Case based scenario of managing Hypercalcemic emergency

1. Management of Hypercalcemic
Crisis

2. Hypercalcemia
• Definition :Total Serum Calcium(bound +
ionized ) > 10.6 mg/dl or ionized calcium > 5.3
mg/dl.

3. Clinical manifestations
Manifestations of hypercalcemia (S calcium > 12 mg/dl)
Acute Chronic
Gastrointestinal Anorexia
Nausea, Vomiting
Dyspepsia
Constipation
Pancreatitis
Renal Polyuria
Polydipsia
Nephrolithiasis
Nephrocalcinosis
Neurological Depression
Confusion
Stupor, coma
Weakness
Cardiac Short Q-T interval bradycardia
I degree AV block
Hypertension

4. Hypercalcemic crisis
Accepted definition
• Serum calcium > 14 mg/dl associated with
rapid deterioration of the central nervous ,
cardiac, gastrointestinal and renal function
(Ziegler R.. J Am Soc Nephrol 2001; 12: S3–9)

5. Etiology
• Etiology
Primary Hyperparathyroidism (PHPT) in majority.
Incidence 1.6-6 %
Malignancy –advanced disease & poor prognosis
• Parathyroid adenoma-> 85 %
Large
Polyglandular
Rarely ectopic
Parathyroid carcinoma-4%
• Histopathology (Microcystic pattern, Intracytoplasmic vacuole,
necrosis, fibrosis)- SGPGIMS, Lucknow
Decompensation could be triggered by immobilization, intercurrent illness,
inadvertent Vit D supplementation, drugs (Thiazides, Lithium, antacids)

6. Literature review –Hypercalcemic crisis
& PHPT
• Duration 1958-2011
• n-=499
• Mean age 43.94 y
• M=165,F=300
• Mean S Calcium-18 mg/dl
• Symptoms-
Frequent
Nephrolithiasis
Constipation
Peptic Ulcers (non
healing)
Osteoporosis
Less frequent
Cardiac
CNS changes
Gurrado A et al Endokrynologia Polska 2012;63 ;494-502

7. Diagnostic tests
Establish or refute the diagnosis of PHPT
• Elevated or inappropriately normal i PTH -
PHPT
• Imaging
USG Neck (High frequency 12/15 MHz
transducers)
Sestamibi Scan (dual phase)
Assist in doing a focused parathyroidectomy

8. Management
• Medical management-bridge to
parathyroidectomy
• Lowering calcium levels
Correcting dehydration and enhancing renal
excretion of calcium
Decreasing Osteoclast mediated bone
resorption

9. Therapy
Hypercalcemic
crisis
Hydration
Inhibiting
Bone
reorption
Calciuresis
Dialysis

10. Promoting calciuresis-Hydration
• Patients are dehydrated and have lost sodium (renal
tubular absorption is suppressed by hypercalcemia
• IV fluid-0.9% Saline
• Initial rate 200-300 ml/h subsequently maintain urine
output of 100-150 ml/h (≈ 3-4 L in first 24 h)
• Intravascular volume expansion increases GFR→
increases calcium filtration .Sodium promotes
calciuresis at distal nephron
• Leads to 1.6-2.4 mg/dl reduction in serum calcium
• Caution-Poor cardiac reserve/impaired renal function
Am J Med 2015;128 (3) : 239-244

11. Promoting calciuresis-Loop diuretics
• Block calcium re-absorption in the ascending
loop of Henle
• Administer only after rehydration
• Furosemide 40-80 mg /day
• Combined with hydration reduce Serum
Calcium by 4 mg/dl
• Useful in those with reduced cardiac function
and mild renal impairment
Am J Med 2015;128 (3) : 239-244

12. Inhibiting bone resorption-
Bisphosphonates
N Engl J Med 2002; 346:642

13. Bisphosphonates
• Effective in lowering calcium to near normal .
• Approved drugs for hypercalcemia -Pamidronate,
Zoledronic acid
• Unless contraindicated should be considered first
line therapy in conjunction with volume
replacement
• Side effects-Flu like syndrome,
hypophosphatemia, nephrotoxicity,hypocalcemia
• Mitigates postoperative hypocalcemia(‘hungry
bone syndrome’)

14. Bisphosphonates
Dose & administration
Pamidronate Zoledronic acid
Dose 60-90 mg 4mg
Mode of
administration
IV infusion over 2 h Infusion over 15 min
Efficacy - Considered better;
achieves reduction in S
Calcium earlier
Dose modification *
e GFR 30-60 ml/min
e GFR < 30 ml/min
No change
Extend the infusion for
4-6 h
Reduction in dose
Not recommended
* Kidney International (2008) 74, 1385–1393

15. Calcitonin
• Reduces osteoclastic action , promotes calciuresis,
inhibits calcium absorption from intestine
• Not effective as monotherapy
• Used in conjunction with bisphosphonates as it has
faster onset of action
• Calcitonin 4-8 mg IU/kg im or sc every 6-12 h.Peak
decrease occurs in 2-6 h
• Down regulation of receptors in bone and kidney leads
to tachyphylaxis .
• Side effects-Nausea, flushing, local site reaction
,hypersensitivity

16. Dialysis
• Patients with renal insufficiency
• Patients refractory to other therapy
• Either peritoneal dialysis or hemodialysis can
be effective.

17. Glucocorticoids
Utility in limited subset
• Suppresses growth of lymphoid neoplasia
lymphoma and leukemia
• Suppresses 1 α hydroxylase in activated
macrophage
Vit D intoxication, granulomatous disorders
• Other actions- reduces bone resorption and
increases renal excretion of Calcium
• Drug & dose-Hydrocortisone 200-300 mg iv over
24 h/Prednisolone 1-2 mg/kg for 3-5 days

18. Therapies-Comparative table
Treatment Onset of action Duration of
action
Reduction in
Serum Calcium
Advantages
Hydration with
Saline
Hours During infusion 1-3 mg/d; Corrects
dehydration
Infusion plus
loop diuretics
Hours During infusion 4 mg/dl Rapid onset
Bisphosphonstes 1-2 days 10-14 days Returns to
normal in
majority
High potency
Calcitonon Hours 1-2 days - Rapid onset of
action
Dialysis Hours Till 24-48 h
after
3-12 mg/dl Only effective
modality for
moderate to
severe renal
impairment

19. Therapies of hypercalcemia
Serum Calcium (mg/dl) Therapy
< 12mg/dl Rehydration
12-15mg/dl Rehydration +Bisphosphonates/Calcitonin
>15 mg/dl Rehydration + Forced saline diuresis
+
Bisphosphonates/Calcitonin
Dialysis if in renal failure
Glucocorticoids (specific condition)

20. PHPT & Hypercalcemic crisis-
SGPGIMS ,Lucknow

21. HIHC-SGPGIMS, Lucknow
SGPGIMS, Lucknow (1989-2010)
Number of patients 37 (Male-12.Female-25
Mean age 39 ± 15
Clinical presentation Bone pain, Fracture, proximal muscle weakness,
Mental status changes, Pancreatitis significantly
higher
Serum Calcium (mg/dl) 15.14 ± 1.06
i PTH (pg/ml) 890.33 ± 163.7
Treatment Saline , loop diuretics, Bisphosphonates
Decrease in Serum Calcium 4.5 days
Post operative hypocalcemia
(symptomatic )
12/37
Mortality 3/37 ( pancreatitis & sepsis/Cerebral
mets/unknown)

22. Conclusion
• Hypercalcemic crisis is a rare endocrine
emergency
• PHPT is the most common etiology
• Hydration and bisphosphonates are first line
therapy
• Medical therapy is a bridge to definitive
treatment i.e. Surgery
• Long term outcomes with combined therapy
have shown excellent outcomes

23. THANK YOU

24. Newer therapies
• Cinacalcet 30 mg x bid oral titrated to 90 mg x
QID daily for hypercalcemia due to
parathyroid carcinoma
• Denusomab- Monoclonal antibody against
RANKL
Used in hypercalcemia of malignancy
No role in hypercalcemic crisis