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Hypercalcemia

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For Internists and Critical care physcians

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  • 1.  
  • 2. Hypercalcemia Ahmed Elshebiny University of Menoufyia
  • 3. Case : History
    • A 41-year-old woman was brought by her husband to the emergency department with a history of 72 hours of epigastric pain, nausea, repeated vomiting, and altered mental status. Her blood calcium was found to be 18.9 mg per deciliter (4.7 mmol per liter).
    • Alcoholic, peptic ulcer, analgesics for back pain
  • 4. Examination
    • On physical examination,
    • the blood pressure was 160/90 mm Hg,
    • the heart rate 100 beats per minute, and
    • the temperature 37.4°C.
    • The patient was disoriented and intermittently writhing in pain.
    • Her skin turgor was poor, and her oral mucosa was dry.
    • The cardiac examination was significant only for tachycardia, and
    • the pulmonary examination was normal.
    • There was epigastric tenderness on palpation but no rebound tenderness.
    • The patient was responsive to simple commands and was not tremulous.
    • There were no other significant neurologic findings.
  • 5. Investigations
  • 6. Specific investigations
    • Intact parathyroid= undetectable
    • 25 hydroxy vitamin D = normal
    • PTH related protein= normal
    • Calcium fall with hydration only
    • Computed tomography (CT) of the neck revealed no parathyroid masses. CT of the chest was normal. Abdominal CT showed an edematous pancreas with surrounding infiltration of the mesenteric fat, a finding consistent with acute pancreatitis. No bone lesions were noted on the chest or abdominal CT scans.
  • 7. Diagnosis
    • In response to further questioning, the patient reported that during the days before admission she had consumed the contents of entire containers of Tums and a preparation containing sodium bicarbonate (Alka-Seltzer, Bayer) because of the severe abdominal pain. She did not consume any other medications or supplements.
    • This history, together with the laboratory-test results, establishes the "milk alkali syndrome" as the primary diagnosis
  • 8. Milk Alkali Syndrome
    • The pathogenesis of the milk alkali syndrome involves a reduction in the ability of the kidney to excrete excess calcium.
    • This reduction is secondary to a decrease in the glomerular filtration rate (due to renal vasoconstriction and hypovolemia) and to a significant increase in tubular reabsorption of calcium (secondary to metabolic alkalosis).
    • The plasma PTH level decreases with the rise in the serum calcium level.
    • Thus, the constellation of excess oral intake of calcium and milk, plus impaired renal function, may result in PTH suppression, hypercalcemia, and hyperphosphatemia.
    • In cases of chronic ingestion of excessive alkaline calcium preparations and milk, metastatic calcifications and occasionally nephrocalcinosis may occur, 7 whereas such complications are not expected with acute milk alkali syndrome, as in the present case.
  • 9. Calcium
    • Plays a role inside (intracellular) and outside (extarcellular) cells
    • Functions of calcium
          • Muscle contraction
          • Nerve conduction
          • Coagulation
          • Enzyme and electrolyte regulation
          • Hormone release and exocytosis
          • Cell division
    • Calcium enters extra-cellular fluid from intestine and bone
    • Calcium is excreted through kidneys
    • Calcium is tightly controlled by hormones (PTH, Calcitriol, calcitonin)
    • Human body contains 1100 g calcium
  • 10.  
  • 11.  
  • 12.  
  • 13. Hypercalcemia
    • For hypercalcemia to develop, the normal calcium regulation system must be overwhelmed by an excess of PTH, Calcitriol, some other serum factor that can mimic these hormones, or a huge calcium load.
    • Between 20 and 40% of patients with cancer develop hypercalcemia at some point in their disease
    • the most common serious electrolyte presenting in adults with malignancies
    • primary hyperparathyroidism is considerably higher in women.
    • Hyperparathyroidism and malignancy increases with age
    • Breast cancer is one of the most common malignancies responsible for hypercalcemia.
  • 14. PTH dependent hypercalcemia
    • Primary hyperpara( adenoma commonly)
    • Tertiary hyperparathyroidism
    • FHH
    • MEN syndromes
    • Lithium therapy
  • 15. PTH independent hypercalcemia
    • Malignancy related
    • Vitamin D related( Granulomas, infections, toxcicity, williams syndrome)
    • Other endocrine( hyperthyroidism, pheochromocytoma, adrenal insufficiency, islet cell tumor)
    • Miscellaneous( immobilization, milk alkali, other medications)
  • 16. Hypercalcemia of Hyperparathyroid
    • Primary: Usually adenoma
    • Secondary
    • tertiary
    • Hypophosphatemia and elevated urine calcium
    • Surgery
    • Complications of surgery
  • 17. PTH and calcium measurment
    • PTH assay
    • PTH related protein
    • Total calcium
    • Ionized calcium
  • 18. FHH
    • Autosomal dominant,
    • usually mild elevation
    • Shift of the set point
    • Urine calcim is low
    • Previous history of normal calcium rules out FHH
  • 19. Hypercalcemia of Malignancy
    • Secretion of PTH related peptide
    • Osteoclastic activation
    • Secretion of vitamin D
    • Unknown mechanisms
    • Common with( Breast cancer with bone metastasis, lung cancer, multiple myeloma, Hodgikins, pancreatic islet tumors, cholangiocarcinoma and adenocarcinomas)
  • 20. Symptoms
    • Depends on the underlying disease and rate of increase in serum calcium
    • Mild elevations in calcium levels usually have few or no symptoms
    • Manifestations include
          • Nausea, vomiting, abd pain, stones, constipation, pancreatitis, ulcer
          • Polyuria, polydepsia, nocturia
          • Weakness and vague muscle and Joint aches
          • Altered mental state, lethargy, depression, Headache , confusion
          • Coma
    • Hypercalcemia of malignancy
    • Hypercalcemia of Hyperparathroid
  • 21. Examination
    • Mental state
    • Pulse and blood pressure
    • Abdomen
    • Reflexes and muscle power
    • Hydration
    • Malignancy
    • Other specific disease
    • Band keratopathy
  • 22. ECG
    • Short Q-T
    • Prolonged P-R
    • At high levels …. Wide QRS
    • Flat or inverted T
    • Variable degrees of Heart block
    • N.B. Digoxin effects are amplified
  • 23. Phosphate and Chloride
    • Serum phosphate levels tend to be low or normal in primary hyperparathyroidism and hypercalcemia of malignancy.
    • Phospate levels are elevated in hypercalcemia secondary to vitamin D–related disorders or thyrotoxicosis.
    • Serum chloride levels usually are higher than 102 mEq/L in hyperparathyroidism and less than this value in other forms of hypercalcemia.
  • 24. Investigations and DD
  • 25. Vitamin D metabolism
  • 26. Treatment
    • Hydration
    • Loop diuretics (avoid thiazide)
    • Biphosphonates and other medications
    • Dialysis
    • Surgery
    • Chemo or radiotherapy for malignancy
  • 27. Medications used to treat Hypercalcemia Medications used to treat Hypercalcemia Bisphosphonates Calcitonin Gallium nitrate (Ganite) Plicamycin Glucocorticoids Phosphate Cinacalcite Pamidronate Zolidronic acid Etidronate
  • 28. Acute management
    • Rehdrate + or - lasix
    • Bisphosphonate
    • Other Medicate
    • Calcitonin
    • May be phosphate
  • 29. Chronic management
    • Indications of surgery in hyperparathyroidism
    • Biphosphonates
    • Cortisone in myeloma
    • Cortisone in granulomas and /or hydroxy chloroquine or ketokonazole
    • Cinacalcet
  • 30. Take home points
    • Majority of hypercalcemias are caused by hyperparathyroid or malignancy but others other sought when the diagnosis is not clear
    • Symptoms are usually subtle
    • Severer hypercalcemia(stones , bones, moans and groans)
    • History + PTH levels are the essentials for diagnosis
    • Acute management focuses on hydration the other medications
    • Chroni management focuses on the underlying aetiology
  • 31. References
    • Washington subspecialty consult: Endocrinology 2009
    • Kumar and Klark’s Medicine 2009
    • E-medicine online text book – emergency medicine/ and Nephrology
    • Nejm CASES, 2008
  • 32. THANK YOU