Hypercalcemia overview

# Overview
Hypercalcemia (in UK English Hypercalcaemia) is an elevated calcium level in the blood. (Normal range: 9-10.5 mg/dL or 2.2-2.6 mmol/L). It can be an asymptomatic laboratory finding, but because an elevated calcium level is often indicative of other diseases, a diagnosis should be undertaken if it persists. It can be due to excessive skeletal calcium release, increased intestinal calcium absorption, or decreased renal calcium excretion.
- Calcium is the most abundant mineral in the the body
- 99% of the calcium in the body is stored in the bone
- Calcium in the plasma is either ionized or protein-bound and readily available for use
- An increase in total plasma calcium concentration above 10.4 mg/dL signifies hypercalcemia
- Serum concentration is regulated through parathyroid hormone (PTH), vitamin D and calcitonin

# Historical Perspective
In 1932, L. I. Pugsley AND Hans Selye, described the histological changes in the bone due to parathyroid hormone action and calcium metabolism in rat experiments. In the same year, Iftakhar Jahan and Robert F. Pitts described effect of parathyroid hormone in decreasing calcium and magnesium excretion.

# Classification
There are several ways in which hypercalcemia may be classified. Common Terminology Criteria for Adverse Events (CTCAE) grade classifies hypercalcemia into 4 grades on the basis of corrected serum calcium (CSC). Hypercalcemia may be classified according to severity into 3 groups including mild, moderate, and severe hypercalcemia. Hypercalcemia associated with malignancy may be classified according to mechanism of increased production of calcium.

# Pathophysiology
Normal calcium homeostasis is maintained by parathyroid hormone and vitamin D. Normally, parathyroid hormone increases serum calcium and magnesium concentration, and decreases serum phosphate concentration. Secretion of parathyroid hormone from parathyroid gland is stimulated by low serum calcium. Parathyroid glands have calcium-sensing receptors responsible for sensing extracellular ionized calcium. Calcium and magnesium provides a negative feedbackfor secretion of parathyroid hormone. Hypercalcemia may result due to increase in secretion of parathyroid hormone (PTH), most common cause. Other mechanism of hyperlcacemia include secretion of parathyroid hormone-related protein (PTHrP) by tumor cells, which has similar action as parathyroid hormone, excess intake of calcium or vitamin D, and production of vitamin D by macrophages in granulomatous diseases.

# Causes
Hypercalcemia is most commonly caused by hyperparathyroidism and malignancy. Other causes of hypercalcemia include hyperthyroidism, vitamin D toxicity, increased calcium intake, granulomatous diseases ( such sarcoidosis), and various renal disorders.

# Differentiating Hypercalcemia from Other Diseases
Various common causes of hypercalcemia should be differentiated from each other.

# Epidemiology and Demographics
The prevalence of hypercalcemia in the cancer patient is approximately 3286.23 per 100,000 individuals over the period of 2009 to 2013 in the United States.

# Risk Factors
Common risk factors in the development of hypercalcemia include postmenopausal women, age group 50-60 year, family history of hyperparathyroidism, history of familial syndromes, and renal diseases.

# Screening
There is insufficient evicence to recommend routine screening for hypercalcemia.

# Natural History, Complications, and Prognosis
Mild hypercalcemia is usually asymptomatic and goes undetected in a large number of patients. Furthermore, it commonly reflects in routine laboratory exams. Hypercalcemia may complicated various organ systems including renal (most commonly), gastrointestinal, and skelatal. Prognosis of hypercalcemia is usually excellent after treatment.

# Diagnosis

## Diagnostic Study of Choice
Serum calcium levels is the study of choice for the diagnosis of hypercalcemia. However, a panel of tests may be required to reach the underlying cause of hypercalcemia.

## History and Symptoms
The symptoms of hypercalcemia are same irrespective of etiology. Neurological symptoms are common in hypercalcemia as normal neurological processes requires optimal serum extracellular concentration. The patient may have a positive history of kidney stones, bone pain and tenderness, gastrointestinal symptoms. "Bones, stones, groans, and psychic moans" is a saying which may help remember the signs and symptoms of hypercalcemia.

## Physical Examination
Physical examination of patients with hypercalcemia is usually unremarkable. Patients may have physical findings due to severe hypercalcemia and other complications.

## Laboratory Findings
Routine panel is recommended for patients suspected of hypercalcemia to diagnosed the underlying cause.

## Electrocardiogram
Most common finding on ECG due to hypercalcemia is short QT interval.

## X-ray
X-ray is essential to rule out various causes of hypercalcemia such as hyperparathyroidism, malignancy, and sarcoidosis.

## CT Scan
CT scan may be helpful in the diagnosis of hypercalcemia due to malignancy such as renal cell carcinoma.

### MRI
MRI is not useful in diagnosis of hypercalcemia. However, MRI may be helpful in the diagnosis of  causes of hypercalcemia including hyperparathyroidism, renal cell carcinoma, and lung cancer.

## Echocardiography and Ultrasound
Ultrasound is not useful in diagnosis of hypercalcemia. However, ultrasound may be helpful in the diagnosis of causes of hypercalcemia including renal cell carcinoma and hyperparathyroidism.

## Other Imaging Findings
There are no other imaging findings associated with hypercalcemia.

## Other Diagnostic Studies
There are no other diagnostic studies associated with hypercalcemia.

# Treatment

## Medical Therapy

## Surgery
Parathyroidectomy is usually indicated for patients with hypercalcemia due to hyperparathyroidism.

## Primary Prevention
There is no establish method for primary prevention of hypercalcemia.

## Secondary Prevention
There is no establish method for secondary prevention of hypercalcemia. However, effective measures should be applied for secondary prevention primary hyperparathyroidism, which is the most common cause of hypercalcemia.