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Hypothyroidism Powered By Docstoc
					Calcium Disorders
      William E. Clutter, M.D.
      Associate Professor of Medicine




          Department of Internal Medicine
          Division of Endocrinology, Metabolism & Lipid Research
Calcium regulation
   Albumin binding – ionized vs total calcium
    • Corrected Ca = Ca (mg/dl) + 0.8 (4 – albumin in g/dl)


 Parathyroid hormone
 1,25 (OH)2 Vitamin D


   PTH-related peptide (PTHrP)
   Cytokines
 Calcium balance

                      BONE (1 kg)


                   500 mg         500 mg


      Net 175 mg                           Net 175 mg
GUT                 ECF CALCIUM                         KIDNEY
                            1000 mg
Hypercalcemia: clinical signs
   GI:
    • Nausea, vomiting, abdominal pain
    • Constipation
   Renal:
    • Polyuria, dehydration
    • Renal failure
   Neurological
    • Fatigue
    • Confusion
    • Stupor, coma
Hypercalcemia: major causes

  Primary hyperparathyroidism (PHPT)
  Malignancy
  Others
Hyperparathyroidism: causes
   Primary
    • Adenoma (90%)
    • Multiple gland enlargement (10%)
       – MEN 1
       – MEN 2A
       – Familial hyperparathyroidism
    • Carcinoma (<1%)
    • Familial benign hypercalcemia (FBH)
   Secondary (normo- or hypocalcemic)
    • Renal failure
    • Vitamin D deficiency
Malignant hypercalcemia: major causes
   PTHrP - mediated
    • Breast carcinoma
    • Squamous carcinoma (lung, head & neck, esophagus)
    • Renal carcinoma
   Cytokine - mediated
    • Myeloma (lymphoma, leukemia)
Hypercalcemia: other causes
   Drugs:
    •   Vitamin D
    •   Calcium carbonate (milk alkali syndrome)
    •   Lithium
    •   PTH
    •   Vitamin A


 Sarcoidosis, other granulomatous disorders
 Hyperthyroidism
Hypercalcemia: presentations
   Chronic, mild-moderate
    • Often asymptomatic
    • Cause: primary hyperparathyroidism
    • Issues: parathyroidectomy or not


   Acute, severe
    • Symptomatic
    • Cause: malignant hypercalcemia (rarely others)
    • Issues: treat hypercalcemia, find & treat cause
Primary hyperparathyroidism

  F:M 3:1
  Usually > 50 y/o
  Presentation:
     •   Asymptomatic hypercalcemia (>50%)
     •   Renal stones (20%)
     •   Decreased bone density
     •   Symptoms of hypercalcemia (<5%)
Hypercalcemia: evaluation
   Duration >6 months or renal stones: PHPT
   Signs of malignancy, other rare causes
   Medications (including OTC, supplements)
   Family history

   Plasma PTH
    • Normal or elevated: primary hyperpararthyroidism
    • Low: other causes
  Primary hyperparathyroidism: Rx
        Indications for parathyroidectomy:
          •   symptomatic hypercalcemia
          •   kidney stones
          •   bone density T-score < -2.5 SD
          •   plasma calcium >(ULN + 1) mg/dl
          •   age <50 years
          •   (urine calcium >400 mg/24 hr)



NIH consensus Panel JCEM 87:5353, 2002
Parathyroid Localization

                        Sestamibi scans




Left lower parathyroid adenoma    Mediastinal parathyroid adenoma
Primary hyperparathyroidism: pitfalls
    Positive family history:
     • Evaluate for MEN 1 or 2A
     • Evaluate for FBH
        – FE Ca <0.01
        – Evaluate family
        – CaSR gene analysis


    Concomitant vitamin D deficiency
     • PTH disproportionately high
     • More severe post-op hypocalcemia
     • Replete if 25-OH vitamin D <20 ng/dl
Primary hyperparathyroidism: pitfalls

   Diagnose before imaging!
    • False positive and negative sestamibi scans


   Normal ionized calcium:
    • Primary vs secondary hyperparathyroidism
Primary Hyperparathyroidism
   Follow-up of unoperated:
    •   Normal calcium intake
    •   Annual calcium, creatinine
    •   Biannual bone mass
    •   Bisphosphonate for osteoporosis
    •   Cinacalcet (calcimimetic) ?

   Indications for surgery
    • Declining bone mass or renal function
    • Worsening hypercalcemia
Nonparathyroid hypercalcemia
   Repeat history (especially drugs)
   Vitamin D toxicity suspected: 25 (OH) vitamin D
   Sarcoidosis suspected: 1,25 (OH)2 vitamin D
   Malignancy suspected:
    •   SPEP, UPEP
    •   Bone scan
    •   Chest & abdominal CT
    •   Biopsy
    •   PTHrp
Severe hypercalcemia:
   Principles of therapy
    • Expand ECF volume
    • Increase urinary calcium excretion
    • Decrease bone resorption


   Indications for therapy
    • Symptoms of hypercalcemia
    • Plasma [Ca] >12 mg/dl
Severe hypercalcemia: therapy
   Restore ECF volume
    • Normal saline rapidly
    • Positive fluid balance >2 liters in first 24 hr
   Saline diuresis
    • Normal saline 100-200 ml/hr (replace potassium)
   Zoledronic acid 4 mg IV over 15 min
    • if plasma [Ca] >14 mg/dl or >12 mg/dl after
      rehydration
    • Monitor plasma calcium QD
   Myeloma or vitamin D toxicity:
    • prednisone 30 mg BID
Hypocalcemia: clinical signs

   Paresthesias
   Tetany (carpopedal spasm)
   Trousseau’s, Chvostek’s signs
   Seizures
   Chronic: cataracts, basal ganglia Ca
Trousseau’s sign
Hypocalcemia: causes
   Hypoparathyroidism
    • Surgical
    • Autoimmune
    • Magnesium deficiency
   PTH resistance (pseudohypoparathyroism)

 Vitamin D deficiency
 Vitamin D resistance


   Other: renal failure, pancreatitis, tumor lysis
Hypocalcemia: evaluation

 Confirm low corrected & ionized calcium
 History:
    •   Neck surgery
    •   Other autoimmune endocrine disorders
    •   Causes of Mg deficiency
    •   Malabsorption
    •   Family history
Hypocalcemia: evaluation
   Physical exam:
    • Signs of tetany
    • Signs of pseudohypoparathyroidism
       – Short metacarpals
       – Short stature, round face
   Lab
    • PTH
    • Creatinine, Mg, P, alkaline phosphatase
    • 25-OH vitamin D
   Hypocalcemia: evaluation
       Cause           Phosphate   Alk phos    Other
Hypoparathyroidism      High       Normal     PTH low


PTH resistance          High       Normal     PTH high


Vitamin D deficiency    Low         High      25-OHD low


Vitamin D resistance    Low         High
Hypocalcemia: acute therapy

   IV calcium infusion
    • 1-2 gm Ca gluconate (10-20 ml) IV over 10 min
    • 6 gm Ca gluconate/500 cc D5W over 6 hr
    • Follow plasma Ca & P Q 4-6 hr & adjust rate


   IV or oral calcitriol 0.25-2 mcg/day

   Oral calcium carbonate 1-2 gm BID-TID
Hypocalcemia: chronic therapy
 Oral calcitriol 0.25-2 mcg/day
 Calcium carbonate 1-2 gm BID-TID

				
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posted:3/28/2008
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