What Is The HPA Axis?

Corey Schuler, RN, MS, CNS, DC

What Is The HPA Axis?

The human body must properly respond to stressors in order to continue to adapt and thrive. When stressors are identified as contributing factors to illness or a barrier to a health goal, clinicians are faced with two fundamental methods of helping the patient. First, certain stressors can be reduced, eliminated, or reframed based on how the patient handles those stressors. Second, the clinician can recommend interventions to support the HPA axis, the system primarily responsible for the sequelae of bodily responses due to stress.

What is the HPA axis?

The hypothalamic-pituitary-adrenal axis, or the HPA axis, refers to the interconnectedness of three glands.

The hypothalamus is part of the forebrain and lives under the thalamus.

The pituitary resides in the brain in its very own cranial structure known as the sella turcica, which comes from the Latin for Turkish seat or saddle. It is a bilobar (two lobes) gland with the anterior and posterior aspects secreting their own set of chemical signals.

The adrenal glands each sit atop the kidney and have both interior and exterior structures named the medulla and cortex, respectively. The alternative name for the adrenal glands is the suprarenal glands. So why are these glands given the “axis” designation? Simply stated, these glands work in concert as a central component of the endocrine system.

What does the HPA axis do?

The HPA axis is one of the systems that help humans make sense of the world around them. The gastrointestinal system, the skin, and other senses also contribute to this function. The hypothalamus receives signals from the rest of the body via circulation which is unique for the brain. Part look-out and part orchestra conductor, the hypothalamus provides signals back to the rest of the body often with the help of the powerful signals of the pituitary and the adrenal glands.

Healthy Stress Response

The graphic illustrates how a stressor causes the hypothalamus to produce and secrete corticotropic releasing hormone (CRH also known as CRF). CRH acts on the CRH receptor of the anterior pituitary which then secretes ACTH (adrenocorticotropic hormone) and ultimately signals the adrenal cortex to produce and secrete the corticosteroid cortisol. Cortisol circulates throughout the bloodstream acting on multiple tissues but eventually also signals the hypothalamus to limit further CRH secretion.1

A diagram of the HPA Axis - a healthy stress response.

What is HPA axis suppression?

Given that cortisol can suppress the ability of the hypothalamus to secrete CRH, it makes sense that exogenous corticosteroids from outside the body may also suppress the entire HPA axis. The best examples of exogenous corticosteroids are medically used systemic steroids such as prednisone or dexamethasone. However, other phenomena can alter the function of the HPA axis. This HPA axis dysfunction may be within normal limits of how the human body can adapt and change to its environment or be pathological. Continued and persisting HPA axis dysfunction, even within normal limits, is thought to be straining to downstream tissues including cellular responsiveness to other hormones such as insulin3.

The HPA axis and cortisol function

Cortisol is the most common marker of HPA axis function. It lasts in the body a bit longer than many other hormones and is measurable in blood, urine, and saliva. However, cortisol is not inherently bad. Cortisol supports immune function, supports acute energy needs, and stimulates gluconeogenesis456. Therefore, the focus of assessment and treatment is not exclusively cortisol but rather the entire HPA axis. Balancing the HPA axis and thus managing cortisol levels is the goal when helping those patients respond to stressors.

Clinicians routinely and astutely recognize the contributions of stressors to health and well-being and advise managing stress if possible. HPA axis activation is the result of stress and HPA axis suppression is the result of chronic stress, and these terms have largely replaced terms such as hypercortisolism and adrenal fatigue respectively.

Terms and explanations aside, there is little question that assessment and support of the HPA axis is fundamental pillar of integrative medicine.


  1. Slominski A. Br J Dermatol. 2009;160(2):229-232. doi:10.1111/j.1365-2133.2008.08958.x
  2. Hepsen S, Sencar E, et al. Diabetes Res Clin Pract. 2020;161:108081. doi:10.1016/j.diabres.2020.108081
  3. Sharma VK, Singh TG. Curr Diabetes Rev. 2020;16(6):546-556. doi:10.2174/1573399815666191111152248
  4. Kadmiel M, Cidlowski JA. rends Pharmacol Sci. 2013;34(9):518-530. doi:10.1016/j.tips.2013.07.003
  5. Lee DY, Kim E, Choi MH. BMB Rep. 2015 Apr;48(4):209-16.
  6. Kuo T, McQueen A, et al., Adv Exp Med Biol. 2015;872:99-126.

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