Hypercalcemia

1
Hypercalcemia

• By Ri ???

2
Introduction

• 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

3
Definition

• 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 gt
  10.5 mg/dl(gt2.5 m mol/L ) or ionized serum
  calcium gt 5.6 mg/dl ( gt1.4 m mol/L )

4
Definition

• Severe hypercalemia is defined as total serum
  calcium gt 14 mg/dl (gt 3.5 mmol/L)
• Hypercalcemic crises is present when severe
  neurological symptoms or cardiac arrhythmias are
  present in a patient with a serum calcium gt 14
  mg/dl (gt 3.5 mmol/L) or when the serum calcium is
  gt 16 mg/dl (gt 4 mmol/L)

5
(No Transcript)
6
Pathophysiology

• Parathyroid hormone (PTH), 1,25-dihydroxyvitamin
  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

7
Pathophysiology

• 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

8
Pathophysiology

• 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

9
Clinical Manifestations

• 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

10
Clinical Manifestations

• Renal porlyuria , nephrolithiasis
• GI anorexia , nausea , vomiting , constipation
  , Pancreatitis , PUD
• Neuro- psychiatric weakness , fatigue ,
  confusion , stupor , coma

11
Clinical Manifestations

• Cardiovascular Shortened QT interval on
  electrocardiogram,, bradyarrhythmias and heart
  block and cardiac arrest
• Cornea band keratopathy

12
Differential Diagnosis

• 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

13
Differential Diagnosis

• The most common cause of hypercalcemia is primary
  hyperparathyroidism, and malignancy is the second
  most common cause - together they account for gt
  90 of cases
• primary hyperparathyroidism is usually secondary
  to a parathyroid adenoma (85), parathyroid
  hyperplasia (15) and rarely due to a parathyroid
  carcinoma (lt 1)

14
Differential Diagnosis

• 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

15
Differential Diagnosis

• Malignancy increases osteoclastic activity by two
  mechanisms - production of a PTH-like 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)

16
Differential Diagnosis

• Granulomatous disease
• sarcoidosis?tuberculosis?leprosy ?
  berylliosis
• histoplasmosis/coccidiomycosis
• disseminated candidiasis/cryptococcosis
• Non-parathyroid endocrine disorders
• Hyperthyroidism ?adrenal insufficiency
• pheochromocytoma

17
Differential Diagnosis

• Vitamin D intoxication
• increased gastro-intestinal absorption of
  calcium
• Mild alkali syndrome
• increased gastro-intestinal absorption of
  calcium
• Drugs
• lithium?thiazide diuretics , vitamin A

18
Differential Diagnosis

• Familial hypocalciuric hypercalcemia
• Chronic renal insufficiency
• Immobilisation and high bone turnover
• Pagets disease of bone

19
Evaluation

• 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

20
Evaluation

• Primary hyperparathyroidism PTH?
• MALIGNANCY
• 1.solid tumors(humoral hypercalcemia) PTHrP?
  , PTH?
• 2.Multiple myeloma and breast
  cancer(osteolytic hypercalcemia ) alkaline
  phosphatase ?, PTH?

21
Evaluation

• Granulomatous(sarcoidosis, tuberculosis,
  Hodgkin's lymphoma) calcitriol (1,25-OH vitamin
  D3 ) ?, PTH?
• Familial hypocalciuric hypercalcemia
• 24-hour urinary calcium ?, PTH ?

22
(No Transcript)
23
Treatment

• Saline/fluid hydration
• --increases renal calcium excretion
• ---2 to 4 L IV daily for 1 to 3 days
• Biphosphonates
• ---inhibition bone resorption
• ---Pamidronate (Aredia), 60 to 90 mg IV over
  4 hours

24
Treatment

• Calcitonin
• ----inhibition bone resorption and increases
  renal calcium excretion
• ----4 to 8 IU per kg IM or SQ every 6 hours
  for 24 hours
• Plicamycin (Mitharmycin)
• ----decreases bone resorption
• ----25 mcg per kg per day IV over 6 hours for
  3 to 8 doses

25
Treatment

• Gallium nitrate
• -----inhibition bone resorption
• -----100 to 200 mg per m2 IV over 24 hours for
  5 days
• Glucocorticoids
• ----Inhibits vitamin D conversionto
  calcitriol
•  -----Hydrocortisone, 200 mg IV daily for 3
  days
• Hemodialysis
• ---used in patients with renal failure

26
Treatment

• Clinical indications for surgery in patients with
  primary hyperparathyroidism
• 1.significant symptoms of hypercalcemia
• 2.nephrolithiasis
• 3.decreased bone mass (gt 2 standard deviations
  below mean for age)
• 4.serum calcium gt 12mg/dl
• 5.age lt 50 years
• 6.infeasibility of long-term follow-up

27
Treatment

• 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

28
Treatment

• 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

29
Treatment

• Medical management of other disorders
• --prednisone and low-calcium diet ( lt 400 mg/day
  )
• Medical management of hypercalcemia in
  sarcoidosis
• --a low dose of prednisone (10 - 20 mg/day) is
  usually adequate

30
Thank you for your attention !