Elsevier

Nutrition

Volume 30, Issues 7–8, July–August 2014, Pages 948-952
Nutrition

Case report
Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis

https://doi.org/10.1016/j.nut.2014.02.019Get rights and content

Abstract

Objective

Refeeding syndrome can occur in several contexts of relative malnutrition in which an overaggressive nutritional support is started. The consequences are life threatening with multiorgan impairment, and severe electrolyte imbalances. During refeeding, glucose-involved insulin secretion causes abrupt reverse of lipolysis and a switch from catabolism to anabolism. This creates a sudden cellular demand for electrolytes (phosphate, potassium, and magnesium) necessary for synthesis of adenosine triphosphate, glucose transport, and other synthesis reactions, resulting in decreased serum levels. Laboratory findings and multiorgan impairment similar to refeeding syndrome also are observed in acute thiamine deficiency. The aim of this study was to determine whether thiamine deficiency was responsible for the electrolyte imbalance caused by tubular electrolyte losses.

Methods

We describe two patients with leukemia who developed acute thiamine deficiency with an electrolyte pattern suggestive of refeeding syndrome, severe lactic acidosis, and evidence of proximal renal tubular dysfunction.

Results

A single thiamine administration led to rapid resolution of the tubular dysfunction and normalization of acidosis and electrolyte imbalance. This demonstrated that thiamine deficiency was responsible for the electrolyte imbalance, caused by tubular electrolyte losses.

Conclusions

Our study indicates that, despite sharing many laboratory similarities, refeeding syndrome and acute thiamine deficiency should be viewed as separate entities in which the electrolyte abnormalities reported in cases of refeeding syndrome with thiamine deficiency and refractory lactic acidosis may be due to renal tubular losses instead of a shifting from extracellular to intracellular compartments. In oncologic and malnourished patients, individuals at particular risk for developing refeeding syndrome, in the presence of these biochemical abnormalities, acute thiamine deficiency should be suspected and treated because it promptly responds to thiamine administration.

Introduction

Thiamine deficiency can occur in anorexia nervosa, in leukemia/cancer [1], in patients receiving unsupplemented total parenteral nutrition (TPN) [2], in children fed with defective soy-based infant formulas [3], or in individuals who chronically abuse alcohol [4]. Clinical features of thiamine deficiency include neurologic, cardiovascular, and metabolic manifestations [2]. Furthermore, acute thiamine deficiency has been considered a component of refeeding syndrome (RS), a potentially lethal condition characterized by severe electrolyte and fluid imbalance [5]. RS was originally described in grossly malnourished prisoners released from concentration camps during World War II who presented with heart failure, neurologic complications with convulsions, and coma following refeeding [5], [6]. RS characteristically occurs when malnourished and starved individuals receive high-carbohydrate feeding leading to a sudden change of the energy sources, from fat to carbohydrates, which causes a sustained increase in insulin secretion. The insulin action induces a sudden shift of salt from the extracellular to the intracellular compartment. The laboratory hallmark of RS is hypophosphatemia; additional features include reduced plasma potassium and magnesium levels, hyperglycemia, metabolic acidosis, along with sodium and water retention causing fluid overload [4], [7], [8]. The consequences of these severe changes can be life threatening. High-risk conditions include recent weight loss, secondary to poor caloric intake or nutrient losses [8]. Patients with malignancy are at particular risk for developing RS, because they frequently develop malnutrition and depletion of micronutrients and electrolytes as a consequence of their treatment. An excessive parenteral carbohydrate supply may act as a trigger for RS, especially if glucose supply is not adequately supplemented with vitamins and oligoelements [4], [9]. Interestingly, laboratory findings similar to RS are also observed in acute thiamine deficiency [1]. In this paper, we report on two children with leukemia who developed acute thiamine deficiency and showed an electrolyte pattern of RS, whose pathogenetic mechanism was due to a severe proximal renal tubular dysfunction that promptly responded to thiamine administration.

This infant presented at 5 mo of age with intestinal bleeding, severe anemia, and thrombocytopenia leading to the diagnosis of B-cell leukemia. She was enrolled in the International Collaborative Treatment Protocol for Children under 1 y of age (INTERFANT 2006). During the consolidation phase, a few days after the first administration of intravenous (IV) high-dose methotrexate 5000 mg/m2, the child presented with diarrhea and vomiting treated by parenteral hydration with 5% glucose saline solution for 1 wk. Total parenteral nutrition (TPN) support with a glucose concentration of 33% was started on the following day (day 0), when a second dose of IV methotrexate 5000 mg/m2 was administered. Feeding difficulties persisted and TPN was continued. On day 19, clinical conditions further deteriorated with appearance of tachypnea and lethargy. Blood gas analysis revealed severe metabolic acidosis (pH 6.9, normal value [nv] 7.32–7.48; base excess [BE] −25 mEq/L, nv –2/+3; HCO3– 5 mEq/L), high anion gap (21 mEq/L), hyperlactatemia (13.3 mMol/L, nv 0.4–2.2, 120 mg/dL, nv 4–20), and moderate hyperglycemia (158 mg/dL). Further laboratory findings showed severe hypophosphatemia (0.9 mg/dL), hypokalemia (2.5 mEq/L), and hypomagnesemia (1.4 mg/dL). As shown in Table 1, mineral and electrolyte imbalance was consistent with proximal tubular dysfunction with renal loss of phosphate, magnesium, and potassium. Despite IV administration of large-dose bicarbonate, up to 10 mEq/kg, and electrolyte supplementation, clinical conditions and severe metabolic acidosis and electrolyte imbalance further deteriorated. Continuous veno-venous hemofiltration was started on day 20 but caused only slight improvement. On day 21, examination of urinary organic acids showed a characteristic pattern seen in thiamine deficiency [1] (Fig. 1). Soon after 300 mg thiamine administration, we observed an almost immediate improvement of clinical conditions with complete normalization of metabolic acidosis within 3 h (Fig. 2). In the following 24 to 48 h, blood electrolyte abnormalities fully recovered with normalization of blood lactate and urine organic acid profile. Proximal tubular dysfunction completely resolved in the following days (Table 1).

This young boy was diagnosed with acute myeloid leukemia at the age of 9 y. He was enrolled in the Italian Protocol AIEOP LAM 2002. During the first chemotherapy course, he developed persistent vomiting requiring TPN with a 33% glucose concentration (day 0). On day 19, he suddenly developed mental status changes, hypothermia, hypotension, and tachypnea. Cerebral magnetic resonance imaging showed bilateral high-intensity signals of basal ganglia. Blood gas analysis revealed severe metabolic acidosis (pH 6.8; BE −29 mEq/L; HCO3– 3 mEq/L; anion gap 35 mEq/L), hyperlactatemia (15.5 mMol/L, 140 mg/dL), and hyperglycemia (270 mg/dL). Further laboratory findings showed hypophosphatemia (1.2 mg/dL), hypokalemia (2.4 mEq/L), and hypomagnesemia (1.2 mg/dL). Similar to patient 1, urinary investigation showed evidence of proximal renal tubular dysfunction (Table 1). Attempts to correct metabolic acidosis with IV sodium bicarbonate were ineffective. Reviewing of his TPN prescription showed that vitamin supplementation was missed. Thiamine deficiency was confirmed by analysis of plasma levels (30 nmol/L, nv 66.5–200) and by analysis of urinary organic acids, which showed a characteristic profile. Three hours after administration of 300 mg thiamine, metabolic acidosis disappeared; electrolyte abnormalities and renal tubular function fully recovered within 5 d (Table 1).

Section snippets

Discussion

Malnourished patients presenting with acute illnesses receiving parenteral hydration with high-concentration glucose solutions or treated with enteral or parenteral nutrition without adequate vitamin supplementation, are at high risk for developing RS [1], [5], [7], [10], [11]. Thiamine deficiency, which often is listed among the causes of RS, may cause metabolic, neurologic and cardiovascular symptoms, similar to RS [12]. As frequently observed in children with leukemia receiving chemotherapy,

Conclusion

Oncologic and malnourished patients should be carefully monitored to avoid severe electrolyte abnormalities related to thiamine deficiency, a life-threatening condition that, if promptly recognized, dramatically responds to thiamine administration. However, further studies with more patients are necessary to support our findings.

References (22)

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    AM conceptualized and designed the study, carried out data collection and analyses, drafted the initial manuscript, and reviewed and approved the final manuscript as submitted. GV carried out the initial analyses, drafted the initial manuscript, and approved the final manuscript as submitted. VC performed the data collection, participated in its design and coordination, and helped to draft the manuscript. ML performed the data collection, participated in its design and coordination, and approved the final manuscript as submitted. CR carried out the instrumental data analyses, participated in the interpretation of data and participated in its design and coordination, and helped to draft the manuscript. FE participated in its design and coordination, critically reviewed the manuscript, and approved the final manuscript as submitted. CDV designed the data collection instruments, coordinated and supervised data collection, critically reviewed the manuscript, and approved the final manuscript as submitted. All authors read and approved the final manuscript. The authors declare that they have no competing interests.

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