8 paul hypocalcemia cerc 2014 - mcmaster …€¦ · blood calcium increases absorption ... •...
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HYPOCALCEMIA
Terri L. Paul MD FRCPC Cert Endo Endocrinology & Metabolism
Western University
Faculty/Presenter Disclosure • Faculty: Terri Paul
• Rela0onships with commercial interests:* – Grants/Research Support: Amgen, Lilly, Novar0s – Speakers Bureau/Honoraria: Amgen, Lilly, AbboF – Consul0ng Fees: N/A – Other: N/A
Disclosure of Commercial Support • This program has received financial support from Eli Lilly/ Boehringer
Ingelheim, Novo Nordisk, Pfizer, Sanofi, Astra/BMS, Merck, NovarPs, Serono/EMD, Jannssen in the form of an Unrestricted EducaPonal Grant
• This program has not received in-‐kind support from any commercial organizaPon
• Poten0al for conflict(s) of interest:
Terri Paul has received funding from Amgen, Lilly, NovarPs supporPng this program.
• Mi0ga0ng Poten0al Bias • PresentaPon had been developed independently by Dr. Paul
with no input from supporPng industry.
Calcium Regulation Bone
Releases calcium &
phosphorus
Increased blood calcium
Increases absorption of dietary calcium &
phosphorus
Small and
Large Bowel
Liver
Kidney
Sunlight or diet
Vitamin D
Parathyroids Sense low blood Ca & increases PTH secretion
↑ PTH
Calcitrol (1,25(OH)2D)
Calcitrol (1,25(OH)2D)
25(OH)D
♦ Increases calcitrol formation ♦ Decreases excretion of calcium ♦ Increases excretion of phosphorus
D. Hanley
Calcium Homeostasis
Total serum Ca 2.12-2.62 mmol/l Ionized Ca 1.1-1.3 mmol/l (50%) Protein bound Ca 0.9-1.1 mmol/l (40%) Complexed Ca 0.18 mmol/l (10%) Change in Albumin of 1 gm/l causes a
change in Ca of 0.02 mmol/l
Calcium Homeostasis
Change in Albumin of 1 gm/l causes a change in Ca of 0.02 mmol/l
So if Ca of 2.0 with albumin of 20, what is
actual Ca? Ca = Serum Ca + [0.02 X (Normal Albumin
– Patient Albumin)]
Calcium Homeostasis
Change in Albumin of 1 gm/l causes a change in Ca of 0.02 mmol/l
So if Ca of 2.0 with albumin of 20, what is
actual Ca? Ca = Serum Ca + [0.02 X (Normal Albumin
– Patient Albumin)] 2.0 + [0.02 X (40-20)] = (20 X 0.02) + 2.0 = 2.4
Hypocalcemia
Hypocalcemia Serum Calcium< 2.12 mmol/L Results from: • Failure to secrete PTH • Failure to respond to PTH • Deficiency of Vitamin D • Failure to respond to Vitamin D • Rarely, acute complexation of Ca
Symptoms of Hypocalcemia
Acute: • Severe Hypocalcemia Tetany – parasthesias, carpo-‐pedal
spasm, laryngeal spasm, convulsions • Mild Hypocalcemia Chvostek’s and Trousseau’s signs
bradycardia, impaired cardiac contracPlity, and prolongaPon of the QT interval
Symptoms of Hypocalcemia
Chronic: • Neuropsychiatric symptoms –
papilledema, confusion, lassitude • Catarcts • Dry skin, brittle nails • Basal cell ganglia calcification
EPology of Hypocalcemia
PTH Deficient : low Ca, high phosphate, low PTH
• Hypoparathyroidism • Surgical • Idiopathic (polyglandular endocrinopathies)
PTH Resistant: low Ca, high phosphate, high PTH
• Vitamin D deficiency • Pseudohypoparathyroidism: Inherited, two forms 1a or b and 2, lack of response to PTH
Pseudohypoparathyroidism • Type 1a, resistance to
PTH (GNAS1 mutation) in kidney and bone
• Round facies, short stature, short metacarpal and metatarsal bones (Albright’s hereditary osteodystrophy)
• Pseudopseudohypo-parathyroidism has same phenotype but no PTH insensitivity
EPology of Hypocalcemia
Vitamin D Deficient: low Ca, low phosphate, high PTH More common than PTH disorders
• Malabsorption – fat soluble vitamin • Renal failure, liver failure • Drugs (phenytoin) • Diet (rare) • Lack of exposure to sun • Rickets, osteomalacia
EPology of Hypocalcemia Minor: • Hypoalbuminemia • Hypomagnesemia – ETOH, malabsorption • Pancreatitis • Inappropriate ADH secretion • Tumor lysis, rhabdomyolosis, sepsis • Massive transfusion
Hypoparathyroidism Vitamin D deficiency
Calcium Low Low
Phosphate High Low
Alk Phos Normal High
PTH Low High
Treatment of Hypocalcemia
• Management of hypocalcemia depends upon the severity and acuity of symptoms.
• In paPents with acute symptomaPc hypocalcemia, intravenous calcium gluconate is the preferred therapy,
• Chronic hypocalcemia is treated with oral calcium and vitamin D supplements.
Treatment of Hypocalcemia
Acute: • Calcium gluconate
10 mls of a 10% soluPon IV over 10 minutes Followed by 20-‐80 mls over 8 hours in NS
Chronic: • Vitamin D: 0.5 mg/day (50,000IU) or
1,25 diOH (calcitriol) 0.25 -0.05 mcg BID
• Calcium supplements
Calcium infusion in Severe Hypocalcemia
• IV Calcium infusion in severe hypocalcemia calcium (1 to 2 g of calcium gluconate, equivalent to 90 to 180 mg elemental calcium, in 50 mL of 5 percent dextrose) can be infused over 10 to 20 minutes.
• The calcium should not be given more rapidly, because of the risk of serious cardiac dysfuncPon, including systolic arrest.
• This dose of calcium gluconate will raise the serum calcium concentraPon for only two or three hours; as a result, it should be followed by a slow infusion of calcium in paPents with persistent hypocalcemia.
Calcium infusion in Severe Hypocalcemia
• Either 10 percent calcium gluconate (90 mg of elemental calcium per 10 mL) or 10 percent calcium chloride (270 mg of elemental calcium per 10 mL) can be used to prepare the infusion soluPon
• Calcium gluconate is usually preferred because it is less likely to cause Pssue necrosis if extravasated.
• An IV soluPon containing 1 mg/mL of elemental calcium is prepared by adding 11 g of calcium gluconate (equivalent to 990 mg elemental calcium) to normal saline or 5 percent dextrose water to provide a final volume of 1000 mL.
• This soluPon is administered at an iniPal infusion rate of 50 mL/hour (equivalent to 50 mg/hour).
• The dose can be adjusted to maintain the serum calcium concentraPon at the lower end of the normal range (with the serum calcium corrected for any abnormaliPes in serum albumin as noted above).
• PaPents typically require 0.5 to 1.5 mg/kg of elemental calcium per hour.
Calcium infusion in Severe Hypocalcemia
The infusion should be prepared with the following consideraPons: • The calcium should be diluted in dextrose and water or saline
because concentrated calcium soluPons are irritaPng to veins. • The intravenous soluPon should not contain bicarbonate or
phosphate, which can form insoluble calcium salts. If these anions are needed, another intravenous line (in another limb) should be used.
Intravenous calcium should be conPnued unPl the paPent is receiving an effecPve regimen of oral calcium and vitamin D.
Calcitriol, in a dose of 0.25 to 0.5 mcg twice daily, is the preferred preparaPon of vitamin D for paPents with severe acute hypocalcemia because of its rapid onset of acPon (hours).
Treatment of Hypoparathyroidism
Goals of therapy are to • Relieve symptoms • Maintain the serum calcium concentraPon in the low-‐normal range 2.0 to 2.1 mmol/L
• Aiainment of higher values is not necessary and is usually limited by the development of hypercalciuria due to the loss of renal calcium retaining effects of PTH
Oral calcium
• 1500 to 2000 mg of elemental calcium given as calcium carbonate or calcium citrate daily, in divided doses.
• Calcium carbonate is 40 percent elemental calcium, so that 1250 mg of calcium carbonate contains 500 mg of elemental calcium.
• The dose of elemental calcium is listed on most supplement labels.
• Calcium carbonate is the least expensive, it may be less well-‐absorbed in older paPents and those who have achlorhydria. These paPents do beier with calcium citrate
Treatment of Hypoparathyroidism
• The iniPal dose of calcitriol is typically 0.25 to 0.5 mcg twice daily.
• Major side effects are hypercalcemia and hypercalciuria, which, if chronic, can cause nephrolithiasis, nephrocalcinosis, and renal failure.
• Hypercalciuria is the earliest sign of toxicity and can develop in the absence of hypercalcemia
Treatment of Hypoparathyroidism • Aker iniPaPng therapy, serum and urinary calcium should be measured frequently (two-‐week intervals)
• Then every six months to one year once a stable dose is achieved.
• Hypercalciuria and, if present, hypercalcemia usually resolve in a few days aker cessaPon of therapy in paPents treated with calcitriol.
• In contrast, recovery is slower in paPents treated with vitamin D, but can be accelerated by a short course of glucocorPcoid therapy
Treatment of Hypoparathyroidism
• Some paPents with hypoparathyroidism require a thiazide diurePc (25 to 100 mg daily), with or without dietary sodium restricPon, to decrease urinary calcium excrePon
Treatment of Hypocalcemia Compound Trade Name Potency vs
D3 Onset action
days Offset action
D3 cholecalciferol
25,000- 100,000 U
1 10-14 Weeks to months
D2 ergocalciferol
25,000- 100,000 U
1 10-14 Weeks to months
Dihydrotachy-sterol
Hytackerol 5-10 4-7 7-21 days
Calcifediol 25OHvitD3
Calderol 10-15 7-10 weeks
*Alphacalcidiol 1aOHvit D3
One-alpha 0.25-2 ug/d
1000 1-2 2-3 days
*Calcitriol 1,25diOHvitD3
Rocaltrol 0.25-2 ug/d
1000 1-2 2-3 days
Recombinant PTH therapy
• Hypoparathyroidism is one of the few remaining hormonal insufficiencies for which hormone replacement therapy is unavailable
• Recombinant human parathyroid hormone (teriparaPde) is not approved for the treatment of hypoparathyroidism because of high cost and the necessity for twice daily injecPons.
• However it has been shown to normalize serum calcium while maintaining normocalciuria
Hypoparathyroidism and Pregnancy
• Calcitriol requirements decrease during lactaPon • Serum calcium concentraPons should be measured frequently during late pregnancy and lactaPon in women with hypoparathyroidism who may have a rise in serum calcium, requiring a decrease in calcitriol dose.
• The requirement for calcitriol will return to antepartum levels with cessaPon of lactaPon
Vitamin D deficiency
• NutriPonal vitamin D deficiency is typically treated with 50,000 internaPonal units of vitamin D2 or D3 weekly for six to eight weeks
• Followed by rouPne vitamin D replacement of 1000-‐2000 IU daily
Pseudohypoparathyroidism • The long-‐term treatment pseudohypoparathyroidism is similar to the treatment of hypocalcemia caused by other forms of hypoparathyroidism.
• PaPents with pseudohypoparathyroidism infrequently develop hypercalciuria with calcium and vitamin D therapy.
• Goal of treatment with calcium and vitamin D is to maintain normocalcemia
• A typical starPng dose of calcitriol is 0.25 mcg twice daily.
• Approximately 1 to 2 gm of elemental calcium daily (in divided doses) is recommended
Hypomagnesemia • Hypomagnesemia induces resistance to parathyroid
hormone (PTH) and diminishes PTH secrePon • MalabsorpPon, chronic alcoholism, and cisplaPn therapy
are most common causes • If the serum magnesium concentraPon is low, 2 g (16 meq)
of magnesium sulfate should be infused as a 10 percent soluPon over 10 to 20 minutes, followed by 1 gram (8 meq) in 100 mL of fluid per hour.
• Persistent hypomagnesemia, as occurs in some paPents with ongoing gastrointesPnal (eg, malabsorpPon) or renal losses, requires supplementaPon with oral magnesium, typically 300 to 400 mg daily divided into three doses