Cortisol Dysregulation: Causes, Symptoms & Management

Three-quarters of American adults are afflicted by stress that affects their mental, emotional, and physical health. This staggering number highlights just how pervasive stress has become in the modern world. 

Cortisol dysregulation, often a result of chronic stress, is a common yet frequently misunderstood condition. This stress hormone is meant to help us cope with life's challenges, but when it goes awry, it can wreak havoc on our physical and emotional well-being. 

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The Role of Cortisol in the Body

Cortisol is a steroid hormone produced by the adrenal glands in response to stress and other stimuli.

Cortisol has many important functions, regulating various aspects of human health:

• Mobilizing energy reserves to ensure a steady supply of glucose 
• Stress response
• Sleep-wake cycle
• Increasing blood pressure
• Reducing inflammation

Normal Cortisol Levels

Under normal conditions, cortisol exhibits a characteristic diurnal pattern, meaning it follows a peak-trough pattern throughout the day. The highest levels occur in the morning, about 30 minutes after waking up. After cortisol peaks, it gradually declines over the course of the day, reaching its lowest point in the late evening and early night. (19) 

This pattern is important to understand because normal cortisol levels are dependent upon the time of day cortisol levels are measured. Additionally, the method by which cortisol is measured will influence normal levels:

• Serum Cortisol: AM 6.2-19.4 μg/dL; PM: 2.3−11.9 μg/dL
• Urine Cortisol: AM 10-130 ng/mg; PM 0-14 ng/mg
• Salivary Cortisol: AM 3.7-9.5 ng/mL; PM 0.4-1.0 ng/mL

Understanding Cortisol Dysregulation

Cortisol dysregulation encompasses irregularities in the body's production and control of cortisol. It spans a spectrum, with Addison's disease (insufficient cortisol) and Cushing's syndrome (excessive cortisol) at the extremes. Within this spectrum, cortisol can vary in quantity and timing of release, deviating from its typical patterns. This deviation can manifest as imbalances in cortisol levels throughout the day or in response to stressors.

What Causes Cortisol Dysregulation?

Pathologic cortisol dysregulation refers to abnormalities in cortisol secretion primarily caused by underlying medical conditions, such as Addison's disease or Cushing's syndrome. These conditions involve structural or functional changes in the adrenal glands or other parts of the endocrine system, leading to persistent and severe alterations in cortisol levels. (22, 24) 

In the absence of frank pathology, cortisol dysregulation can be attributed to hypothalamic-pituitary-adrenal (HPA) dysfunction (sometimes called "adrenal fatigue"). The HPA axis is the neuroendocrine system responsible for regulating cortisol production in response to stress. 

There are three stages of HPA dysfunction: 

• Stage 1: HPA hyper-responsiveness (high cortisol)
• Stage 2: HPA resistance and adaptation 
• Stage 3: HPA hypo-responsiveness (low cortisol)

What causes HPA dysfunction? Simply stated – chronic stress. Mental, emotional, and physical stressors continually signal the hypothalamus to activate the HPA axis to fight the perceived danger. Stressors include (9, 16):  

• Emotional stress (e.g., high-stress jobs, grief, and other major life changes)
• Inadequate sleep 
• High-intensity exercise without adequate recovery 
• Poor diet and nutrient insufficiencies
• Chronic infections
• Exposure to environmental toxins

The Impact of Dysregulated Cortisol 

Cortisol dysregulation, whether due to excessive or insufficient levels, can have profound effects on both mental and physical health, contributing to the development and progression of chronic diseases. Sustained cortisol abnormalities have been associated with (12, 13):  

• Advanced aging
• Chronic inflammation
• Mood disorders, such as depression and anxiety
• Chronic fatigue syndrome 
• Neurodegeneration and cognitive decline
• Metabolic dysfunction 
• Cardiovascular disease
• Immune dysfunction 

Symptoms of Cortisol Dysregulation

Cortisol dysregulation can manifest through a variety of symptoms, reflecting the hormone's widespread influence on bodily functions.

The following signs and symptoms are hallmarks of high cortisol levels: 

• Weight gain, particularly in the upper body, face, and abdomen
• High blood pressure
• Muscle wasting 
• Easy bruising
• Slow wound healing 
• Menstrual irregularities
• Excessive hair growth (hirsutism)
• Increased risk of osteoporosis and bone fractures

Characteristic signs and symptoms of insufficient cortisol levels include:

• Chronic fatigue and weakness
• Weight loss and decreased appetite
• Low blood pressure and blood sugar
• Darkening of the skin (hyperpigmentation)
• Nausea, vomiting, and diarrhea
• Muscle or joint pain

Medical Treatments for Cortisol Dysregulation

Pathologic cortisol dysregulation (i.e., Cushing's syndrome and Addison's disease) requires medical interventions to normalize cortisol levels.

If the underlying cause of Cushing's syndrome is a hormone-secreting tumor, surgery or radiation therapy may be necessary to remove or shrink the tumor. In cases where Cushing's syndrome is due to exogenous use of glucocorticoid medications, modifying the type and dose of medication is necessary. (22) 

The cornerstone of treatment for Addison's disease involves replacing the deficient hormones, particularly cortisol and aldosterone.

Lifestyle modifications, such as stress reduction techniques, maintaining a balanced diet, regular exercise, and avoiding excessive alcohol and caffeine consumption, can support standard medical management and improve the quality of life for individuals with cortisol dysregulation. (22, 24) 

Prevention Strategies

The prevention and treatment of functional cortisol abnormalities revolve around preserving normal HPA axis signaling. Treatment strategies should encompass healthfully managing stress, reducing inflammation, and optimizing nutrition:

• Avoid and remove stressors when possible
• Practice stress management techniques, such as deep breathing, meditation, and yoga, to reduce stress caused by unavoidable triggers
• Maintain healthy relationships
• Prioritize quality sleep
• Exercise regularly 
• Eat a balanced, anti-inflammatory diet that is built around unprocessed, nutrient-dense foods
• In some cases, stress-relieving and anti-inflammatory supplements can complement these foundational lifestyle habits to establish healthy cortisol levels.

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Key Takeaways

• Cortisol dysregulation represents a complex interplay of hormonal imbalances that can profoundly impact physical and mental health. The manifestations of cortisol dysregulation are diverse and often challenging to navigate. 
• Effective management of cortisol dysregulation involves a multifaceted approach, including stress reduction techniques, adequate sleep, healthy nutrition, and regular exercise. In some cases, hormone replacement therapy and surgical interventions may be required to restore hormonal balance.