Ganite) 100 mg/m2/d IV for 5
days in 1 L of NS or 5 Dextrose - Cinacalcet (Sensipar) - 30 mg PO od (increases
sensitivity of calcium sensing receptor)
46Take Home Points
- Hypercalcemia is often asymptomatic
- Screen all suspected by doing Sr Calcium
- If elevated, do I-PTH and follow algorithm
- 90 Hyperparathyroidism and malignancy
- Vitamin D toxicity is an important cause
- Thiazide diuretics common cause, Vitamin A
- Adequate hydration - N Saline Furosemide
- Calcitonin Zoledronic acid main stay of Rx.