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Anorexia nervosa, re-feeding syndrome and  endocrine sequelae      Mark Daly
Why this talk…..Traditionally eating disorders have been looked afterby either gastro-enterologists or endocrinologistswit...
Anorexic woman from Walesto be force fed, judge ordersA woman with "severe" anorexia who wanted to beallowed to die is to ...
A not unusual pathway      of care…..19 yr old girl, admitted BMI of 12Intermittent institutionalised care since age 9 wit...
Admission criteriaBased on recent change in the context of absoluteBMI, physiological and functional parameters
Physical concern                    Concern        AdmitBMI                 <14            <12Wt loss (kg/week)   >0.5    ...
Physical concern(2)            Concern       AdmitNA+         <135          <130K+          <3.5          <3.0Mg2+        ...
O/EWell presentedGross cachexiaHypotensive and bradycardicPre-pubertal
Initial investigationsHb 11.0,WCC 2.0, Plts 78Na+ 127, K+ 3.1, urea 1.8, creat 38, PO4- 0.75ECG bradycardia, long QT
Initial planMedical  Initial assessment     Na+, K+, Urea, Creat, glucose, CRP     Mg2+, PO4-, Ca2+     Albumin, liver enz...
Initial planNutritional   5 kcal per kg stepping up over 5-7days to weight gain   levels (+500kcal over estimates from Hen...
Initial planBehavioural/other restrictions   Normal foods in preference to supplements   Bed rest/commode/wheelchair   Awa...
ProgressDay 3, non-compliance with feeding planNon-compliance with activityReviewed with psychFormal sectionAdvised likely...
ProgressDay 5, intermittent compliance with feeding planReviewed with psychRazor blades and salt sachets removedNG feeding...
ProgressDay 8Hypokalaemia and hypophosphataemia requiring IVreplacementSubsequent weight gain back to BMI 15Established we...
Anorexia nervosa
What is anorexia nervosa?Anorexia nervosa is defined as:  intense fear of weight gain  Weight consistently < 85th percenti...
Types of Anorexia• Purging  – Weight loss achieved by    vomiting, laxatives, or    diuretics                             ...
CausesAnorexia Nervosa patients tend to have   Low self-evaluation   Come from competitive, high-achieving, and protective...
SymptomsDramatic weight lossPreoccupation withweight, food, calories, fat grams, anddietingRefusal to eat certain foods, o...
EpidemiologyUK     1 in 250 females     1 in 2000 malesSMR 9.5Mortality of 0.6% per yearHigher in those presenting after a...
50 years of treatment                  outcomesComparison of outcomes 1950-1999 to gauge whether anyimprovement over time....
Outcome measuresBroad outcome measures: death, recovery, improvement,chronicity.Symptom normalization measures: weight, me...
“The mortality rate was muchlower in the group of youngerpatients than that in the groupwith a much wider age at onsetof i...
“Anorexia nervosa did notlose its relatively poorprognosis in the20th century.”Outcome of Anorexia Nervosain 119 Patient S...
Re-feeding syndromeFirst described in American Japanese POWPrecipitated cardiac failureclinical features of refeeding synd...
Re-feeding syndrome -  pathophysiologyinsulin is decreased due to a reduced oral carbohydrates.fat and protein stores are ...
How do we manage it?Risk is obviousDegree of risk is notAssume risk is reduced after 1 week of good intakeAND weight gainO...
Exeter protocol(with thanks to Roderick Warren) Assume high risk in all cases. Medical inpatients with anorexia nervosa wh...
Exeter protocolBloods before feeding:Sodium, potassium, urea, creatinine, glucose, CRPMagnesium, phosphate, calciumAlbumin...
Exeter protocolDaily bloods while risk of refeeding syndrome is high:•Sodium, potassium, urea, creat, glucose, magnesium, ...
Exeter protocolMild deficiency (3.0 – 3.5 mmol/L)• Sando-K or equivalent, 4-8 tablets dailyModerate-severe deficiency (<3....
Exeter protocolMild deficiency (>0.5 mmol/L and not falling rapidly) • Phosphate-Sandoz 2 tablets,three times dailyModerat...
Exeter protocolMild deficiency (>0.6 mmol/L)   Magnesium glycerophosphate 2 tablets, twice daily.   May cause GI irritatio...
Exeter protocol- calciumrarely necessary. Correction of hypomagnesaemia may improve calciumlevels. Administration of phosp...
A more unusual case….DouglasTo GP, Feb 2010Weight loss feeling tiredRecent junior Exeter chiefs playerCreat high at 110, g...
DouglasFt4 12.3, cortisol 594, fsh 0.6, lh 0.4, PRL 208, testo 0.8GH 15.1, IGF1 8.668kg BMI 20.9, prior weight 111kg 6 mth...
Anorexia and fertilityVery little data in men for longer termTesto crashes during acute illnessSeems to be less marked tha...
ConlcusionsBehaviourally challengingStrong leadershipNeed to be physiologically alert
Eating disorder presentation
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  1. 1. Anorexia nervosa, re-feeding syndrome and endocrine sequelae Mark Daly
  2. 2. Why this talk…..Traditionally eating disorders have been looked afterby either gastro-enterologists or endocrinologistswith the support of psychiatryThere are few conditions where such strongleadership is necessary in the best interests of thepatient and may go counter to the instincts or wishesof members of staff
  3. 3. Anorexic woman from Walesto be force fed, judge ordersA woman with "severe" anorexia who wanted to beallowed to die is to be force fed in her "bestinterests" by order of a High Court judge.She was being looked after in a community hospitalunder a palliative care regime whose purpose was toallow her to die in comfortTreatment - "does not merely entail bodily intrusionof the most intimate kind, but the overbearing of Eswill in a way that she experiences as abusive".
  4. 4. A not unusual pathway of care…..19 yr old girl, admitted BMI of 12Intermittent institutionalised care since age 9 withAnorexia nervosaAdmitted because of recent further weight loss,minimal intake for 1 weekAgreed for a voluntary admission
  5. 5. Admission criteriaBased on recent change in the context of absoluteBMI, physiological and functional parameters
  6. 6. Physical concern Concern AdmitBMI <14 <12Wt loss (kg/week) >0.5 >1BP <90/70 <80/60Postural drop >10 >20Pulse <50 <40Temp <35 <34Muscular Uses arms to Can’t standstrength standWBC <4 <2Hb <11 <9Plts <130 <110
  7. 7. Physical concern(2) Concern AdmitNA+ <135 <130K+ <3.5 <3.0Mg2+ If depleted If depletedPo4- If depleted If depletedECGqtc >450msec >450 or arrhythmiaALT >45 >90Bilirubin >20 >40Alk phosp >110 >200Albumin <35 <32
  8. 8. O/EWell presentedGross cachexiaHypotensive and bradycardicPre-pubertal
  9. 9. Initial investigationsHb 11.0,WCC 2.0, Plts 78Na+ 127, K+ 3.1, urea 1.8, creat 38, PO4- 0.75ECG bradycardia, long QT
  10. 10. Initial planMedical Initial assessment Na+, K+, Urea, Creat, glucose, CRP Mg2+, PO4-, Ca2+ Albumin, liver enzymes, INR FBC, ferritin, folate, B12 FSH, LH Oest or testo Thiamine 300mg daily, vit b complex strong 2 tabs od, multivit generic, sandophosp 2 tabs tds Pabrinex
  11. 11. Initial planNutritional 5 kcal per kg stepping up over 5-7days to weight gain levels (+500kcal over estimates from Henry equation (10kcal per kg if BMI>16) Menu plans agreed with patient
  12. 12. Initial planBehavioural/other restrictions Normal foods in preference to supplements Bed rest/commode/wheelchair Away from window, no fans Restrictions according to Mental health status Compliance essential
  13. 13. ProgressDay 3, non-compliance with feeding planNon-compliance with activityReviewed with psychFormal sectionAdvised likely need to progress to NG feeding inabsence of compliance and/or weight gainInformed of need to search belongings
  14. 14. ProgressDay 5, intermittent compliance with feeding planReviewed with psychRazor blades and salt sachets removedNG feeding under restraint, NG re-positioned/replaced 5 times first 24 hrsBolus feeds under restraint during periods of non-compliance
  15. 15. ProgressDay 8Hypokalaemia and hypophosphataemia requiring IVreplacementSubsequent weight gain back to BMI 15Established weight stability at BMI 15 on oral intakeand basic mobilityDischarged to OP ED services
  16. 16. Anorexia nervosa
  17. 17. What is anorexia nervosa?Anorexia nervosa is defined as: intense fear of weight gain Weight consistently < 85th percentile for age and height(In women) three consecutive missed periods Together with one of following: refusal to admit seriousness of weight loss undue influence of shape or weight on one’s self-image disturbed experience in one’s shape or weight DSM-IV-TR
  18. 18. Types of Anorexia• Purging – Weight loss achieved by vomiting, laxatives, or diuretics Restricting Weight loss achieved by restricting calories Following diets, fasting, and exercising to excess
  19. 19. CausesAnorexia Nervosa patients tend to have Low self-evaluation Come from competitive, high-achieving, and protective families Set perfectionist standards Intensely concerned with how others perceive them Fear falling short of expectations Genetics Culture Idealize thinness Have poor body image Feel shame, depressed, and dissatisfied with their own bodies
  20. 20. SymptomsDramatic weight lossPreoccupation withweight, food, calories, fat grams, anddietingRefusal to eat certain foods, or wholecategories of food (e.g. no carbohydrates)Denial of hungerExcessive, rigid exercise regimenWithdrawal from usual friends andactivitiesWeight loss and dieting become primaryconcerns in life.Constant excuses to avoid mealtimesAnxiety about gaining weight or being fat
  21. 21. EpidemiologyUK 1 in 250 females 1 in 2000 malesSMR 9.5Mortality of 0.6% per yearHigher in those presenting after age 20
  22. 22. 50 years of treatment outcomesComparison of outcomes 1950-1999 to gauge whether anyimprovement over time.119 studies conducted 1950-19995,590 patients, adolescents and adultsFollow-ups clustered into three time frames: - fewer than 4 years after hospitalization; - 4-10 years; - more than 10 years after Steinhausen HC. Am J Psychiatry. 2002.
  23. 23. Outcome measuresBroad outcome measures: death, recovery, improvement,chronicity.Symptom normalization measures: weight, menstruation,eating behaviorPsychopathologies such as affective disorders, OCD,anxiety, substance abuse. Steinhausen HC. Am J Psychiatry. 2002
  24. 24. “The mortality rate was muchlower in the group of youngerpatients than that in the groupwith a much wider age at onsetof illness. The rates ofrecovery, improvement, andchronicity were more favorablein the group with the youngerpatients.”Outcome of Anorexia Nervosain 119 Patient Series by Durationof Follow-Up and Age at Onset.A total of 577 patients had lessthan 4 years of follow-up, 2,132had 4–10 years of follow-up, and 438 had more than 10years of follow-up. Steinhausen HC. Am J Psychiatry. 2002
  25. 25. “Anorexia nervosa did notlose its relatively poorprognosis in the20th century.”Outcome of Anorexia Nervosain 119 Patient Series byDuration of Follow-Up andTime Period of Study.A total of 577 patients had lessthan 4 years of follow-up, 2,132had 4–10 years of follow-up, and 438 had more than 10years of follow-up. Steinhausen HC. Am J Psychiatry. 2002.
  26. 26. Re-feeding syndromeFirst described in American Japanese POWPrecipitated cardiac failureclinical features of refeeding syndrome rhabdomyolysis, leucocyte dysfunction, respiratory failure, cardiac failure, hypotension, arrhythmias, seizures, coma, and sudden deathDriven by low serum phosphate (<0.5)
  27. 27. Re-feeding syndrome - pathophysiologyinsulin is decreased due to a reduced oral carbohydrates.fat and protein stores are catabolizedIntracellular loss of electrolytes, esp. phosphate.intracellular phosphate stores can be depleted despite normalserum phosphate concentrationsa sudden shift from fat to carbohydrate metabolism -secretionof insulin increases -stimulates cellular uptake of phosphate,usually occurs within four days of starting to feed again.Phosphate is necessary for ATP from ADP and AMP
  28. 28. How do we manage it?Risk is obviousDegree of risk is notAssume risk is reduced after 1 week of good intakeAND weight gainOften use telemetry – some centres use itcontinuously for all patientsECG daily is essential
  29. 29. Exeter protocol(with thanks to Roderick Warren) Assume high risk in all cases. Medical inpatients with anorexia nervosa who require inpatient feeding are almost always at high risk of refeeding syndrome. However, NICE guidance (2006 – CG32) states that the risk is high if: • One of: BMI<16, weight loss >15% in last 3-6 months, little or no nutrition >10 days, low potassium/phosphate/magnesium levels prior to feeding. • Two of: BMI <18.5, weight loss >10% in last 3-6 months, little or no nutrition >5 days, history of alcohol abuse or use of insulin/chemotherapy/antacids/diuretics/(laxatives)
  30. 30. Exeter protocolBloods before feeding:Sodium, potassium, urea, creatinine, glucose, CRPMagnesium, phosphate, calciumAlbumin, liver enzymes, INRFBC, ferritin, folate, B12FSH, LH, oestradiol (females) or testosterone (males)Thiamine: 300mg per dayVitamin B Complex (Strong): 2 tablets, once per day Multivitamins:generic, 1 tablet, once per day Phosphate-Sandoz: 2 tablets, threetimes daily
  31. 31. Exeter protocolDaily bloods while risk of refeeding syndrome is high:•Sodium, potassium, urea, creat, glucose, magnesium, phosphate, calciumBloods once-twice weekly when stable (after 3-4 days ofsustained feeding and no electrolyte abnormalities):Sodium, potassium, urea, creatinine, glucoseMagnesium, phosphate, calciumAlbumin, liver enzymesFBC
  32. 32. Exeter protocolMild deficiency (3.0 – 3.5 mmol/L)• Sando-K or equivalent, 4-8 tablets dailyModerate-severe deficiency (<3.0 mmol/L)• Intravenous, using pre-prepared bags of 1 litre 0.9%saline with 40 mmol potassium chloride, given overat least 4 hours (but usually longer e.g. 12 hours).Anorexic patients may be chronically hypokalaemic.
  33. 33. Exeter protocolMild deficiency (>0.5 mmol/L and not falling rapidly) • Phosphate-Sandoz 2 tablets,three times dailyModerate-severe deficiency (<0.5 mmol/L, or higher but falling)• Intravenous, using pre-prepared bags of Phosphates Polyfusor, 500ml over 24hours.– monitor calcium. Will precipitate if co-infused with calcium – always avoid infusingmagnesium or calcium through the same cannula.– check levels after 24 hours.IV phosphate. Various recommendations suggest 9, 12 or 18 mmol administered over12 hours. However, the use of an entire Polyfusor bag (containing 50 mmolphosphate) has been shown to be a simple, effective and safe approach. Mildhyperphosphataemia is not uncommon (levels up to 1.57 mmol/L have been seen) –consider a smaller dose (e.g. 250 ml over 12 hours) for less severehypophosphataemia.
  34. 34. Exeter protocolMild deficiency (>0.6 mmol/L) Magnesium glycerophosphate 2 tablets, twice daily. May cause GI irritation/diarrhoea. Avoid with co-admin with phosphateModerate-severe deficiency (<0.6 mmol/L) IV magnesium sulphate, 20 mmol over 12 hours, or 40 mmol over 24 hours. Can be given faster in emergencies Will precipitate if co-infused with phosphate – always used a separate cannula.Magnesium levels may drop rapidly after correction -several days of IV replenishment may be required beforethey become stable.
  35. 35. Exeter protocol- calciumrarely necessary. Correction of hypomagnesaemia may improve calciumlevels. Administration of phosphate may lower calcium levels.Asymptomatic mild-moderate deficiencyCalcichew, 1-3 tablets daily.Do not administer at same time as phosphate – insoluble CaPO4 will form.Symptomatic or severe deficiency• IV calcium chloride or calcium gluconate, 10 mmol over at least 10 min(but usually longer e.g. 1 hour).Followed by infusion of 40 mmol over 24 hours.Must be diluted before administration
  36. 36. A more unusual case….DouglasTo GP, Feb 2010Weight loss feeling tiredRecent junior Exeter chiefs playerCreat high at 110, glucose 2.1, Hb12.6, WCC 3.4Subsequent fall in WCC, rise in ALT
  37. 37. DouglasFt4 12.3, cortisol 594, fsh 0.6, lh 0.4, PRL 208, testo 0.8GH 15.1, IGF1 8.668kg BMI 20.9, prior weight 111kg 6 mths earlierClinically cachectic, lanugo hair, but post-pubertalAdmitted – psych confirmed significant ANWeight regain to 76kg, BMI 23Partial recovery of pancytopaenias, no recovery ofgonadotrophins despite weight regain and 2 trials oftestosterone cessation
  38. 38. Anorexia and fertilityVery little data in men for longer termTesto crashes during acute illnessSeems to be less marked than in femalesPartly an adaptive responseMany recovered anorexic patients go on tosuccessful pregnancies
  39. 39. ConlcusionsBehaviourally challengingStrong leadershipNeed to be physiologically alert
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