Traumatic brain injury (TBI) is a major public health problem and the leading cause of disability among young adults [1]. Approximately 134 to 600 people per 100,000 are injured each year, which has a negative impact on the country's economy. Road traffic accidents (RTAs) are the leading cause of TBI globally. TBI is most prevalent in lower middle income countries (LMICs), in which 90% of all RTA associated TBI occurs. Survivors of severe TBI usually experience a slew of physical, endocrine, and neuropsychiatric consequences that necessitate their reliance on others.[2]

When a human is exposed to any immense variety of noxious or potentially noxious stimuli, there is an increased secretion of adrenocorticotropic hormone (ACTH) and a consequent rise in the circulating cortisol. Thus, this cortisol is known as stress hormone. This rise is essential for survival [3]. Cortisol levels respond within minutes to stress, whether physical (trauma, surgery and exercise), psychological (anxiety and depression) or physiologic (hypoglycemia and fever). The reasons why glucocorticoid levels protect the organism under stress are not understood, but in conditions of cortisol deficiency, such stresses may cause hypotension, shock and death [4].

Cortisol is synthesized in the adrenal cortex. The daily secretion of cortisol ranges between 40 and 80μmol with a pronounced circadian cycle. The plasma cortisol tends to rise and fall. The bursts are more frequent in the morning and less frequent in the evening (circadian rhythm). ACTH is a polypeptide hormone secreted by anterior pituitary and stimulates the adrenal cortex for the synthesis of corticosteroids. ACTH is also related to the circadian rhythm in many animals including human beings [5-6].

In a study done by Hannon MJ et.al the frequency of low serum cortisol level in traumatic brain injury patients was reported 78%. [7]

Total 150 patients fulfilling the inclusion criteria were enrolled in the study. Patients with TBI were included from the emergency department or out-patient department, Bolan Medical College/Neurosurgery department. Informed consent from all patients was taken. For further examination and assessment, the patients were enrolled in Neuro-ICU. The morning serum cortisol levels were measured on day 5 after admission. Information including name, age, gender, GCS, serum cortisol level, history of steroid use, and hypothalamic-pituitary dysfunction was recorded on a predesigned proforma. Frequency of low cortisol level was recorded as per operational definition. All the data was entered and analyzed using SPSS 21. Quantitative data like age, GCS, BMI and serum cortisol level at day 5 after admission were presented by the mean and standard deviation. Qualitative data like gender and low cortisol level were presented by frequencies and percentages. Effect modifiers were controlled through stratification of age, BMI, GCS and gender. Chi-Square test was performed and p-value ≤ 0.05 was taken as significant.

Total of 150 patients fulfilling inclusion and exclusion criteria were selected to determine the frequency of low cortisol level in traumatic brain injury patients.

Age distribution of the patients was done, it showed that out of 150 patients, 89.3 %( n=134) were in age group of 18-40 years and 10.7 %( n=16) were in age group of 41-70 years. Mean age was calculated as 32.38±6.97 years. (Table No. 1)

Distribution of GCS was 5.71±1.04. Distribution of BMI was 26.99±3.89 kg/m2.  Distribution of serum cortisol level at day 5 after admission was 286.53±60.43 nm/L. (Table No.2)

Gender distribution of the patients was done, it showed that 70.0 %( n=105) were male and 30.0% ( n=45) were females.  Frequency of low cortisol level was 58.0%. (Table No. 3)

The data was stratified for age, BMI group, GCS group and gender shown in Table No. 4 respectively.

Table no. 1 Distribution of age

Mean ± SD = 32.38±6.97 years

Table no. 2: Distribution of GCS, BMI and serum cortisol level at day 5 after admission

Figure No. 3 Distribution of gender, low cortisol level

Table no. 4 Stratification for low cortisol level with respect to age group, BMI and gender using chi-square test

Traumatic brain injury is non-degenerative brain damage induced by an external mechanical force, which results in temporary or permanent neurological dysfunction or, Impairment of cognition. [8] TBI is the biggest cause of death and disability among young people, according to a new meta-analysis. Approximately 134 to 600 people per 100,000 are injured each year, which has a negative impact on the country's economy. [9] Survivors of severe TBI usually experience a slew of physical, endocrine, and neuropsychiatric consequences that necessitate their reliance on others. Among the numerous problems associated with TBI, neuroendocrine hypopituitarism has been found to account for 27–47 percent of patients. There is a lack of agreement on conventional diagnostic testing characteristics. [8] TBI is a major source of illness and mortality in both developed and undeveloped nations. [9] According to a recent meta-analysis, traumatic brain injury affects 134 to 600 people per 100,000 people per year, with adult men having the highest prevalence, making it one of the leading causes of mortality and disability, particularly among young guys. [10] TBI-induced hypopituitarism is one of the most underdiagnosed forms of neuroendocrine dysfunction. The frequency of PTHP (post- traumatic hypopituitarism) among long-term TBI survivors ranges from 1 – 83 percent, with a considerable influence on morbidity and death. TBI is a relatively unknown cause of hypopituitarism. Severe TBI has a usually bad prognosis, and the existence of undiagnosed neuroendocrine problems may deteriorate the prognosis even further. [11-12] The idiopathic etiology of this syndrome, the non-specificity of symptoms, and the absence of a consensus for screening for post-traumatic hypopituitarism have all contributed to the under diagnosis of this devastating disorder. [13] In addition to these, post-traumatic hypopituitarism contributes to the patient's neuropsychiatric symptoms, which have a detrimental influence on the prognosis of traumatic brain damage. The American College of Society of Critical Care Medicine coined the term critical illness-related corticosteroid insufficiency (CIRCI) to describe impairment of the hypothalamic pituitary adrenal (HPA) axis at any level, including the hypothalamus, pituitary/adrenal glands, as well as corticosteroid resistance at the peripheral level of target tissues. CIRCI was proposed to replace "primary/ central and secondary corticosteroid insufficiency" since it described thalamic, pituitary, or adrenal gland dysfunction.[14,15] Because of the consequences of glucocorticoid insufficiency, the hypothalamic-pituitary-adrenal axis is of particular relevance in the acute setting of traumatic brain injury. Glucocorticoid shortage can result in life-threatening hyponatremia and hypotension that need pressor assistance.[16] CIRCI is distinguished by an excessive and prolonged inflammatory response as well as corticosteroid resistance, resulting in an insufficient corticosteroid response to acute stress. [17-18] In the case of trauma, at least a plasma cortisol level evaluation should be performed to establish a baseline. Low plasma cortisol levels are linked to an increased risk of death and long term pituitary impairments. In patients with traumatic brain injury who have low baseline blood cortisol levels, hydrocortisone supplementation should be given. [19] In current study we determine the frequency of low cortisol level in traumatic brain injury patients. We found that out of 150 patients, mean age was 32.38±6.97 years, GCS 5.71±1.04, BMI was 26.99±3.89 kg/m2 and serum cortisol level at day 5 after admission was 286.53±60.43 nm/L. There were 70.0% male and 30.0 % were females. Frequency of low cortisol level was 58.0%. TBI suffers from a lack of standardized testing protocols. In the majority of instances, diagnosing adrenal insufficiency (AI) in an intensive care unit (ICU) remains exceedingly challenging. [20-22] AI accounts for around 30 to 50 percent of patients in rehabilitation facilities following a head injury. There is a paucity of research on adrenal function in the first ten days after a stressful event when therapeutic care must be commenced. [23] The vast majority of them have a GH (growth hormone) deficiency, whereas some have another anterior pituitary hormonal deficiency. [24] There is also a strong overlap between chronic TBI sequelae and clinical hypopituitarism features. Changes in the blood-brain barrier, free radical-induced damage, and enhanced apoptosis are some of the pathophysiological pathways that contribute to long-term repercussions following TBI.[25] Hypopituitarism has mild clinical manifestations. Growth hormone (GH), adrenocorticotrophic (ACTH), gonadotropin, and thyroidal insufficiency, as well as diabetes insipidus (DI), have all been observed in the chronic phase following TBI. [26-28] Cortisol levels and vasopressor usage had an inverse connection, as did cortisol levels within 24 hours after damage and etomidate use. High-dose propofol and pentobarbital use was closely linked to reduced cortisol levels. [29] Another research, done by Hari et al, identified hormonal abnormalities in 39 of the 56 patients 70% during the initial examination. Pituitary inadequacies continue after 6 and 12 months in 7 and 8 persons, respectively. The most prevalent diagnosis are hypogonadotropic hypogonadism, hypothyroidism, and growth hormone deficiency. The initial severe TBI and involvement of many hormones suggested long-term hypopituitarism. [30] Chen et al. discovered that 52.2 percent of severe TBI patients had CIRCI, and TBI associated CIRCI was strongly associated with not only increased mortality but also more frequent complications such as pneumonia and gastrointestinal bleeding, both of which have been linked to poor outcomes in TBI patients. [31] Bensalah et al, observed a 44.4 percent prevalence of PTHP at 3 months, which dropped to 34.3 percent at 12 months. [32-33] The higher incidence of PTHP in the Bensala et al, study compared to the Klose et al. study (11%) might be explained in part by smaller patient numbers (n = 46) and milder TBI in Klose's trial, in which 22 (50%) of patients had modest CT abnormalities. [34-36] A research found a 12-month prevalence of PTPH similar to what Schneider et al, Popovic et al and Agha et al, reported.[37]

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