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HYPERCALCEMIA

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* * 64 yrs male - hyper parathyroid storm with a serum calcium level of 16.4 mg% Serum calcium level 12 mg % at any time Episodes of hyper parathyroid crisis ... – PowerPoint PPT presentation

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Title: HYPERCALCEMIA


1
HYPERCALCEMIA
  • Dr R V S N Sarma., M.D., M.Sc.,
  • Consultant Physician and Chest Specialist

visit www.drsarma.in
2
Hypercalcemia
  • 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

3
Important 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.

4
Physiology 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 ??

5
Calcium Homeostasis
6
Calcium Homeostasis
7
Calcium Metabolism
(1,000 mg/day)
8
How 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
9
Corrected 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

10
Vitamin D Metabolism
Supplements Vitamin D 2
Calcitriol (Active)
11
Formation of Calcitriol
12
Calcium Homeostasis
13
Hypercalcemia Grading
14
Hypercalcemia
15
Causes of Hypercalcemia
16
The 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.

17
Parathyroid 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

18
Vitamin 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

19
Malignancy
  • 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

20
Medications
  • Thiazide diuretics (usually mild) - common
  • Lithium for depressive illnesses
  • Milk-alkali syndrome (calcium antacids)
  • Vitamin A intoxication (including
  • analogs used to treat acne)

21
Endocrine Diseases
  • Hyperthyroidism
  • Adrenal insufficiency
  • Acromegaly
  • Pheochromocytoma

22
Genetic 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

23
Hypercalcemia - Clinical
24
Clinical Features
  • Renal stones
  • Nephrolithiasis
  • Nephrogenic Diabetes Insipidus
  • Dehydration
  • Nephrocalcinosis

25
Clinical Features
  • Skeleton bones
  • Bone pains
  • Arthritis
  • Osteoporosis
  • Osteitis fibrosa cystica in HPTH

26
Clinical Features
  • Abdominal Moans
  • Nausea, vomiting
  • Severe anorexia, weight loss
  • Constipation (not relieved by Rx.)
  • Abdominal pain (vague and diffuse)
  • Pancreatitis
  • Peptic ulcer disease

27
Clinical Features
  • Psychological Groans
  • Impaired concentration
  • Impaired memory, Depression
  • Confusion, stupor, coma
  • Lethargy and severe fatigue
  • Extreme muscle weakness
  • Corneal calcification (band keratopathy)

28
Clinical 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

29
Algorithmic Approach
Normal calcium
Hypocalcemia
30
Algorithmic Approach
31
Algorithmic Approach
Endocrine
32
Serum Ca and I-PTH
33
Hyperparathyroidism
  • 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

34
Sestamibi Nuclear Scan
64 yrs male - hyper parathyroid storm with a
serum calcium level of 16.4 mg
35
Criteria 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

36
Vitamin 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

37
Hypercalcemia 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

38
Medications 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.

39
Other 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

40
Treatment
  • 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

41
The Four Rx Modalities
42
Hydration 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

43
Calcitonin
  • 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.

44
Bisphosphonates
  • 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.

45
Other 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)

46
Take 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.
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