Clinical biochemistry of calcium and vitamin D

Transcription

1 Clinical biochemistry of calcium and vitamin D Dr Andrew Day Consultant in Clinical Biochemistry and Metabolic Medicine University Hospitals Bristol NHS Trust andrew.day@uhbristol.nhs.uk

2 A 48-year old man had progressively worsening constipation and tiredness DEPARTMENT OF CLINICAL BIOCHEMISTRY Calcium 2.68 mmol/l Calcium (adjusted) 2.78 mmol/l Albumin 36 g/l Creatinine 86 μmol/l egfr >60 ml/min/1.73 m Urea 5.4 mmol/l Sodium 142 mmol/l Potassium 4.5 mmol/l The two commonest causes of hypercalcaemia are..?

3 Causes of hypercalcaemia Primary Hyperparathyroidism Commonest in the community Often mild and stable Malignancy Humoral effect (PTHrP) Metastatic bone disease Myeloma 90% Less common causes Tertiary hyperparathyroidism in CKD Granulomatous diseases (e.g. sarcoidosis) Vitamin D toxicity (high dose, rare) Severe thyrotoxicosis Addison disease Milk alkali syndrome Familial hypocalciuric hypercalcaemia

4 Next investigation? PTH EDTA sample (plus SST for Ca, PO4 and creatinine) Ideally reach lab within 4 hours

5 Diagnosis? DEPARTMENT OF CLINICAL BIOCHEMISTRY Parathyroid hormone 8.2 pmol/l Calcium 2.58 mmol/l Calcium (adjusted) 2.68 mmol/l Albumin 36 g/l Phosphate 0.72 mmol/l Creatinine 86 μmol/l Primary hyperparathyroidism (but send 24-hour urine and blood sample for calculation of calcium:creatinine clearance ratio, to exclude FBHH)

6 Diagnosis? DEPARTMENT OF CLINICAL BIOCHEMISTRY Parathyroid hormone 4.2 pmol/l Calcium 2.58 mmol/l Calcium (adjusted) 2.68 mmol/l Albumin 36 g/l Phosphate 0.72 mmol/l Creatinine 86 μmol/l Still consistent with primary hyperparathyroidism (PTH inappropriately normal )

7 Diagnosis? DEPARTMENT OF CLINICAL BIOCHEMISTRY Parathyroid hormone <0.6 pmol/l Calcium 2.58 mmol/l Calcium (adjusted) 2.68 mmol/l Albumin 36 g/l Phosphate 0.72 mmol/l Creatinine 86 μmol/l Primary hyperparathyroidism excluded. Investigate other causes

8 Next investigations? DEPARTMENT OF CLINICAL BIOCHEMISTRY TSH 1.2 miu/l OH vitamin D 68 nmol/l Serum protein electrophoresis Urine Bence Jones protein Normal pattern Negative Most likely differential diagnoses malignancy or sarcoidosis

9 A 45-year old woman with worsening Crohn s disease developed paraesthesiae, carpopedal spasm and had a seizure DEPARTMENT OF CLINICAL BIOCHEMISTRY Calcium 1.50 mmol/l Calcium (adjusted) 1.80 mmol/l Albumin 25 g/l 35-50

10 Why adjust a calcium result? Only ionised calcium is active and regulated How can we meaningfully measure active calcium? Measure free ionised calcium? Usually impossible Change reference range as albumin falls? Hopelessly impractical Adjust calcium to take account for low albumin Pragmatic solution Ca adj. = Ca tot (40-albumin)

11

12 Actions of PTH Net effect: Calcium Phosphate N.B. PTH requires Mg 2+ for secretion and action

13 Actions of Vitamin D Net effect: Calcium Phosphate N.B. Impaired vitamin D hydroxylation in CKD

14 Causes of hypocalcaemia ARTEFACTUAL HYPOCALCAEMIA Low albumin Unsuitable sample Citrate/EDTA tube HYPOPARATHYROIDISM Parathyroid loss Surgery Autoimmune Agenesis Reduced function Hypomagnasaemia Cinacalcet Neonatal PTH resistance Hypomagnasaemia REDUCED CALCIUM AVAILABILITY Vitamin D deficiency Poor diet Malabsorption Lack of sunlight Chronic kidney disease Drugs Bone resorption inhibitors Bisphosphonates Denusomab Proton pump inhibitors Increased vitamin D metabolism Phenytoin

15 Causes of hypocalcaemia LOW IONISED CALCIUM Hyperventilation CALCIUM CHELATION Acute pancreatitis Rhabdomyolysis Massive tumour lysis Large blood transfusions

16 Why does hyperventilation cause symptomatic hypocalcaemia?

17 Investigation of hypocalcaemia (adjusted calcium <2.20 mmol/l) Clinical assessment Risk of vitamin D deficiency Magnesium deficiency CKD Post-surgical hypoparathyroidism Other biochemistry tests Phosphate Magnesium Creatinine and egfr PTH Vitamin D PO4 & PTH Vit D deficiency Drugs e.g. bisphosphonates PO4 & PTH Hypomagnasaemia Hypoparathyroidism Drugs e.g. cinacalcet PO4 & PTH CKD Tumour lysis Rhabdomyolysis Acute pancreatitis

18 A 45-year old woman with worsening Crohn s disease developed paraesthesiae, carpopedal spasm and had a seizure DEPARTMENT OF CHEMICAL PATHOLOGY Calcium 1.50 mmol/l Calcium (adjusted 1.80 nmol/l Albumin 25 g/l Phosphate 0.69 mmol/l Magnesium 0.42 nmol/l hydroxyvitamin D 8 nmol/l Sufficient >50 Parathyroid hormone 12.8 pmol/l

19

20 Testing for Vitamin D

21 Vitamin D metabolism

22 A 42-year old Somalian woman attends for a well-woman check DEPARTMENT OF CHEMICAL PATHOLOGY Total 25-hydroxy Vitamin D 20.3 nmol/l (25-hydroxy Vitamin D2) <6.0 nmol/l (25-hydroxy Vitamin D3) 20.3 nmol/l <30 nmol/l nmol/l >50 nmol/l Vitamin D deficiency Vitamin D may be suboptimal Sufficient vitamin D This assay does NOT detect 1α-hydroxycholecalciferol

23 Regarding vitamin D WHICH OF THE FOLLOWING STATEMENTS ABOUT VITAMIN D ARE CORRECT? 1 Each test costs approximately 10 2 Testing is now recommended in all groups who are at risk of deficiency 3 Testing is important prior to treatment with daily doses above 400 IU because of risk of toxicity 4 Testing is recommended in people with unexplained myalgia or widespread pain 5 Monitoring during therapy is recommended only in patients with malabsorption, ongoing symptoms or suspected poor compliance

24 Regarding vitamin D WHICH OF THE FOLLOWING STATEMENTS ABOUT VITAMIN D ARE CORRECT? 1 Each test costs approximately 10 2 Testing is now recommended in all groups who are at risk of deficiency 3 Testing is important prior to treatment with daily doses above 400 IU because of risk of toxicity 4 Testing is recommended in people with unexplained myalgia or widespread pain 5 Monitoring during therapy is recommended only in patients with malabsorption, ongoing symptoms or suspected poor compliance

25 National Osteoporosis Society May 2013 (

26

27 Most people don t need a vitamin D test

28 Most people don t need a vitamin D test

29 Most people don t need a vitamin D test Most adults get enough from sunlight in spring / summer 10 mcg in autumn and winter Little or no sun exposure, or dark skin 10 mcg all year round Children age mcg all year round Breastfed babies up to mcg daily

30 Who should have a vitamin D test? Confirmed osteomalacia Prior to treatment of osteoporosis with potent anti-resorptive Rx Zoledronate Denosumab Other bone diseases (e.g. Paget s) before starting bisphosphonate

31 Who should have a vitamin D test? Patients with symptoms that could be attributed to vitamin D deficiency Suspected osteomalacia Chronic widespread bone pain Proximal muscle weakness Waddling gait or change in gait

32 Who should have a vitamin D test? Other specific indications for vitamin D testing Malabsorption Newly diagnosed primary hyperparathyroidism Unexplained hypocalcaemia Sup. If <50 nmol/l and recheck [Ca] within 2/52? Pre-treatment vitamin D <30 nmol/l Concerns re. poor compliance

33 Who should have a vitamin D test? Asymptomatic individuals at high risk of vitamin D deficiency Do not routinely test vit D in these groups

34 Who should have a vitamin D test? Although vitamin D deficiency is highly prevalent, universal screening of asymptomatic populations is not recommended

35

36 Risk Factors? Symptoms? Treat Investigate Vitamin D Calcium and phosphate LFT U&E? PTH

37 Vit D <30 Vit D Vit D >50 Loading dose 300,000 U Information and advice Supplement 800 U/day Retesting is not routinely indicated

38