Adrenal Health: Understanding HPA Axis Dysfunction

The adrenal glands are one of the most widely discussed, but least understood portions of endocrine health. Many of us have heard or used terms like “burnout”, “adrenal fatigue”, or uttered “my cortisol must be high” during periods of acute or extended stress. The previously mentioned verbiage, while commonly used, is often misleading, attributing non-optimal changes in adrenal output to disease or dysfunction of the adrenal glands themselves. In this article, we aim to dispel common misunderstandings of the adrenal glands, discuss HPA Axis dysfunction, and explore common symptoms and health disparities associated with disruption of adrenal output.

What are the adrenal glands? What do they do?

The adrenals are two small glands located on the top of kidneys. They are comprised of two primary sections; the adrenal cortex and the adrenal medulla. The adrenal medulla is responsible for the synthesis of catecholamines, such as epinephrine and norepinephrine (adrenaline and noradrenaline), that play a pivotal role in our survival mechanism(s), specifically, flight or fight response. The adrenal cortex is responsible for the synthesis of glucocorticoids, such as cortisol, mineralocorticoids, such as aldosterone, and sex hormones, like testosterone and estrogen (synthesized from DHEA).

What is cortisol?

Cortisol is a steroid hormone most often associated with stress response. During acute bouts of stress, serum cortisol increases to prepare the body for flight or fight by increasing blood glucose and blood pressure, increasing the brain’s glucose uptake, and down regulating non-essential body processes to facilitate increased survival rate of perceived stressor or danger. Additionally, cortisol modulates inflammatory response, immune function, mood, sleep patterns, and protein catabolism (break down). Given the numerous physiologic functions influenced by cortisol, too much or too little of this hormone, or disruption to its normal circadian rhythm can lead to the development of long-term health disparities, such a hyperglycemia, insulin resistance, obesity, hypertension, compromised immune response, gastrointestinal problems, mood disturbance, and insomnia.

Adrenal Dysfunction VERSUS HPA-Axis Dysfunction

Primary dysfunction or disease of the adrenal glands, such as Cushing Syndrome or Addison’s Disease, are very rare. The majority of patients experiencing adrenal related symptoms are often struggling with dysfunction of the hypothalamic-pituitary-adrenal axis, the communication loop that regulates the output of cortisol (and other adrenal hormones) throughout the course of the day. The hypothalamus of the brain produces a hormone called corticotrophin-releasing hormone (CRH), stimulating the anterior pituitary to release adrenocorticotropin hormone (ACTH), which stimulates the adrenal glands release of stress and sex hormones. This pathway of neuroendocrine communication runs on a loop of negative-feedback, which simplistically infers that the down stream path of stimulus will continue until the hypothalamus is “told” that the output is no longer needed. The primary stimulus that starts this hormone cascade is stress. It is important to understand that the neuroendocrine system is responsive to stress, but does not differentiate types of stress; mental, emotional, physical or illness related stress will elicit the same stimulus to the HPA-Axis, though the degree may vary.

Cortisol generally follows a normal diurnal pattern, raising abruptly upon awakening to increase alertness and cognition, known as the cortisol awakening response, then slowly declining throughout the course of the day, generally reaching it lowest point late night to early morning to facilitate restful sleep.  Acute or temporary peaks in cortisol may occur throughout the course of the day, should a person(s) encounter an unexpected stressor.

Many patients suffering from adrenal related symptoms are experiencing negative changes to the diurnal pattern of cortisol, generally driven by a maladaptation of the HPA axis as a response to prolonged stress exposure or poor stress management. Acutely, patients may experience a general increase of cortisol throughout the day while still following an appropriate diurnal pattern, however, this is generally short lived. As HPA Axis dysfunction progresses, patients may experience various iterations of diurnal pattern dysfunction, e.g., an inadequate awakening cortisol response, leading to excessive morning fatigue and cognitive decline, an abrupt mid-afternoon crash,  often resulting in negative mood changes or feeling of needing to nap, or an upward trend in the evening, causing extended suppression of normal melatonin release and upregulation of physiologic stress response, causing disruption of sleep quality. Long term disruption of the HPA Axis and diurnal cortisol rhythm can also contribute to disruption of other endocrine function. When left untreated, patient’s suffering from HPA axis dysfunction will often experience secondary dysfunction of the hypothalamic-pituitary-gonadal axis and hypothalamic-pituitary-thyroid axis, resulting in drops of sex hormone and thyroid hormone values, exacerbating adrenal related symptoms and health disparities.

Appropriate assessment of the adrenals often extends beyond normal blood testing. Evaluation of diurnal cortisol pattern is essential to understand the function of the HPA Axis throughout the course of the day and effectively develop an intervention program. Patients that are suspicious they may be suffering from adrenal related symptoms often need to undergo salivary or urinary testing, like a DUTCH Test, that allows providers to gather multiple data points throughout the course of a 24-hour period of times and evaluate the storage, metabolism and clearance of stress and sex hormones. Treatment is often a combination of nutraceuticals, adrenal adaptogens, lifestyle modification, and stress management skill development.

Author: Joseph Matovich

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