Hypercalcemia

Hypercalcemia is a medical condition that has garnered significant attention from healthcare professionals and the general public alike. As a doctor, it is crucial to delve into the intricacies of this condition to provide accurate and comprehensive information to those seeking a better understanding of hypercalcemia. In the following sections, we will explore these aspects in greater detail, shedding light on this important health topic.

What is Hypercalcemia?

Hypercalcemia refers to a condition in which the concentration of calcium in the blood surpasses normal levels. Calcium, a vital mineral in the body, is meticulously regulated by the parathyroid glands, kidneys, and bones. When the delicate balance is disrupted, particularly when the parathyroid glands secrete excessive amounts of parathyroid hormone (PTH), it can trigger an increased release of calcium into the bloodstream, resulting in hypercalcemia. However, elevated calcium levels can also stem from other factors, such as certain types of cancer, vitamin D toxicity, and various medical conditions. Understanding the underlying causes of hypercalcemia is crucial for accurate diagnosis and effective treatment.

The manifestation of hypercalcemia symptoms can vary significantly depending on the severity and duration of the condition. In mild cases, individuals may not experience any noticeable symptoms. However, as the condition progresses, a range of signs and symptoms may emerge.

Common symptoms

• Abdominal pain: Individuals with hypercalcemia may experience stomach discomfort, nausea, and vomiting.
• Bone pain: Elevated calcium levels can lead to aching bones, weakness, and muscle fatigue.
• Confusion and cognitive impairment: Severe cases of hypercalcemia can cause mental confusion, disorientation, and even coma.
• Constipation: Hypercalcemia can slow down bowel movements, resulting in constipation.
• Depression and anxiety: Some individuals may experience mood changes, including depression and anxiety.
• Fatigue and weakness: Hypercalcemia can cause overall muscle weakness, fatigue, and a general feeling of being unwell.
• Polyuria and polydipsia: Elevated calcium levels can lead to increased urine production and excessive thirst.

In more severe cases of hypercalcemia, patients may face serious complications such as kidney stones, abnormal heart rhythms, and even cardiac arrest. It is crucial to seek prompt medical attention if symptoms persist or worsen over time, as early intervention can prevent further complications and improve overall health outcomes.

There are various causes of hypercalcemia. Some of the common ones include:

• Primary hyperparathyroidism: Overactivity of one or more parathyroid glands leading to excessive parathyroid hormone (PTH) production.
• Cancer: Certain types of cancer, such as lung, breast, kidney, and multiple myeloma, can cause hypercalcaemia by secreting proteins that mimic PTH or by metastasising to bone and releasing calcium.
• Vitamin D intoxication: High doses of vitamin D can increase calcium absorption from the gut.
• Dietary excess: Consuming too much calcium, especially with high doses of vitamin D, can lead to hypercalcaemia (milk-alkali syndrome).
• Medications: Certain medications, such as thiazide diuretics, lithium, and excessive use of calcium and vitamin D supplements.
• Bone disorders: Conditions like Paget's disease, especially with dehydration or prolonged immobilisation.
• Endocrine disorders: Hyperthyroidism can cause increased bone resorption, leading to hypercalcaemia.
• Granulomatous diseases: Sarcoidosis, tuberculosis, and leprosy can cause hypercalcaemia.

Recognising the underlying cause is crucial for effectively managing hypercalcaemia symptoms and preventing complications.

Who does Hypercalcemia affect?

• Postmenopausal women: More susceptible to primary hyperparathyroidism.

• Cancer patients: Especially those with lung, breast, kidney, and blood cancers.

• People with vitamin D disorders: Excessive vitamin D intake or impaired metabolism.

• Individuals with certain genetic disorders: Familial hypocalciuric hypercalcaemia and multiple endocrine neoplasia type 1.

• Patients taking specific medications: Thiazide diuretics, lithium, and excessive calcium and vitamin D supplements.

• People with chronic kidney disease: Impaired calcium excretion and vitamin D metabolism.

• Individuals with granulomatous diseases: Sarcoidosis, tuberculosis, and leprosy.

• Those with prolonged immobilisation: Increased bone resorption due to inactivity.

If hypercalcemia is not adequately treated, it can lead to a range of serious complications:

• Kidney stones and Kidney Failure: Elevated calcium levels can promote the formation of kidney stones and potentially lead to renal failure.
• Bone disease: Hypercalcemia may cause weakening of the bones, osteoporosis, and an increased risk of fractures.
• Neurological symptoms: Severe cases of hypercalcemia can result in confusion, depression, and even coma.
• Cardiovascular issues: High calcium levels can contribute to hypertension and heart problems.
• Gastrointestinal symptoms: Hypercalcemia may cause nausea, vomiting, constipation, and pancreatitis.

Promptly addressing hypercalcemia and its underlying causes is essential to prevent these potentially life-threatening complications and ensure optimal patient outcomes.

Preventing hypercalcemia involves a combination of lifestyle adjustments, careful management of medications and supplements, and regular medical check-ups.

1. Lifestyle adjustments

• Stay hydrated: Drinking plenty of water can help lower elevated blood calcium levels and prevent kidney stones.
• Avoid excessive calcium and vitamin D intake: Be cautious with calcium supplements and vitamin D, as high doses can lead to hypercalcemia. The milk-alkali syndrome, for instance, can occur when large amounts of calcium bicarbonate supplements are taken along with high doses of vitamin D.
• Maintain physical activity: Regular exercise, especially strength training, can promote bone health and reduce the risk of hypercalcemia associated with immobilisation.

2. Medication and supplement management

• Follow medical advice: Always consult your healthcare provider before taking any dietary supplements, vitamins, or minerals to avoid excessive intake of calcium or vitamin D.
• Monitor medications: Be aware of medications that can induce hypercalcemia, such as lithium, thiazide diuretics, and high doses of vitamin A and D.

3. Regular check-ups

• Family history: If you have a family history of hypercalcemia, hyperparathyroidism, or kidney stones, discuss your risk with your healthcare provider.
• Routine blood tests: Hypercalcemia is often detected through routine blood tests. Regular health check-ups can help identify the condition early and guide appropriate hypercalcemia treatment.

Hypercalcemia is typically diagnosed through a combination of clinical evaluation and laboratory testing.

• Routine blood tests: Hypercalcemia is often detected during routine blood tests, such as a comprehensive metabolic panel (CMP) or basic metabolic panel.
• Symptom evaluation: Healthcare providers look for hypercalcemia symptoms such as fatigue, muscle weakness, recurrent nephrolithiasis, bone pain, constipation, and changes in mental status.
• Laboratory testing
  • Initial testing includes measuring serum calcium levels and albumin to calculate corrected calcium levels.
  • Additional tests may include parathyroid hormone (PTH) testing, urine calcium, and 24-hour urine collection.
  • Ionised calcium testing may be performed if albumin levels are low or to confirm abnormal values.
• Imaging tests: If primary hyperparathyroidism is suspected, imaging tests such as ultrasound, parathyroid sestamibi scan, four-dimensional CT scan, and PET choline scan may be ordered to locate any growths or enlargement of the parathyroid glands.

Once diagnosed, appropriate hypercalcemia treatment can be initiated based on the underlying cause and severity of the condition.

Hypercalcemia treatment depends on its severity and underlying cause. The aim is to lower calcium levels, prevent complications, and manage the root cause effectively.

1. Medications for Hypercalcemia

• Bisphosphonates: Pamidronate, etidronate, and alendronate help inhibit bone resorption, reducing calcium release into the bloodstream. These are commonly used in hypercalcemia due to malignancy.
• Monoclonal Antibody Therapy: Denosumab is effective in cases where bisphosphonates are not well tolerated. It prevents excessive bone breakdown and calcium release.
• Antidote for Rapid Calcium Reduction: Calcitonin lowers blood calcium levels quickly by inhibiting bone resorption and increasing calcium excretion.
• Glucocorticoids: Prednisone is used when hypercalcemia is caused by certain cancers, inflammatory conditions, or vitamin D toxicity, helping reduce calcium absorption from the gut.
• Calcimimetic Agents: Cinacalcet is used to control overactive parathyroid glands, particularly in conditions like primary and secondary hyperparathyroidism.
• Minerals: Potassium phosphate helps lower calcium levels by binding with excess calcium and promoting its excretion.

​​2. Additional Treatment Approaches

• Hydration & Diuretics: Increasing fluid intake and using loop diuretics (e.g., furosemide) help enhance calcium excretion through urine.
• Dialysis: In severe cases, dialysis may be required to rapidly lower dangerously high calcium levels.
• Parathyroidectomy: For primary hyperparathyroidism caused by a benign tumour, surgical removal of the affected parathyroid gland is usually curative.

It is crucial to seek medical attention if you experience any hypercalcemia symptoms or have risk factors associated with elevated calcium levels.

• Symptoms: If you notice signs of hypercalcaemia such as excessive thirst, frequent urination, digestive problems, confusion, or muscle weakness, contact your healthcare provider. Getting prompt treatment is important.
• Family history: If you have a family history of hypercalcemia or related conditions, consult your healthcare provider to discuss your risk. They can advise on preventive measures and screening.
• Medication concerns: If you are taking medications or supplements that could potentially cause hypercalcemia, such as lithium or high doses of vitamin D, monitor your condition closely and consult your healthcare provider. Dose adjustments or alternative treatments may be necessary.

• Common causes: Hypercalcemia is most commonly caused by primary hyperparathyroidism, certain cancers, excessive vitamin D intake, and immobilisation. Understanding the underlying hypercalcemia causes is key to prevention and treatment.
• Symptoms to watch for: Elevated blood calcium symptoms include excessive thirst, frequent urination, fatigue, bone pain, digestive issues, confusion, and muscle weakness. Recognising these signs can lead to timely diagnosis.
• Prevention strategies: Preventing hypercalcemia involves staying hydrated, avoiding excessive calcium and vitamin D intake, maintaining physical activity, following medical advice on supplements and medications, and having regular check-ups.
• Seeking medical attention: Consult a doctor if you experience hypercalcemia symptoms, have a family history of related conditions, or have concerns about medications that may affect calcium levels. Prompt treatment can prevent complications.