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|Year : 2014 | Volume
| Issue : 3 | Page : 280-284
Dynamic pituitary hormones change after traumatic brain injury
Ping Zheng, Bin He, Wusong Tong
Department of Neurosurgery, Shanghai Pudong New Area People's Hospital, Shanghai, China
|Date of Submission||16-Jan-2014|
|Date of Decision||07-Apr-2014|
|Date of Acceptance||30-May-2014|
|Date of Web Publication||18-Jul-2014|
Department of Neurosurgery, Shanghai Pudong New area People's Hospital, Shanghai
Source of Support: This study was supported by a Grant for the Promotion of Science, the Ministry of Health, Pudong New area, Shanghai China (grant PW2011A-13), Conflict of Interest: None
Objective: To study the dynamic changes of pituitary hormones in traumatic brain injury (TBI) and to correlate the severity and neurological outcome. Patients and Methods: Dynamic changes in the pituitary hormones were evaluated in 164 patients with TBI on day-1, day-7, day-14, day-21, and day-28 post injury. Admission TBI severity and long-term outcome were assessed with Glasgow Coma Scale (GCS) score and Glasgow Outcome Scale (GOS) score. The pituitary hormonal changes were correlated with TBI severity and outcome. Results: Of the 164 patients included in the study, pituitary dysfunction was found in 84 patients and in the remaining 80 patients pituitary function was normal. Most of the pituitary hormone deficiencies observed resolved over time; however, a significant proportion of patients had pituitary dysfunction at one month post injury. The hormones associated with poor outcome included growth hormone, thyrotropic hormone, and gonadotropic hormone. Conclusion: Dynamic changes of pituitary hormones in patients with TBI may reflect the severity of injury and also determine the outcome. Deficiency of growth hormone, gonadotropic hormone, and thyrotropic hormone can adversely affect neurological outcome.
Keywords: Hypopituitarism, pituitary, pituitary dysfunction, traumatic brain injury
|How to cite this article:|
Zheng P, He B, Tong W. Dynamic pituitary hormones change after traumatic brain injury. Neurol India 2014;62:280-4
| » Introduction|| |
Traumatic brain injury (TBI) is associated with lasting functional disability.  Some of the functional disability was attributed to post TBI hypopituitarism (HPT), , The reported incidence of post TBI hypopituitarism varied between 21% and 54%.  However, few studies have addressed the dynamic changes of pituitary hormones in the acute and subacute stages with initial severity and neurological outcomes. In this study, we dynamically evaluated the pituitary hormones within one month post TBI and also examined its correlation with the initial severity of injury and neurological outcome.
| » Patients and Methods|| |
The study prospectively enrolled 164 patients with TBI patients (94 males and 70 females; age range, 23-73 years; mean age 48 years) between July 2011 and April 2013. The study protocol was approved by the institutional review board. Written patient consent was obtained from patient or family relatives before inclusion in the study.
All patients had hormone testing at post injury day-1, day-7, day-14, day-21, and day-28. Clinical data collected included age, gender, initial Glasgow Coma Scale (GCS) score, and Glasgow Outcome Scale (GOS) score at 6 months. GCS score of 13-15 was considered mild TBI, 9-12 as moderate TBI, and ≤ 8 as severe TBI. TBI patients with hormone replacement before and after brain insults and those with diabetes mellitus and other endocrine diseases were excluded from the study. None of the patients had history of any known pituitary disorders, and none were taking medications that would affect hypothalamopituitary function.
Blood samples were primarily collected at 7 am in all the enrolled subjects. Upon collection, each sample was centrifuged, aliquoted in polypropylene cryovials, and stored at −80° Celsius until the time of hormonal assay. Hypopituitarism (HPT) was defined with single or multiple pituitary axis deficiency in accordance with our previous report.  All hormone levels were measured using radioimmunoassay.
The neurological outcome was evaluated using GOS at 6 months post injury. GOS: 5 = good recovery, 4 = moderate disability, 3 = severe disability, 2 = persistent vegetative status, and 1 = death.
For statistical analysis, we used SPSS 20.0 (Chicago, IL). We compared demographic data such as age and GOS scores using the one-way ANOVA among the groups, and Chi-square test for categorical data. All hormone profiles were compared between groups (according to the severity of TBI) with repetitive ANOVA. In addition, we tried to define the correlation between pituitary dysfunction and initial injury severity and neurological outcome. Value P < 0.05 was considered statistically significant.
| » Results|| |
Demographic data are summarized in [Table 1]. There were no significant differences in regard to age and gender distribution among these groups. The incidence of HPT in patients with GCS 3-8, 9-12, and 13-15 scores was 63.5%, 58.3%, and 30.2%, respectively (P < 0.01).
Hormone profiles in subgroup patients with different brain severity
The incidence of post TBI hypopituitarism in the total cohort was 51.2% at day-28. The different hormone profiles are listed in [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5],[Figure 6],[Figure 7] and [Figure 8]. For luteinizing hormone (LH) [Figure 1], there was no significant difference on day-28 post injury. However, the LH level was much higher in patients with GCS score 3-8 as compared to other two groups at day-14 post injury.
Follicle stimulating hormone (FSH) increased dramatically in patients with severe TBI as compared to other two groups on day-1 post injury [Figure 2]. There was progressive decline in FSH over a period of time in patients with severe TBI. However, in patients with mild and moderate TBI, FSH level recovered to different degrees [Figure 2]. The cortisol level showed a similar trend [Figure 3]. Testosterone [Figure 4] and growth hormone (GH) levels [Figure 5] declined in patients with moderate and severe TBI. Furthermore, these two hormones recovered to normal level in only patients with mild TBI at one month post injury. Prolactin (PRL) levels [Figure 6] increased in the acute stage in patients with severe TBI, and there was a significant difference on day-28 post injury among the three groups. However, there was no significant difference in PRL levels between the GCS 3-8 and GCS 9-12 group. Tri-iodothyronine (FT3) and free thyroxine (FT4) were much less in patients with moderate and severe TBI groups compared to patients with mild TBI. There was also significant difference among the three groups on the day-28 [Figure 7] and [Figure 8].
We found a correlation between FSH, T, GH, FT3 and FT4 levels and the neurological outcome (P < 0.05). The GH level was also associated with the initial GCS score (P < 0.05). However, we did not find any correlation between the other hormones studied and age, gender and the GOS score [Table 2].
| » Discussion|| |
The results of this study replicate and further extend previous work by demonstrating the dynamic change of pituitary hormones in TBI patients in both acute and subacute stages. Importantly, our data delineate TBI subpopulations with unique hormone profiles as risk factors for poor neurological outcome. Specifically, patients with decreased FSH, testosterone, GH, FT3, and FT4 are at high risk for poor neurological outcome, and this finding represents a potential biomarker for early interventions.
In our study, the cortisol level remained relatively constant over time in patients with mild and moderate TBI. However, in patients with severe TBI, the cortisol level increased initially and declined gradually but continued to remain abnormal at one month post injury. This may suggest that cortisol might be a contributing factor to pituitary dysfunction, particularly in severe TBI patients; this observation was similar to that in a previous study.  The observation, decline in FSH, LH, and testosterone levels in TBI patients is similar to a previous work.  Our analyses extend beyond the concept of generalized hypogonadism to shed light on their role in predicting outcome after TBI. To differentiate the effect of gender on sex hormones in TBI patients, we assessed the testosterone level in only male patients and FSH and LH levels only in female patients, because previous studies found significant differences regarding FSH, LH, and testosterone levels in male and female patients. 
The findings in regard to thyroid functions post TBI are uncertain. Helmy et al., reported the decreased T3 and normal T4 after brain injury, and the increased TSH was related to poor outcome.  In our study, both FT3 and FT4 were decreased in patients with TBI with a different degree of recovery within one month post injury. The progressive decline of serum GH levels provides a rationale for why TBI patients may benefit from acute GH replacement after TBI. However, GH replacement resulted in significant elevation in GH level, higher than circulating level,  making it necessary to reassess the relation between hormone levels and neurological outcomes.
In this study, we also found that the deficiency of GH, sex hormone, and thyrotropin were associated with poor neurological outcomes. Previous studies reported that GH replacement therapy could partially improve neurological outcome in TBI patients.  This unsatisfactory result might be related to deficiencies in other types of pituitary hormones. Therefore, we suggested that personalized hormone profiles be validated before the hormone replacement in order to obtain better neurological outcomes. 
In conclusion, although most of the pituitary hormone deficiencies recover over time following TBI, there are substantial percentages of pituitary hormone deficiencies at one month post injury. Therefore, screening the pituitary function after TBI is important, especially in patients with severe TBI. Moreover, strong associations between presence of deficiencies in growth hormone, gonadotropic, and thyrotropic functions were correlated with long-term neurological outcomes.
| » Acknowledgements|| |
This study was supported by a Grant for the Promotion of Science, the Ministry of Health, Pudong New area, Shanghai China (grant PW2011A-13).
| » References|| |
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2]
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