Ep 218 – Hypercalcaemia

In this episode, Dr Hannah Rosa discusses hypercalcaemia and how it can be managed in five steps. She reviews when to suspect hypercalcaemia and the most common causes of a raised calcium. She also covers further investigations that can be undertaken in primary care, management in secondary care and follow-up in primary care. At the end, there is a chance to put the learning into a clinical context with a quick quiz.

Key take-home points

• Hypercalcaemia is defined as a serum calcium concentration of 2.6 mmol/L or more on two occasions, following adjustment for the serum albumin concentration.
• It is important to identify hypercalcaemia, as it can lead to acute and chronic effects on cardiac tissue, the renal system and bone health.
• Checking a serum calcium should be considered for people with chronic non-differentiated symptoms, for example, frequent urination, increased thirst, digestive problems, fatigue, mild confusion, bone, muscle or joint pain, anxiety, irritability, low mood, apathy and insomnia.
• Hypercalcaemia can be classified as mild (2.6–3 mmol/L), moderate (3–3.5 mmol/L), or severe (more than 3.5 mmol/L).
• If an initial blood test suggests mild hypercalcaemia and the patient is asymptomatic or has mild symptoms, the serum calcium level should be repeated after 1 week to confirm the diagnosis.
• If the initial blood test suggests moderate hypercalcaemia with no symptoms and no known or suspected malignancy, the calcium level should be repeated within a week, liaising with the on-call endocrinology team if uncertain.
• If the initial blood test shows moderate hypercalcaemia with symptoms present, or the patient has a known malignancy, a repeat test should be arranged urgently, with a low threshold for admission (especially if the patient is dehydrated or confused) and contact a specialist if uncertain; if the repeat test confirms moderate hypercalcaemia, or the patient is symptomatic, immediate same-day referral to hospital or specialist liaison should be considered.
• If the initial or repeat blood test suggests severe hypercalcaemia, or the patient has severe symptoms, an emergency hospital admission should be arranged for further assessment and management.
• The most common cause of hypercalcaemia is primary hyperparathyroidism, which causes a calcium level of 2.5 mmol/L or more alongside high or inappropriately normal parathyroid hormone (PTH).
• The second most common cause of hypercalcaemia is hypercalcaemia of malignancy, which is not PTH-mediated; PTH levels are appropriately suppressed or undetectable in the presence of a raised serum calcium.
• For a person with a confirmed diagnosis of primary hyperparathyroidism who has not had parathyroid surgery, or whose surgery has not been successful, monitoring of serum calcium, vitamin D and urea and electrolytes should be arranged every 12 months, with further monitoring by dual-energy X-ray absorptiometry scan, renal ultrasound scan and cardiovascular risk assessment as appropriate; re-referral to endocrinology should be considered if symptoms develop, the calcium level increases (especially if the adjusted serum calcium is 2.85 mmol/L or more), or complications develop.
• For a person who has had successful parathyroid surgery for primary hyperparathyroidism, calcium levels should be checked annually, following specialist advice about monitoring any complications such as osteoporosis or renal stones.

Key references

1. Sadiq NM, Anastasopoulou C, Patel G, et al. Hypercalcemia. StatPearls [Internet]. 2024 https://www.ncbi.nlm.nih.gov/books/NBK430714/.
2. NICE. 2019 https://www.nice.org.uk/guidance/ng132.
3. Turner JJO. Clin Med (Lond). 2017;17(3):270-273. doi: 10.7861/clinmedicine.17-3-270.
4. Soto-Pedre E, Newey PJ, Leese GP. J Clin Endocrinol Metab. 2023;108(10):e1117-e1124. doi: 10.1210/clinem/dgad201.
5. Asonitis N, Angelousi A, Zafeiris C, et al. Horm Metab Res. 2019;51(12):770-778. doi: 10.1055/a-1049-0647.
6. Rout P, Hashmi MF, Patel C. Milk-Alkali syndrome. StatPearls [Internet]. 2024 https://www.ncbi.nlm.nih.gov/books/NBK557500/.
7. Na D, Tao G, Shu-Ying L, et al. BMC Endocr Disord. 2021;21(1):170. doi: 10.1186/s12902-021-00838-y.