From the Guidelines
Hypercalcemia symptoms include polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, and myalgia, with severe cases leading to mental status changes, bradycardia, and hypotension. The clinical presentation of hypercalcemia depends on the severity and acuity of onset, with mild or moderate hypercalcemia often causing symptoms such as polyuria, polydipsia, nausea, confusion, vomiting, abdominal pain, and myalgia 1. Patients may also present with severe dehydration and acute renal failure.
Severity of Hypercalcemia
When hypercalcemia is severe (> 14.0 mg/dL), patients may develop more serious symptoms, including 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 of Hypercalcemia
The management of hypercalcemia includes oral hydration for mild cases, and rehydrating with IV crystalloid fluids not containing calcium, along with loop diuretics (e.g., furosemide) as needed after correction of intravascular volume for moderate to severe cases 1. Bisphosphonates (clodronate, pamidronate, and zoledronic acid) are usually effective, and additional therapeutic options such as glucocorticoids, gallium nitrate, and salmon calcitonin may be considered 1.
Key Considerations
It is essential to recognize the symptoms of hypercalcemia early, as untreated hypercalcemia can lead to serious complications, including kidney damage, osteoporosis, and neurological problems. The median survival after discovery of hypercalcemia of malignancy in patients with lung cancer is about 1 month 1, highlighting the importance of prompt diagnosis and management.
From the Research
Hypercalcemia Symptoms
- Hypercalcemia affects approximately 1% of the worldwide population, with mild hypercalcemia being 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 of malignancy is typically rapid in onset, with higher serum calcium levels, and more severe symptoms, including marked anemia 3
- Primary hyperparathyroidism tends to be associated with lower serum calcium levels and a longer duration of hypercalcemia, with symptoms such as kidney calculi, hyperchloremic metabolic acidosis, and metabolic bone disease osteitis fibrosa cystica 3
Causes of Hypercalcemia
- Primary hyperparathyroidism and malignancy are responsible for greater than 90% of all cases of hypercalcemia 2, 3
- Other causes of hypercalcemia include granulomatous disease, endocrinopathies, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A 2
- Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes 2
Treatment of Hypercalcemia
- Treatment of hypercalcemia should be started with hydration, and loop diuretics may be required in individuals with renal insufficiency or heart failure to prevent fluid overload 3
- Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia, and intravenous bisphosphonates such as zoledronic acid or pamidronate are used for long-term control of severe or symptomatic hypercalcemia 3, 4
- Glucocorticoids are effective in hypercalcemia due to lymphoma or granulomatous diseases, and dialysis is generally reserved for those with severe hypercalcemia complicated with kidney failure 3, 5