3. Intended Learning Outcomes
–Review calcium metabolism
–Describe symptoms of hypercalcemia
–Review the etiology of hypercalcemia
–Discuss the treatments for
hypercalcemia
–Conclusions
4. Intended Learning Outcomes
–Review calcium metabolism
–Describe symptoms of hypercalcemia
–Review the etiology of hypercalcemia
–Discuss the treatments for
hypercalcemia
–Conclusions
5. Calcium metabolism
• Absorption from GI tract is by passive diffusion
and active transport
• Most of the calcium is reabsorbed by the kidney
– net loss is about 2%
• Calcium is controlled by both PTH and
calcitonin
7. Calcium
• Total calcium
- Free (ionized) calcium (50%)
- Protein bound calcium (40%)
- Calcium complexed with organic and inorganic
molecules (10%)
8. Role of albumin
High albumin states (volume depletion or
multiple myeloma) may lead to
pseudohypercalcemia.
Low albumin states like malnutrition, total
serum calcium may appear low while
ionized calcium is again not very affected.
Ca2+= serum Ca2+ + 0.8 x [normal alb-patient alb]
9. Intended Learning Outcomes
–Review calcium metabolism
–Describe symptoms of hypercalcemia
–Review the etiology of hypercalcemia
–Discuss the treatments for
hypercalcemia
–Conclusions
11. Renal (stones)
• Polyuria
• Renal insufficiency (rarely seen in mild disease,
although in severe cases may cause a reversible
drop in GFR)
• Nephrolithiasis
• Nephrogenic DI
13. Neuro-psychiatric (Groans)
• Depression
• Anxiety
• Cognitive dysfunction
• Lethargy, confusion, stupor, and coma may
occur in patients with severe hypercalcemia
• More likely to occur in the elderly and in those
with rapidly rising calcium concentrations
15. Cardiovascular
• Increases myocardial contractility and irritability
• Shortened QT interval
• Prolonged PR
• Wide QRS complexes
• Calcium deposition in coronary arteries and
myocardial fibers
• Hypertension
16. Intended Learning Outcomes
–Review calcium metabolism
–Describe symptoms of hypercalcemia
–Review the etiology of hypercalcemia
–Discuss the treatments for
hypercalcemia
–Conclusions
21. Medications
> 10.3 mg% I-PTH
High/Normal PTH
Low
Vit D Toxicity
Milk-Alkali
Cancers/
Lymphoma
Low PTHrP
Approaching the diagnosis
22. Case
• 40/ W noted to have mild elevations in
serum calcium on routine testing.
Calcium at the last two visits is 10.4-
10.6 mg/dL.
• She is relatively asymptomatic.
• You obtain labs:
• PTH:
• 120
23.
24. Case
• 40/ W asymptomatic hypercalcemia
• You obtain labs:
• PTH: 120
• Phos: 2.0
• Vitamin D (25OHD): 40
• Creatinine: 1.0
• Albumin: 4.0
• Likely diagnosis: ?
25. Medications
> 10.3 mg% I-PTH
High/Normal PTH
Low
Vit D Toxicity
Milk-Alkali
Cancers/
Lymphoma
Low PTHrP
Approaching the diagnosis
26. Case
• 40/ W noted to have mild elevations in serum calcium on
routine testing. Calcium at the last two visits is 10.4-10.6
mg/dL.
• She is relatively asymptomatic.
• You obtain labs:
• PTH: 120
• Phos: 2.0
• Vitamin D (25OHD): 40
• Creatinine: 1.0
• Albumin: 4.0
• Likely diagnosis: Primary hyperparathyroidism
27. Primary Hyperparathyroidism
• Most common cause in the outpatient setting
• Renal calculi seen in 15-20%
• Classic bone disease (brown tumors, osteitis
fibrosa cystica, subperiosteal resorption) is
rarely seen
• Increased risk for vertebral fractures
28. Familial Hypocalciuric
Hypercalcemia (FHH)
• Rare, autosomal dominant condition
• caused by an inactivating disorder of calcium-
sensing receptors (CaSR)
• PTH normal to mildly elevated, mild hypercalcemia
• Fractional excretion of calcium is lower than 1%,
despite hypercalcemia.
• Genetic testing is not often required
• ClCa/ClCr= (Uca X SCr) X (Sca X UCr)
• A ratio of 0.01 or less is typically with FHH
29. Case
• 70/M with history of renal cell carcinoma. Calcium
levels are noted to be recently elevated at 13.0
mg/dL.
• You obtain labs:
- PTH: 23
- Phos: 2.1
- Vitamin D: 40
- Creatinine: 1.0
- Albumin 3.6
- PTH-rP: 1.0 (High)
30. > 10.3 mg% I-PTH
Low PTHrP
Low
Vit D Toxicity
Milk-Alkali
Cancers/
Lymphoma
High/Normal PTH
Approaching the diagnosis
31. Case
• 70/M with history of renal cell carcinoma. Calcium
levels are noted to be recently elevated at 13.0 mg/dL.
• You obtain labs:
- PTH: 23
- Phos: 2.1
- Vitamin D: 40
- Creatinine: 1.0
- Albumin 3.6
- PTH-rp: 1.0 (High)
- Likely diagnosis: Hypercalcemia of malignancy
32. Humoral Hypercalcemia of
Malignancy
• Usually have obvious malignant disease
• Most common cause for inpatient
hypercalcemia
• PTH is low, PTH-rP is elevated
• Associated with localized bone destruction
33. Case
• 51/M presents with fatigue and trouble concentrating with a
5-lb weight loss. Calcium levels are noted to be recently
elevated at 13.0 mg/dL.
• You obtain labs:
- PTH: 17
- Phos: 3.0
- CXR: Hilar lymphadenopathy
24 hour urine calcium is elevated
- Vitamin D: 27, Creatinine is normal
- DHVD: 110
- Likely diagnosis: Hypercalcemia due to granulomatous
disease
34. Hypercalcemia associated with
granulomatous diseases
• Sarcoidosis is most commonly associated
although can occur in any granulomatous
disease
• Increased activation of 1α hydroxylase that
converts 25OHD to 1,25(OH)2D
35. Intended Learning Outcomes
–Review calcium metabolism
–Describe symptoms of hypercalcemia
–Review the etiology of hypercalcemia
–Discuss the treatments for
hypercalcemia
–Conclusions
36. Treatment
• Asymptomatic or mildly symptomatic patients do
not require immediate treatment
• Chronic hypercalcemia with no symptoms 12-14
mg/dl can be monitored as well
• > 14 mg/dl needs treatment even if asymptomatic
37. Treatment
• Correction of dehydration/volume depletion
• Correction of any electrolyte abnormalities
• Discontinuation of medications that may cause
calcium elevation
• Reduction of dietary calcium in states of
intestinal hyperabsorption (vitamin D
intoxication and milk alkali)
• Weight bearing or mobilization
38. The Four Rx Modalities
I.V. Saline
Hydration &
Diuresis
Gluco-
Corticoids
Anti-
resorptives
Calcitonin
I.M/S.C.
39. • Agents that decrease the release of calcium from
bone or increase the uptake of calcium into bone
• Agents that increased urinary excretion of
calcium
• Agents that reduce intestinal absorption of
calcium
Treatment
40. • IV fluids
Depending on clinical status
200-300 ml/hour to maintain UO of 100-150
ml/hour
Dehydration can make hypercalcemia worse by
impairing the renal excretion of calcium
Treatment
41. Salmon Calcitonin
• IM or SQ injections at dose of 4 IU/kg
• At 6-12 hour intervals
• Modest reductions and low toxicity profile
• Vitamin D intoxication and immobilization
• Acts quickly
• Escape phenomenon may develop in 48 hours
42. Bisphosphonates
• Inhibit release of calcium by interfering with
osteoclast mediated bone resorption
• More potent than saline and calcitonin
• Can be used for hypercalcemia of any cause
• Max effect seen in 2-4 days
• Also used to prevent hypercalcemia and skeletal
events in malignancy
43. Bisphosphonates
• Pamidronate 60 or 90 mg IV over 2-4 hours
• Zoledronic acid (ZA) 4 mg over 15 minutes
• ZA preferred due to quicker infusion time
• Side effects (low grade fever, myalgias,
osteonecrosis of the jaw, atypical fractures)
45. • Agents that decrease the release of calcium from
bone or increase the uptake of calcium into bone
• Agents that increased urinary excretion of
calcium
• Agents that reduce intestinal absorption of
calcium
Treatment
46. Loop diuretics
• WITH SALINE
• Correct volume depletion first!
• 80-120 mg every 2-6 hours
• Monitor lytes, large losses of K and Mg
• Fallen out of favor:
1) Better drugs
2) Frequent monitoring of lytes
48. • Agents that decrease the release of calcium from
bone or increase the uptake of calcium into bone
• Agents that increased urinary excretion of
calcium
• Agents that reduce intestinal absorption of
calcium
Treatment
49. Glucocorticoids
• Vitamin D intoxication or endogenous
production of calcitriol (sarcoidosis, TB)
• Prednisone 20-40 mg
• Lowers calcium in 2-5 days
50. Intended Learning Outcomes
–Review calcium metabolism
–Describe symptoms of hypercalcemia
–Review the etiology of hypercalcemia
–Discuss the treatments for
hypercalcemia
–Conclusions
51. Conclusion
• Most common cause of hypercalcemia in the
outpatient setting is primary
hyperparathyroidism
• Most common cause of hypercalcemia in the
inpatient setting is malignancy
• Establishing the cause is important for treatment
decisions
Calcium is important for a number of intracellular reactions including muscle contraction, nerve cell activity, release of hormone through the process of exocytosis and activation of several enzymes, blood coagulation and structural integrity of teeth and bone. 99% of the body calcium is in the bones in the form of hydroxyapatite cyrstals. The next largest pool is the intracellular calcium. Smallest pool is in the ECF. Regulation of calcium involves the control of calcium movement between ECF, bone, GI tract and kidneys.
Kidney serves as a route for excretion
Actual % may vary with health and disease
80% is albumin bound
Mild hypercalcemia: Asymptomatic
Non specific symptoms
Gastrointestinal symptoms are probably related to the depressive action of hypercalcemia on the autonomic nervous system and resulting smooth-muscle hypotonicity
Calcium between 12-14 mg/dl maybe well tolerated if elevated chronically
Acute rises: polyuria, polydipsia, dehydration, anorexia, nausea, muscle weakness, and changes in sensorium
PHPT – most common cause in the ambulatory setting
PHPT – most common cause in the ambulatory setting
PHPT – most common cause in the ambulatory setting
The underlying pathophysiology of HPT is caused by excessive secretion of parathyroid hormone (PTH), which leads to increased bone resorption by osteoclasts, increased intestinal calcium absorption, and increased renal tubular calcium reabsorption. The consequent hypercalcemia is also often accompanied by low-normal or decreased serum phosphate levels because PTH inhibits proximal tubular phosphate reabsorption.
Hypercalcemia of malignancy: 30% of individuals with cancer develop hypercalcemia– typically late in the disease course. Calcium levels are generally higher
Hypercalcemia of malignancy: 30% of individuals with cancer develop hypercalcemia– typically late in the disease course. Calcium levels are generally higher
Usually, this term is applied to patients with excessive tumoral production of PTH-related peptide (PTHrP).
The predominant mechanism for the development of hypercalcemia and hypercalciuria is increased intestinal absorption of calcium induced by elevated calcitriol levels,
Activity of this enzyme is under negative feedback control in normal tissues. However, in granulomatous disorders, normal feedback inhibition is abolished, probably by the effects of interferon gamma.
Cautious use when EGFR 35 or less
ONJ: Limited relevance when used for management of acute hypercalcemia
