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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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