Risk factors and predictive model of adrenocortical insufficiency in patients with traumatic brain injury

doi:10.5847/wjem.j.1920-8642.2021.03.003

Abstract

Abstract:

BACKGROUND: Neuroendocrine dysfunction after traumatic brain injury (TBI) has received increased attention due to its impact on the recovery of neural function. The purpose of this study is to investigate the incidence and risk factors of adrenocortical insufficiency (AI) after TBI to reveal independent predictors and build a prediction model of AI after TBI.

METHODS: Enrolled patients were grouped into the AI and non-AI groups. Fourteen preset impact factors were recorded. Patients were regrouped according to each impact factor as a categorical variable. Univariate and multiple logistic regression analyses were performed to screen the related independent risk factors of AI after TBI and develop the predictive model.

RESULTS: A total of 108 patients were recruited, of whom 34 (31.5%) patients had AI. Nine factors (age, Glasgow Coma Scale [GCS] score on admission, mean arterial pressure [MAP], urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, diffuse axonal injury [DAI], and skull base fracture) were probably related to AI after TBI. Three factors (urinary volume [X₄], serum sodium level [X₅], and DAI [X₈]) were independent variables, based on which a prediction model was developed (logit P= -3.552+2.583X₄+2.235X₅+2.269X₈).

CONCLUSIONS: The incidence of AI after TBI is high. Factors such as age, GCS score, MAP, urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, DAI, and skull base fracture are probably related to AI after TBI. Urinary volume, serum sodium level, and DAI are the independent predictors of AI after TBI.

Key words: Adrenocortical insufficiency, Risk factor, Predictor, Traumatic brain injury

Gui-long Feng, Miao-miao Zheng, Shi-hong Yao, Yin-qi Li, Shao-jun Zhang, Wei-jing Wen, Kai Fan, Jia-li Zhang, Xiao Zhang. Risk factors and predictive model of adrenocortical insufficiency in patients with traumatic brain injury[J]. World Journal of Emergency Medicine, 2021, 12(3): 179-184.

Figures/Tables 3

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References 23

1	Cheng PX, Yin P, Ning PS, Wang LJ, Cheng XJ, Liu YN, et al. Trends in traumatic brain injury mortality in China, 2006-2013: a population-based longitudinal study. PLoS Med. 2017; 14(7):e1002332.
2	Vella MA, Crandall ML, Patel MB. Acute management of traumatic brain injury. Surg Clin N Am. 2017; 97(5):1015-30. doi: 10.1016/j.suc.2017.06.003
3	Tanriverdi F, Kelestimur F. Neuroendocrine disturbances after brain damage: an important and often undiagnosed disorder. J Clin Med. 2015; 4(5):847-57. doi: 10.3390/jcm4050847 pmid: 26239451
4	Dusick JR, Wang C, Cohan P, Swerdloff R, Kelly DF. Pathophysiology of hypopituitarism in the setting of brain injury. Pituitary. 2012; 15(1):2-9. doi: 10.1007/s11102-008-0130-6
5	Olivecrona Z, Dahlqvist P, Koskinen LO. Acute neuro-endocrine profile and prediction of outcome after severe brain injury. Scand J Trauma Resusc Emerg Med. 2013; 21:33. doi: 10.1186/1757-7241-21-33
6	Tapp ZM, Godbout JP, Kokiko-Cochran ON. A tilted axis: maladaptive inflammation and HPA axis dysfunction contribute to consequences of TBI. Front Neurol. 2019; 10:345. doi: 10.3389/fneur.2019.00345 pmid: 31068886
7	Powner DJ, Boccalandro C. Adrenal insufficiency following traumatic brain injury in adults. Curr Opin Crit Care. 2008; 14(2):163-6. doi: 10.1097/MCC.0b013e3282f57528 pmid: 18388678
8	Cohan P, Wang C, McArthur DL, Cook SW, Dusick JR, Armin B, et al. Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med. 2005; 33(10):2358-66. doi: 10.1097/01.CCM.0000181735.51183.A7
9	Pazderska A, Pearce SH. Adrenal insufficiency - recognition and management. Clin Med (Lond). 2017; 17(3):258-62.
10	Ntali G, Tsagarakis S. Traumatic brain injury induced neuroendocrine changes: acute hormonal changes of anterior pituitary function. Pituitary. 2019; 22(3):283-95. doi: 10.1007/s11102-019-00944-0
11	Herman JP, McKlveen JM, Solomon MB, Carvalho-Netto E, Myers B. Neural regulation of the stress response: glucocorticoid feedback mechanisms. Braz J Med Biol Res. 2012; 45(4):292-8. doi: 10.1590/S0100-879X2012007500041
12	Liyanarachchi K, Ross R, Debono M. Human studies on hypothalamo-pituitary-adrenal (HPA) axis. Best Pract Res Clin Endocrinol Metab. 2017; 31(5):459-73. doi: 10.1016/j.beem.2017.10.011
13	Shwe S, Witchey L, Lahham S, Kunstadt E, Shniter I, Fox JC. Retrospective analysis of eFAST ultrasounds performed on trauma activations at an academic level-1 trauma center. World J Emerg Med. 2020; 11(1):12-7. doi: 10.5847/wjem.j.1920-8642.2020.01.002
14	Bernard F, Outtrim J, Lynch AG, Menon DK, Matta BF. Hemodynamic steroid responsiveness is predictive of neurological outcome after traumatic brain injury. Neurocrit Care. 2006; 5(3):176-9. doi: 10.1385/NCC:5:3
15	Kgosidialwa O, Agha A. Hypopituitarism post traumatic brain injury (TBI): review. Ir J Med Sci. 2019; 188(4):1201-6. doi: 10.1007/s11845-019-02007-6 pmid: 30931510
16	Gray S, Bilski T, Dieudonne B, Saeed S. Hypopituitarism after traumatic brain injury. Cureus. 2019; 11(3):e4163.
17	Tsagarakis S, Tzanela M, Dimopoulou I. Diabetes insipidus, secondary hypoadrenalism and hypothyroidism after traumatic brain injury: clinical implications. Pituitary. 2005; 8(3-4):251-4. pmid: 16508710
18	Capatina C, Paluzzi A, Mitchell R, Karavitaki N. Diabetes insipidus after traumatic brain injury. J Clin Med. 2015; 4(7):1448-62. doi: 10.3390/jcm4071448
19	Rajagopal R, Swaminathan G, Nair S, Joseph M. Hyponatremia in traumatic brain injury: A practical management protocol. World Neurosurg. 2017; 108:529-33. doi: S1878-8750(17)31517-6 pmid: 28899834
20	Hannon MJ, Thompson CJ. Neurosurgical hyponatremia. J Clin Med. 2014; 3(4):1084-104. doi: 10.3390/jcm3041084 pmid: 26237593
21	Kolmodin L, Sekhon MS, Henderson WR, Turgeon AF, Griesdale DE. Hypernatremia in patients with severe traumatic brain injury: a systematic review. Ann Intensive Care. 2013; 3(1):35. doi: 10.1186/2110-5820-3-35 pmid: 24196399
22	Jenkins R, Morris NA, Haac B, Besien RV, Stein DM, Badjatia N, et al. Outcome predictors for severely brain-injured patients directly admitted or transferred from emergency departments to a trauma center. World J Emerg Med. 2020; 11(2):120-1. doi: 10.5847/wjem.j.1920-8642.2020.02.010 pmid: 32076479
23	Jeong JH, Kim YZ, Cho YW, Kim JS. Negative effect of hypopituitarism following brain trauma in patients with diffuse axonal injury. J Neurosurg. 2010; 113(3):532-8. doi: 10.3171/2009.10.JNS091152

Variables	AI group (n=34)	Non-AI group (n=74)	t/χ² or Z value	P-value
Gender			0.390 (t/χ²)	0.532
Male (n=75)	25 (33.3)	50 (66.7)
Female (n=33)	9 (27.3)	24 (72.7)
Age			4.301 (t/χ²)	0.038
≥60 years (n=33)	15 (45.5)	18 (54.5)
<60 years (n=75)	19 (25.3)	56 (74.7)
Body temperature			2.363 (t/χ²)	0.124
Normal (n=83)	23 (27.7)	60 (72.3)
Abnormal (n=25)	11(44.0)	14 (56.0)
MAP			11.540 (t/χ²)	0.001
Normal (n=80)	18 (22.5)	62 (77.5)
Abnormal (n=28)	16 (57.1)	12 (42.9)
Pulse			0.764 (t/χ²)	0.382
Normal (n=76)	22 (28.9)	54 (71.1)
Abnormal (n=32)	12 (37.5)	20 (62.5)
Respiratory			1.801 (t/χ²)	0.180
Normal (n=79)	22 (27.8)	57 (72.2)
Abnormal (n=29)	12 (41.4)	17 (58.6)
Urinary volume			19.649 (t/χ²)	0.000
Normal (n=85)	18 (21.2)	67 (78.8)
Abnormal (n=23)	16 (69.6)	7 (30.4)
Serum sodium level			19.423 (t/χ²)	0.000
Normal (n=62)	9 (14.5)	53 (85.5)
Abnormal (n=46)	25 (54.3)	21 (45.7)
Cerebral hernia			7.940 (t/χ²)	0.005
No (n=82)	20 (24.4)	62 (75.6)
Yes (n=26)	14 (53.8)	12 (46.2)
Frontal lobe contusion			4.541 (t/χ²)	0.033
No (n=48)	10 (20.8)	38 (79.2)
Yes (n=60)	24 (40.0)	36 (60.0)
Cisterna ambiens hemorrhage			0.518 (t/χ²)	0.472
No (n=37)	10 (27.0)	27 (73.0)
Yes (n=71)	24 (33.8)	47 (66.2)
DAI			11.540 (t/χ²)	0.001
No (n=80)	18 (22.5)	62 (77.5)
Yes (n=28)	16 (57.1)	12 (42.9)
Skull base fracture			7.889 (t/χ²)	0.005
No (n=74)	17 (23.0)	57 (77.0)
Yes (n=34)	17 (50.0)	17 (50.0)
GCS score			-3.838 (Z)	0.000
13-15 (n=57)	9 (15.8)	48 (84.2)
9-12 (n=26)	11 (42.3)	15 (57.7)
3-8 (n=25)	14 (56.0)	11 (44.0)

Variables	Assignment description
Age (X₁)	(≥60 years)=0, (<60 years)=1
GCS (X₂)	(13-15)=0, (9-12)=1, (3-8)=2
Mean arterial pressure (X₃)	(80-110 mmHg)=0, (<80 mmHg or >110 mmHg)=1
Urinary volume (X₄)	(400-2,500 mL/d)=0, (<400 mL/d or >2,500 mL/d)=1
Serum sodium level (X₅)	(135-145 mmol/L)=0, (<135 mmol/L or >145 mmol/L)=1
Cerebral hernia (X₆)	No=0, Yes=1
Frontal lobe contusion (X₇)	No=0, Yes=1
DAI (X₈)	No=0, Yes=1
Skull base fracture (X₉)	No=0, Yes=1
AI (dependent variable)	No=0, Yes=1

Variables	β	S.E.	Wald	df	P	Exp (B)
Age	-1.172	0.640	3.356	1	0.067	0.310
Glasgow Coma Scale score	0.618	0.469	1.736	1	0.188	1.855
Mean arterial pressure	1.214	0.830	2.137	1	0.144	3.367
Urinary volume	2.583	0.807	10.241	1	0.001	13.243
Serum sodium level	2.235	0.730	9.376	1	0.002	9.349
Cerebral hernia	-0.893	0.836	1.141	1	0.285	0.409
Frontal lobe contusion	-0.411	0.699	0.345	1	0.557	0.663
Diffuse axonal injury	2.269	1.076	4.442	1	0.035	9.665
Skull base fracture	1.210	0.651	3.451	1	0.063	3.353
Constant	-3.552	0.950	13.970	1	0.000	0.029

[1]	Ahammed Mekkodathil, Ayman El-Menyar, Talat Chughtai, Ahmed Abdel-Aziz Bahey, Ahmed Labib Shehatta, Ali Ayyad, Abdulnasser Alyafai, Hassan Al-Thani. Initial serum electrolyte imbalances and mortality in patients with traumatic brain injury: a retrospective study [J]. World Journal of Emergency Medicine, 2025, 16(4): 331-339.
[2]	Lingjie Cao, Yuanyuan Pei, Xiaolu Ma, Liping Guo, Fengtao Yang, Fange Shi, Pengfei Wang, Dilu Li, Kunyu Yang, Jihong Zhu. A risk prediction model for acute kidney injury following acute heart failure in an emergency department cohort in China [J]. World Journal of Emergency Medicine, 2025, 16(4): 348-356.
[3]	Qing Tang, Hongxin Wang, Hao Wang, Jiaqi Xu, Xin Luo, Shuxin Hua, Lijun Wang, Yanfen Chai. Risk factors for death in patients with acute diquat poisoning [J]. World Journal of Emergency Medicine, 2025, 16(3): 225-230.
[4]	Qingliu Zheng, Changyun Liu, Lingying Le, Qiqi Wu, Zhihong Xu, Jiyan Lin, Qiuyun Chen. ICU-acquired weakness in critically ill patients at risk of malnutrition: risk factors, biomarkers, and early enteral nutrition impact [J]. World Journal of Emergency Medicine, 2025, 16(1): 51-56.
[5]	Fengxia Du, Jun Zha, Yan Li, Lichao Fang, Shuyu Xia, Youjia Yu. Risk factors for postpartum posttraumatic stress disorder after emergency admission [J]. World Journal of Emergency Medicine, 2024, 15(2): 121-125.
[6]	Xinlei Wang, Yao Sun, Xiaoyu Ni, Shu Zhang. Development and validation of an emergency bloodstream infection score for predicting in-hospital mortality in patients with community-acquired bloodstream infections [J]. World Journal of Emergency Medicine, 2023, 14(4): 280-286.
[7]	Xiao-guang Zhu, Jia-mei Jiang, Yong-xia Li, Jing Gao, Wei Wu, Qi-ming Feng. Development and validation of a nomogram for predicting survival in patients with acute pancreatitis [J]. World Journal of Emergency Medicine, 2023, 14(1): 44-48.
[8]	Hong-yan Wei, Wen-jie Liang, Bin Li, Ling-yu Wei, An-qi Jiang, Wei-dong Chen, Peng-hao Guo, Jia Xu. Clinical characteristics and risk factors of Talaromyces marneffei infection in human immunodeficiency virus-negative patients: A retrospective observational study [J]. World Journal of Emergency Medicine, 2021, 12(4): 281-286.
[9]	Wei Guo, Lin-yu Ran, Ji-hong Zhu, Qing-gang Ge, Zhe Du, Fei-long Wang, Wei-bo Gao, Tian-bing Wang. Identifying critically ill patients at risk of death from coronavirus disease [J]. World Journal of Emergency Medicine, 2021, 12(1): 18-23.
[10]	Tian Xu, Ya Li, Li-ding Zhao, Guo-sheng Fu, Wen-bin Zhang. Predictors of recurrent angina in patients with no need for secondary revascularization [J]. World Journal of Emergency Medicine, 2021, 12(1): 42-47.
[11]	Kou Kou, Xiang-yu Hou, Jian-dong Sun, Kevin Chu. Current pre-hospital traumatic brain injury management in China [J]. World Journal of Emergency Medicine, 2014, 5(4): 245-254.
[12]	Liza Victoria S Escobedo, Joseph Habboushe, Haytham Kaafarani, George Velmahos, Kaushal Shah, Jarone Lee. Traumatic brain injury: A case-based review [J]. World Journal of Emergency Medicine, 2013, 4(4): 252-259.
[13]	Xue-zhong Xing, Yong Gao, Hai-jun Wang, Quan-hui Yang, Chu-lin Huang, Shi-ning Qu, Hao Zhang, Hao Wang, Qing-ling Xiao, Ke-lin Sun. Risk factors and prognosis of critically ill cancer patients with postoperative acute respiratory insufficiency [J]. World Journal of Emergency Medicine, 2013, 4(1): 43-47.
[14]	Gan-nan Wang, Jin-song Zhang, Wei-juan Cao, Hao Sun, Jing Zhang, Yao Wang, Hang Xiao. Association of ALOX5, LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China [J]. World Journal of Emergency Medicine, 2013, 4(1): 32-37.
[15]	Xue-zhong Xing, Hai-jun Wang, Chu-lin Huang, Quan-hui Yang, Shi-ning Qu, Hao Zhang, Hao Wang, Yong Gao, Qing-ling Xiao, Ke-lin Sun. Two acute kidney injury risk scores for critically ill cancer patients undergoing non-cardiac surgery [J]. World Journal of Emergency Medicine, 2012, 3(4): 278-281.