Case Presentation: The patient was a 74-year-old male with past medical history significant for atrial fibrillation and Type II Diabetes Mellitus who presented due to 5 days of diarrhea and change in mental status. Per family, the patient had poor oral intake for the past week. Pertinent vitals included heart rate of 123 beats/minute, respirations at 22 breaths/minute, and blood pressure of 118/90 mmHg. Physical exam was pertinent for Glasgow Coma Scale score of 12 and dry mucous membranes; pertinent labs included bicarbonate of 15 mmol/L, creatinine of 0.76 mg/dL, glucose of 109 mg/dL, and anion gap of 22 mEq/L. Urinalysis showed 2+ ketones. Lactic acid was within normal limits. Given no clinical signs of diabetic ketoacidosis, the patient was started on fluids and dextrose for possible starvation ketoacidosis. Despite fluids and resumption of oral intake, anion gap and mentation did not improve. Thyroid stimulating hormone and free T4 were checked and resulted at < 0.01 μlU/ml and 4.40 ng/dL, respectively. Endocrinology was consulted and the patient was started on methimazole and prednisone. After initiation of hyperthyroidism treatment, bicarbonate improved to 25 mmol/L and anion gap decreased to 10mmol/L. His mental status also improved back to baseline.
Discussion: Anion gap metabolic acidosis is a common clinical challenge. The mnemonic MUDPILES aids in etiological identification but remains incomplete, as exemplified by the present case. Hyperthyroidism is noted to be a rare etiology of diabetic ketoacidosis (DKA) and non-diabetic ketoacidosis (NDKA) metabolic acidosis. Studies demonstrate that hyperthyroid patients exhibit increased beta-2 adrenergic receptors in adipocytes, enhancing lipolysis and fatty acid release. Moreover, elevated norepinephrine levels in subcutaneous adipose tissue have also been reported suggesting that thyroid hormone increases lipolysis by local release of norepinephrine. These factors collectively contribute to the development of ketoacidosis.In our patient, NDKA due to starvation was initially considered as a potential etiology for metabolic acidosis. However, bicarbonate levels rarely drop below 17 to 18 mmol/L unless there are prolonged periods of fasting (>3 weeks). In contrast, severe ketoacidosis can develop with shorter fasting periods in hyperthyroid patients. In addition, the improvement in metabolic acidosis following the initiation of anti-thyroid therapy supports hyperthyroidism as the driving cause of metabolic acidosis for our patient. Unlike NDKA, DKA is a life-threatening endocrine emergency. Thyroid storm (TS) is fatal manifestation of hyperthyroidism with high mortality rate between 10% to 20%. Both DKA and TS have overlapping pathophysiology disrupting glucose and lipid metabolism and manifest with similar clinical features including anion gap metabolic acidosis, making diagnosis challenging. Furthermore, TS and DKA share predisposing factors, implying a common trigger may initiate both. Given the potential for a fatal outcome, it is imperative to consider TS as a concurrent diagnosis in patients with atypical presentation of DKA with refractory metabolic acidosis.
Conclusions: Thyroid hormone exerts significant influence on adipose tissue and glucose metabolism, thereby predisposing to ketoacidosis when dysregulated. Recognizing hyperthyroidism as an often-overlooked cause of metabolic acidosis is crucial to preventing severe, potentially fatal complications associated with endocrine emergencies.