The Case | A lockdown-related metabolic acidosis.

A 43-year-old woman presented with tachycardia and multiple episodes of vomiting (at least 15 times). Her medical history was remarkable for eating disorders and 7 pregnancies (5 to full term). From the time of lockdown due to the COVID-19 pandemic, she had remained at home, without her spouse but with her children, while continuing to breastfeed her 3-month-old baby. During this period, she felt depressed and began to be anorexic. She lost 4 kg in 3 weeks. Her main food supply consisted of sweetened soft drinks. She denied having consumed any alcohol (including methanol or ethylene glycol) or having taken any medication. On physical examination, she presented with polypnea (30/min) and epigastric pain. Her blood pressure was 136/85 mm Hg, her heart rate was 160 beats/min, and she was clinically volume depleted. Arterial blood gas revealed a blood pH of 7.08, an arterial PCO2 of 15.4 mm Hg, and a plasma bicarbonate concentration of 4.5 mmol/l (Table 1). Her plasma anion gap was elevated. Lactate level was within the normal limit. Beta-hydroxybutyrate level was above 8 mmol/l and blood alcohol concentration was negative. Of note, she was hypoglycemic (3.3 mmol/l).Table 1Laboratory findingsParameterNormal rangeAt presentationpH7.38–7.427.08Arterial PCO2 (mm Hg)35–4515.4HCO3 (mmol/l)22–274.5Lactate (mmol/l)<21.1Anion gap (mmol/l)<1223Glucose (mmol/l)3.9–5.83.3Beta-hydroxybutyrate (mmol/l)<0.6>8Ethanol (g/l)<0.1<0.1Sodium (mmol/l)136–146144Potassium (mmol/l)3.4–4.54.2Chloride (mmol/l)98–107120Albumin (g/l)35–5229Serum creatinine (μmol/l)62–10663 Open table in a new tab The patient was transferred to the critical care nephrology unit. What is the diagnosis? This patient presented with metabolic acidosis with an appropriate respiratory response. Elevation of the plasma anion gap led to a search for acid accumulation. The delta anion gap was less than the delta bicarbonate consistent with a component of hyperchloremic acidosis. Lactic acidosis was quickly eliminated. Ingestion of a toxin that generates an organic acid was ruled out as the patient denied salicylate, methanol, ethylene glycol, or acetaminophen intake. The remarkably high beta-hydroxybutyrate levels were consistent with ketoacidosis. Diabetic ketoacidosis was eliminated because the patient’s glucose level was low, and her hemoglobin A1C level was normal (5.3%). Alcoholic ketoacidosis was also unlikely because she denied any alcohol consumption and her blood alcohol concentration was negative. Because of the low blood glucose level, anorexia, and continued breastfeeding, a diagnosis of lactation ketoacidosis was made. Developments were favorable under volume expansion and restoration of carbohydrate intake. On day 3, plasma bicarbonate concentration was restored to normal. Additional evaluation revealed hyperthyroidism (serum thyroid-stimulating hormone < 0.01 mUI/l) with a high level of free T4 (56 pmol/l; reference range between 12 and 22 pmol/l) and free T3 (8.3 pmol/l; reference range between 3.6 and 6.8 pmol/l). A diagnosis of Graves’ disease was made based on the presence of antibodies against the thyroid-stimulating hormone receptor. Thus, we started an antithyroid treatment with carbimazole. Lactation ketoacidosis (sometimes referred to as “bovine ketoacidosis”) is a severe subset of starvation ketoacidosis that has been rarely described in lactating women.1Chernow B. Finton C. Rainey T.G. O’Brian J.T. “Bovine ketosis” in a nondiabetic postpartum woman.Diabetes Care. 1982; 5: 47-49Crossref PubMed Scopus (20) Google Scholar Although starvation ketoacidosis is usually mild, lactation ketoacidosis can be life-threatening with profound acidemia (see Figure 1 for pathogenesis). In addition to insufficient carbohydrate supply due to fasting, lactating women have extra glucose demands, leading to low glucose levels. As a result, insulin levels fall, and glucagon levels rise. This leads to the release of fatty acids from adipose tissue (via lipolysis) and the formation of ketoacids in the liver.2Mohammad M.A. Sunehag A.L. Chacko S.K. et al.Mechanisms to conserve glucose in lactating women during a 42-h fast.Am J Physiol Endocrinol Metab. 2009; 297: E879-E888Crossref PubMed Scopus (24) Google Scholar An additional explanatory factor could be the high levels of hepatic carnitine during breastfeeding—carnitine being indispensable for ketogenesis.3McGarry J.D. Foster D.W. Hormonal control of ketogenesis. Biochemical considerations.Pediatr Res. 1986; 20: 806-809PubMed Google Scholar Briefly, this metabolic process is based on the oxidation of fatty acids to acetyl-CoA and finally ketone bodies (such as beta-hydroxybutyric acid, acetoacetate, and acetone).3McGarry J.D. Foster D.W. Hormonal control of ketogenesis. Biochemical considerations.Pediatr Res. 1986; 20: 806-809PubMed Google Scholar This process takes place when there is a combination of low levels of insulin and high levels of glucose counterregulatory hormones (such as glucagon, cortisol, thyroid hormone, adrenaline). Ketogenesis leads to high anion gap metabolic acidosis when the generation rate of ketoacids exceeds their removal via oxidation and excretion. Symptoms are nonspecific, with nausea, vomiting, malaise, weight loss, and hypoglycemia possibly developing. Patients using extreme low-caloric ketogenic diets to lose weight may develop marked ketoacidosis. Although its management is not well established, the main treatment is to restore insulin secretion with increased carbohydrate intake. Our patient had an additional precipitating factor—hyperthyroidism4Martinez B. Ortiz R.M. Thyroid hormone regulation and insulin resistance: insights from animals naturally adapted to fasting.Physiology. 2017; 32: 141-151Crossref PubMed Scopus (20) Google Scholar—which is known to reduce the pancreatic beta cell responsiveness to insulin. This factor might explain the severity of this case. This patient also had a component of hyperchloremic metabolic acidosis. This may be due to the loss of ketoacid salts in her urine. Unlike other cases published in the literature, our patient was not able to resume breastfeeding. This event may also be considered in relation to the psychological consequences of the COVID-19 lockdown in a patient overwhelmed by domestic responsibilities. Lactation ketoacidosis is a rare but easily managed cause of high anion gap metabolic acidosis. Physicians should be aware of this condition, particularly in women with known eating disorders. All the authors declared no competing interests.