Symptom management: Hypercalcemia

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1 Symptom management: Hypercalcemia Dr Claire Higham NLCFN National Conference 2016 Consultant Endocrinologist The Christie Hospital Manchester, UK

2 Hypercalcemia of malignancy 2-30% of patients with cancer associated with a poor prognosis - 50% die within 30 months diagnosis of underlying cause is important -alters prognosis and management

3 John Chris 64 SCLC T3 N2 M0 carboplatin and etoposide chemotherapy serum Corrected Calcium 2.88 mmol/l ( )

4 John Chris 64 serum Corrected Calcium 2.88 mmol/l ( ) Is Chris symptomatic?

5 Symptoms and Signs of hypercalcemia

6 Symptoms and Signs of hypercalcemia moans

7 Symptoms and Signs of hypercalcemia bones

8 Symptoms and Signs of hypercalcemia stones

9 Symptoms and Signs of hypercalcemia and abdominal groans

10 John Chris 64 SCLC T3 N2 M0 carboplatin and etoposide chemotherapy serum Corrected Calcium 2.88 mmol/l ( ) asymptomatic phosphate 0.83 mmol/l ( ) ALP 99 IU/L (25-110)

11 John Chris 64 SCLC T3 N2 M0 carboplatin and etoposide chemotherapy serum Corrected Calcium 2.88 mmol/l ( ) asymptomatic what is the cause of the hypercalcemia? phosphate 0.83 mmol/l ( ) ALP 99 IU/L (25-110)

12 Calcium Metabolism DiGirolamo DJ, et al. Nat Rev Rheumatol. 2012;8(11):

13 Calcium Metabolism DiGirolamo DJ, et al. Nat Rev Rheumatol. 2012;8(11):

14 Calcium Metabolism DiGirolamo DJ, et al. Nat Rev Rheumatol. 2012;8(11):

15 Calcium Metabolism DiGirolamo DJ, et al. Nat Rev Rheumatol. 2012;8(11):

16 Calcium Metabolism Primary Hyperparathyroidism DiGirolamo DJ, et al. Nat Rev Rheumatol. 2012;8(11):

17 Calcium Metabolism Actions of PTH to increase serum calcium - increases bone resorption - increases renal calcium absorption - Increases gut absorption of calcium via 1,25 vitd DiGirolamo DJ, et al. Nat Rev Rheumatol. 2012;8(11):

18 Hypercalcemia Primary hyperparathyroidism Ca ++ PTH

19 Hypercalcemia PTHrP release Primary hyperparathyroidism Ca ++ PTH

20 Hypercalcemia PTHrP release Primary hyperparathyroidism PTH Ca ++ PTH

21 Calcium Metabolism PTHrP +ve +ve -ve Ca2+ DiGirolamo DJ, et al. Nat Rev Rheumatol. 2012;8(11):

22 Hypercalcemia PTHrP release Primary hyperparathyroidism PTH Ca ++ PTH

23 Hypercalcemia of malignancy PTHrP most common cause of hypercalcemia of malignancy PTHrp mimics renal and bone effects of PTH squamous cell carcinoma of lung most frequent underlying cause associated with a very poor prognosis (2 months)

24 PTHrP Hypercalcemia of malignancy PTH Ca ++ PTH

25 Hypercalcemia of malignancy PTHrP Osteolytic mets PTH Ca ++ PTH Calcitriol (1,25 vitd3) (ectopic PTH)

26 Hypercalcemia of malignancy PTHrP Primary hyperparathyroidism Osteolytic mets PTH Ca ++ PTH Calcitriol (1,25 vitd3) (ectopic PTH)

27 Hypercalcemia of malignancy PTHrP Primary hyperparathyroidism Osteolytic mets PTH Ca ++ PTH Calcitriol (1,25 vitd3) (ectopic PTH)

28 John Chris 64 SCLC T3 N2 M0 carboplatin and etoposide chemotherapy serum Corrected Calcium 2.88 mmol/l ( ) asymptomatic phosphate 0.83 mmol/l ( ) ALP 99 IU/L (25-110)

29 Hypercalcemia diagnostic pathway Elevated serum calcium Check repeat (total serum corrected for albumin or ionised)

30 Hypercalcemia diagnostic pathway Elevated serum calcium Check repeat (total serum corrected for albumin or ionised) Measure intact serum PTH levels (+vitamin D!)

31 Hypercalcemia diagnostic pathway Elevated serum calcium Check repeat (total serum corrected for albumin or ionised) Measure intact serum PTH levels (+vitamin D!) suppressed PTH

32 Hypercalcemia diagnostic pathway Elevated serum calcium Check repeat (total serum corrected for albumin or ionised) Measure intact serum PTH levels (+vitamin D!) suppressed PTH Non-PTH mediated hypercalcemia Likely PTHrP

33 Hypercalcemia diagnostic pathway Elevated serum calcium Check repeat (total serum corrected for albumin or ionised) Measure intact serum PTH levels (+vitamin D!) Elevated or high normal PTH

34 Hypercalcemia diagnostic pathway Elevated serum calcium Check repeat (total serum corrected for albumin or ionised) Measure intact serum PTH levels (+vitamin D!) Elevated or high normal PTH Primary hyperparathyroidism (consider FHH)

35 Hypercalcemia diagnostic pathway Elevated serum calcium Check repeat (total serum corrected for albumin or ionised) Measure intact serum PTH levels low normal PTH Does patient have malignancy? If so consider dual pathology

36 Hypercalcemia diagnostic pathway Elevated serum calcium Check repeat (total serum corrected for albumin or ionised) Measure intact serum PTH levels (+vitamin D!) Elevated or high normal PTH low normal PTH suppressed PTH Primary hyperparathyroidism (consider FHH) Does patient have malignancy? If so consider dual pathology Non-PTH mediated hypercalcemia

37 Hypercalcemia diagnostic pathway Non-PTH mediated hypercalcemia Measure: - PTHrp - 1,25 dihydroxyvitamin D hydroxyvitamin D PTHrp 1,25 OHvitD 25OHvitD HHM Lymphoma, granulomatous disorder Vitamin D intoxication

38 Hypercalcemia diagnostic pathway Non-PTH mediated hypercalcemia Measure: - PTHrp - 1,25 dihydroxyvitamin D hydroxyvitamin D If normal then measure: -SPEP UPEP Serum free light chains Multiple myeloma Other diagnoses vita, hyperthyroidism

39 John Mary 64 Squamous cell lung carcinoma Presented with thirst, polyuria, bit confused Corrected Calcium 3.2 mmol/l ( ) Phosphate 0.83 mmol/l ( ) ALP 99 IU/L (25-110)

40 John Mary 64 Squamous cell lung carcinoma Before doing anything: take bloods! Presented with thirst, polyuria, bit confused Corrected Calcium 3.2 mmol/l ( ) Phosphate 0.83 mmol/l ( ) ALP 99 IU/L (25-110) Calcium, Phosphate, ALP U+E s PTH and vitamin D

41 John Mary 64 Squamous cell lung carcinoma Before doing anything: take bloods! Presented with thirst, polyuria, bit confused Corrected Calcium 3.2 mmol/l ( ) Phosphate 0.83 mmol/l ( ) ALP 99 IU/L (25-110) Calcium, Phosphate, ALP U+E s PTH and vitamin D PTH PTHrP

42 No guidelines specific to hypercalcemia of malignancy Definitive treatment relies on management of underlying cancer

43

44 1

45 2 1-2 months

46 3 PTH

47 Denosumab for Treatment of Hypercalcemia of Malignancy (refractory to IV bisphosphonates) J Clin Endocrinol Metab, September 2014, 99(9):

48 Hypercalcemia of malignancy PTHrP Primary hyperparathyroidism Osteolytic mets PTH Ca ++ PTH Calcitriol (1,25 vitd3) (ectopic PTH)

49 Conclusions: Hypercalcemia of malignancy hypercalcemia of malignancy is common associated with a poor prognosis diagnosis of underlying cause is important - alters prognosis and management - measure calcium, vitamin D and PTH management of hypercalcemia - 0.9% saline and zolendronic acid - denosumab in resistant cases