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. 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 and in Japan, 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.
J Endo Soc. 2022;6(10) © 2022 Endocrine Society