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Hypercalcemia of Malignancy


Hypercalcemia of malignancy is a condition characterized by elevated levels of calcium in the blood, which is often associated with cancer. It is a common paraneoplastic syndrome and can occur in various types of malignancies.


{{Short description|High calcium (Ca2+) level in the blood serum}}
==Pathophysiology==
{{Infobox medical condition (new)
 
| name            = Hypercalcaemia
Hypercalcemia of malignancy can occur through several mechanisms:
| synonyms        = Hypercalcemia
 
| image          = Ca-TableImage.svg
* '''Humoral Hypercalcemia of Malignancy (HHM):''' This is the most common mechanism and is caused by the secretion of parathyroid hormone-related peptide (PTHrP) by the tumor. PTHrP mimics the action of parathyroid hormone (PTH), leading to increased bone resorption and renal tubular reabsorption of calcium.
| caption        = Calcium within the [[periodic table]]
 
| field          = [[Endocrinology]]
* '''Osteolytic Metastases:''' Certain cancers, such as breast cancer and multiple myeloma, can metastasize to bone, causing local osteolysis and release of calcium into the bloodstream.
| symptoms        = [[Abdominal pain]], bone pain, [[confusion]], [[Depression (mood)|depression]], [[weakness]]<ref name=BMJ2015/><ref name=EU2010/>
 
| complications  = [[Kidney stones]], [[Heart arrhythmia|abnormal heart rhythm]], [[cardiac arrest]]<ref name=BMJ2015/><ref name=EU2010/>
* '''Vitamin D Secretion:''' Some lymphomas can produce active vitamin D (calcitriol), leading to increased intestinal absorption of calcium.
| onset          =
 
| duration        =
==Clinical Presentation==
| types          =
| causes          = [[Primary hyperparathyroidism]], [[cancer]], [[sarcoidosis]], [[tuberculosis]], [[Paget's disease of bone|Paget disease]], [[multiple endocrine neoplasia]], [[vitamin D toxicity]]<ref name=BMJ2015/><ref name=PMH2016/>
| risks          =
| diagnosis      = [[Blood serum]] level > 2.6&nbsp;mmol/l ([[corrected calcium]] or [[ionized calcium]])<ref name=BMJ2015/><ref name=EU2010/>
| differential    =
| prevention      =
| treatment      = Underlying cause, [[intravenous fluids]], [[furosemide]], [[calcitonin]], [[pamidronate]], [[hemodialysis]]<ref name=BMJ2015/><ref name=EU2010/>
| medication      =
| prognosis      =  
| frequency      = 4 per 1,000<ref name=BMJ2015/>
| deaths          =  
}}
Hypercalcemia generally develops as a late complication of malignancy; its appearance has grave prognostic significance.


==Pathophysiology==
Patients with hypercalcemia of malignancy may present with a variety of symptoms, which can be remembered by the mnemonic "stones, bones, groans, and psychiatric overtones":
It remains unclear, however, whether death is associated with hypercalcemic crisis (uncontrolled or recurrent progressive hypercalcemia) or with advanced disease.  
 
* '''Renal:''' Nephrolithiasis (kidney stones), polyuria, and dehydration.
* '''Skeletal:''' Bone pain and fractures.
* '''Gastrointestinal:''' Nausea, vomiting, constipation, and abdominal pain.
* '''Neurological:''' Confusion, lethargy, and in severe cases, coma.
 
==Diagnosis==
 
The diagnosis of hypercalcemia of malignancy involves:
 
* '''Serum Calcium Levels:''' Elevated total and ionized calcium levels.
* '''Parathyroid Hormone (PTH) Levels:''' Typically low or suppressed in hypercalcemia of malignancy.
* '''PTHrP Levels:''' Elevated in cases of humoral hypercalcemia of malignancy.
* '''Bone Scans and Imaging:''' To identify osteolytic lesions or metastases.
 
==Treatment==
 
The management of hypercalcemia of malignancy includes:
 
* '''Hydration:''' Intravenous fluids to promote renal excretion of calcium.
* '''Bisphosphonates:''' Such as zoledronic acid or pamidronate, to inhibit bone resorption.
* '''Calcitonin:''' Provides a rapid but short-term reduction in calcium levels.
* '''Denosumab:''' A monoclonal antibody that inhibits RANKL, used in cases refractory to bisphosphonates.
* '''Glucocorticoids:''' Particularly effective in cases of vitamin D-mediated hypercalcemia.
* '''Dialysis:''' In severe cases where other treatments are ineffective.
 
==Prognosis==
 
The prognosis of hypercalcemia of malignancy is generally poor, as it often indicates advanced disease. The condition requires prompt treatment to prevent complications and improve quality of life.
 
==See Also==
 
* [[Paraneoplastic syndrome]]
* [[Multiple myeloma]]
* [[Breast cancer]]
* [[Lymphoma]]
 
==External Links==


==Symptoms==
* [American Cancer Society](https://www.cancer.org/)
Symptoms include central nervous system impairment such as delirium with prominent symptoms of personality change, cognitive dysfunction, disorientation, incoherent speech, and psychotic symptoms such as hallucinations and delusions, smooth muscle hypotonicity, and altered cardiovascular function.
* [National Cancer Institute](https://www.cancer.gov/)


Treatment is similar to the treatment of [[hypercalcemia]] plus treatment of the underlying malignancy.
{{Medical conditions}}
{{stub}}
{{Oncology}}
{{Mineral metabolic pathology}}
[[Category:Endocrine disorders]]
{{Paraneoplastic syndromes}}
[[Category:Oncology]]
{{Authority control}}
[[Category:Calcium metabolism disorders]]
[[Category:Electrolyte disturbances]]
[[Category:Calcium]]
[[Category:Abnormal clinical and laboratory findings for blood]]
[[Category:RTTNEURO]]
[[Category:Medical mnemonics]]

Latest revision as of 12:37, 31 December 2024

Hypercalcemia of Malignancy

Hypercalcemia of malignancy is a condition characterized by elevated levels of calcium in the blood, which is often associated with cancer. It is a common paraneoplastic syndrome and can occur in various types of malignancies.

Pathophysiology[edit]

Hypercalcemia of malignancy can occur through several mechanisms:

  • Humoral Hypercalcemia of Malignancy (HHM): This is the most common mechanism and is caused by the secretion of parathyroid hormone-related peptide (PTHrP) by the tumor. PTHrP mimics the action of parathyroid hormone (PTH), leading to increased bone resorption and renal tubular reabsorption of calcium.
  • Osteolytic Metastases: Certain cancers, such as breast cancer and multiple myeloma, can metastasize to bone, causing local osteolysis and release of calcium into the bloodstream.
  • Vitamin D Secretion: Some lymphomas can produce active vitamin D (calcitriol), leading to increased intestinal absorption of calcium.

Clinical Presentation[edit]

Patients with hypercalcemia of malignancy may present with a variety of symptoms, which can be remembered by the mnemonic "stones, bones, groans, and psychiatric overtones":

  • Renal: Nephrolithiasis (kidney stones), polyuria, and dehydration.
  • Skeletal: Bone pain and fractures.
  • Gastrointestinal: Nausea, vomiting, constipation, and abdominal pain.
  • Neurological: Confusion, lethargy, and in severe cases, coma.

Diagnosis[edit]

The diagnosis of hypercalcemia of malignancy involves:

  • Serum Calcium Levels: Elevated total and ionized calcium levels.
  • Parathyroid Hormone (PTH) Levels: Typically low or suppressed in hypercalcemia of malignancy.
  • PTHrP Levels: Elevated in cases of humoral hypercalcemia of malignancy.
  • Bone Scans and Imaging: To identify osteolytic lesions or metastases.

Treatment[edit]

The management of hypercalcemia of malignancy includes:

  • Hydration: Intravenous fluids to promote renal excretion of calcium.
  • Bisphosphonates: Such as zoledronic acid or pamidronate, to inhibit bone resorption.
  • Calcitonin: Provides a rapid but short-term reduction in calcium levels.
  • Denosumab: A monoclonal antibody that inhibits RANKL, used in cases refractory to bisphosphonates.
  • Glucocorticoids: Particularly effective in cases of vitamin D-mediated hypercalcemia.
  • Dialysis: In severe cases where other treatments are ineffective.

Prognosis[edit]

The prognosis of hypercalcemia of malignancy is generally poor, as it often indicates advanced disease. The condition requires prompt treatment to prevent complications and improve quality of life.

See Also[edit]

External Links[edit]