The Case | Elevated lactate and osmolar gap after levothyroxine overdose
Authors: Gary D. Rothberger, Anish K. Desai, Sairah Sharif, Shalinee A. Chawla, Shayan Shirazian
Journal: Kidney International (2015)

A 42-year-old woman with hypothyroidism was brought to the emergency department (ED) after collapsing at home. As per her family she was seen in her usual state of health 2 h prior to presentation. She admitted to the ED physician that she attempted suicide by ingesting 15 tablets of levothyroxine, 88 mcg each. In the ED vital signs were blood pressure 160/100, heart rate 130, respiratory rate 24, and temperature 97.9 F. On examination, she had waxing and waning sensorium and had difficulty following simple commands. Diffuse muscle hypotonia and bilateral hyporeflexia were present; there were no other positive findings on physical examination. She was given intravenous fluids, propylthiouracil, propranolol, and hydrocortisone for treatment of thyrotoxicosis. Laboratory data are shown in Table 1. Given her elevated arterial lactate, a pill count of her husband’s metformin was performed and was found to be intact. Urine toxicology was negative and blood alcohol level was undetectable. A head CT ruled out any acute vascular process or space-occupying lesion. Urine microscopy is shown in Figure 1.Table 1Laboratory values on presentationParametersValueReference rangeSodium142 mEq/l138–145Potassium4.3 mEq/l3.7–5.2Chloride117 mEq/l103–112Bicarbonate<10 mEq/l23–33BUN11 mg/dl8–21Creatinine0.8 mg/dl0.4–1.0Glucose123 mg/dl73–107Serum osmolality408 osm278–316TSH0.44 μIU/ml0.36–5.8Free T44.32 ng/dl0.89–1.76pH6.937.35–7.45pCO211 mm Hg35–48pO2191 mm Hg83–108Calculated arterial bicarbonate2.5 mmol/l18–23Arterial lactate16 mmol/l0.5–2.2Salicylate1.3 mg/dl15–25Acetaminophen<1 μg/mlSerum alcohol<10 mg/dlUrine pH5.0Urine specific gravity1.012Abbreviations: BUN, blood urea nitrogen; TSH, thyroid-stimulating hormone. Open table in a new tab Abbreviations: BUN, blood urea nitrogen; TSH, thyroid-stimulating hormone. What is the differential diagnosis? What is the cause of her elevated arterial lactate? Urine microscopy showed ‘envelope-shaped’ calcium oxalate crystals. The presence of delirium, high anion gap metabolic acidosis, osmolar gap, and urinary calcium oxalate crystals led to a presumptive diagnosis of ethylene glycol (EG) poisoning. This diagnosis was made despite elevated arterial lactate, which is not typical of EG poisoning.1.Jacobsen D. Hewlett T.P. Webb R. et al.Ethylene glycol intoxication: evaluation of kinetics and crystalluria.Am J Med. 1988; 84: 145Abstract Full Text PDF PubMed Scopus (133) Google Scholar Fomipezole, thiamine, and pyridoxine were given and nephrology was consulted for urgent hemodialysis (HD). After one session of HD, arterial pH increased to 7.54, while arterial lactate decreased to 2.1 mmol/l. Fomipezole was continued for 4 days until the osmolar gap decreased to <15 mosm/l. Her renal function remained normal and on hospital day 5 she was transferred to a psychiatric facility. At that time, serum ethylene glycol level was found to be 182 mg/dl and methanol was negative, confirming the diagnosis. The toxicity of EG results from its metabolites, glycolate, glyoxalate, and oxalate.2.Morgan T.J. Clark C. Clague A. Artifactual elevation of measured plasma L-lactate concentration in the presence of glycolate.Crit Care Med. 1999; 27: 2177-2179Crossref PubMed Scopus (57) Google Scholar These metabolites produce an anion gap metabolic acidosis, and contribute to renal toxicity through direct damage to the renal tubule caused by glycolate and through tubular obstruction from oxalic acid crystals.1.Jacobsen D. Hewlett T.P. Webb R. et al.Ethylene glycol intoxication: evaluation of kinetics and crystalluria.Am J Med. 1988; 84: 145Abstract Full Text PDF PubMed Scopus (133) Google Scholar Therapy in EG poisoning relies on preventing conversion of EG to toxic metabolites with fomepizole and removing the parent compound and toxic metabolites from the blood by hemodialysis. Our patient had elevated arterial lactate levels without evidence of hypoperfusion or hypoxia, which normalized after HD. EG poisoning does not directly produce a significant lactic acidosis.2.Morgan T.J. Clark C. Clague A. Artifactual elevation of measured plasma L-lactate concentration in the presence of glycolate.Crit Care Med. 1999; 27: 2177-2179Crossref PubMed Scopus (57) Google Scholar The elevated arterial lactate level seen in our case is artifact, caused by cross-reaction of EG metabolites with lactate analyzers. Our arterial blood gas analyzer (GEM4000, Instrumentation Laboratory, Bedford, MA), a ‘point-of-care’ whole-blood analyzer, uses L-lactate oxidase to convert lactate to pyruvate and hydrogen peroxide; the latter is used as an indirect measure of arterial lactate. Glycolate and glyoxalate can also react with L-lactate oxidase and cause a false lactate elevation.2.Morgan T.J. Clark C. Clague A. Artifactual elevation of measured plasma L-lactate concentration in the presence of glycolate.Crit Care Med. 1999; 27: 2177-2179Crossref PubMed Scopus (57) Google Scholar,3.Pernet P. Bebeteau-Burnat B. Vaubourdolle M. False elevation of blood lactate reveals ethylene glycol poisoning.Am J Emerg Med. 2009; 27: 132.e1-132.e2Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Analyzers that use lactate dehydrogenase to measure lactate have no cross-reaction with EG metabolites.3.Pernet P. Bebeteau-Burnat B. Vaubourdolle M. False elevation of blood lactate reveals ethylene glycol poisoning.Am J Emerg Med. 2009; 27: 132.e1-132.e2Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar In general, L-lactate oxidase analyzers test whole blood and can be used at point of care, while lactate dehydrogenase analyzers commonly test plasma, which requires separation from whole blood at a central laboratory.2.Morgan T.J. Clark C. Clague A. Artifactual elevation of measured plasma L-lactate concentration in the presence of glycolate.Crit Care Med. 1999; 27: 2177-2179Crossref PubMed Scopus (57) Google Scholar Suspected cases of EG poisoning can have lactate measured with both a whole-blood ‘point-of-care’ analyzer and a plasma analyzer.2.Morgan T.J. Clark C. Clague A. Artifactual elevation of measured plasma L-lactate concentration in the presence of glycolate.Crit Care Med. 1999; 27: 2177-2179Crossref PubMed Scopus (57) Google Scholar A resulting ‘lactate gap’ may be a useful surrogate marker of EG toxicity.3.Pernet P. Bebeteau-Burnat B. Vaubourdolle M. False elevation of blood lactate reveals ethylene glycol poisoning.Am J Emerg Med. 2009; 27: 132.e1-132.e2Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar