Download Hypercalcemia

Hypercalcemia
Introduction
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The skeleton contains 99 percent of total
body calcium; the remaining 1 percent
circulates throughout the body
One half of circulating calcium is free
(ionized) calcium, the only form that has
physiologic effects.
The remainder is bound to albumin,
globulin, and other inorganic molecules
Corrected calcium = (4.0 mg/dl - [plasma
albumin]) X 0.8 + [serum calcium]
Definition
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Normal serum calcium levels are 8 to 10
mg/dL (2.0 to 2.5 mmol/L)
Normal ionized calcium levels are 4 to
5.6 mg /dL (1 to 1.4 mmol per L)
Hypercalcemia is defined as total serum
calcium > 10.5 mg/dl(>2.5 m mol/L ) or
ionized serum calcium > 5.6 mg/dl ( >1.4
m mol/L )
Definition
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Severe hypercalemia is defined as total
serum calcium > 14 mg/dl (> 3.5
mmol/L)
Hypercalcemic crises is present when
severe neurological symptoms or
cardiac arrhythmias are present in a
patient with a serum calcium > 14 mg/dl
(> 3.5 mmol/L) or when the serum
calcium is > 16 mg/dl (> 4 mmol/L)
Pathophysiology
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Parathyroid hormone (PTH), 1,25dihydroxyvitamin D3 (calcitriol), and
calcitonin control calcium homeostasis in
the body
Hypercalcemia is caused by Increased
bone resorption, increased
gastrointestinal absorption of calcium,
and decreased renal excretion of
calcium
Pathophysiology
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PTH increases osteoclastic bone
resorption , increases renal tubular
resorption of calcium , increases calcitriol,
which indirectly raises serum calcium
levels
1,25-dihydroxyvitamin D3 (calcitriol)
increases the absorption of calcium and
phosphate in the gut
Pathophysiology
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Calcitonin Inhibits osteoclast resorption ,
promotes Ca++ and PO4 excretion
PTH-related peptide (PTHrP) binds the
PTH receptor and mimics the biologic
effects of PTH on bones and the kidneys
Clinical Manifestations
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Hypercalcemia leads to hyperpolarization
of cell membranes
Patients with levels of calcium between
10.5 and 12 mg /dl can be asymptomatic.
When the serum calcium level rises
above this stage, multisystem
manifestations become apparent
Clinical Manifestations
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Renal : porlyuria , nephrolithiasis
GI : anorexia , nausea , vomiting ,
constipation , Pancreatitis , PUD
Neuro- psychiatric : weakness , fatigue ,
confusion , stupor , coma
Clinical Manifestations
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Cardiovascular : Shortened QT interval
on electrocardiogram,, bradyarrhythmias
and heart block and cardiac arrest
Cornea : band keratopathy
Differential Diagnosis
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Hyperparathyroidism : most common
Malignancy : second most common ,
(severe hypercalcemia and hypercalcemic
crises))
squamous carcinoma of the lung、 breast
cancer、 renal cell cancer ,head and neck
squamous cancer、 multiple
myeloma ,hematogenous and lymphomatous
malignancies
Differential Diagnosis
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The most common cause of
hypercalcemia is primary
hyperparathyroidism, and malignancy
is the second most common cause together they account for > 90% of cases
primary hyperparathyroidism is usually
secondary to a parathyroid adenoma
(85%), parathyroid hyperplasia (15%)
and rarely due to a parathyroid carcinoma
(< 1%)
Differential Diagnosis
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Primary hyperparathyroidism rarely
produces severe hypercalcemia and/or a
hypercalcemic crises, unless renal
insufficiency +/- dehydration is
superimposed on the underlying
hyperparathyroidism
Malignancy accounts for the majority of
cases of severe hypercalcemia and
hypercalcemic crises
Differential Diagnosis
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Malignancy increases osteoclastic activity
by two mechanisms - production of a PTHlike substance called PTH-related protein
= PTHrP (humoral hypercalcemia of
malignancy - HHM - 80% of cases) and
due to local osteoclastic activity secondary
to bone metastasis (local osteolytic
hypercalcemia of malignancy - 20% of
cases)
Differential Diagnosis
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Granulomatous disease :
sarcoidosis、tuberculosis、leprosy 、 berylliosis
histoplasmosis/coccidiomycosis
disseminated candidiasis/cryptococcosis
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Non-parathyroid endocrine
disorders :
Hyperthyroidism 、adrenal insufficiency
pheochromocytoma
Differential Diagnosis
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Vitamin D intoxication:
increased gastro-intestinal absorption of
calcium
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Mild alkali syndrome :
increased gastro-intestinal absorption of
calcium
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Drugs :
lithium、thiazide diuretics , vitamin A
Differential Diagnosis
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Familial hypocalciuric hypercalcemia
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Chronic renal insufficiency
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Immobilisation and high bone
turnover :
Pagets disease of bone
Evaluation
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Evaluation of a patient with hypercalcemia
( should include a careful history and
physical examination focusing on
clinical manifestations of hypercalcemia,
risk factors for malignancy, causative
medications, and a family history of
hypercalcemia-associated conditions
Evaluation
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Primary hyperparathyroidism : PTH↑
MALIGNANCY :
1.solid tumors(humoral hypercalcemia) :PTHrP↑ ,
PTH↓
2.Multiple myeloma and breast cancer(osteolytic
hypercalcemia ) : alkaline phosphatase
↑, PTH↓
Evaluation
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Granulomatous(sarcoidosis, tuberculosis,
Hodgkin's lymphoma) : calcitriol (1,25-OH
vitamin D3 ) ↑, PTH↓
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Familial hypocalciuric hypercalcemia :
24-hour urinary calcium ↓, PTH ↑
Treatment
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Saline/fluid hydration :
--increases renal calcium excretion
---2 to 4 L IV daily for 1 to 3 days
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Biphosphonates :
---inhibition bone resorption
---Pamidronate (Aredia), 60 to 90 mg IV over 4
hours
Treatment
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Calcitonin :
----inhibition bone resorption and increases
renal calcium excretion
----4 to 8 IU per kg IM or SQ every 6 hours for
24 hours
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Plicamycin (Mitharmycin) :
----decreases bone resorption
----25 mcg per kg per day IV over 6 hours for 3
to 8 doses
Treatment
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Gallium nitrate :
-----inhibition bone resorption
-----100 to 200 mg per m2 IV over 24 hours for
5 days
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Glucocorticoids :
----Inhibits vitamin D conversionto
calcitriol
-----Hydrocortisone, 200 mg IV daily for 3 days
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Hemodialysis :
---used in patients with renal failure
Treatment
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Clinical indications for surgery in
patients with primary
hyperparathyroidism :
1.significant symptoms of hypercalcemia
2.nephrolithiasis
3.decreased bone mass (> 2 standard deviations
below mean for age)
4.serum calcium > 12mg/dl
5.age < 50 years
6.infeasibility of long-term follow-up
Treatment
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Medical management of primary
hyperparathyroidism :
---medical therapy with drugs have not been shown
to affect the eventual outcome
---estrogens (premarin 1.25mg/day) preserve bone
mass in post-menopausal females
---well-hydrated by drinking 2 - 3 litres of fluid, and
8 - 10 g of salt daily
--dietary restriction of calcium is not necessary ,
thiazide diuretics must not be used
---oral phosphate should only be used if
symptomatic hypercalcemia cannot be corrected
surgically
Treatment
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Medical management of
hypercalcemia in cancer patients :
---2 - 3 litres per day + 8 - 10g of salt/day
---pamridonate can be used prn every few weeks to
keep the serum calcium in the normal range
---prednisone (20 - 50 mg bid) is only useful in
certain malignancies eg. multiple myeloma and
certain lymphomas
Treatment
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Medical management of other
disorders :
--prednisone and low-calcium diet ( < 400 mg/day )
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Medical management of
hypercalcemia in sarcoidosis :
--a low dose of prednisone (10 - 20 mg/day) is
usually adequate