Examining Stress: The HPA Axis & Sympathetic-Adrenal-Medullary System

Corey Schuler, RN, MS, CNS, DC

While the adrenal glands are often pointed to as responsible for handling the normal stress response, they may instead be target organs of two intersecting systems. The hypothalamus-pituitary-adrenal (HPA) axis is the endocrine response to stressors producing adrenocorticotropic hormone (ACTH) from the pituitary gland with measurable changes in levels of plasma cortisol and salivary cortisol as produced in the adrenal cortex. The sympathetic-adrenal-medullary system produces epinephrine and norepinephrine and measurable changes in heart rate are seen. It is important not to oversimplify this relationship as HPA responses habituate to repeated stress exposure. In effect, the body responds better and better to the same stressor. The sympathetic system shows rather uniform activation patterns with repeated stress exposure.1

The Role of Rumination

The HPA may also not habituate to repeated stress exposure. In this situation, the same stressor causes the same set of physiological functions as if it were a new, unique stressor. Repetitive and unwanted past-centered negative thinking, also known as rumination, is related with non-habituation of the HPA axis stress response.2 Even in primary care settings, our encouragement to reduce rumination within our patients may offer benefit when the stress response is a factor in one’s health goals.

Combining information from both systems provides a cross-reference to determine if the stress response is in an early-, mid-, or late-stage. The adrenal release of cortisol may be under dual control of both ACTH and preganglionic sympathetic neurons.3

Salivary Cortisol Testing

Salivary cortisol is also affected by psychological stimulation.4 However, its utility as a predictable marker has come into question. Saliva is probably one of the most studied oral correlates of stress. Being controlled by both sympathetic and parasympathetic fibers, the salivary glands are controlled by various factors. While stimulation of the parasympathetic fibers leads to normal vasodilation and increased secretion of saliva, sympathetic stimulation produces a complex series of reactions with little or no effect. Experiments on emotional states on salivary composition suggest that pH of saliva changes under stress.5 One measureable marker in saliva that changes in response to stress is the immune function marker secretory IgA (S-IgA).6 7 8 9

Ultimately, knitting together a patient’s story in regards to responses to new stressors, repeated stressors, immune function, and certain physiological measures are critical components to direct the methods in which we choose to support our patients under stress.


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3. Hellhammer DH et al. Psychoneuroendocrinology 2009; 34:163–171.
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9. McClelland DC et al. J Human Stress. 1980;6(2):11-9.