How Does a Concussion Disrupt the Hypothalamic-Pituitary-Adrenal Axis?
The hormonal consequences of head injury and why fatigue, mood, and stress intolerance after concussion may have an endocrine cause
Why Hormones Matter in Concussion Recovery
Fatigue that does not respond to rest. A stress response that seems far out of proportion to the demands placed on it. Temperature dysregulation, weight changes, mood instability, reduced libido, and a pervasive sense that something is ‘off’ in a way that is hard to articulate. These are symptoms many post-concussion patients experience. They are also the hallmarks of endocrine dysfunction and the connection is not coincidental.
The hypothalamic-pituitary-adrenal (HPA) axis is one of the body’s primary regulatory systems, coordinating the stress response, metabolism, immune function, and the hormonal signals that govern almost every aspect of physiological function. Concussion can disrupt this axis directly, through mechanical damage to the pituitary gland and hypothalamus, and indirectly, through the inflammatory and vascular consequences of brain injury. The result is post-traumatic hypopituitarism, or a broader HPA dysregulation which is far more common than most clinicians or patients are aware.
What Is the HPA Axis?
The hypothalamic-pituitary-adrenal axis is a cascade of signalling between three key structures: the hypothalamus (in the brain), the pituitary gland (just below it, connected by a delicate stalk), and the adrenal glands (above the kidneys). Under normal conditions, this axis regulates cortisol, the body’s primary stress hormone, along with thyroid-stimulating hormone, growth hormone, the sex hormones (via gonadotropins), and antidiuretic hormone.
These hormones do not just govern the stress response. They regulate energy metabolism, inflammation, sleep-wake cycles, immune function, reproductive function, and the brain’s own neuroplasticity and repair mechanisms. Disruption to any part of this axis has consequences that ripple through the entire physiology.
How Does Concussion Damage the HPA Axis?
Direct mechanical injury
The pituitary gland is particularly vulnerable in head trauma. Its blood supply comes from a fine network of portal vessels that are susceptible to shearing and compression forces during the acceleration-deceleration of a concussion. Vascular disruption to these vessels can cause ischemic damage to pituitary tissue and pituitary cells, once lost, do not regenerate readily.
The hypothalamus is similarly vulnerable. It sits in a central position in the skull and can be affected by the diffuse axonal injury, microhemorrhage, and inflammatory pressure changes that accompany even mild traumatic brain injury.
Indirect damage via inflammation
The neuroinflammatory cascade that follows a concussion generates inflammatory mediators - cytokines, oxidative stress, that impair the function of both the hypothalamus and the pituitary independently of direct mechanical damage. The HPA axis is disrupted not only when the physical structures are injured, but when the physiological environment in which they operate is sufficiently disturbed.
Autoimmune mechanisms
A subset of post-traumatic hypopituitarism cases appear to involve autoimmune mechanisms where the immune system is generating antibodies against pituitary antigens following the breakdown of blood-brain barrier integrity that accompanies TBI. This is a less well-understood pathway but one that is increasingly recognised in the literature as contributing to the persistence of hormonal dysfunction well beyond the acute phase of injury.
How Common Is Post-Traumatic Hypopituitarism?
More common than most people know. A systematic review and meta-analysis by Glynn and Agha, published in the journal Pituitary, found that the prevalence of post-traumatic hypopituitarism in TBI survivors is between 27 and 31% , affecting approximately one in three survivors of moderate to severe TBI over the long term (Glynn & Agha, 2019).
A 2025 review in Acta Neurologica Belgica reported that up to 40% of individuals with moderate to severe TBI may develop post-traumatic hypopituitarism, with consequences including adrenal insufficiency, hypothyroidism, hypogonadism, and growth hormone deficiency (Soltani et al., 2025).
Critically, the same review noted that “comprehensive, cross-disciplinary care and individualized treatment plans are crucial to improve outcomes.” Hormone assessment is not routinely included in standard concussion care protocols, which means this complication goes largely undetected and untreated in a significant proportion of those affected.
“Approximately one in three survivors of moderate to severe TBI develop measurable pituitary dysfunction. This is almost never assessed in standard concussion care.”
Which Hormones Are Most Commonly Affected?
Growth hormone
Growth hormone deficiency is the most frequently reported hormonal deficit following TBI. Despite its name, growth hormone in adults plays a critical role in metabolism, body composition, bone health, cognitive function, and emotional regulation. Deficiency presents as fatigue, reduced muscle mass, increased fat distribution, impaired memory and concentration, and emotional lability. Symptoms that overlap substantially with post-concussion syndrome and are frequently attributed to the head injury without testing the underlying endocrine status.
Cortisol (via the adrenal axis)
When the hypothalamus or pituitary fails to signal adequately to the adrenal glands, cortisol production is insufficient. Adrenal insufficiency following TBI, while less common than growth hormone deficiency, can produce extreme fatigue, low blood pressure, poor stress tolerance, salt craving, and immune dysregulation. This can be a life-limiting condition that is simply missed in the absence of appropriate hormonal testing.
Thyroid hormones
Hypothyroidism secondary to impaired TSH production from the pituitary can produce fatigue, cold intolerance, weight gain, brain fog, and depression, again, a symptom picture that overlaps considerably with post-concussion syndrome and that is frequently not differentiated from the neurological consequences of the injury itself.
Sex hormones
Gonadotropin deficiency can produce reduced testosterone (in men) or disrupted menstrual cycles (in women), with consequences for energy, mood, bone density, and recovery capacity. These changes are frequently unnoticed or attributed to other causes, particularly in younger patients.
What Should Be Done?
The first step is awareness, both for patients and for practitioners, that hormonal assessment after concussion is clinically warranted, not unnecessary. Standard blood panels requested after a head injury rarely include the pituitary or adrenal markers needed to identify this dysfunction.
Functional hormone assessment including morning cortisol, TSH and free thyroid hormones, sex hormones, and growth hormone markers provides a picture of the HPA axis that standard concussion care misses entirely. Where deficiencies/excesses are identified, they can be addressed through naturopathic approaches that support adrenal and pituitary function, modulate the inflammatory drivers of hormonal disruption, and address the nutritional and stress factors that compound the problem.
For many people with persistent post-concussion symptoms, discovering and addressing a hormonal component transforms the recovery trajectory.
References
Glynn N, Agha A. The frequency and the diagnosis of pituitary dysfunction after traumatic brain injury. Pituitary. 2019;22(3):249–260. https://doi.org/10.1007/s11102-019-00938-y
Soltani Z, et al. Endocrine dysfunction post-traumatic brain injury: challenges and therapeutic approaches. Acta Neurol Belg. 2025;125(3):649–660. https://doi.org/10.1007/s13760-025-02755-6
Sav A, et al. Pituitary pathology in traumatic brain injury: a review. Pituitary. 2019;22(3):201–211. https://doi.org/10.1007/s11102-019-00958-8