From the Guidelines
Hypercalcemia typically presents with symptoms such as polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, and myalgia, which can progress to severe dehydration, acute renal failure, and mental status changes if left untreated. The clinical symptoms of hypercalcemia depend on the severity and acuity of onset, with mild or moderate hypercalcemia often causing symptoms like polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, and myalgia 1.
Common Symptoms
- Polyuria
- Polydipsia
- Nausea
- Confusion
- Vomiting
- Abdominal pain
- Myalgia
When hypercalcemia is severe (> 14.0 mg/dL), patients may develop mental status changes, bradycardia, and hypotension 1. The diagnostic evaluation includes measuring serum concentrations of intact parathyroid hormone (iPTH), parathyroid hormone-related protein (PTHrP), 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D, calcium, albumin, magnesium, and phosphorus.
Management
The management of hypercalcemia includes oral hydration for mild cases, and rehydrating with IV crystalloid fluids not containing calcium, giving loop diuretics (eg, furosemide) as needed after correction of intravascular volume, and using bisphosphonates (clodronate, pamidronate, and zoledronic acid) for moderate to severe hypercalcemia 1. Additional therapeutic options such as glucocorticoids, gallium nitrate, and salmon calcitonin may be considered 1.
Prompt medical attention is necessary, especially when calcium levels exceed 14 mg/dL, as this constitutes a medical emergency that can lead to cardiac arrest and death if left untreated. The median survival after discovery of hypercalcemia of malignancy in patients with lung cancer is about 1 month 1, highlighting the importance of early diagnosis and treatment.
From the Research
Symptoms of Hypercalcemia
The symptoms of hypercalcemia can vary depending on the severity of the condition.
- Mild hypercalcemia is usually asymptomatic, but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people 2.
- Severe hypercalcemia can cause nausea, vomiting, dehydration, confusion, somnolence, and coma 2, 3.
- Hypercalcemia can also cause bone pain, kidney stones, and abdominal cramps 3.
Causes of Hypercalcemia
Hypercalcemia can be caused by a variety of factors, including:
- Primary hyperparathyroidism (PHPT) or malignancy, which account for approximately 90% of cases 2.
- Granulomatous disease, such as sarcoidosis, and endocrinopathies, such as thyroid disease 2.
- Immobilization, genetic disorders, and medications, such as thiazide diuretics and supplements, such as calcium, vitamin D, or vitamin A 2.
- Sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, although these account for less than 1% of causes 2.
Treatment of Hypercalcemia
The treatment of hypercalcemia depends on the underlying cause and severity of the condition.
- Mild hypercalcemia usually does not require acute intervention, but may be managed with observation and monitoring 2.
- Severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 2, 3.
- Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas) 2, 4.
- Bisphosphonates, such as pamidronate and zoledronic acid, are effective in reducing serum calcium levels and improving symptoms, but may be associated with an increased risk of serum creatinine elevations in patients with preexisting renal dysfunction 5.