Frequency of Adrenal Insufficiency in Patients With Hypoglycemia in an Emergency Department

A Cross-Sectional Study

Tetsuya Kawahara; Maiko Tsuji; Naoki Tominaga; Nagahiro Toyama; Mikio Toda


J Endo Soc. 2022;6(10) 

In This Article

Abstract and Introduction


Context: In most patients presenting with hypoglycemia in emergency departments, the etiology of hypoglycemia is identified. However, it cannot be determined in approximately 10% of cases.

Objective: We aimed to identify the causes of unknown hypoglycemia, especially adrenal insufficiency.

Methods: In this cross-sectional study, we evaluated the etiology of hypoglycemia among patients in our emergency department with hypoglycemia (plasma glucose level < 70 mg/dL (3.9 mmol/L)] between April 1, 2016 and March 31, 2021 using a rapid adrenocorticotropic hormone (ACTH) test.

Results: There were 528 cases with hypoglycemia included [52.1% male; median age 62 years (range 19–92)]. The majority [389 (73.7%)] of patients were using antidiabetes drugs. Additionally, 33 (6.3%) consumed alcohol; 17 (3.2%) had malnutrition; 13 (2.5%), liver dysfunction; 12 (2.3%), severe infectious disease; 11 (2.1%), malignancy; 9 (1.7%), heart failure; 4 (0.8%), insulin autoimmune syndrome; 3 (0.6%), insulinoma; 2 (0.4%) were using hypoglycemia-relevant drugs; and 1 (0.2%) suffered from non-islet cell tumor. Rapid ACTH tests revealed adrenal insufficiency in 32 (6.1%). In those patients, serum sodium levels were lower (132 vs 139 mEq/L, P < 0.01), eosinophil counts were higher (14 vs 8%, P < 0.01), and systolic blood pressure was lower (120 vs 128 mmHg, P < 0.05) at baseline than in patients with the other etiologies.

Conclusion: The frequency of adrenal insufficiency as a cause of hypoglycemia was much higher than what we anticipated. When protracted hypoglycemia of unknown etiology is recognized, we recommend that the patient is checked for adrenal function using a rapid ACTH test.


If one considers all patients with altered mentation presenting in the emergency department, hypoglycemia has been identified as the underlying process in approximately 7% of cases.[1] While the most common causes of hypoglycemia are antidiabetes drugs, there are many other causes of hypoglycemia, and in approximately 10% of cases, the etiology of hypoglycemia cannot be determined,[2,3] and glucose infusion is routinely used to maintain patients' blood glucose levels.

Adrenal insufficiency (AI) is 1 cause of hypoglycemia. AI is the lack of cortisol (glucocorticoid) and/or aldosterone (mineralocorticoid) secretions from adrenal glands. AI is classified as primary (Addison disease), caused by diseases of the adrenal cortex; secondary, caused by impaired adrenocorticotropic hormone (ACTH) secretion due to pituitary abnormalities; and tertiary, caused by insufficient corticotropin-releasing hormone (CRH) secretion and function because of hypothalamic dysfunction.[4–6] The prevalence of primary AI is estimated at between 82 and 144 cases per million population in Western societies[7,8] compared to an estimated 138 to 142 cases per million population in Japan.[9,10] The currently estimated incidences of this disorder are 4.4 to 6.0 and 6.6 new cases per million population per year in Western societies[11] and in Japan,[9] respectively, and it presents most often between 30 and 50 years of age.[10,12,13] Secondary AI occurs more frequently than primary AI.[10,14] Its estimated prevalence is 150 to 280 per million,[15,16] and affected patients are often diagnosed in their 60s.[10,17] The most common cause of tertiary AI is chronic exogenous administration of synthetic glucocorticoids, which causes prolonged suppression of hypothalamic CRH secretion through negative feedback mechanisms.[18,19] Patients with chronic AI may develop acute AI (adrenal crisis) under stress such as infection, surgery, etc. Adrenal crisis is a fatal condition that causes circulatory disorders due to an absolute or relative deficiency of glucocorticoids. The estimated incidence is 6 to 8 and 6.3 per 100 chronic AI patients per year in Western societies and Japan, respectively.[10,16] Therefore, detecting AI is critical in emergency medical care.

The objective of this study was to identify the cause of hypoglycemia of unknown etiology, especially AI, in emergency departments.