Cortisol

What it is

Cortisol is the primary glucocorticoid hormone produced by the adrenal glands, under the control of the hypothalamic-pituitary-adrenal (HPA) axis. It plays a central role in the stress response, blood glucose regulation, immunity and inflammation. Its level is naturally highest in the morning (circadian peak around 8 am) and falls progressively through the day.

Cortisol shares the same steroidogenic pathway as adrenal androgens: the same enzymatic cascade that produces cortisol in the adrenal glands also generates DHEA-S. Adrenal overactivity can therefore simultaneously elevate both cortisol and androgens.

Why it matters in PCOS

Cushing's syndrome — chronic hypercortisolism — can almost perfectly mimic PCOS: menstrual irregularities, anovulation, central obesity, hirsutism, acne, weight gain, and insulin resistance. It is rare (approximately 1–3 cases per 100,000 per year), but its prevalence in women with an atypical PCOS presentation (marked obesity, specific Cushingoid features: purple striae, skin fragility) justifies screening.

The reference screening test is the 1 mg overnight dexamethasone suppression test (1 mg taken at 11 pm, cortisol measured the following morning at 8 am): a post-suppression cortisol < 50 nmol/L (< 1.8 µg/dL) excludes Cushing's with good sensitivity. An abnormal result warrants specialist investigation.

Beyond Cushing's, a mild HPA axis dysregulation is frequently observed in PCOS: mildly elevated cortisol responses to stress, accelerated cortisol metabolism, and compensatory ACTH rebound. This indirectly contributes to the adrenal androgen excess (elevated DHEA-S) seen in a subset of PCOS cases.

Normal values

• Morning cortisol (8 am): 190–690 nmol/L (7–25 µg/dL)
• 24-hour urinary free cortisol: < 50–100 µg/24h (laboratory-dependent)
• 1 mg overnight dexamethasone suppression: post-cortisol < 50 nmol/L = normal
• Late-night salivary cortisol (11 pm): < 4 nmol/L (sensitive Cushing's marker)

When is it measured?

A basal cortisol alone is not very specific (it varies with stress, time of day, and cycle phase). It is measured fasting in the morning around 8 am. When Cushing's syndrome is clinically suspected (specific Cushingoid features), the dexamethasone suppression test or 24-hour urinary free cortisol is ordered. These tests are not part of the standard PCOS panel but are requested in atypical presentations.

Key takeaways

• Cushing's can mimic PCOS — consider in atypical presentations
• Normal morning cortisol: 7–25 µg/dL; measure fasting around 8 am
• Cushing's screening: 1 mg dexamethasone suppression test (result < 1.8 µg/dL = reassuring)
• Mild HPA axis dysregulation common in PCOS → contributes to elevated DHEA-S
• Basal cortisol alone is insufficient to screen for Cushing's