Hypercalcemia

Welcome to PT 635 Pathophysiology of Complex Patient Problems This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!

Original Editors - Whitney Browning & Natalie Elliott from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Lead Editors - Your name will be added here if you are a lead editor on this page.  Read more.

Definition/Description

Hypercalcemia is characterized by elevated calcium levels in the blood. It may include symptoms associated with the musculoskeletal, neurological, cardiovascular, and gastrointestinal systems. Hypercalcemia is often a sign or symptom of other disease occurring within the body. Normal calcium levels range from 8.2-10.2 mg/dL. Mild hypercalcemia occurs when this level raises to 12mg/dL and severe hypercalcemia is classified as serum calcium at 14mg/dL.

Prevalence

Hypercalcemia is a rather common medical emergency. Between 20-40% of patients suffering from cancer develp this during the course of their disease. It is considered the most common serious electrolyte presenting in adults with malignancies. This disorder often occurs in cases of metastatic bone disease with osteolytic lesion, breast cancer and myeloma. This is related to an increase in bone resorption caused by tumor cell production of parathyroid hormone-related protein that stimulates osteoclasts. It is also associated with primary hyperparathyroidism which occurs in 25 per 100,000 individuals and 75 per 100,000 hospitalized patients. This condition is the most common cause of mild hypercalcemia and can be treated through outpatient care. More than 50,000 cases occur in the U.S. each year. 

Characteristics/Clinical Presentation

System	Signs/symptoms
Musculoskeletal	Muscle pain, tenderness, and weakness Muscle spasms Bone pain (worse at night and with weightbearing) Pathological fracture
Central Nervous System	Drowsiness, lethargy, coma Irritability, personality changes Confusion Headaches Depression, memory loss, difficulty concentrating Visual disturbances Balance/coordination problems Changes in deep tendon reflexes (hypo/hyperreflexia) Change in muscle tone ( in individuals with pre-existing neurological condition) Positive Babinski and/or clonus reflex Changes in bowel/bladder function
Gastrointenstinal	Anorexia (loss of appetite) Nausea/vomiting Constipation Dehydration Excessive thirst
Cardiovascular	Hypertension Arrythmia Cardiac arrest

Associated Co-morbidities

Hypercalcemia can lead to many other complications such as:

• Osteoporosis: if the bones continue to release calcium into the blood, it could lead to this disease. 
• Kidney stones: this could be caused by too much calcium accumulation in the urine, leading to crystal formation in the kidneys.
• Kidney failure: Severe hypercalcemia can lead to damage in the kidneys and possibly cause permanent loss of kidney function.
• Nervous system deficits: Severe hypercalcemia can lead to dementia and confusion.
• Arrythmias: Hypercalcemia can affect the electrical impulses of cardiac muscle, causing irregular heartbeats.
• Primary Hyperparathyroidism: This is often associated with hypercalcemia because it causes an increased release of parathyroid hormone (PTH) which raises serum calcium levels.

Medications

Medication	Treatment Effect	Side Effects
Loop Diuretics (ex; furosemide)	Flushes out excess calcium from system	Frequent urination, arrythmias, electrolyte imbalances, dizziness, muscle cramps/weakness, extreme fatigue, blurred vision, confusion, headache, dehydration, fever, sore throat, cough, skin rash, loss of appetite, nausea, vomiting
Intravenous Biphosphonates	Prevent bone breakdown, reduce bone pain, reduce the number of pathologic fractures	Heartburn, headache, constipation, diarrhea, muscle and joint pain
Calcitonin	Reduce bone reabsorption and slow bone loss	Warmth/redness of the skin, itching of the skin, nausea, loss of appetite, stomach pain, vomiting, skin rash, increased urination, eye pain, swelling in the feet, swelling or irritation at injection site (if injection was given)
Glucocorticoids	Help to counter the effect of excess Vitamin D	Elevated pressure in the eyes, fluid retention that may cause swelling in the legs, increased blood pressure, mood swings, weight gain
Hemodialysis	Remove excess waste and calcium from the bloodstream	Hypotension, muscle cramps, itching, difficulty sleeping, anemia, pericarditis, hyperkalemia, infection, depression

Diagnostic Tests/Lab Tests/Lab Values

Hypercalcemia is diagnosed by blood tests revealing increased serum calcium levels. However, other tests may need to be done in order to determine the underlying cause of hypercalcemia. These may include: 

• Chest X-Ray
• CT Scan
• MRI
• Mammogram

These tests may help determine whether you have lung cancer, breast cancer, other malignancies, or sarcoidosis (a granulomatous disease of the lungs). 

http://www.the-hospitalist.org/SpringboardWebApp/userfiles/hosp/image

Etiology/Causes

Common causes of hypercalcemia include: 

• Overactivity of parathyroid glands
• Cancer-specifically lung and breast cancer as well as multiple myeloma can increase the risk of hypercalcemia. This is considered to be due to the fact that some malignant tumors can produce a protein that acts simlar to the parathyroid hormone which stimulates the release of calcium from the bones into the bloodstream. 
• Other disease effects-some people with cancer that causes them to spend increased time laying down or in bed may cause bones to release calcium into the blood due to the lack of weightbearing.
• Medications-Lithium, a drug used to treat bipolar disorder, may increase the release of parathyroid hormone and cause hypercalcemia. Also, Thiazie diuretics can cause elevated calcium levels by decreasing the amount of calcium excreted in the urine. 
• Supplements-eating or drinking too much calcium or Vitamin D
• Dehydration-less fluid in your blood causes the calcium levels to increase

Systemic Involvement

As stated in the chart above, hypercalcemia can present with symptoms in mutliple systems. Usually, the first signs and symptoms are noticed in the musculoskeletal system causing muscle pain, spasms, or bone pain. However, each patient will present differently depending on the severity and organ system involved. 

Medical Management (current best evidence)

Mild Hypercalcemia (defined as corrected total serum calcium level lower than 12 mg/dL (<6 mEq/L or 3.0 mmol/L)

• Hydration (IV fluids) followed by observation; this option should be considered for asymptomatic patients who are about to be treated for tumors that are likely to respond to antineoplastic treatment (ex: lymphoma, breast cancer, ovarian cancer, head and neck carcinoma, and multiple myeloma).
• Additional interventions should be directed toward controlling nausea and vomiting, encouraging mobility, noting febrile episodes. 
• Minimal use of sedating medications.

Moderate to Severe Hypercalcemia (defined as corrected total serum calcium equal to 12 to 14 mg/dL (6–7 mEq/L or 3.0–3.5 mmol/L)

• Rehydration is the essential first step replenishing extracellular fluid, restoring intravascular volume, and saline diuresis
• Hypocalcemic agents 
  
• Moderate doses of furosemide (20–40 mg every 12 hours) increase saline-induced urinary calcium excretion and are useful in preventing or managing fluid overload in adequately rehydrated patients. 
• Surgery; resulting from primary hyperparathyroidism, urgent parathyroidectomey.

Prevention

Preventive measures include:

• Ensuring adequate fluid intake of 3 to 4 L (100–140 fl oz per day if not contraindicated)
• Salt intake
• Nausea and vomiting control
• Encouraging patient mobility
• Attention to febrile episodes
• Cautious use or elimination of drugs that may complicate management ( ex: drugs that inhibit urinary calcium excretion or decrease renal blood flow, contain calcium, vitamin D, vitamin A, or other retinoids)
  

Physical Therapy Management (current best evidence)

• Weightbearing exercises to prevent osteoporosis and immobility
• Prevention of fractures 
• Ensure adequate hydration
• Quality of life measures
• Strength/ROM
• Patient and Family Education

Alternative/Holistic Management (current best evidence)

• Increase fluid intake
• Substitute with sea salt in diet
• Decease consumption of dietary calcuim and Vitamin D 
• Avoid pasteurized dairy products, low-fat dairy products, and processed foods high in polyunsaturated fats and low in saturated fats
• Probiotics

Differential Diagnosis

• Hyperparathyroidism
• Malignancy
• Sarcoidosis
• Lithium, Salicylate, Theophylline Toxicity
• Thyroid Toxicity
• Vitamin Toxicity
• Tuberculosis

Case Reports/ Case Studies

add links to case studies here (case studies should be added on new pages using the case study template)

http://www.aapsus.org/articles/6.pdf

Resources

National Cancer Institute

MayoClinic

WebMD

American Academy of Family Physicians

Recent Related Research (from Pubmed)

see tutorial on Adding PubMed Feed

http://www.ncbi.nlm.nih.gov/pubmed/?term=hypercalcemia

References

 see adding references tutorial.

1. Goodman CC, Snyder TEK. Differential Diagnosis for Physical Therapists: Screening for Referral. 5th ed. St. Louis, MO: Elsevier Saunders; 2013. 

2. Hypercalcemia [Internet]. MayoClinic. 2012 [updated 2012 Aug 10]. Available from: 

http://www.mayoclinic.com/health/hypercalcemia/DS00976/DSECTION=causes

3. Diuretics and High Blood Pressure: Uses, Side Effects, and More [Internet]. WebMD. 2013. Available from: 

http://www.webmd.com/hypertension-high-blood-pressure/guide/diuretic-treatment

4. A Practical Approach to Hypercalcemia [Internet]. Am Fam Physician. 2003 May 1;67(9):1959-1966. Available from: 

http://www.aafp.org/afp/2003/0501/p1959.html

5. Hypercalcemia in Emergency Medicine [Internet]. Medscape. 2010 [updated 2010 Sep 1]. Available from: 

http://emedicine.medscape.com/article/766373-overview#a0199

6. Hemodialysis: Risks [Internet]. MayoClinic. 2012 [updated 2012 Aug 10]. Available from: 

http://www.mayoclinic.com/health/hemodialysis/MY00281/DSECTION=risks

7. Hypercalcemia Treatments and Drugs [Internet]. MayoClinic. 2012 [updated 2012 Aug 10]. Available from: 

http://www.mayoclinic.com/health/hypercalcemia/DS00976/DSECTION=treatments%2Dand%2Ddrugs

8. Biphosphonates Uses, Side Effects, Types, Effectiveness [Internet]. WebMD. 2013. Available from: 

http://www.webmd.com/osteoporosis/bisphosphonates-for-osteoporosis

9. Calcitonin Side Effects [Internet]. Drugs.com. 2013. Available from: 

http://www.drugs.com/sfx/calcitonin-side-effects.html

10. Prednisone and other corticosteroids: Balance the risks and benefits [Internet]. MayoClinic. 2012 [updated 2012 Aug 10]. Available from: 

http://www.mayoclinic.com/health/steroids/HQ01431

11. Hypercalcemia, causes, symptoms, remedies [Internet]. Growyouthful.com. 2013. Available from: 

http://growyouthful.com/ailment/hypercalcemia-high-calcium.php