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Calcium disorder

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Calcium disorder

  1. 1. Calcium Disorders William E. Clutter, M.D. Associate Professor of Medicine Department of Internal Medicine Division of Endocrinology, Metabolism & Lipid Research
  2. 2. Calcium regulation <ul><li>Albumin binding – ionized vs total calcium </li></ul><ul><ul><li>Corrected Ca = Ca (mg/dl) + 0.8 (4 – albumin in g/dl) </li></ul></ul><ul><li>Parathyroid hormone </li></ul><ul><li>1,25 (OH) 2 Vitamin D </li></ul><ul><li>PTH-related peptide (PTHrP) </li></ul><ul><li>Cytokines </li></ul>
  3. 3. Calcium balance ECF CALCIUM GUT KIDNEY BONE (1 kg) Net 175 mg Net 175 mg 500 mg 500 mg 1000 mg
  4. 4. Hypercalcemia: clinical signs <ul><li>GI: </li></ul><ul><ul><li>Nausea, vomiting, abdominal pain </li></ul></ul><ul><ul><li>Constipation </li></ul></ul><ul><li>Renal: </li></ul><ul><ul><li>Polyuria, dehydration </li></ul></ul><ul><ul><li>Renal failure </li></ul></ul><ul><li>Neurological </li></ul><ul><ul><li>Fatigue </li></ul></ul><ul><ul><li>Confusion </li></ul></ul><ul><ul><li>Stupor, coma </li></ul></ul>
  5. 5. Hypercalcemia: major causes <ul><li>Primary hyperparathyroidism (PHPT) </li></ul><ul><li>Malignancy </li></ul><ul><li>Others </li></ul>
  6. 6. Hyperparathyroidism: causes <ul><li>Primary </li></ul><ul><ul><li>Adenoma (90%) </li></ul></ul><ul><ul><li>Multiple gland enlargement (10%) </li></ul></ul><ul><ul><ul><li>MEN 1 </li></ul></ul></ul><ul><ul><ul><li>MEN 2A </li></ul></ul></ul><ul><ul><ul><li>Familial hyperparathyroidism </li></ul></ul></ul><ul><ul><li>Carcinoma (<1%) </li></ul></ul><ul><ul><li>Familial benign hypercalcemia (FBH) </li></ul></ul><ul><li>Secondary (normo- or hypocalcemic) </li></ul><ul><ul><li>Renal failure </li></ul></ul><ul><ul><li>Vitamin D deficiency </li></ul></ul>
  7. 7. Malignant hypercalcemia: major causes <ul><li>PTHrP - mediated </li></ul><ul><ul><li>Breast carcinoma </li></ul></ul><ul><ul><li>Squamous carcinoma (lung, head & neck, esophagus) </li></ul></ul><ul><ul><li>Renal carcinoma </li></ul></ul><ul><li>Cytokine - mediated </li></ul><ul><ul><li>Myeloma (lymphoma, leukemia) </li></ul></ul>
  8. 8. Hypercalcemia: other causes <ul><li>Drugs: </li></ul><ul><ul><li>Vitamin D </li></ul></ul><ul><ul><li>Calcium carbonate (milk alkali syndrome) </li></ul></ul><ul><ul><li>Lithium </li></ul></ul><ul><ul><li>PTH </li></ul></ul><ul><ul><li>Vitamin A </li></ul></ul><ul><li>Sarcoidosis, other granulomatous disorders </li></ul><ul><li>Hyperthyroidism </li></ul>
  9. 9. Hypercalcemia: presentations <ul><li>Chronic, mild-moderate </li></ul><ul><ul><li>Often asymptomatic </li></ul></ul><ul><ul><li>Cause: primary hyperparathyroidism </li></ul></ul><ul><ul><li>Issues: parathyroidectomy or not </li></ul></ul><ul><li>Acute, severe </li></ul><ul><ul><li>Symptomatic </li></ul></ul><ul><ul><li>Cause: malignant hypercalcemia (rarely others) </li></ul></ul><ul><ul><li>Issues: treat hypercalcemia, find & treat cause </li></ul></ul>
  10. 10. Primary hyperparathyroidism <ul><li>F:M 3:1 </li></ul><ul><li>Usually > 50 y/o </li></ul><ul><li>Presentation: </li></ul><ul><ul><li>Asymptomatic hypercalcemia (>50%) </li></ul></ul><ul><ul><li>Renal stones (20%) </li></ul></ul><ul><ul><li>Decreased bone density </li></ul></ul><ul><ul><li>Symptoms of hypercalcemia (<5%) </li></ul></ul>
  11. 11. Hypercalcemia: evaluation <ul><li>Duration >6 months or renal stones: PHPT </li></ul><ul><li>Signs of malignancy, other rare causes </li></ul><ul><li>Medications (including OTC, supplements) </li></ul><ul><li>Family history </li></ul><ul><li>Plasma PTH </li></ul><ul><ul><li>Normal or elevated: primary hyperpararthyroidism </li></ul></ul><ul><ul><li>Low: other causes </li></ul></ul>
  12. 12. Primary hyperparathyroidism: Rx <ul><li>Indications for parathyroidectomy: </li></ul><ul><ul><li>symptomatic hypercalcemia </li></ul></ul><ul><ul><li>kidney stones </li></ul></ul><ul><ul><li>bone density T-score < -2.5 SD </li></ul></ul><ul><ul><li>plasma calcium >(ULN + 1) mg/dl </li></ul></ul><ul><ul><li>age <50 years </li></ul></ul><ul><ul><li>(urine calcium >400 mg/24 hr) </li></ul></ul>NIH consensus Panel JCEM 87:5353, 2002
  13. 13. Parathyroid Localization Sestamibi scans Left lower parathyroid adenoma Mediastinal parathyroid adenoma
  14. 14. Primary hyperparathyroidism: pitfalls <ul><li>Positive family history: </li></ul><ul><ul><li>Evaluate for MEN 1 or 2A </li></ul></ul><ul><ul><li>Evaluate for FBH </li></ul></ul><ul><ul><ul><li>FE Ca <0.01 </li></ul></ul></ul><ul><ul><ul><li>Evaluate family </li></ul></ul></ul><ul><ul><ul><li>CaSR gene analysis </li></ul></ul></ul><ul><li>Concomitant vitamin D deficiency </li></ul><ul><ul><li>PTH disproportionately high </li></ul></ul><ul><ul><li>More severe post-op hypocalcemia </li></ul></ul><ul><ul><li>Replete if 25-OH vitamin D <20 ng/dl </li></ul></ul>
  15. 15. Primary hyperparathyroidism: pitfalls <ul><li>Diagnose before imaging! </li></ul><ul><ul><li>False positive and negative sestamibi scans </li></ul></ul><ul><li>Normal ionized calcium: </li></ul><ul><ul><li>Primary vs secondary hyperparathyroidism </li></ul></ul>
  16. 16. Primary Hyperparathyroidism <ul><li>Follow-up of unoperated: </li></ul><ul><ul><li>Normal calcium intake </li></ul></ul><ul><ul><li>Annual calcium, creatinine </li></ul></ul><ul><ul><li>Biannual bone mass </li></ul></ul><ul><ul><li>Bisphosphonate for osteoporosis </li></ul></ul><ul><ul><li>Cinacalcet (calcimimetic) ? </li></ul></ul><ul><li>Indications for surgery </li></ul><ul><ul><li>Declining bone mass or renal function </li></ul></ul><ul><ul><li>Worsening hypercalcemia </li></ul></ul>
  17. 17. Nonparathyroid hypercalcemia <ul><li>Repeat history (especially drugs) </li></ul><ul><li>Vitamin D toxicity suspected: 25 (OH) vitamin D </li></ul><ul><li>Sarcoidosis suspected: 1,25 (OH) 2 vitamin D </li></ul><ul><li>Malignancy suspected: </li></ul><ul><ul><li>SPEP, UPEP </li></ul></ul><ul><ul><li>Bone scan </li></ul></ul><ul><ul><li>Chest & abdominal CT </li></ul></ul><ul><ul><li>Biopsy </li></ul></ul><ul><ul><li>PTHrp </li></ul></ul>
  18. 18. Severe hypercalcemia: <ul><li>Principles of therapy </li></ul><ul><ul><li>Expand ECF volume </li></ul></ul><ul><ul><li>Increase urinary calcium excretion </li></ul></ul><ul><ul><li>Decrease bone resorption </li></ul></ul><ul><li>Indications for therapy </li></ul><ul><ul><li>Symptoms of hypercalcemia </li></ul></ul><ul><ul><li>Plasma [Ca] >12 mg/dl </li></ul></ul>
  19. 19. Severe hypercalcemia: therapy <ul><li>Restore ECF volume </li></ul><ul><ul><li>Normal saline rapidly </li></ul></ul><ul><ul><li>Positive fluid balance >2 liters in first 24 hr </li></ul></ul><ul><li>Saline diuresis </li></ul><ul><ul><li>Normal saline 100-200 ml/hr (replace potassium) </li></ul></ul><ul><li>Zoledronic acid 4 mg IV over 15 min </li></ul><ul><ul><li>if plasma [Ca] >14 mg/dl or >12 mg/dl after rehydration </li></ul></ul><ul><ul><li>Monitor plasma calcium QD </li></ul></ul><ul><li>Myeloma or vitamin D toxicity: </li></ul><ul><ul><li>prednisone 30 mg BID </li></ul></ul>
  20. 20. Hypocalcemia: clinical signs <ul><li>Paresthesias </li></ul><ul><li>Tetany (carpopedal spasm) </li></ul><ul><li>Trousseau’s, Chvostek’s signs </li></ul><ul><li>Seizures </li></ul><ul><li>Chronic: cataracts, basal ganglia Ca </li></ul>
  21. 21. Trousseau’s sign
  22. 22. Hypocalcemia: causes <ul><li>Hypoparathyroidism </li></ul><ul><ul><li>Surgical </li></ul></ul><ul><ul><li>Autoimmune </li></ul></ul><ul><ul><li>Magnesium deficiency </li></ul></ul><ul><li>PTH resistance (pseudohypoparathyroism) </li></ul><ul><li>Vitamin D deficiency </li></ul><ul><li>Vitamin D resistance </li></ul><ul><li>Other: renal failure, pancreatitis, tumor lysis </li></ul>
  23. 23. Hypocalcemia: evaluation <ul><li>Confirm low corrected & ionized calcium </li></ul><ul><li>History: </li></ul><ul><ul><li>Neck surgery </li></ul></ul><ul><ul><li>Other autoimmune endocrine disorders </li></ul></ul><ul><ul><li>Causes of Mg deficiency </li></ul></ul><ul><ul><li>Malabsorption </li></ul></ul><ul><ul><li>Family history </li></ul></ul>
  24. 24. Hypocalcemia: evaluation <ul><li>Physical exam: </li></ul><ul><ul><li>Signs of tetany </li></ul></ul><ul><ul><li>Signs of pseudohypoparathyroidism </li></ul></ul><ul><ul><ul><li>Short metacarpals </li></ul></ul></ul><ul><ul><ul><li>Short stature, round face </li></ul></ul></ul><ul><li>Lab </li></ul><ul><ul><li>PTH </li></ul></ul><ul><ul><li>Creatinine, Mg, P, alkaline phosphatase </li></ul></ul><ul><ul><li>25-OH vitamin D </li></ul></ul>
  25. 25. Hypocalcemia: evaluation Cause Hypoparathyroidism PTH resistance Vitamin D deficiency Vitamin D resistance Phosphate High High Low Low Other PTH low PTH high 25-OHD low Alk phos Normal Normal High High
  26. 26. Hypocalcemia: acute therapy <ul><li>IV calcium infusion </li></ul><ul><ul><li>1-2 gm Ca gluconate (10-20 ml) IV over 10 min </li></ul></ul><ul><ul><li>6 gm Ca gluconate/500 cc D5W over 6 hr </li></ul></ul><ul><ul><li>Follow plasma Ca & P Q 4-6 hr & adjust rate </li></ul></ul><ul><li>IV or oral calcitriol 0.25-2 mcg/day </li></ul><ul><li>Oral calcium carbonate 1-2 gm BID-TID </li></ul>
  27. 27. Hypocalcemia: chronic therapy <ul><li>Oral calcitriol 0.25-2 mcg/day </li></ul><ul><li>Calcium carbonate 1-2 gm BID-TID </li></ul>

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