Mrs AG

Mrs AGMrs AG

Presenting complaintPresenting complaint

Mrs AGMrs AG 75 years old75 years old Admitted 19/9/07Admitted 19/9/07 5 day history 5 day history

Uncontrolled shakingUncontrolled shaking NauseaNausea Poor appetitePoor appetite Feeling ‘lousy’Feeling ‘lousy’

History of presenting History of presenting complaintcomplaint

Previous cancer of the breastPrevious cancer of the breast Had mastectomy and radiotherapy Apr Had mastectomy and radiotherapy Apr

20062006 Diagnosed with bony metastatic disease Diagnosed with bony metastatic disease

Summer 2007Summer 2007


Commenced on sodium clodronate Commenced on sodium clodronate 1.6grams/day in August 20071.6grams/day in August 2007

Stopped after 2 days due to diarrhoeaStopped after 2 days due to diarrhoea Restarted 3Restarted 3rdrd Sept 2007 at 400mg/day Sept 2007 at 400mg/day Stopped on the 14Stopped on the 14thth Sept due to Sept due to

diarrhoeadiarrhoea


Then developed Then developed NauseaNausea Poor appetitePoor appetite Uncontrollable shakingUncontrollable shaking Paraesthesiae in hands and legsParaesthesiae in hands and legs Muscle crampsMuscle cramps Unable to mobiliseUnable to mobilise

Past medical historyPast medical history

Metastatic Ca. breastMetastatic Ca. breast

HypertensionHypertension

HypercholesterolaemiaHypercholesterolaemia

Drug historyDrug history

AllergiesAllergies

Penicillin and Penicillin and ErythromycinErythromycin

Aspirin 75mg ODAspirin 75mg OD Atorvastatin 10mg Atorvastatin 10mg

ONON Lisinopril 20mg ODLisinopril 20mg OD Allopurinol 100mg ODAllopurinol 100mg OD Anastrazole 1mg ODAnastrazole 1mg OD Frusemide 40mg ODFrusemide 40mg OD Esomeprazole 20mg Esomeprazole 20mg

ODOD

Social and Family Social and Family HistoryHistory

Lives with husbandLives with husband Independent in all ADL’s normallyIndependent in all ADL’s normally Non-smoker, moderate alcoholNon-smoker, moderate alcohol

No family history of noteNo family history of note

On examinationOn examination

TremulousTremulous TachycardicTachycardic BP 160/86BP 160/86 AfebrileAfebrile RR 20, Sats 97% on airRR 20, Sats 97% on air

On examinationOn examination

Clear chestClear chest Abdo soft and non-tenderAbdo soft and non-tender Marked resting and action tremorMarked resting and action tremor Peripheral paraesthesiaePeripheral paraesthesiae No signs of DVTNo signs of DVT

InvestigationsInvestigations

ECG – Sinus tachycardia, normal QTECG – Sinus tachycardia, normal QT CXR – Some areas of shadowing CXR – Some areas of shadowing

right and left lung fields ??metsright and left lung fields ??mets Previous CT abdo/pelvis – Previous CT abdo/pelvis –

widespread sclerotic bony lesions, ?widespread sclerotic bony lesions, ?lung metslung mets

InvestigationsInvestigations

Bloods on admissionBloods on admission

WCC 8.5, Hb 12.8WCC 8.5, Hb 12.8 Na 145, K 3.8, Urea 5.5, Creat 71Na 145, K 3.8, Urea 5.5, Creat 71 Corr Ca Corr Ca 2+ 2+ 1.361.36, PO , PO 44

1.601.60 LFT’s normal except Alk phos 166LFT’s normal except Alk phos 166 TSH and haematinics normalTSH and haematinics normal

ImpressionImpression

Profound hypocalcaemia secondary Profound hypocalcaemia secondary to bisphosphonate therapy and to bisphosphonate therapy and frusemidefrusemide

TreatmentTreatment

Commenced on Calcichew D3 Forte 2 Commenced on Calcichew D3 Forte 2 tabs ODtabs OD

Given 10mls of 10% calcium Given 10mls of 10% calcium gluconategluconate

Further 100mls of 10% calcium Further 100mls of 10% calcium gluconate * 2gluconate * 2

Magnesium 5 grams infused (Mg level Magnesium 5 grams infused (Mg level 0.15 prior to infusion)0.15 prior to infusion)

Frusemide stoppedFrusemide stopped

Further testsFurther tests

Short synacthen test – normal Short synacthen test – normal responseresponse

PTH 5.5 (1.6 – 6.9)PTH 5.5 (1.6 – 6.9) PTH appears low for degree of PTH appears low for degree of

hypocalcaemia, this may be due to hypocalcaemia, this may be due to hypomagnesaemia which can interfere hypomagnesaemia which can interfere with physiological release of PTH in with physiological release of PTH in hypocalcaemiahypocalcaemia

Further testsFurther tests

Vitamin D levelVitamin D level 15.315.3

<10 – deficiency<10 – deficiency 10-20 – may indicate deficiency10-20 – may indicate deficiency >20 - adequate>20 - adequate

Patient progressPatient progress

24/9/0724/9/07 Feeling much better. No longer shaking Feeling much better. No longer shaking

as much, no paraesthesia, no crampsas much, no paraesthesia, no cramps Mobile with zimmer frameMobile with zimmer frame

Ca Ca 2+ 2+ 2.11, Mg 0.532.11, Mg 0.53

25/9/0725/9/07 Mobile independently on ward – Mobile independently on ward –

discharged homedischarged home

HypocalcaemiaHypocalcaemia

Hypocalcaemia occurs when calcium Hypocalcaemia occurs when calcium is lost from the extra cellular fluid in is lost from the extra cellular fluid in greater quantities than can be greater quantities than can be replaced by the intestine or bone.replaced by the intestine or bone.

Symptoms/signs of Symptoms/signs of hypocalcaemiahypocalcaemia

Paraesthesiae of distal extremities and Paraesthesiae of distal extremities and circumoral areacircumoral area

Chvostek and Trousseau signsChvostek and Trousseau signs Muscle crampsMuscle cramps LaryngospasmLaryngospasm TetanyTetany SeizuresSeizures Prolonged QT interval which can progress Prolonged QT interval which can progress

to VF or heart blockto VF or heart block

Causes of hypocalcaemiaCauses of hypocalcaemia

Vitamin D Vitamin D deficiencydeficiency

HypomagnesaemiaHypomagnesaemia Loop diureticsLoop diuretics HypoparathyroidisHypoparathyroidis

mm PseudohypoparathyPseudohypoparathy

roidismroidism Chronic renal Chronic renal

failurefailure

Post Post parathyroidectomyparathyroidectomy

RhabdomyolysisRhabdomyolysis Malignant diseaseMalignant disease Acute pancreatitisAcute pancreatitis Septic shockSeptic shock


Hypoparathyroidism Hypoparathyroidism Deficiency of PTH leads to increased Deficiency of PTH leads to increased

renal calcium excretion and decreased renal calcium excretion and decreased intestinal calcium absorption (secondary intestinal calcium absorption (secondary to reduced 1,25(OH)to reduced 1,25(OH)22DD33 production) production)

(Note: PTH stimulates renal (Note: PTH stimulates renal hydroxylation of 25(OH)Dhydroxylation of 25(OH)D33 to to 1,25(OH)1,25(OH)22DD33))


PseudohypoparathyroidismPseudohypoparathyroidism Rare hereditary disorderRare hereditary disorder Affects target-cell response to PTHAffects target-cell response to PTH PTH is raisedPTH is raised Patients can have shortened Patients can have shortened

metacarpals and metatarsals along with metacarpals and metatarsals along with short stature.short stature.


MalignancyMalignancy Prostate and breast can cause increased Prostate and breast can cause increased

osteoblastic activity leading to increased osteoblastic activity leading to increased bone formation and hypocalcaemia.bone formation and hypocalcaemia.

Rapid cell destruction secondary to Rapid cell destruction secondary to chemotherapy increases serum chemotherapy increases serum phosphorus. This complexes with serum phosphorus. This complexes with serum calcium leading to hypocalcaemia.calcium leading to hypocalcaemia.


RhabdomyolysisRhabdomyolysis Release of cellular phosphorus, again Release of cellular phosphorus, again

binding to serum calcium causing binding to serum calcium causing hypocalcaemia.hypocalcaemia.


Renal failureRenal failure Reduced phosphorus excretion with Reduced phosphorus excretion with

continued intestinal phosphorus continued intestinal phosphorus absorption leads to absorption leads to hyperphosphataemiahyperphosphataemia

This leads to decreased conversion of This leads to decreased conversion of 25(OH)D25(OH)D33 to 1,25(OH) to 1,25(OH)22DD33

This leads to decreased intestinal This leads to decreased intestinal calcium absorption.calcium absorption.


Hypocalcaemia and Hypocalcaemia and hypomagnesaemia often co-existhypomagnesaemia often co-exist

Can be due to decreased absorption Can be due to decreased absorption or poor dietary intake.or poor dietary intake.

Hypomagnesaemia impairs PTH Hypomagnesaemia impairs PTH secretion and can interfere with its secretion and can interfere with its peripheral action.peripheral action.


PancreatitisPancreatitis Release of pancreatic lipase causing Release of pancreatic lipase causing

degradation of retroperitoneal omental degradation of retroperitoneal omental fatfat

Binding of calcium in the peritoneum Binding of calcium in the peritoneum resulting in hypocalcaemia.resulting in hypocalcaemia.

Septic shockSeptic shock Unknown mechanismUnknown mechanism

DiscussionDiscussion

There are a number of reports of There are a number of reports of symptomatic hypocalcaemia symptomatic hypocalcaemia following intravenous following intravenous bisphosphonate therapy. However, bisphosphonate therapy. However, this is uncommon with oral therapy.this is uncommon with oral therapy.

Usually, compensatory mechanisms, Usually, compensatory mechanisms, i.e. increase in PTH secretion act to i.e. increase in PTH secretion act to correct calcium levels.correct calcium levels.

DiscussionDiscussion Newer, more potent bisphosphonates Newer, more potent bisphosphonates

may reduce the effects of PTH on bone may reduce the effects of PTH on bone resorption.resorption.

Hypomagnesaemia can impair the Hypomagnesaemia can impair the compensatory increase in PTH secretion.compensatory increase in PTH secretion.

Patients should have calcium and vitamin Patients should have calcium and vitamin D status checked along with magnesium, D status checked along with magnesium, phosphate and renal function levels prior phosphate and renal function levels prior to commencing potent bisphosphonate to commencing potent bisphosphonate therapy. therapy.

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Mrs AG