In around 10% of patients presenting to the emergency department (ED) with hypoglycemia, the cause of hypoglycemia is indeterminate. A study from Japan has found that 6% of such patients had adrenal insufficiency. The study findings are published in the Journal of the Endocrine Society.¹

This single center study set out to investigate the etiology of unexplained hypoglycemia among 528 patients who presented to the ED between April 2016 and March 2021 with blood glucose level less than 70 mg/dL. Of these, 507 (96.0%) were symptomatic and presented to the ED with symptoms such as tremor, palpitations, sweating, hunger, paresthesia, dizziness, weakness, and confusion. Men constituted 52% of the entire cohort and the median age of the study group was 62 years. The mean plasma glucose levels were 48.5 mg/dL in the ED.

Analysis of data to explore the etiologies showed that the majority of patients (73.7%) were on antidiabetes medicines. History of alcohol consumption was found in 6.3%; another 3.2% had malnutrition, 2.5% had liver dysfunction, 2.3% had severe infectious disease, 2.1% had been diagnosed with a malignancy, 1.7% were in heart failure. Other conditions detected were insulin autoimmune syndrome (0.8%), insulinoma (0.6%) and non-islet cell tumor (0.2%). Less than 0.5% were using hypoglycemia-relevant drugs.

All study participants, except those in whom the hypoglycemia was due to antidiabetes drugs, underwent rapid adrenocorticotropic hormone (ACTH) test to detect the rate of adrenal insufficiency, which was also the primary study outcome. Thirty-two (6.1%) patients were found to have adrenal insufficiency defined as peak serum cortisol levels of <18 μg/dL. Out of these 32 patients, 3 had primary adrenal insufficiency (Addison’s disease), 27 had secondary (pituitary), while the remaining 2 had tertiary (hypothalamic) adrenal insufficiency.

Among the 3 patients with Addison’s disease, 1 patient had a fungal infection, 1 had a bilateral adrenal metastasis of lung cancer and 1 had 21-hydeoxylase deficiency. All patients with secondary adrenal insufficiency had isolated ACTH deficiency. And, the two patients with tertiary adrenal insufficiency had been using steroids for a long time.

At baseline, patients with adrenal insufficiency also had lower sodium levels (132 vs 139 mEq/L, lower systolic BP (120 vs 128 mmHg) and eosinophilia (14 vs 8%) compared to patients with other causes of hypoglycemia.

This study demonstrates adrenal insufficiency also as one among other causes of hypoglycemia. “The frequency of adrenal insufficiency as a cause of hypoglycemia was much higher than what we anticipated,”, write the authors. Although more patients had secondary and tertiary adrenal insufficiency than primary, nevertheless patients with primary adrenal insufficiency are at risk of hypoglycemia, especially nocturnal. Hence, in cases where no etiology of protracted hypoglycemia can be determined along with features of hyponatremia, hypotension and/or eosinophilia, rapid ACTH test should be done to rule out adrenal insufficiency, whether primary, secondary or tertiary, as a cause for the hypoglycemia. This could avoid the routine use of glucose infusion to maintain blood glucose levels, when it is not really required and also ensure timely detection of adrenal insufficiency, which can be potentially fatal if an adrenal crisis develops.

Reference

1. Kawahara T, et al. Frequency of adrenal insufficiency in patients with hypoglycemia in an emergency department: a cross-sectional study. J Endocr Soc. 2022 Aug 4;6(10):bvac119. doi: 10.1210/jendso/bvac119.