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1. Mrs AG
3. History of presenting complaint
Previous cancer of the breast
Had mastectomy and radiotherapy Apr 2006
Diagnosed with bony metastatic disease Summer 2007
4. History of presenting complaint
Commenced on sodium clodronate 1.6grams/day in August 2007
Stopped after 2 days due to diarrhoea
Restarted 3rd Sept 2007 at 400mg/day
Stopped on the 14th Sept due to diarrhoea
5. History of presenting complaint Then developed
Nausea
Poor appetite
Uncontrollable shaking
Paraesthesiae in hands and legs
Muscle cramps
Unable to mobilise
6. Past medical history
Metastatic Ca. breast
Hypertension
Hypercholesterolaemia
7. Drug history
Allergies
Penicillin and Erythromycin
Aspirin 75mg OD
Atorvastatin 10mg ON
Lisinopril 20mg OD
Allopurinol 100mg OD
Anastrazole 1mg OD
Frusemide 40mg OD
Esomeprazole 20mg OD
8. Social and Family History
Lives with husband
Independent in all ADL’s normally
Non-smoker, moderate alcohol
No family history of note
9. On examination
Tremulous
Tachycardic
BP 160/86
Afebrile
RR 20, Sats 97% on air
10. On examination
Clear chest
Abdo soft and non-tender
Marked resting and action tremor
Peripheral paraesthesiae
No signs of DVT
11. Investigations
ECG – Sinus tachycardia, normal QT
CXR – Some areas of shadowing right and left lung fields ??mets
Previous CT abdo/pelvis – widespread sclerotic bony lesions, ?lung mets
12. Investigations Bloods on admission
WCC 8.5, Hb 12.8
Na 145, K 3.8, Urea 5.5, Creat 71
Corr Ca 2+ 1.36, PO 4 1.60
LFT’s normal except Alk phos 166
TSH and haematinics normal
13. Impression
Profound hypocalcaemia secondary to bisphosphonate therapy and frusemide
14. Treatment Commenced on Calcichew D3 Forte 2 tabs OD
Given 10mls of 10% calcium gluconate
Further 100mls of 10% calcium gluconate * 2
Magnesium 5 grams infused (Mg level 0.15 prior to infusion)
Frusemide stopped
15. Further tests Short synacthen test – normal response
PTH 5.5 (1.6 – 6.9)
PTH appears low for degree of hypocalcaemia, this may be due to hypomagnesaemia which can interfere with physiological release of PTH in hypocalcaemia
16. Further tests Vitamin D level
15.3
<10 – deficiency
10-20 – may indicate deficiency
>20 - adequate
17. Patient progress 24/9/07
Feeling much better. No longer shaking as much, no paraesthesia, no cramps
Mobile with zimmer frame
Ca 2+ 2.11, Mg 0.53
25/9/07
Mobile independently on ward – discharged home
18. Hypocalcaemia
Hypocalcaemia occurs when calcium is lost from the extra cellular fluid in greater quantities than can be replaced by the intestine or bone.
19. Symptoms/signs of hypocalcaemia Paraesthesiae of distal extremities and circumoral area
Chvostek and Trousseau signs
Muscle cramps
Laryngospasm
Tetany
Seizures
Prolonged QT interval which can progress to VF or heart block
20. Causes of hypocalcaemia Vitamin D deficiency
Hypomagnesaemia
Loop diuretics
Hypoparathyroidism
Pseudohypoparathyroidism
Chronic renal failure Post parathyroidectomy
Rhabdomyolysis
Malignant disease
Acute pancreatitis
Septic shock
21. Causes of hypocalcaemia Hypoparathyroidism
Deficiency of PTH leads to increased renal calcium excretion and decreased intestinal calcium absorption (secondary to reduced 1,25(OH)2D3 production)
(Note: PTH stimulates renal hydroxylation of 25(OH)D3 to 1,25(OH)2D3)
22. Causes of hypocalcaemia Pseudohypoparathyroidism
Rare hereditary disorder
Affects target-cell response to PTH
PTH is raised
Patients can have shortened metacarpals and metatarsals along with short stature.
23. Causes of hypocalcaemia Malignancy
Prostate and breast can cause increased osteoblastic activity leading to increased bone formation and hypocalcaemia.
Rapid cell destruction secondary to chemotherapy increases serum phosphorus. This complexes with serum calcium leading to hypocalcaemia.
24. Causes of hypocalcaemia Rhabdomyolysis
Release of cellular phosphorus, again binding to serum calcium causing hypocalcaemia.
25. Causes of hypocalcaemia Renal failure
Reduced phosphorus excretion with continued intestinal phosphorus absorption leads to hyperphosphataemia
This leads to decreased conversion of 25(OH)D3 to 1,25(OH)2D3
This leads to decreased intestinal calcium absorption.
26. Causes of hypocalcaemia Hypocalcaemia and hypomagnesaemia often co-exist
Can be due to decreased absorption or poor dietary intake.
Hypomagnesaemia impairs PTH secretion and can interfere with its peripheral action.
27. Causes of hypocalcaemia Pancreatitis
Release of pancreatic lipase causing degradation of retroperitoneal omental fat
Binding of calcium in the peritoneum resulting in hypocalcaemia.
Septic shock
Unknown mechanism
28. Discussion There are a number of reports of symptomatic hypocalcaemia following intravenous bisphosphonate therapy. However, this is uncommon with oral therapy.
Usually, compensatory mechanisms, i.e. increase in PTH secretion act to correct calcium levels.
29. Discussion Newer, more potent bisphosphonates may reduce the effects of PTH on bone resorption.
Hypomagnesaemia can impair the compensatory increase in PTH secretion.
Patients should have calcium and vitamin D status checked along with magnesium, phosphate and renal function levels prior to commencing potent bisphosphonate therapy.