Adrenal Insufficiency in Patients With Hypoglycemia in an ED

Abstract and Introduction

Abstract

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.

Introduction

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.

Table 1. Etiologies of hypoglycemia
Etiologies	Antidiabetes drugs	Alcohol abuse	Malformation	Liver dysfunction	Severe infection	Malignancy	Heart failure	Insulin-autoimmune	Insulinoma	hypoglycemia-related drugs	Unknown	Non-islet cell tumor	Adrenal insufficiency
Subjects^a	389 (73.7)	35 (6.6)	18 (3.4)	13 (2.5)	19 (3.6)	15 (2.8)	9 (1.7)	4 (0.8)	3 (0.6)	2 (0.4)	2 (0.4)	1 (0.2)	32 (6.1)
Cooccurrence of AI^b	—	2 (5.7)	1 (5.6)	0 (0)	7 (36.8)	4 (26.7)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)	14 (43.8)
Without AI	389 (73.7)	33 (6.3)	17 (3.2)	13 (2.5)	12 (2.3)	11 (2.1)	9 (1.7)	4 (0.8)	3 (0.6)	2 (0.4)	2 (0.4)	1 (0.2)	—

Table 2. Differences between non-AI and AI regarding the response to rapid ACTH test
		AI (n = 32)
Serum cortisol levels, μg/dL (reference range 4.5–21.1)	Non-AI (n = 107)	Primary (n = 3)	Secondary (n = 27)	Tertiary (n = 2)	P-values
Baseline	8.5 ± 1.3	4.3 ± 2.0	4.5 ± 1.5	3.9 ± 1.3	0.035*
After 30 minutes	19.7 ± 4.1	8.1 ± 3.6	7.3 ± 2.3	5.6 ± 2.8	0.007**
After 60 minutes	23.9 ± 5.7	9.2 ± 4.0	9.8 ± 3.4	8.1 ± 3.5	0.004**

Table 3. Clinical manifestation of hypoglycemia
	Antidiabetes drugs	Alcohol abuse	Malformation	Liver dysfunction	Severe infection	Malignancy	Heart failure	Insulin autoimmune	Insulinoma	hypoglycemia-related drugs	Unknown	Non-islet cell tumor	Adrenal insufficiency	P-values
Subjects, n (%)	389 (73.7)	33 (6.3)	17 (3.2)	13 (2.5)	12 (2.3)	11 (2.1)	9 (1.7)	4 (0.8)	3 (0.6)	2 (0.4)	2 (0.4)	1 (0.2)	32 (6.1)
Age, years	61	65	67	59	71	68	70	65	58	69	71	68	63	ns
Male, %	49	71	60	50	54	56	50	50	67	50	50	100	52	ns
BMI kg/m²	23.6	20.5	19.8	22.7	21.7	18.2	20.7	22.5	27.1	24.6	21.3	19.7	21.5	ns
Systolic BP, mmHg	137	129	128	134	129	128	125	134	132	130	128	129	120	0.039*
Plasma glucose, mg/dL	47	51	56	52	51	53	59	46	50	62	45	50	48	ns
Hemoglobin, mg/dL	14.6	13.7	11.9	13.4	13.7	11.6	12.9	14.7	15.9	13.8	13.5	11.6	12.4	ns
White blood cells, μL	5200	4600	3900	4100	12800	4800	6200	3500	4800	6700	5100	8500	3900	ns
Lymphocyte, %	36	40	32	31	40	27	35	31	42	39	46	28	39	ns
Eosinocyte, %	4	8	5	10	8	5	6	11	8	6	7	9	14	0.002**
Total cholesterol, mg/dL	239	211	166	223	206	178	219	221	243	207	175	178	184	ns
Serum Na, mEq/L	143	137	135	140	147	139	141	140	139	141	138	136	132	0.007**
Serum K, mEq/L	4	3.0	3.4	4.1	3.8	3.5	3.9	4.1	3.6	3.7	5.6	3.8	3.9	ns
CRP, mg/dL	0.58	0.84	0.72	1.12	18.6	3.25	1.70	1.12	0.75	1.03	2.37	8.13	2.06	ns

Table 3. Clinical manifestation of hypoglycemia

Antidiabetes drugs

Alcohol abuse

Malformation

Liver dysfunction

Severe infection

Malignancy

Heart failure

Insulin autoimmune

Insulinoma

hypoglycemia-related drugs

Unknown

Non-islet cell tumor

Adrenal insufficiency

P-values

Subjects, n (%)

389 (73.7)

33 (6.3)

17 (3.2)

13 (2.5)

12 (2.3)

11 (2.1)

9 (1.7)

4 (0.8)

3 (0.6)

2 (0.4)

1 (0.2)

32 (6.1)

Age, years

Male, %

100

BMI kg/m²

23.6

20.5

19.8

22.7

21.7

18.2

20.7

22.5

27.1

24.6

21.3

19.7

21.5

Systolic BP, mmHg

137

129

128

134

129

128

125

134

132

130

128

129

120

0.039*

Plasma glucose, mg/dL

Hemoglobin, mg/dL

14.6

13.7

11.9

13.4

13.7

11.6

12.9

14.7

15.9

13.8

13.5

11.6

12.4

White blood cells, μL

5200

4600

3900

4100

12800

4800

6200

3500

4800

6700

5100

8500

3900

Lymphocyte, %

Eosinocyte, %

0.002**

Total cholesterol, mg/dL

239

211

166

223

206

178

219

221

243

207

175

178

184

Serum Na, mEq/L

143

137

135

140

147

139

141

140

139

141

138

136

132

0.007**

Serum K, mEq/L

3.0

3.4

4.1

3.8

3.5

3.9

4.1

3.6

3.7

5.6

3.8

3.9

CRP, mg/dL

0.58

0.84

0.72

1.12

18.6

3.25

1.70

1.12

0.75

1.03

2.37

8.13

2.06

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

A Cross-Sectional Study

Abstract and Introduction

Abstract

Introduction

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

A Cross-Sectional Study

Abstract and Introduction

Abstract

Introduction

Tables

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

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