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Hypercalcemia

Disease Details

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Description: Hypercalcemia is a condition characterized by an abnormally high level of calcium in the blood.
Type: Hypercalcemia describes elevated calcium levels in the blood. While it is often due to non-genetic causes such as hyperparathyroidism, certain genetic conditions can result in hypercalcemia.

1. Type: Metabolic disorder.
2. Type of genetic transmission: Hypercalcemia can be transmitted in an autosomal dominant manner in conditions like familial hypocalciuric hypercalcemia (FHH).
Signs And Symptoms: The neuromuscular symptoms of hypercalcaemia 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. This results in diminished deep tendon reflexes (hyporeflexia), and skeletal muscle weakness.Other symptoms include cardiac arrhythmias (especially in those taking digoxin), fatigue, nausea, vomiting (emesis), loss of appetite, abdominal pain, & paralytic ileus. If kidney impairment occurs as a result, manifestations can include increased urination, urination at night, and increased thirst. Psychiatric manifestation can include emotional instability, confusion, delirium, psychosis, and stupor. Calcium deposits known as limbus sign may be visible in the eyes.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 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 or coma. In the gut this causes constipation. Hypocalcaemia causes the opposite by the same mechanism.
Prognosis: The prognosis for hypercalcemia depends on the underlying cause and the severity of the condition. Mild hypercalcemia, often caused by primary hyperparathyroidism, can be relatively well-managed with monitoring and treatment, leading to a good prognosis. Severe hypercalcemia, often due to malignancies, can be life-threatening and requires prompt, aggressive treatment. The overall outcome largely hinges on timely diagnosis, effective management of the underlying cause, and the patient’s overall health and coexisting conditions.
Onset: Onset: Hypercalcemia can develop gradually over time or occur suddenly, depending on the underlying cause.

Duration: The duration of hypercalcemia can vary. Acute hypercalcemia may resolve quickly with treatment, while chronic hypercalcemia may persist and require long-term management depending on the cause.
Prevalence: The prevalence of hypercalcemia varies depending on the population and underlying causes. In the general population, it is relatively rare, with an estimated prevalence of about 1%. However, it is more common in certain groups, such as individuals with primary hyperparathyroidism (which affects approximately 1-3 per 1,000 people) or malignancies, where the prevalence can be significantly higher.
Epidemiology: Epidemiology of hypercalcemia:

Hypercalcemia, characterized by elevated levels of calcium in the blood, has varied epidemiology depending on its underlying causes.

1. **Primary Hyperparathyroidism:** This is the most common cause of hypercalcemia in the general population, often diagnosed in postmenopausal women. The prevalence is approximately 1-7 per 1,000 people.

2. **Malignancy-Associated Hypercalcemia:** This is the second most common cause and is more prevalent in hospitalized patients. It occurs in about 10-30% of cancer patients, particularly those with cancers such as breast cancer, lung cancer, and multiple myeloma.

3. **Other Causes:** Less common causes include vitamin D intoxication, granulomatous diseases (e.g., sarcoidosis), and certain medications (e.g., thiazide diuretics). Each of these conditions contributes variably to the overall incidence of hypercalcemia.

Overall, the prevalence and incidence of hypercalcemia depend on the population studied and the presence of underlying health conditions or contributing factors.
Intractability: Hypercalcemia, or elevated calcium levels in the blood, is not inherently intractable. It can often be managed or treated depending on the underlying cause, which may include conditions such as hyperparathyroidism, certain cancers, or excessive intake of calcium or vitamin D. Treatment options vary widely and may include medications, surgery, or addressing the underlying disease. Early diagnosis and appropriate management are key to effectively controlling hypercalcemia.
Disease Severity: Hypercalcemia can range from mild to severe, depending on the underlying cause and the level of calcium in the blood. Mild cases may be asymptomatic or cause minor symptoms, while severe hypercalcemia can lead to serious complications such as kidney failure, cardiac arrhythmias, and neurological disturbances. Prompt diagnosis and management are crucial to prevent significant morbidity and potential mortality.
Healthcare Professionals: Disease Ontology ID - DOID:12678
Pathophysiology: Hypercalcemia refers to an elevated level of calcium in the blood. The pathophysiology of hypercalcemia can involve several mechanisms:

1. **Increased Bone Resorption**: Conditions such as primary hyperparathyroidism and malignancies can lead to excessive breakdown of bone tissue, releasing calcium into the bloodstream.

2. **Increased Gastrointestinal Absorption**: Excessive intake of calcium or vitamin D can increase the absorption of calcium from the gastrointestinal tract into the blood.

3. **Decreased Renal Excretion**: Conditions such as renal failure, thiazide diuretic use, and certain genetic disorders can impair the kidneys' ability to excrete calcium, leading to its accumulation in the blood.

Overall, hypercalcemia results from an imbalance between calcium intake, absorption, and excretion, often influenced by hormonal and pathological conditions.
Carrier Status: Hypercalcemia is not a condition that's associated with a carrier status. It is characterized by an abnormally high level of calcium in the blood. This condition can be caused by various factors including hyperparathyroidism, certain cancers, excessive vitamin D intake, and other health conditions. If you have specific concerns about hypercalcemia, consulting with a healthcare professional will provide you with the most accurate information tailored to your situation.
Mechanism: Hypercalcemia is characterized by elevated calcium levels in the blood. Here are the mechanisms and molecular mechanisms involved:

### Mechanism:
1. **Increased Bone Resorption**: Calcium is released into the bloodstream from bones, often due to conditions like hyperparathyroidism or cancer.
2. **Increased Intestinal Absorption**: Excessive intake of calcium or vitamin D can enhance calcium absorption from the gastrointestinal tract.
3. **Decreased Renal Excretion**: Conditions affecting kidney function can reduce calcium excretion, leading to accumulation in the blood.

### Molecular Mechanisms:
1. **Parathyroid Hormone (PTH)**:
- **Function**: PTH increases calcium levels by stimulating bone resorption, increasing renal reabsorption of calcium, and promoting the activation of vitamin D.
- **Hyperparathyroidism**: Elevated PTH levels due to adenomas or hyperplasia result in increased bone resorption and calcium release.

2. **Vitamin D**:
- **Function**: Enhances gastrointestinal absorption of calcium.
- **Excess Vitamin D**: Overproduction or intoxication with vitamin D elevates calcium absorption and blood levels.

3. **Cytokines and Growth Factors**:
- **Cancer Pathophysiology**: Tumors secrete factors like parathyroid hormone-related protein (PTHrP), which mimic PTH activity, leading to bone resorption and hypercalcemia.

4. **Renal Mechanisms**:
- **Calcium Transport in Kidneys**: Involves proteins such as TRPV5 and TRPV6 (transporter channels), calbindins (calcium-binding proteins), and NCX1 (sodium-calcium exchanger).
- **Dysregulation**: Impaired function or expression of these proteins can disrupt calcium reabsorption, contributing to hypercalcemia.

5. **Signaling Pathways**:
- **RANKL/OPG Pathway**: Regulates osteoclast differentiation and activity. Increased RANKL or decreased osteoprotegerin (OPG) leads to enhanced bone resorption.
- **MAPK and PI3K/Akt Pathways**: Involved in cellular responses to PTH and PTHrP, affecting bone metabolism and calcium homeostasis.

Understanding these mechanisms provides insight into therapeutic targets for managing hypercalcemia, such as PTH surgery, vitamin D regulation, and inhibitors of bone resorption.
Treatment: Treatment for hypercalcemia involves multiple approaches depending on the severity and underlying cause. Here are the main strategies:

1. **Hydration**: Intravenous (IV) fluids, typically saline, are administered to promote kidney function and excrete excess calcium.

2. **Diuretics**: After adequate hydration, loop diuretics like furosemide may be used to further enhance calcium excretion through urine.

3. **Bisphosphonates**: Medications such as pamidronate or zoledronic acid inhibit bone resorption and are effective for hypercalcemia of malignancy.

4. **Calcitonin**: This hormone can help lower blood calcium levels rapidly but is usually used for short-term management due to tachyphylaxis.

5. **Glucocorticoids**: Steroids like prednisone may be used in cases of hypercalcemia due to granulomatous diseases or certain lymphomas.

6. **Dialysis**: In severe or life-threatening cases, hemodialysis may be necessary to remove excess calcium.

7. **Addressing the Underlying Cause**: Treatment also involves managing the primary condition causing hypercalcemia, such as parathyroidectomy for hyperparathyroidism or treating malignancies.

Consultation with a healthcare professional is essential for tailoring the treatment to the individual's specific needs and conditions.
Compassionate Use Treatment: For hypercalcemia, off-label or experimental treatments may include:

1. **Calcitonin**: Though not typically first-line for hypercalcemia, it can be used to quickly lower calcium levels in severe cases.
2. **Bisphosphonates**: Medications like zoledronic acid or pamidronate, typically used for osteoporosis, can help manage hypercalcemia, particularly when linked to malignancy.
3. **Denosumab**: A monoclonal antibody generally used for osteoporosis and bone metastases, applied off-label for hypercalcemia refractory to bisphosphonates.
4. **Cinacalcet**: Primarily approved for secondary hyperparathyroidism, this medication can be used off-label to manage hypercalcemia by increasing the sensitivity of calcium-sensing receptors.

Experimental treatments and compassionate use are typically reserved for severe cases unresponsive to standard therapies and may include investigational drugs contingent on clinical trial availability and regulatory approval.
Lifestyle Recommendations: For hypercalcemia, lifestyle recommendations generally include:

1. **Hydration:** Increase fluid intake, particularly water, to help prevent kidney stones and to help flush excess calcium out of the system.
2. **Diet:** Limit intake of calcium-rich foods and supplements. Reduce consumption of dairy products, fortified foods, and calcium supplements.
3. **Exercise:** Engage in regular physical activity to support bone health and overall well-being.
4. **Avoid Certain Medications:** Avoid or consult with a healthcare provider about medications that can increase calcium levels (e.g., thiazide diuretics).
5. **Limit Alcohol and Caffeine:** Reduce intake of alcohol and caffeine, as they can affect calcium levels and bone health.

Always consult with a healthcare provider for personalized medical advice.
Medication: Medications commonly used to treat hypercalcemia include:

1. **Bisphosphonates**: Zoledronic acid and pamidronate can help to reduce calcium levels by inhibiting bone resorption.
2. **Calcitonin**: This hormone can be used to lower calcium levels more rapidly, though its effect is generally short-term.
3. **Glucocorticoids**: Prednisone may be used, especially in cases of hypercalcemia due to vitamin D toxicity or certain cancers.
4. **Denosumab**: This is an option for patients who do not respond to bisphosphonates.
5. **Hydration and diuretics**: Intravenous saline can help to enhance renal calcium excretion, and loop diuretics like furosemide can further increase calcium excretion once the patient is adequately hydrated.

Always consult with a healthcare provider for the most appropriate treatment option based on individual circumstances.
Repurposable Drugs: Repurposable drugs for hypercalcemia may include:
1. **Bisphosphonates** (e.g., alendronate, risedronate) – often used for osteoporosis but can help reduce calcium levels.
2. **Calcitonin** – typically used for osteoporosis and Paget’s disease but can lower calcium levels quickly.
3. **Glucocorticoids** (e.g., prednisone) – can be effective particularly in hypercalcemia associated with granulomatous diseases and some cancers.
4. **Denosumab** – initially developed for osteoporosis but can also be used to lower calcium in cases resistant to bisphosphonates.

Please provide additional specified details if you need further information on other aspects of hypercalcemia or its treatment.
Metabolites: Hypercalcemia refers to elevated calcium levels in the blood. Key metabolites related to this condition include:

1. **Parathyroid Hormone (PTH)**: Increased levels of PTH, often due to hyperparathyroidism, can lead to hypercalcemia by increasing calcium reabsorption from bones and the kidneys and enhancing calcium absorption in the intestines.

2. **Vitamin D Metabolites**: Elevated levels of active vitamin D (calcitriol) enhance calcium absorption from the intestines, which can contribute to hypercalcemia.

3. **Calcium**: Directly measured in the blood. Elevated serum calcium indicates hypercalcemia.

Understanding the interplay between these metabolites is crucial for diagnosing and managing hypercalcemia.
Nutraceuticals: There are no established nutraceuticals specifically recommended for treating hypercalcemia. However, certain lifestyle and dietary modifications may help manage calcium levels. Always consult with a healthcare professional for appropriate diagnosis and treatment options.
Peptides: Hypercalcemia often involves elevated levels of calcium in the blood. It can be associated with peptides such as parathyroid hormone (PTH) or parathyroid hormone-related peptide (PTHrP). Both of these can influence calcium levels by increasing bone resorption, enhancing renal calcium reabsorption, and promoting the activation of vitamin D to increase intestinal calcium absorption. Elevated PTHrP is commonly linked to malignancies.