What are the effects of increased cortisol levels on the body?

Effects of Increased Cortisol

Increased cortisol levels cause widespread metabolic, cardiovascular, musculoskeletal, and psychiatric complications that significantly increase morbidity and mortality, with effects ranging from insulin resistance and weight gain to osteoporosis, hypertension, and immunosuppression. 1

Metabolic and Endocrine Effects

Cortisol elevation drives insulin resistance and promotes development of metabolic syndrome through multiple mechanisms. 2 The hormone opposes insulin action in the liver, impairs effective management of excess calorie intake, and promotes a lipogenic program that leads to:

• Hyperglycemia and diabetes mellitus development through glucocorticoid-induced insulin resistance 1, 3
• Weight gain and central obesity with preferential visceral fat deposition, occurring in >30% of patients on long-term therapy 1
• Lipodystrophy affecting >30% of patients, with raised triglycerides and metabolic syndrome 1
• Increased appetite and failure to trigger satiety, leading to excess calorie intake 1

The American Heart Association notes that elevated cortisol correlates directly with metabolic syndrome components including blood pressure, fasting glucose, insulin levels, and waist circumference. 4

Cardiovascular Effects

Elevated cortisol substantially increases cardiovascular disease risk through multiple pathways:

• Hypertension develops in >30% of patients with chronic cortisol elevation 1, 3
• Increased risk of acute myocardial infarction, with dose-response relationship documented 1
• Cerebrovascular disease risk elevation 1
• Higher mortality risk: men with high morning cortisol show 63% increased mortality (HR=1.63), while women with high evening cortisol show 82% increased mortality (HR=1.82) 3

Musculoskeletal Effects

Cortisol exerts profound catabolic effects on bone and muscle tissue:

• Osteoporosis and reduced bone mineral density, particularly with prolonged use (≥90 days) 1
• Hip/femur fractures with documented dose-response relationship 1
• Vertebral fractures occurring in 21-30% of patients on long-term therapy 1
• Muscle protein loss and myopathy through mobilization of amino acids for gluconeogenesis 1
• Avascular necrosis of femur, humerus, and long bones 1

Immunologic and Infectious Complications

• Lower resistance to infection due to immunosuppression 1, 3
• Impaired wound healing 1

Ophthalmologic Effects

• Cataracts and glaucoma with long-term exposure 1
• Blurred vision 1
• Other ophthalmologic disorders 1

Gastrointestinal Effects

• Peptic ulcers with dose-response relationship documented 1
• Gastric irritation 1
• Pancreatitis 1

Psychiatric and Neurologic Effects

Cortisol elevation profoundly affects mental health and cognition:

• Mood disorders and mood swings 1
• Sleep disturbances and insomnia occurring in >30% of patients 1
• Depression, with severe cases causing incomplete dexamethasone suppression 4, 5
• Nervousness and restlessness 1

The American Psychological Association notes that chronic psychological stress activates the HPA axis, producing physiological hypercortisolism that correlates with myocardial infarction risk through cortisol-mediated mechanisms. 4

Dermatologic Effects

• Skin disorders and alopecia 1
• Acne 1
• Easy bruising 1
• Increased growth of body hair 1

Reproductive and Hormonal Effects

• Menstrual disorders and hormonal changes 1
• Adrenal suppression occurring in >30% of patients 1
• Adrenal insufficiency with long-term use 1

Dose and Duration Considerations

The severity of cortisol effects follows both dose-response and duration-dependent patterns:

• Adverse effects become more significant at daily exposures >5 mg prednisolone equivalent 1
• Risk rises exponentially with increasing daily dose 1
• Short-term therapy (<21 days) causes primarily insomnia and gastrointestinal disturbances 1
• Longer-term therapy (≥90 days) results in clinically significant weight gain and increased fracture risk 1

Clinical Implications

Untreated hypercortisolism carries significant morbidity and mortality from these complications. 6 The Endocrine Society emphasizes that early diagnosis and treatment are critical to prevent progression of these effects, with treatment depending on the underlying etiology. 6

Common pitfall: Cortisol levels within normal range at standard 0800h or 1700h testing may miss pathological elevations occurring during the 24-hour circadian rhythm, sometimes reaching immunosuppressive levels. 7 Evening cortisol >50 nmol/L (>1.8 μg/dL) indicates loss of normal circadian rhythm and warrants further evaluation. 6, 8