1. This lecture was conducted during the Nephrology Unit Grand Ground by a Sub-intern under Nephrology Division, Department of Medicine in King Saud University.
Nephrology Division is NOT responsible for the content of the presentation for it is intended for learning and /or education purpose only.

2. Alhanouf Alsughier
Hypercalcemia

3. calcium level
A normal serum calcium level is 8-10 mg/dL (2-2.5 mmol/L)
hypercalcemia is serum calcium level greater than 10.5 mg/dL (>2.5 mmol/L). classified as follows:
Mild: Total Ca mg/dL (2.5-3 mmol/L) or Ionized Ca mg/dL (1.4-2 mmol/L)
Moderate: Total Ca mg/dL (3-3.5 mmol/L) or Ionized Ca 8-10 mg/dL (2-2.5 mmol/L)
Hypercalcemic crisis: Total Ca mg/dL (3.5-4 mmol/L) or Ionized Ca mg/dL (2.5-3 mmol/L)

4. Pathophysiology
Hypercalcemia affects nearly every organ system in the body, but it particularly affects the CNS and kidneys.
Mild hypercalcemia may not produce any symptoms.
With modest hypercalcemia, most patients begin to feel fatigued.
The CNS effects are thought to be due to the direct depressant effect of hypercalcemia.

5. Renal Renal effects include nephrolithiasis from the hypercalciuria.
Distal renal tubular acidosis may be observed, and the increase in urine pH and hypocitraturia also may contribute to stone disease.
Nephrogenic diabetes insipidus occurs from medullary calcium deposition and inhibition of aquaporin-2, the arginine-vasopressin–regulated water channel.
Renal function may decrease due to hypercalcemia-induced renal vasoconstriction or if hypercalcemia is prolonged from calcium deposition (nephrocalcinosis) and interstitial renal disease.

6. Cardiac
High calcium levels also affect the conducting system of the heart and cause cardiac arrhythmias. Calcium has a positive inotropic effect. Hypercalcemia also causes hypertension, presumably from renal dysfunction and direct vasoconstriction.

7. GI
The GI manifestations of hypercalcemia include anorexia, nausea, vomiting, and constipation.
Prolonged hypercalcemia tends to cause high gastrin levels, which may contribute to peptic ulcer disease and may lead to pancreatitis or the deposition of calcium in any soft tissue. This deposition of calcium is especially prevalent if phosphorous levels also are elevated, as in renal failure.

8. The severity of symptoms is related not only to the absolute calcium level but also to how fast the rise in serum calcium occurred. Serum calcium levels greater than approximately 15 mg/dL usually are considered to be a medical emergency and must be treated aggressively.

9. syncope from arrhythmias
presentation
CNS
Lethargy
Weakness
Confusion
Coma
Renal
Polyuria
Nocturia
Dehydration
Renal stones
Renal failure GI
Constipation
Nausea
Anorexia
Pancreatitis
Gastric ulcer
Cardiac
syncope from arrhythmias

10. Physical GI CNS Cardiac Renal Confusion Hypotonia Hyporeflexia Paresis
Coma
Renal
Volume depletion
Signs of renal failure GI
Fecal impaction (from constipation)
Signs of pancreatitis
Signs of malignancy (eg, enlarged liver or masses)
Cardiac
Arrhythmias
Hypotension
Shortened QT interval

11. Causes Hyperparathyrodism Malignancy (lung, breast, and myeloma)
PTH- like peptid
Bone metastatic
Sarcodosis
Prolong immobilization
Hyperthyrodism
Familial hypocalciuric hypercalcemia
Drug:HCTZ

12. Causes of hypercalcemia that are related to the parathyroid include the following:
Primary hyperparathyroidism
Solitary adenoma
Generalized hyperplasia
Multiple endocrine neoplasia type 1 or type 2A

13. Laboratory Studies
Immunoreactive PTH and ionized calcium should be simultaneously measured.
PTH levels should be suppressed in hypercalcemia; thus, the presence of normal PTH levels with elevated calcium levels suggests mild hyperparathyroidism.
Hyperparathyroidism may be part of multiple endocrine neoplasia type 1, ie, Wermer syndrome.

14. Laboratory Studies
Malignancy is one of the most common causes and must be excluded.
If calcium levels have been elevated for an unknown duration, the patient should be evaluated for the presence of malignancy.
Breast, lung, and kidney cancers should be considered, as should multiple myeloma, lymphoma, and leukemia.
Rapidly rising calcium levels should increase suspicion of malignancy.

15. Laboratory Studies
Renal function should be evaluated and thyroid-stimulating hormone should be checked to help rule out hyperthyroidism.

16. Imaging Studies
Chest radiographs always should be performed to help rule out lung cancer or sarcoidosis.
Other radiographs should be considered to help evaluate for possible malignancies, metastases, or Paget disease.
Mammograms should be considered to help rule out breast cancer, and CT scan and ultrasound should be considered to help rule out renal cancer.
When a biochemical diagnosis of primary hyperparathyroidism is made, CT scan, ultrasound, MRI, and radionuclide imaging of the parathyroid gland may be helpful to assist with preoperative localization.

17. Treatment Volume expansion and saline diuresis: Clcitonin
The first therapy for symptomatic hypercalcemia is volume repletion.
More severe cases require saline infusion with concomitant loop diuretics (eg, furosemide) to increase calcium excretion and lower levels rapidly.
Clcitonin
Bisphosphonates inhibit osteoclastic bone resorption and are effective in the treatment of hypercalcemia due to conditions causing increased bone resorption and malignancy-related hypercalcemia. (Pamidronate)

18. Reduction of gastrointestinal calcium absorption:
Reduction of dietary calcium and vitamin D intake
In vitamin D toxicity or extrarenal synthesis of 1,25(OH) D3 (eg, in sarcoidosis), prednisone may help reduce plasma calcium levels by reducing intestinal calcium absorption.
Oral phosphate

19. Surgical care for hypercalcemia :
Removal of 1 or more parathyroid glands due to prolonged hypercalcemia. This is particularly appropriate if evidence of nephrolithiasis, osteoporosis, reduction of renal function, neuromuscular symptoms, or radiographic bone disease is present.
Hypercalcemia due to malignancy, especially if due to a tumor that is producing PTHrP, may require surgical resection of the tumor.

20. Thank you

21. Reference
Medscape
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