Hypercalcemia

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Hypercalcemia

• Ayesha Shaikh
• Emory Family Medicine Residency Program

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Introduction

• 62 years old Nepali female
• Cc Hypertension, indigestion and fatigue since
  past many years.

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HPI

• 1- Hypertension for 10 years , treated with
  Amlodipine 5 mg in Nepal. CXR and blood tests
  normal at the time of immigration 1 month ago.
  Denies
• 2- Epigastric abdominal pains since past many
  years, non radiating, dull, 4/10, unrelated to
  the type or timing of food ingestion. Denies
  nausea, vomiting, diarrhea, constipation.
• 3- Fatigue for many years. No change in weight,
  mood or limitations in daily activity. Denies
  depressive symptoms.
• One prior FPC visit at Dunwoody Clinics for
  Medicines refill and necessary labs ordered.

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• PMH Hypertension, no prior hospitalizations
• PSH none
• SH recent immigrant, lives with family
  consisting of children and grand children. Good
  social support system. Daily chores. Denies smoke
  or alcohol.
• ROS Irritable mood,
• Meds Amlodipine 5 mg
• No OTC medicine use
• NKDA

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Physical exam

• Petit elderly female, no acute distress
• Vitals Height 5 1 Weight 100 lbs BMI20
• T 98.6 P 61 BP 154/98 RR 12
• Chest
• CVS
• Abd normal inspection, palpation, percussion and
  auscultation
• Neuro Cranial nerves intact, no motor or sensory
  deficit. Gait normal, reflexes 2
• ENT Non palpable thyroid gland

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Labs and tests

• CBC normal
• BMP Na 141 K 4.3,
• Bun/creat 10/0.80
• Glucose 95
• Calcium 11.0
• albumin 4.6
• Chloride 107
• CO2 21
• LFT WNL

• TSH 0.86
• Lipid profile T.Chol 186
• TG 87
• LDL 117
• HDL 52
• Urine Microalbumin/cr 0.2/30 7
• EKG
• Previous labs!
• Calcium 10.9

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Assessment and Plan

• Hypertension Amlodipine 5 mg
• Hypercalcemia Fup labs PTH
• Gastritis Pepcid
• Backache Lumbar spine X ray
• Health maintenance Flu vaccine and plan RPE
  visit.

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Test results

• PTH 127 (ref 10-65 pg/ml)
• Lumber DJD
• Parathyroid scan Right lower Parathyroid adenoma
• Follow up Blood pressures gt 150/90 mmhg,
  increased amlodipine dose and added HCTZ later
• Endocrinology referral for primary
  hyperparathyroidsism

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Endocrinology workup

• Exclude underlying secondary hyperparathyroidism,
  since low vitamin D levels very common in
  mountains of Himalayas.
• 25 hydroxyVitaminD levels 10 (30-80)
• Vitamin D replacement 50,000 units /week for 8
  weeks. Recheck calcium and Vit D levels thereafter

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Hypercalcemia

• Introduction 1/500, incidental finding
• The skeleton contains 98 percent of total body
  calcium the remaining 2 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

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Defination

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

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Defination

• 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)

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Pathophysiology

• Parathyroid hormone (PTH), 1,25-dihydroxyvitami
  n 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

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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

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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

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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

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Evaluation

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

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Evaluation

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

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TREATMENT

• Clinical indications for surgery in patients with
  primary hyperparathyroidism
• Significant symptoms of hypercalcemia
• Nephrolithiasis
• Decreased bone mass
• Serum Calcium gt 12 mg/dl
• Agelt 50 years
• Infeasibility of longterm follow up

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Pharmacologic options

• Normal Saline 2-4 L IV daily for 1-3 days
• Enhances filtration and excretion of CA.
• Indication Ca gt 14 mg/dl, moderate Calcium with
  symptoms
• Caution may exacerbate heart failure in elderly
  patients. Lowers Calcium by 1-3 mg/dl

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Pharmacologic options

• Furosemide 10-20 mg IV as necessary
• Inhibits calcium resorption in distal renal
  tubule.
• Indication following aggressive hydration
• Caution hypokalemia, dehydration if used before
  intravascular volume is restored

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Pharmacologic options

• Bisphosphonates
• Pamidronate
• Zoledronic acid
• Inhibits osteoclast action and bone resporption
• Indication hypercalcemia of malignancy

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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
• 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

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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

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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

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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

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References

• Carroll M, Schade D. A Practical Approach to
  Hypercalcemia. American Family Physician. May 1,
  2003.
• Taniegra E. Hyperparathyroidism. American Family
  Physician. January 15, 2004.