Does anorexia nervosa cause elevated Adrenocorticotropic hormone (ACTH) and cortisol levels?

Does Anorexia Nervosa Cause Elevated ACTH and Cortisol?

Yes, anorexia nervosa causes elevated cortisol levels, but ACTH levels are typically normal or elevated rather than suppressed, reflecting a dysregulated hypothalamic-pituitary-adrenal (HPA) axis with impaired feedback mechanisms. 1, 2

Cortisol Elevation in Anorexia Nervosa

Cortisol levels are consistently elevated in underweight patients with anorexia nervosa across multiple measures:

• 24-hour mean plasma cortisol concentrations are significantly elevated (10.6-11.4 μg/dL) compared to controls (6.8-7.4 μg/dL), representing approximately 50-60% increases 2, 3
• Urinary free cortisol excretion is markedly increased (205-225 μg/day) compared to controls (65-116 μg/day), demonstrating 2-3 fold elevations 2, 4, 3
• Cortisol production rates are elevated relative to body size at 0.591 mg/kg/day and 16.4 mg/m²/day compared to controls at 0.322 mg/kg/day and 11.4 mg/m²/day 3
• These elevations normalize during weight recovery, with cortisol production declining from 24.3 to 17.9 mg/day as patients regain weight 4

ACTH Levels and Feedback Dysregulation

The critical distinction is that ACTH levels are NOT suppressed despite elevated cortisol, indicating HPA axis dysfunction:

• Basal morning plasma ACTH levels remain normal or elevated despite hypercortisolemia, which differs from primary adrenal causes where ACTH would be suppressed 1
• Dexamethasone suppression testing is abnormal, with most patients failing to suppress both ACTH and cortisol after 1 mg dexamethasone administration 1, 2, 3
• This represents an abnormal feedback mechanism where the hypothalamic-pituitary axis fails to respond appropriately to elevated cortisol levels 1

Mechanism of HPA Axis Dysfunction

The hypercortisolemia in anorexia nervosa results from both increased production and decreased metabolism:

• Increased adrenal secretory activity is demonstrated by elevated cortisol production rates, not just slowed metabolism 4, 3
• Prolonged cortisol half-life contributes to sustained elevation, with biological half-life of exogenous cortisol being extended in all tested patients 1
• Blunted cortisol responses to both insulin-induced hypoglycemia and exogenous ACTH stimulation suggest altered adrenal responsiveness 1

Clinical Distinction from Cushing's Syndrome

This pattern differs fundamentally from Cushing's syndrome, though superficial similarities exist:

• In ACTH-independent Cushing's syndrome (adrenal adenoma), ACTH would be suppressed (<5 ng/L) with elevated cortisol 5, 6
• In ACTH-dependent Cushing's disease (pituitary adenoma), ACTH would be frankly elevated (>29 ng/L) with specific diagnostic criteria 5, 6
• In anorexia nervosa, ACTH remains detectable/normal despite elevated cortisol, with impaired dexamethasone suppression reflecting hypothalamic dysregulation rather than autonomous hormone production 1, 2

Weight-Dependent Nature

The HPA axis abnormalities are directly related to malnutrition and weight status:

• Normal-weight patients with bulimia show normal HPA activity on most measures, demonstrating that psychological disturbances alone are insufficient to produce these changes 2
• Recovery with weight gain normalizes cortisol production rates and plasma concentrations 4
• The severity of hypercortisolemia correlates with degree of emaciation, suggesting malnutrition as a primary driver 3

Common Pitfall to Avoid

Do not misdiagnose anorexia nervosa patients as having Cushing's syndrome based on elevated cortisol alone. The key distinguishing features are:

• Context of self-induced weight loss and psychiatric features 7
• Normal or non-suppressed ACTH (not frankly elevated as in Cushing's disease) 1
• Reversibility with nutritional rehabilitation 4
• Absence of autonomous hormone production 1