Traumatic Brain Injury (TBI) is a significant public health concern worldwide, with implications reaching beyond mere physical harm. One of the lesser-known yet highly impactful facets of TBI is its effect on neuroendocrine functions. As our understanding of the human brain continues to evolve, we are beginning to uncover the profound interplay between TBI and the neuroendocrine system. This article aims to delve into the complex relationship between TBI and neuroendocrine changes, illuminating this critical area of research.

The Neuroendocrine System: A Primer

The neuroendocrine system is a complex network that integrates the nervous and endocrine systems. It plays a pivotal role in maintaining homeostasis, regulating various physiological processes such as growth, metabolism, reproduction, and stress response. Central to this system is the hypothalamic-pituitary axis (HPA), which is involved in the secretion of key hormones that regulate these processes.

TBI and Neuroendocrine Changes

TBI often causes damage to areas of the brain involved in neuroendocrine functions, particularly the hypothalamus and pituitary gland. This damage can lead to a cascade of neuroendocrine changes, disrupting the delicate balance of hormones in the body and leading to a variety of health complications.

traumatic brain injury TBI

Pituitary Dysfunction

Pituitary dysfunction is one of the most common neuroendocrine changes following TBI. Studies show that up to 50% of TBI patients may experience some form of pituitary hormone deficiency, with growth hormone (GH) and gonadotropins (LH and FSH) being most commonly affected. Such deficiencies can lead to symptoms like fatigue, decreased muscle strength, sexual dysfunction, and reduced quality of life.

Luteinizing Hormone (LH)

Neuroprotection: Emerging research suggests that LH may have neuroprotective effects. It may play a role in protecting neurons from damage and promoting their survival.
Cognitive Function: There is increasing evidence to suggest that LH and its receptors in the brain may play a role in cognitive functions like memory and learning. However, more research is needed to fully understand this relationship.
Neuroprotection: Emerging research suggests that LH may have neuroprotective effects. It may play a role in protecting neurons from damage and promoting their survival.
Sexual Maturation: LH plays a crucial role in the onset of puberty and sexual maturation. It triggers the production of sex hormones, such as estrogen and testosterone, which are essential for the development of secondary sexual characteristics.
Reproductive Function: In females, LH stimulates ovulation, which is the release of a mature egg from the ovary. In males, it stimulates the production of testosterone, which is vital for sperm production.
Regulation of Menstrual Cycle: In women, LH is responsible for the regulation of the menstrual cycle. It peaks during the middle of the cycle to trigger ovulation and then stimulates the corpus luteum to produce progesterone.

Follicle-Stimulating Hormone (FSH)

Cognitive Function: FSH receptors have been identified in the brain, suggesting a possible role for FSH in cognitive functions. However, the exact nature of this relationship is still under investigation.
Neuroprotection: Preliminary research suggests that FSH, like LH, may have neuroprotective properties, potentially playing a role in the health and survival of neurons.
Bone Health: Some evidence suggests that FSH may play a role in bone health. High levels of FSH have been associated with increased risk of osteoporosis, particularly in postmenopausal women, although the mechanisms are not yet fully understood.
Reproductive Function: FSH plays a pivotal role in the reproductive system. In females, it initiates the growth and maturation of ovarian follicles. In males, it is critical for spermatogenesis, stimulating Sertoli cells in the testes to support sperm production.
Sexual Maturation: Like LH, FSH is also involved in the process of puberty and sexual maturation. It stimulates the development of secondary sexual characteristics by triggering the production of sex hormones.
Regulation of Menstrual Cycle: In women, FSH levels rise during the follicular phase of the menstrual cycle, stimulating the growth of ovarian follicles and the production of estradiol.

Growth Hormone

Brain Development: GH plays a vital role in the development of the brain during childhood and adolescence. It promotes the growth and maturation of neurons and glial cells.
Neuroprotection: GH has been shown to have neuroprotective effects. It can help protect neurons from damage, promote their survival, and stimulate their regeneration.
Sleep Regulation: GH plays a role in regulating sleep patterns. Most of the body's daily production of GH occurs during slow-wave sleep, and disturbances in GH secretion can affect sleep quality.
Cognitive Function: GH is involved in several aspects of cognitive function. It can influence learning, memory, and mental agility. Deficiency or excess of GH can lead to cognitive impairments.
Mood and Behavior: GH can influence mood and behavior. Changes in GH levels have been linked to mood disorders, anxiety, and depression. The mechanism behind this is still not entirely clear and is an area of ongoing research.
Energy Metabolism: GH influences energy metabolism in the brain. It helps to regulate the use of glucose and fatty acids by the brain, which are essential for the brain's energy needs.

Changes in Stress Hormones

Another significant aspect of TBI-induced neuroendocrine changes is alterations in the body's stress response. TBI can lead to persistent dysregulation of the HPA axis, resulting in abnormal cortisol levels, the primary stress hormone. This can manifest as either adrenal insufficiency or Cushing's syndrome, each with its unique set of symptoms and complications.

TBI can cause significant disruptions to the hypothalamic-pituitary-adrenal (HPA) axis, which is a central component of the body's neuroendocrine system. The HPA axis is responsible for the body's response to stress, orchestrating the release of cortisol and other stress hormones to help the body adapt to challenging circumstances. It is also involved in various other physiological functions, such as immune response, digestion, mood and emotions, sexuality, and energy storage and expenditure.

When a TBI occurs, the damage can affect the hypothalamus and pituitary gland, both of which are key components of the HPA axis. The hypothalamus produces corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH). 

ACTH then prompts the adrenal glands to produce cortisol. If the hypothalamus or pituitary gland is damaged due to TBI, this can disrupt the normal functioning of the HPA axis, leading to either a deficiency or overproduction of cortisol. This dysregulation can have serious implications for the individual's health and wellbeing.

HPA axis

For instance, insufficient cortisol production (adrenal insufficiency) can lead to fatigue, low blood pressure, weight loss, mood changes, and, in severe cases, can be life-threatening. On the other hand, excessive cortisol production can result in symptoms associated with Cushing's syndrome, such as weight gain, high blood pressure, glucose intolerance or diabetes, mood disorders, and osteoporosis.

Furthermore, disruption of the HPA axis can also interfere with the body's circadian rhythms, affecting sleep and various physiological processes that follow a daily cycle. The implications of HPA axis dysregulation following TBI are far-reaching, affecting not only the patient's physical health but also cognitive function and psychological wellbeing. Consequently, understanding and addressing the impact of TBI on the HPA axis is crucial for the comprehensive management and recovery of patients with TBI.

Impact on Metabolic Function

Traumatic brain injury can have profound effects on metabolic health, contributing to a variety of complications that can impact a patient's recovery and long-term health. Following a TBI, there is often an acute phase of hypermetabolism, where the body's metabolic rate is significantly increased. This is a response to the increased energy demands of the injured brain for repair and recovery. During this phase, there is typically an increase in the breakdown of proteins, fats, and carbohydrates to meet these heightened energy needs.

However, this hypermetabolic state can lead to muscle wasting and nutritional deficiencies if not adequately managed. Moreover, the damaged brain may have an impaired ability to utilize glucose, the primary energy source for brain cells, leading to a state of cerebral metabolic crisis where the energy demands of the brain exceed the supply. This can exacerbate brain injury and impede recovery.

Furthermore, TBI can disrupt the neuroendocrine system, leading to hormonal imbalances that can affect metabolism. For instance, damage to the hypothalamus or pituitary gland can result in deficiencies in growth hormone and thyroid-stimulating hormone, both of which play key roles in regulating metabolism. Such deficiencies can lead to symptoms like fatigue, weakness, and weight gain, and increase the risk of metabolic disorders such as diabetes and metabolic syndrome.

TBI can also influence the regulation of appetite and satiety by affecting the secretion of hormones like leptin and ghrelin. Disruptions in these hormones can contribute to weight gain and obesity, further exacerbating metabolic health issues.

Diagnosis and Management

Endocrine testing in patients with traumatic brain injury (TBI) is an essential part of the diagnostic and treatment process. The purpose of this testing is to identify any potential dysfunctions in the patient's endocrine system that may have resulted from the injury. This is crucial as TBI can cause damage to the pituitary gland, a small organ located at the base of the brain that serves as the primary regulator of the body's hormone balance.

Immediately following a TBI, it may be challenging to identify endocrine dysfunctions due to the acute changes that occur in hormone levels as a result of the body's stress response to the injury. Therefore, endocrine testing may not occur until several months after the injury, once the acute phase has resolved. However, it's important to note that in some cases, endocrine dysfunction may not become evident until many months or even years after the injury, making long-term follow-up essential.

Typically, endocrine testing involves the measurement of various hormone levels in the blood. This can include the hormones produced by the pituitary gland, such as growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), as well as the hormones these stimulate in other glands, such as cortisol, thyroid hormones, and sex hormones. We use much more extensive hormone panel. 

In some cases, more dynamic testing may be required, involving the administration of a hormone or a hormone-releasing agent followed by timed blood samples to assess the body's response.

Identifying and treating endocrine dysfunction can significantly improve the quality of life and recovery prospects for TBI patients, helping to manage symptoms such as fatigue, mood changes, cognitive impairment, and physical changes related to metabolism and body composition. Despite its importance, endocrine testing is often overlooked in the management of TBI, and there is a need for greater awareness among healthcare providers of the potential for endocrine dysfunction following such injuries.


TBI's impact on neuroendocrine functions is an essential yet often overlooked aspect of brain injury. Recognizing these changes can help healthcare professionals provide comprehensive care to TBI patients, improving their recovery and quality of life. As our understanding of the brain continues to evolve, so too will our ability to mitigate the effects of TBI on the neuroendocrine system.