- Email: [email protected]
To the limit of extreme malnutrition
Nutrition 32 (2016) 146–148
Contents lists available at ScienceDirect
Nutrition journal homepage: www.nutritionjrnl.com
Case report
To the limit of extreme malnutrition Jacob Frølich M.D. *, Camilla Viola Buskbjerg Palm M.D., Rene K. Støving M.D., Ph.D. Centre for Eating Disorders, Department of Endocrinology, Odense University Hospital, Odense, Denmark
a r t i c l e i n f o
a b s t r a c t
Article history: Received 8 June 2015 Accepted 27 August 2015
Extreme malnutrition with body mass index (BMI) as low as 10 kg/m2 is not uncommon in anorexia nervosa, with survival enabled through complex metabolic adaptations. In contrast, outcomes from hunger strikes and famines are usually fatal after weight loss to about 40% below expected body weight, corresponding to BMI 12 to 13 kg/m2 in adults. Thus, many years of adaptation in adolescent-onset anorexia nervosa, supported by supplements of vitamins and treatment of intercurrent diseases, may allow survival at a much lower BMI. However, in the literature only a few cases of survival in patients with BMI <9 kg/m2 have been described. We report on the case of a 29-y-old woman who was successfully treated in a specialized unit. She had a BMI of 7.8 kg/m2. To our knowledge, this level of extreme malnutrition has not previously been reported. The present case emphasizes the importance of adherence to guidelines to decrease refeeding complications. Ó 2016 Elsevier Inc. All rights reserved.
Keywords: Eating disorder Anorexia nervosa Refeeding syndrome
Introduction Prolonged energy deficit and subsequent low body weight are well-known consequences of anorexia nervosa (AN). Metabolic adaptation enables patients with AN to adapt to very low body mass index (BMI) levels [1,2], even surpassing levels known to be fatal in hunger strikes and famines [3,4]. It is clear, however, that there must be a lower weight limit consistent with life. This case report presents a remarkable adaptation to chronic severe malnutrition, what must be regarded as close to the absolute limit in humans. Case presentation A 29-y-old woman, diagnosed with AN at the age of 12, was voluntarily admitted to the emergency room with a 20% weight loss since her latest discharge 8 mo before the present admission. In the 5-y period since her first admission to our nutritional clinic in 2008, she had been hospitalized 15 times for a total of 1096 d (Fig. 1). No funding was secured for this study. JF and RS were responsible for the conception of the study. All authors were responsible for drafting and approval of the final version of the manuscript. Written consent was obtained from the patient before submission. The authors have no financial relationships relevant to this article to disclose. The authors have no conflicts of interest to disclose. * Corresponding author. Tel.: þ45 515 04633; fax: þ45 659 19653. E-mail address: [email protected] (J. Frølich). http://dx.doi.org/10.1016/j.nut.2015.08.024 0899-9007/Ó 2016 Elsevier Inc. All rights reserved.
Numerous prior attempts to sustain BMI levels >14 kg/m2, voluntarily or through coercion, all failed. The effect and sustainability of hospitalization and refeeding have declined since spring 2011, leading to a more palliative approach to treatment. At present, almost 20 y after the debut of disease, she refers herself to nutritional rehabilitation on a solely voluntarily basis, when needed. Her body suffers from the consequences of prolonged malnutrition, such as amenorrhea, severe dental problems, and decreased bone mineral density (T-score lumbar spine –5.9). At admission her body weight was 19.7 kg (height was measured using a wall-mounted stadiometer; weight was measured on a calibrated platform scale). On examination, she was awake and fully conscious. Her general condition was extremely poor, and she was bedridden as she could not stand or lift her head from the pillow. Upon physical examination, she had edema of the lower legs and severe atrophy of the skin with dispersed suggillation and pressure ulcers at the lower back. Stethoscopy of the heart revealed a systolic murmur not known before the present admission. Initial workup revealed hypotension (94/76 mm Hg), relative tachycardia (heart rate 70 bpm), hypothermia (35.3 C), hypoglycemia (blood glucose 37.8 mg/dL), and glycosuria. Four days after admission, her edema had decreased significantly and her weight reached a nadir of 18.7 kg, corresponding to a BMI of 7.8 kg/m2. To our knowledge, this is the lowest BMI ever reported for a patient suffering from AN, or, indeed, for an adult human.
J. Frølich et al. / Nutrition 32 (2016) 146–148
Investigations Blood samples are shown in Table 1. On admission anemia, azotemia, hypernatremia, hypokalemia, hypophosphatemia, and a marked increase in liver enzymes were noted. Urine analysis by chemical strip test showed glycosuria but did not show the presence of protein, blood, nitrites, or leucocytes. Because of suspected immunosuppression, urine and blood cultures were performed; both yielding negative results. A chest x-ray was without signs of chest infection.
147
known complication to hypophosphatemia [6–8]. The anemia was treated with irradiated red blood cells to minimize the risk for transfusion-associated graft-versus-host disease. No further major complication was recorded, and the patient was discharged 12 wk after admission with a weight gain of 43%. At discharge, all blood samples in regard to blood cell counts, liver enzymes, and electrolytes were within normal range. The patient was discharged to the outpatient clinic for further nutritional rehabilitation. Discussion
Treatment Refeeding was carried out in accordance with the National Institute for Health and Care Excellence (NICE) guideline on nutrition support in adults, starting at a maximum of 10 kcal/kg daily, to minimize the risk for refeeding syndrome [5]. A commercially available nutrition solution with 50% of energy derived from carbohydrate, 15% from protein, and 35% from fat was chosen (Resource Complete Nutrition, Nestle HealthCare Nutrition, Florham Park, NJ, USA). Although the patient was severely malnourished, we opted solely for oral administration, without nasogastric tubing, for safe administration and a functional gastrointestinal tract. Supplements of phosphate and potassium were provided according to plasma levels, and supplements of thiamine and vitamin B according to recommendations. Dehydration and hypoglycemia were treated solely with oral fluids. Over a period of 3 wk, the energy content in the diet was gradually increased to reach full demands. Outcome Five days into admission, the red blood cell count decreased to 4.4 mmol/L, which, in combination with reticulocytosis and undetectable levels of haptoglobin, indicated hemolysis, a
Extreme malnutrition and BMIs in the range of 10 to 12 kg/m2 are not uncommon in AN. What characterizes the anorectic weight loss often is a gradual adaptation to low weight, combined with adequate availability of macro- and micronutrients, thereby distinguishing it from the protein–energy malnutrition seen in famines, for example. The question is whether this proposed metabolic adaptation is simply due to a reduction in lean body mass, or to active mechanisms decreasing energy expenditure. Decreased resting energy expenditure adjusted for lean body mass was demonstrated in a group of AN patients (mean BMI 15.6 kg/m2) compared with both rehabilitated AN patients and normal weight controls (P < 0.01 and 0.001, respectively) [9], indicating an active adaptation beyond weight loss per se, a finding supported elsewhere [10]. Several mechanisms have been proposed to explain this metabolic adaptation to weight loss, including thyroid function, cardiovascular function, and decreased levels of leptin [11–13], however, how these factors affect the extremely emaciated state is not clear. What is remarkable about the patient in the present case is the time course of the descending BMI. Since 2011, she had been hospitalized 10 times, with ever decreasing BMI at admissions, but without major somatic or refeeding complications (Fig. 1). At
Table 1 Biochemistry Parameter
Reference values
On admission
Day 7
Day 14
1 mo
2 mo
Hemoglobin (mmol/L) White blood cells (10 x103/mL) Platelets (10 x103/mL) Reticulocytes (10 x103/mL) Haptoglobin (g/L) Albumin (g/L) Creatinine (mmol/L) Urea (mmol/L) Potassium (mmol/L) Sodium (mmol/L) Phosphate (mmol/L) Magnesium (mmol/L) Uric acid (mmol/L) Bicarbonate (mmol/L) KFNT (U/L) LDH (U/L) Bilirubin (mmol/L) ALT (U/L) GGT (U/L) Alkaline phosphatase (U/L) HbA1c (mmol/mol) Proinsulin C-peptide (pmol/L) TSH (10 E-3 IU/L) T3 (nmol/L) T4 (nmol/L)
7.3–9.5 3.5–8.8 165–400 31–97 0.35–1.85 36–50 49–90 2.6–6.4 3.5–4.4 137–145 0.76–1.41 0.71–0.94 0.16–0.35 22–26 0.70–1.30 105–205 5–25 10–45 10–45 35–105 23–45 200–700 0.30–4.00 1.3–2.2 60–130
5.8 3.3 131 – – 32 28 1.9 2.3 128 0.37 0.79 0.06 28.8 0.49 – 21 786 192 185 – – 1.3 1.3 62
4.4 2.17 151 99 <0.08 28 17 3.8 3.8 129 1.23 0.75 – 27.4 – 370 9 261 149 108 27 684 – – –
5.2 2.36 452 – – 31 17 5.2 4 133 1.74 0.71 – 26.9 – 255 7 115 139 126 – – – – –
6.3 3.22 529 65 – 36 31 – 4.3 133 1.64 – – 26.2 1.11 – – – – – – – – – –
7.3 3.14 434 – – 44 36 – 4.3 134 – 0.78 – 25.4 – 188 4 21 26 119 – – – – –
ALT, alanine transaminase; LDH, lactate dehydrogenase; GGT, g-glutamyl transpeptidase; KFNT, coagulation-factor II, VII, X; HbA1c, glycated hemoglobin; T3, triiodothyronine; T4, thyroxine.
148
J. Frølich et al. / Nutrition 32 (2016) 146–148
readmitted twice with BMIs of 7.8 and 7.9 kg/m2, respectively, and the acquired weight gain seems to be increasingly short lived. Despite countless efforts, we have not been able to stabilize her weight at any reasonable level or avoid the need for frequent hospitalization. What is adding to concern is that, although she is alive and doing relatively well, her resistance to infections, dehydration, and gastrointestinal diseases, for example, must be regarded as very low, with a high risk for complications or death.
Fig. 1. BMI course from 2008 to 2013. Periods in which the patient was hospitalized in our nutritional unit are marked in dark gray. Before 2008, the patient had numerous admissions to other eating disorder facilities. The figure shows ever decreasing BMI at both admission and discharge since 2011 despite highly specialized treatment. BMI, body mass index.
the present admission, she was fully conscious and with acceptable values for blood pressure, heart rate, and body temperature, to a degree one most certainly would not expect from a BMI of 7.8 kg/m2 Yet, this is not the first report of adaptation to the extreme in AN. A study of 41 severely malnourished anorectic patients with BMI <11 kg/m2 (range 8.8–10.9 kg/m2), reported that one person died, two suffered from myocardial infarction, and two others from acute pancreatitis [2]. Complications such as neuropathy, mental confusion, and leg edema were resolved in all cases during the refeeding protocol. That a far worse outcome related to a very low BMI also can be the case is illustrated by the report of a 27-y-old Japanese woman admitted to the hospital because of coma. Her BMI at admission was 8.5 kg/m2 and she presented with severe hypoglycemia. Magnetic resonance imaging scan of the brain showed classical features of central pontine myelinolysis, most likely triggered by the hypoglycemic state, and although she survived, she experienced persistent neurologic sequelae [14]. Is this case truly the limit of extreme malnutrition? It is, of course, impossible to say, but as shown in Table 1, every assessed organ system was seriously affected by malnutrition. Blood counts showed pancytopenia, and although we did not perform bone marrow biopsy, these findings could be explained by bone marrow atrophy or gelatinous marrow transformation, both findings related to starvation and seen in AN [15,16]. That the pancytopenic state totally resolves upon refeeding supports the starvation-induced mechanism, in contrast to other hematologic diseases. The combination of non-diabetic glycosuria, hypophosphatemia, and hypouricemia, could be explained by a nonacidotic proximal tubulopathy, possibly induced by depletion of phosphate leading to a shortage of intracellular adenosine triphosphate. This Fanconi-syndrome–like picture has previously been reported in relation to AN [17]. Increased levels of alanine aminotransferase and alkaline phosphatases are common in AN and frequently related to the refeeding syndrome. The markedly elevated alanine aminotransferase at admission is clearly not related to refeeding, but may be explained by a combination of starvation-induced hepatocyte autophagy and decreased blood flow to the liver, resulting in ischemia [18,19]. Ultimately, prolonged hypoglycemia (hemoglobin A1C 27 mmol/mol) and triiodothyronine low in the reference interval are both classical features of starvation [20]. The long-term prognosis must be regarded as very poor. Since the hospitalization described in this case, the patient has been
Conclusion We reported on a case of adaptation to severe malnutrition, taken to a level probably not previously reported. The present case emphasizes the importance of adherence to refeeding guidelines to decrease complications.
References [1] Kosmiski L, Schmiege SJ, Mascolo M, Gaudiani J, Mehler PS. Chronic starvation secondary to anorexia nervosa is associated with an adaptive suppression of resting energy expenditure. J Clin Endocrinol Metab 2014;99:908–14. [2] Rigaud D, Tallonneau I, Brindisi MC, Verges B. Prognosis in 41 severely malnourished anorexia nervosa patients. Clinical Nutrition (Edinburgh, Scotland) 2012;31:693–8. [3] Collins S. The limit of human adaptation to starvation. Nat Med 1995;1:810–4. [4] Peel M. Hunger strikes. BMJ 1997;315:829–30. [5] National Collaborating Centre for Acute Care. Nutrition support in adults: oral nutrition support, enteral tube feeding and parenteral nutrition. London: National Collaborating Centre for Acute Care; 2006. [6] Kaiser U, Barth N. Haemolytic anaemia in a patient with anorexia nervosa. Acta Haematol 2001;106:133–5. [7] Van Dissel JT, Gerritsen HJ, Meinders AE. Severe hypophosphatemia in a patient with anorexia nervosa during oral feeding. Miner Electrolyte Metab 1992;18:365–9. [8] Boateng AA, Sriram K, Meguid MM, Crook M. Refeeding syndrome: treatment considerations based on collective analysis of literature case reports. Nutrition 2010;26:156–67. [9] Russell J, Baur LA, Beumont PJ, Byrnes S, Gross G, Touyz S, et al. Altered energy metabolism in anorexia nervosa. Psychoneuroendocrinology 2001;26:51–63. [10] Polito A, Fabbri A, Ferro-Luzzi A, Cuzzolaro M, Censi L, Ciarapica D, et al. Basal metabolic rate in anorexia nervosa: relation to body composition and leptin concentrations. Am J Clin Nutr 2000;71:1495–502. [11] Onur S, Haas V, Bosy-Westphal A, Hauer M, Paul T, Nutzinger D, et al. L-tri-iodothyronine is a major determinant of resting energy expenditure in underweight patients with anorexia nervosa and during weight gain. Eur J Endocrinol 2005;152:179–84. [12] Romano C, Chinali M, Pasanisi F, Greco R, Celentano A, Rocco A, et al. Reduced hemodynamic load and cardiac hypotrophy in patients with anorexia nervosa. Am J Clin Nutr 2003;77:308–12. [13] Haas V, Onur S, Paul T, Nutzinger DO, Bosy-Westphal A, Hauer M, et al. Leptin and body weight regulation in patients with anorexia nervosa before and during weight recovery. Am J Clin Nutr 2005;81:889–96. [14] Bando N, Watanabe K, Tomotake M, Taniguchi T, Ohmori T. Central pontine myelinolysis associated with a hypoglycemic coma in anorexia nervosa. Gen Hosp Psychiatry 2005;27:372–4. [15] Bredella MA, Fazeli PK, Miller KK, Misra M, Torriani M, Thomas BJ, et al. Increased bone marrow fat in anorexia nervosa. J Clin Endocrinol Metab 2009;94:2129–36. [16] Hutter G, Ganepola S, Hofmann WK. The hematology of anorexia nervosa. Int J Eat Disord 2009;42:293–300. [17] Alexandridis G, Liamis G, Elisaf M. Reversible tubular dysfunction that mimicked Fanconi’s syndrome in a patient with anorexia nervosa. Int J Eat Disord 2001;30:227–30. [18] Kheloufi M, Boulanger CM, Durand F, Rautou PE. Liver autophagy in anorexia nervosa and acute liver injury. Biomed Res Int 2014;2014: 701064. [19] Ramsoekh D, Taimr P, Vanwolleghem T. Reversible severe hepatitis in anorexia nervosa: a case report and overview. Eur J Gastroenterol Hepatol 2014;26:473–7. [20] Winston AP. The clinical biochemistry of anorexia nervosa. Ann Clin Biochem 2012;49:132–43.
Contents lists available at ScienceDirect
Nutrition journal homepage: www.nutritionjrnl.com
Case report
To the limit of extreme malnutrition Jacob Frølich M.D. *, Camilla Viola Buskbjerg Palm M.D., Rene K. Støving M.D., Ph.D. Centre for Eating Disorders, Department of Endocrinology, Odense University Hospital, Odense, Denmark
a r t i c l e i n f o
a b s t r a c t
Article history: Received 8 June 2015 Accepted 27 August 2015
Extreme malnutrition with body mass index (BMI) as low as 10 kg/m2 is not uncommon in anorexia nervosa, with survival enabled through complex metabolic adaptations. In contrast, outcomes from hunger strikes and famines are usually fatal after weight loss to about 40% below expected body weight, corresponding to BMI 12 to 13 kg/m2 in adults. Thus, many years of adaptation in adolescent-onset anorexia nervosa, supported by supplements of vitamins and treatment of intercurrent diseases, may allow survival at a much lower BMI. However, in the literature only a few cases of survival in patients with BMI <9 kg/m2 have been described. We report on the case of a 29-y-old woman who was successfully treated in a specialized unit. She had a BMI of 7.8 kg/m2. To our knowledge, this level of extreme malnutrition has not previously been reported. The present case emphasizes the importance of adherence to guidelines to decrease refeeding complications. Ó 2016 Elsevier Inc. All rights reserved.
Keywords: Eating disorder Anorexia nervosa Refeeding syndrome
Introduction Prolonged energy deficit and subsequent low body weight are well-known consequences of anorexia nervosa (AN). Metabolic adaptation enables patients with AN to adapt to very low body mass index (BMI) levels [1,2], even surpassing levels known to be fatal in hunger strikes and famines [3,4]. It is clear, however, that there must be a lower weight limit consistent with life. This case report presents a remarkable adaptation to chronic severe malnutrition, what must be regarded as close to the absolute limit in humans. Case presentation A 29-y-old woman, diagnosed with AN at the age of 12, was voluntarily admitted to the emergency room with a 20% weight loss since her latest discharge 8 mo before the present admission. In the 5-y period since her first admission to our nutritional clinic in 2008, she had been hospitalized 15 times for a total of 1096 d (Fig. 1). No funding was secured for this study. JF and RS were responsible for the conception of the study. All authors were responsible for drafting and approval of the final version of the manuscript. Written consent was obtained from the patient before submission. The authors have no financial relationships relevant to this article to disclose. The authors have no conflicts of interest to disclose. * Corresponding author. Tel.: þ45 515 04633; fax: þ45 659 19653. E-mail address: [email protected] (J. Frølich). http://dx.doi.org/10.1016/j.nut.2015.08.024 0899-9007/Ó 2016 Elsevier Inc. All rights reserved.
Numerous prior attempts to sustain BMI levels >14 kg/m2, voluntarily or through coercion, all failed. The effect and sustainability of hospitalization and refeeding have declined since spring 2011, leading to a more palliative approach to treatment. At present, almost 20 y after the debut of disease, she refers herself to nutritional rehabilitation on a solely voluntarily basis, when needed. Her body suffers from the consequences of prolonged malnutrition, such as amenorrhea, severe dental problems, and decreased bone mineral density (T-score lumbar spine –5.9). At admission her body weight was 19.7 kg (height was measured using a wall-mounted stadiometer; weight was measured on a calibrated platform scale). On examination, she was awake and fully conscious. Her general condition was extremely poor, and she was bedridden as she could not stand or lift her head from the pillow. Upon physical examination, she had edema of the lower legs and severe atrophy of the skin with dispersed suggillation and pressure ulcers at the lower back. Stethoscopy of the heart revealed a systolic murmur not known before the present admission. Initial workup revealed hypotension (94/76 mm Hg), relative tachycardia (heart rate 70 bpm), hypothermia (35.3 C), hypoglycemia (blood glucose 37.8 mg/dL), and glycosuria. Four days after admission, her edema had decreased significantly and her weight reached a nadir of 18.7 kg, corresponding to a BMI of 7.8 kg/m2. To our knowledge, this is the lowest BMI ever reported for a patient suffering from AN, or, indeed, for an adult human.
J. Frølich et al. / Nutrition 32 (2016) 146–148
Investigations Blood samples are shown in Table 1. On admission anemia, azotemia, hypernatremia, hypokalemia, hypophosphatemia, and a marked increase in liver enzymes were noted. Urine analysis by chemical strip test showed glycosuria but did not show the presence of protein, blood, nitrites, or leucocytes. Because of suspected immunosuppression, urine and blood cultures were performed; both yielding negative results. A chest x-ray was without signs of chest infection.
147
known complication to hypophosphatemia [6–8]. The anemia was treated with irradiated red blood cells to minimize the risk for transfusion-associated graft-versus-host disease. No further major complication was recorded, and the patient was discharged 12 wk after admission with a weight gain of 43%. At discharge, all blood samples in regard to blood cell counts, liver enzymes, and electrolytes were within normal range. The patient was discharged to the outpatient clinic for further nutritional rehabilitation. Discussion
Treatment Refeeding was carried out in accordance with the National Institute for Health and Care Excellence (NICE) guideline on nutrition support in adults, starting at a maximum of 10 kcal/kg daily, to minimize the risk for refeeding syndrome [5]. A commercially available nutrition solution with 50% of energy derived from carbohydrate, 15% from protein, and 35% from fat was chosen (Resource Complete Nutrition, Nestle HealthCare Nutrition, Florham Park, NJ, USA). Although the patient was severely malnourished, we opted solely for oral administration, without nasogastric tubing, for safe administration and a functional gastrointestinal tract. Supplements of phosphate and potassium were provided according to plasma levels, and supplements of thiamine and vitamin B according to recommendations. Dehydration and hypoglycemia were treated solely with oral fluids. Over a period of 3 wk, the energy content in the diet was gradually increased to reach full demands. Outcome Five days into admission, the red blood cell count decreased to 4.4 mmol/L, which, in combination with reticulocytosis and undetectable levels of haptoglobin, indicated hemolysis, a
Extreme malnutrition and BMIs in the range of 10 to 12 kg/m2 are not uncommon in AN. What characterizes the anorectic weight loss often is a gradual adaptation to low weight, combined with adequate availability of macro- and micronutrients, thereby distinguishing it from the protein–energy malnutrition seen in famines, for example. The question is whether this proposed metabolic adaptation is simply due to a reduction in lean body mass, or to active mechanisms decreasing energy expenditure. Decreased resting energy expenditure adjusted for lean body mass was demonstrated in a group of AN patients (mean BMI 15.6 kg/m2) compared with both rehabilitated AN patients and normal weight controls (P < 0.01 and 0.001, respectively) [9], indicating an active adaptation beyond weight loss per se, a finding supported elsewhere [10]. Several mechanisms have been proposed to explain this metabolic adaptation to weight loss, including thyroid function, cardiovascular function, and decreased levels of leptin [11–13], however, how these factors affect the extremely emaciated state is not clear. What is remarkable about the patient in the present case is the time course of the descending BMI. Since 2011, she had been hospitalized 10 times, with ever decreasing BMI at admissions, but without major somatic or refeeding complications (Fig. 1). At
Table 1 Biochemistry Parameter
Reference values
On admission
Day 7
Day 14
1 mo
2 mo
Hemoglobin (mmol/L) White blood cells (10 x103/mL) Platelets (10 x103/mL) Reticulocytes (10 x103/mL) Haptoglobin (g/L) Albumin (g/L) Creatinine (mmol/L) Urea (mmol/L) Potassium (mmol/L) Sodium (mmol/L) Phosphate (mmol/L) Magnesium (mmol/L) Uric acid (mmol/L) Bicarbonate (mmol/L) KFNT (U/L) LDH (U/L) Bilirubin (mmol/L) ALT (U/L) GGT (U/L) Alkaline phosphatase (U/L) HbA1c (mmol/mol) Proinsulin C-peptide (pmol/L) TSH (10 E-3 IU/L) T3 (nmol/L) T4 (nmol/L)
7.3–9.5 3.5–8.8 165–400 31–97 0.35–1.85 36–50 49–90 2.6–6.4 3.5–4.4 137–145 0.76–1.41 0.71–0.94 0.16–0.35 22–26 0.70–1.30 105–205 5–25 10–45 10–45 35–105 23–45 200–700 0.30–4.00 1.3–2.2 60–130
5.8 3.3 131 – – 32 28 1.9 2.3 128 0.37 0.79 0.06 28.8 0.49 – 21 786 192 185 – – 1.3 1.3 62
4.4 2.17 151 99 <0.08 28 17 3.8 3.8 129 1.23 0.75 – 27.4 – 370 9 261 149 108 27 684 – – –
5.2 2.36 452 – – 31 17 5.2 4 133 1.74 0.71 – 26.9 – 255 7 115 139 126 – – – – –
6.3 3.22 529 65 – 36 31 – 4.3 133 1.64 – – 26.2 1.11 – – – – – – – – – –
7.3 3.14 434 – – 44 36 – 4.3 134 – 0.78 – 25.4 – 188 4 21 26 119 – – – – –
ALT, alanine transaminase; LDH, lactate dehydrogenase; GGT, g-glutamyl transpeptidase; KFNT, coagulation-factor II, VII, X; HbA1c, glycated hemoglobin; T3, triiodothyronine; T4, thyroxine.
148
J. Frølich et al. / Nutrition 32 (2016) 146–148
readmitted twice with BMIs of 7.8 and 7.9 kg/m2, respectively, and the acquired weight gain seems to be increasingly short lived. Despite countless efforts, we have not been able to stabilize her weight at any reasonable level or avoid the need for frequent hospitalization. What is adding to concern is that, although she is alive and doing relatively well, her resistance to infections, dehydration, and gastrointestinal diseases, for example, must be regarded as very low, with a high risk for complications or death.
Fig. 1. BMI course from 2008 to 2013. Periods in which the patient was hospitalized in our nutritional unit are marked in dark gray. Before 2008, the patient had numerous admissions to other eating disorder facilities. The figure shows ever decreasing BMI at both admission and discharge since 2011 despite highly specialized treatment. BMI, body mass index.
the present admission, she was fully conscious and with acceptable values for blood pressure, heart rate, and body temperature, to a degree one most certainly would not expect from a BMI of 7.8 kg/m2 Yet, this is not the first report of adaptation to the extreme in AN. A study of 41 severely malnourished anorectic patients with BMI <11 kg/m2 (range 8.8–10.9 kg/m2), reported that one person died, two suffered from myocardial infarction, and two others from acute pancreatitis [2]. Complications such as neuropathy, mental confusion, and leg edema were resolved in all cases during the refeeding protocol. That a far worse outcome related to a very low BMI also can be the case is illustrated by the report of a 27-y-old Japanese woman admitted to the hospital because of coma. Her BMI at admission was 8.5 kg/m2 and she presented with severe hypoglycemia. Magnetic resonance imaging scan of the brain showed classical features of central pontine myelinolysis, most likely triggered by the hypoglycemic state, and although she survived, she experienced persistent neurologic sequelae [14]. Is this case truly the limit of extreme malnutrition? It is, of course, impossible to say, but as shown in Table 1, every assessed organ system was seriously affected by malnutrition. Blood counts showed pancytopenia, and although we did not perform bone marrow biopsy, these findings could be explained by bone marrow atrophy or gelatinous marrow transformation, both findings related to starvation and seen in AN [15,16]. That the pancytopenic state totally resolves upon refeeding supports the starvation-induced mechanism, in contrast to other hematologic diseases. The combination of non-diabetic glycosuria, hypophosphatemia, and hypouricemia, could be explained by a nonacidotic proximal tubulopathy, possibly induced by depletion of phosphate leading to a shortage of intracellular adenosine triphosphate. This Fanconi-syndrome–like picture has previously been reported in relation to AN [17]. Increased levels of alanine aminotransferase and alkaline phosphatases are common in AN and frequently related to the refeeding syndrome. The markedly elevated alanine aminotransferase at admission is clearly not related to refeeding, but may be explained by a combination of starvation-induced hepatocyte autophagy and decreased blood flow to the liver, resulting in ischemia [18,19]. Ultimately, prolonged hypoglycemia (hemoglobin A1C 27 mmol/mol) and triiodothyronine low in the reference interval are both classical features of starvation [20]. The long-term prognosis must be regarded as very poor. Since the hospitalization described in this case, the patient has been
Conclusion We reported on a case of adaptation to severe malnutrition, taken to a level probably not previously reported. The present case emphasizes the importance of adherence to refeeding guidelines to decrease complications.
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