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==Pathophysiology==
==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 gland]]<nowiki/>s have [[calcium]]-sensing receptors responsible for sensing [[extracellular]] ionized [[calcium]]. [[Calcium]] and [[magnesium]] provides a [[negative feedback]]<nowiki/>for [[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==
==Causes==
Hypercalcemia is most commonly caused by [[hyperparathyroidism]] and [[malignancy]]. Other causes of hypercalcemia include [[hyperthyroidism]], [[Hypervitaminosis D|vitamin D toxicity]], increased calcium intake, granulomatous diseases ( such [[sarcoidosis]]), and various renal disorders.


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


==Epidemiology and Demographics==
==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==
==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 disease|renal diseases]].


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


==Natural History, Complications, and Prognosis==
==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==
==Diagnosis==
===Diagnostic Criteria===
===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===
===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 Nursing|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===
Physical examination of patients with hypercalcemia is usually unremarkable. Patients may have physical findings due to severe [[hypercalcemia]] and other complications.


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


===Imaging Findings===
=== 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===
===Other Diagnostic Studies===
There are no other diagnostic studies associated with hypercalcemia.


==Treatment==
==Treatment==
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===Surgery===
===Surgery===
Parathyroidectomy is usually indicated for patients with hypercalcemia due to hyperparathyroidism.
===Primary Prevention===
There is no establish method for primary prevention of hypercalcemia.


===Prevention===
=== 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.


==References==
==References==

Latest revision as of 16:50, 6 July 2018

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Hypercalcemia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Echocardiography or Ultrasound

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

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 calciumParathyroid glands have calcium-sensing receptors responsible for sensing extracellular ionized calciumCalcium 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.

References

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