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.

Alhanouf Alsughier Hypercalcemia

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 10.5-11.9 mg/dL (2.5-3 mmol/L) or Ionized Ca 5.6-8 mg/dL (1.4-2 mmol/L) Moderate: Total Ca 12-13.9 mg/dL (3-3.5 mmol/L) or Ionized Ca 8-10 mg/dL (2-2.5 mmol/L) Hypercalcemic crisis: Total Ca 14-16 mg/dL (3.5-4 mmol/L) or Ionized Ca 10-12 mg/dL (2.5-3 mmol/L)

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.

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.

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.

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.

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.

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

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

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

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

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.

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.

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

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.

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)

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

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.

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