Chapter 02Progression

How HPA dysfunction evolves

The daily cortisol curve flattens in stages. Two systems respond to stress, and under chronic load the balance between them shifts.

Begin
Fig. 02 · The daily cortisol curve
CORTISOL WAKEMIDDAYBED normal curve
Time under chronic stress
Normal · Stage 1 of 4
Optimal02 · Progression

Two systems respond to stress

SNSSeconds
Sympathetic nervous system→Adrenal medulla→Adrenaline
HPAMinutes to hours
Hypothalamus→Pituitary→Adrenal cortex→Cortisol

The HPA response is self-limiting through negative feedback. On the right is its normal daily rhythm.

Stage 1 · Normal

A sharp morning rise, then a steady decline to a low at bedtime. Cortisol's own negative feedback switches off CRH once the job is done.

Stage 2 · Acute

Sympathetic hyperactivation drives exaggerated cortisol release. Cortisol stays high all day, yet its helpful actions begin to decline.

Stage 3 · Chronic

CRH stops being the driver. Output drops and the curve flattens. Arginine vasopressin (AVP) takes over, and cortisol cannot switch it off.

Stage 4 · Exhaustion

HPA reactivity fails and the cortisol response fades. The sympathetic system compensates with more activity: wired, but depleted.

The curve flattens in stages

Under chronic load the balance between the two systems shifts. Side by side, the four curves show the daily rhythm losing its shape: from a clear morning peak to a flat line.