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Stress Hormones — Cortisol, DHEA & the Burnout Connection

Reviewed 10 April 2025

Endocrine Society Clinical Practice Guidelines on Adrenal Insufficiency & Cushing's Syndrome

Educational content only. This information is for general awareness and does not constitute medical advice. Please consult a qualified healthcare provider for any medical concerns or before making health decisions.

Key Facts

7–9 AM

Cortisol peak time

Cortisol follows a strict diurnal rhythm — timing of the test matters critically

Up to 3–5×

Cortisol rise during stress

Physical or psychological stress spikes cortisol sharply within minutes

~10%

DHEA-S decline per decade after 30

DHEA-S falls steadily with age — the opposite of cortisol, which can remain elevated

Since 2019

Burnout (ICD-11 recognised)

WHO formally classified burnout as an occupational phenomenon — measurable physiologically

The Stress Response — Why Cortisol Exists

When the brain perceives danger or stress, the hypothalamus triggers a cascade: CRH → ACTH (from pituitary) → **cortisol** from the adrenal cortex. Cortisol prepares the body to fight or flee:

• Raises blood glucose (for energy)

• Increases heart rate and blood pressure

• Suppresses immune function (to avoid inflammation interfering with escape)

• Enhances alertness and focus

• Diverts blood from gut to muscles

This is life-saving in acute danger. The problem arises when chronic work pressure, financial stress, relationship strain, or poor sleep keeps this alarm activated indefinitely — leading to sustained high cortisol.

Cortisol Testing — What the Numbers Mean

Serum Cortisol (AM):: The standard blood test. Must be collected between 7–9 AM when cortisol is at its natural daily peak.

Normal AM cortisol:: 6–23 µg/dL

High cortisol (hypercortisolaemia) may indicate::

• Cushing's syndrome (tumour driving excess cortisol production)

• Chronic psychological stress or severe depression

• Poorly controlled diabetes

• Alcoholism

• Use of corticosteroid medications

Low cortisol (hypocortisolaemia) may indicate::

• Addison's disease (primary adrenal insufficiency)

• Secondary adrenal insufficiency (pituitary problem)

• Long-term steroid use followed by abrupt discontinuation

24-hour urine cortisol (UFC):: More comprehensive than a single blood sample — captures the entire day's cortisol output and is better for detecting Cushing's syndrome.

Late-night salivary cortisol:: Cortisol should be nearly undetectable at midnight. Elevated late-night cortisol is highly specific for Cushing's syndrome.

DHEA and DHEA-S — The Counter-Stress Hormone

DHEA (Dehydroepiandrosterone): and its sulphated form **DHEA-S** are produced by the adrenal glands. DHEA is a precursor to sex hormones (both testosterone and oestrogen) and has documented anti-inflammatory and neuroprotective effects.

Normal DHEA-S ranges::

• Men (20–24 yrs): 280–640 µg/dL; declines to 70–300 µg/dL by age 60

• Women (20–24 yrs): 160–430 µg/dL

Low DHEA-S is associated with::

• Chronic stress and burnout (adrenal resources exhausted)

• Adrenal insufficiency

• Hypothyroidism

• Ageing (DHEA naturally declines; by age 70 it is ~20% of peak)

Elevated DHEA-S in women: indicates adrenal androgen excess — a key feature of PCOS and congenital adrenal hyperplasia.

The **cortisol:DHEA ratio** is sometimes used in functional medicine to assess adrenal balance — high cortisol with low DHEA suggests maladaptive chronic stress response.

Burnout — A Real Physiological State

Burnout was formally included in the WHO's International Classification of Diseases (ICD-11) in 2019 as an 'occupational phenomenon.' It is characterised by exhaustion, cynicism toward work, and reduced efficacy.

Physiologically, chronic occupational stress can dysregulate the HPA axis, leading to:

• **Initially:** Elevated cortisol and heightened stress reactivity

• **Over months-years:** Blunted cortisol response (hypo-cortisol state), disrupted diurnal rhythm, and low DHEA-S

• **Concurrent findings:** Elevated hs-CRP, disrupted thyroid function (low T3 in some cases), and anaemia

Testing someone suspected of burnout would include: AM cortisol, DHEA-S, thyroid panel, CBC, Vitamin B12, and hs-CRP — looking at the whole physiological picture.

Who Should Consider Cortisol Testing?

• Anyone with symptoms of Cushing's syndrome: rapid weight gain (especially abdominal), round face, purple stretch marks, easy bruising, high blood pressure

• Individuals with persistent unexplained fatigue, especially if worst in morning (consider Addison's)

• People on long-term corticosteroid therapy (monitoring for suppression)

• Individuals with PCOS (high DHEA-S common)

• Those with chronic high-stress lifestyles who want to quantify physiological stress impact

• Always discuss results with an endocrinologist — cortisol is highly sensitive to the timing and conditions of testing

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