Hypercalcaemia

Hypercalcaemia
Classification and external resources
Specialty Endocrinology
ICD-10 E83.5
ICD-9-CM 275.42
DiseasesDB 6196
MedlinePlus 000365
eMedicine med/1068 emerg/260 ped/1062
Patient UK Hypercalcaemia
MeSH D006934

Hypercalcaemia (British English) or hypercalcemia (American English) is an elevated calcium (Ca2+) level in the blood.[1] (Normal range: 8.7–10.4 mg/dL or 2.2–2.5 mmol/L.) It can be an asymptomatic laboratory finding, but because an elevated calcium level is often indicative of other diseases, a workup should be undertaken if it persists. It can be due to excessive skeletal calcium release, increased intestinal calcium absorption, or decreased renal calcium excretion.

Signs and symptoms

The neuromuscular symptoms of hypercalcemia are caused by a negative bathmotropic effect due to the increased interaction of calcium with sodium channels. Since calcium blocks sodium channels and inhibits depolarization of nerve and muscle fibers, increased calcium raises the threshold for depolarization.[2] There is a general mnemonic for remembering the effects of hypercalcaemia: "Stones, Bones, Groans, Thrones and Psychiatric Overtones"

Other symptoms can include fatigue, anorexia, and pancreatitis. Limbus sign seen in eye due to hypercalcemia.

Hypercalcemia has a positive chronotropic effect (increase in heart rate[3]), and a positive inotropic effect (increase in contractility).

Abnormal heart rhythms can also result, and ECG findings of a short QT interval[4] suggest hypercalcaemia. Significant hypercalcaemia can cause ECG changes mimicking an acute myocardial infarction.[5] Hypercalcaemia has also been known to cause an ECG finding mimicking hypothermia, known as an Osborn wave.[6]

Hypercalcaemia can increase gastrin production, leading to increased acidity so peptic ulcers may also occur.

Symptoms are more common at high calcium blood values (12.0 mg/dL or 3 mmol/l). Severe hypercalcaemia (above 15–16 mg/dL or 3.75–4 mmol/l) is considered a medical emergency: at these levels, coma and cardiac arrest can result. The high levels of calcium ions decrease the neuron membrane permeability to sodium ions, thus decreasing the excitability, which leads to hypotonicity of smooth and striated muscle. This explains the fatigue, muscle weakness, low tone and sluggish reflexes in muscle groups. The sluggish nerves also explain drowsiness, confusion, hallucinations, stupor and / or coma. In the gut this causes constipation. Hypocalcaemia causes the opposite by the same mechanism.

Causes

Primary hyperparathyroidism and malignancy account for about 90% of cases of hypercalcaemia.[7][8]

Parathyroid function

Cancer

Micrograph of ovarian small cell carcinoma of the hypercalcemic type. H&E stain.

Vitamin-D disorders

High bone-turnover rates

Kidney failure

Treatments

The goal of therapy is to treat the hypercalcaemia first and subsequently effort is directed to treat the underlying cause.

Initial therapy: fluids and diuretics

Additional therapy: bisphosphonates and calcitonin

Other therapies

Hypercalcaemic crisis

A hypercalcaemic crisis is an emergency situation with a severe hypercalcaemia, generally above approximately 14 mg/dL (or 3.5 mmol/l).[15]

The main symptoms of a hypercalcaemic crisis are oliguria or anuria, as well as somnolence or coma.[16] After recognition, primary hyperparathyroidism should be proved or excluded.[16]

In extreme cases of primary hyperparathyroidism, removal of the parathyroid gland after surgical neck exploration is the only way to avoid death.[16] The diagnostic program should be performed within hours, in parallel with measures to lower serum calcium.[16] Treatment of choice for acutely lowering calcium is extensive hydration and calcitonin, as well as bisphosphonates (which have effect on calcium levels after one or two days).[17]

Other animals

Research has led to a better understanding of hypercalcemia in non-human animals. Often the causes of hypercalcemia have a correlation to the environment in which the organisms live. Hypercalcemia in house pets is typically due to disease, but other cases can be due to accidental ingestion of plants or chemicals in the home.[18] Outdoor animals commonly develop hypercalcemia through vitamin D toxicity from wild plants within their environments.[19]

Household pets

Household pets such as dogs and cats are found to develop hypercalcemia. It is less common in cats, and many feline cases are idiopathic.[18] In dogs, lymphosarcoma, addison’s disease, primary hyperparathyroidism, and chronic renal failure are the main causes of hypercalcemia, but there are also environmental causes usually unique to indoor pets.[18] Ingestion of small amounts of calcipotriene found in psoriasis cream can be fatal to a pet.[20] Calcipotriene causes a rapid rise in calcium ion levels.[20] Calcium ion levels can remain high for weeks if untreated and lead to an array of medical issues.[20] There are also cases of hypercalcemia reported due to dogs ingesting rodenticides containing a chemical similar to calcipotriene found in psoriasis cream.[20] Additionally, ingestion of household plants is a cause of hypercalcemia. Plants such as Cestrum diurnum, and Solanum malacoxylon contain ergocalciferol or cholecalciferol which cause the onset of hypercalcemia.[18] Consuming small amounts of these plants can be fatal to pets. Observable symptoms may develop such as polydipsia, polyuria, extreme fatigue, or constipation.[18]

Outdoor animals

Trisetum flavescens (yellow oat grass)

In certain outdoor environments, animals such as horses, pigs, cattle, and sheep experience hypercalcemia commonly. In southern Brazil and Mattewara India, approximately 17 percent of sheep are affected, with 60 percent of these cases being fatal.[19] Many cases are also documented in Argentina, Papua-New Guinea, Jamaica, Hawaii, and Bavaria.[19] These cases of hypercalcemeia are usually caused by ingesting Trisetum flavescens before it has dried out.[19] Once Trisetum flavescens is dried out, the toxicity of it is diminished.[19] Other plants causing hypercalcemia are Cestrum diurnum, Nierembergia veitchii, Solanum esuriale, Solanum torvum, and Solanum malacoxylon.[19] These plants contain calcitrol or similar substances that cause rises in calcium ion levels.[19] Hypercalcemia is most common in grazing lands at altitudes above 1500 meters where growth of plants like Trisetum flavescens is favorable.[19] Even if small amounts are ingested over long periods of time, the prolonged high levels of calcium ions have large negative effects on the animals.[19] The issues these animals experience are muscle weakness, and calcification of blood vessels, heart valves, liver, kidneys, and other soft tissues, which eventually can lead to death.[19]

See also

References

  1. ↑ "hypercalcemia" at Dorland's Medical Dictionary
  2. ↑ Armstrong, C.M., Cota, Gabriel.; Cota (1999). "Calcium block of Na+ channels and its effect on closing rate". Proceedings of the National Academy of Sciences of the United States of America 96 (7): 4154–4157. Bibcode:1999PNAS...96.4154A. doi:10.1073/pnas.96.7.4154. PMC 22436. PMID 10097179.
  3. ↑ http://www.heartandmetabolism.com/download/30/7.pdf
  4. ↑ http://lifeinthefastlane.com/ecg-library/basics/hypercalcaemia/
  5. ↑ Wesson, L; Suresh, V; Parry, R (2009). "Severe hypercalcaemia mimicking acute myocardial infarction". Clinical Medicine (London) 9 (2): 186–7. doi:10.7861/clinmedicine.9-2-186. PMID 19435131.
  6. ↑ Serafi S, Vliek C, Taremi M (2011) "Osborn waves in a hypothermic patient" The Journal of Community Hospital Internal Medicine Perspectives http://www.jchimp.net/index.php/jchimp/article/view/10742/html
  7. ↑ Table 20-4 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
  8. ↑ Tierney, Lawrence M.; McPhee, Stephen J.; Papadakis, Maxine A. (2006). Current Medical Diagnosis and Treatment 2007 (Current Medical Diagnosis and Treatment). McGraw-Hill Professional. p. 901. ISBN 0-07-147247-9.
  9. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 146200
  10. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 145980
  11. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 145981
  12. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 600740
  13. ↑ Non-Small Cell Lung Cancer~clinical at eMedicine.
  14. ↑ Online 'Mendelian Inheritance in Man' (OMIM) 143880
  15. ↑ Hypercalcemia in Emergency Medicine at Medscape. Author: Robin R Hemphill. Chief Editor: Erik D Schraga. Retrieved April 2011
  16. 1 2 3 4 Ziegler R (February 2001). "Hypercalcemic crisis". J. Am. Soc. Nephrol. 12 Suppl 17: S3–9. PMID 11251025.
  17. ↑ Page 394 in: Roenn, Jamie H. Von; Ann Berger; Shuster, John W. (2007). Principles and practice of palliative care and supportive oncology. Hagerstwon, MD: Lippincott Williams & Wilkins. ISBN 0-7817-9595-8.
  18. 1 2 3 4 5 Hypercalcemia in Dogs and Cats Peterson DVM, DACVIM. M. E., July 2013. Hypercalcemia in Dogs and Cats. The Merck Veternary Manual. Merck Sharp & Dohme, Whitehouse Station, NJ, USA.
  19. 1 2 3 4 5 6 7 8 9 10 Enzootic Calcinosis Gruenberg MS, PhD, DECAR DECBHM. W.G., April 2014. Enzootic Calcinosis. The Merck Veternary Manual. Merck Sharp & Dohme, Whitehouse Station, NJ, USA.
  20. 1 2 3 4 Topical Agents (Toxicity) Khan DVM, MS, PhD, DABVT, S.A., March 2012. Topical Agents (Toxicity). The Merck Veternary Manual. Merck Sharp & Dohme, Whitehouse Station, NJ, USA.
  21. ↑ Dauber, Andrew; Nguyen Thutrang T; Sochett Etienne; Cole David E C; Horst Ronald; Abrams Steven A; Carpenter Thomas O; Hirschhorn Joel N (Nov 2011). "Genetic Defect in CYP24A1, the Vitamin D 24-Hydroxylase Gene, in a Patient with Severe Infantile Hypercalcemia". The Journal of Clinical Endocrinology and Metabolism 97 (2): E268–74. doi:10.1210/jc.2011-1972. PMC 3275367. PMID 22112808.
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