Cortexolone is a precursor to cortisol. Elevated or disrupted levels usually point to enzyme deficiencies or adrenal dysfunctions.
🔺 1. Congenital Adrenal Hyperplasia (CAH) – 11β-Hydroxylase Deficiency
🔧 Cause:
- Deficiency in 11β-hydroxylase (CYP11B1) enzyme.
- Leads to inability to convert cortexolone into cortisol.
- Cortexolone accumulates, along with 11-deoxycorticosterone (DOC).
🧬 Pathophysiology:
- ↓ Cortisol → ↑ ACTH (via feedback loop) → adrenal hyperplasia
- ↑ Cortexolone and DOC → hypertension
- ↑ Androgens → virilization in females and precocious puberty in males
🩺 Clinical Features:
- Hypertension
- Low cortisol
- Elevated 11-deoxycortisol (cortexolone)
- Excess androgens → ambiguous genitalia, hirsutism
- Salt retention (due to DOC’s mineralocorticoid activity)
📊 2. Adrenal Tumors or Hyperplasia
- Rare adrenal tumors (like adrenal adenomas or carcinomas) can cause:
- Elevated cortexolone levels
- Disrupted cortisol balance
- May be found on hormone panels during evaluation of Cushing-like symptoms or adrenal masses
🧠 3. HPA Axis Dysfunction or Stress
- In chronic stress or pituitary disorders, abnormal levels of ACTH can alter the steroidogenic cascade:
- Cortexolone might be elevated if partial enzymatic blockage or cortisol demand is high.
- Often seen in complex endocrine profiles (e.g., ACTH-producing tumors)
🧫 4. Diagnostic Use:
Cortexolone is used diagnostically to assess:
- CAH screening
- CYP11B1 enzyme activity
- Adrenal function under ACTH stimulation tests
🧴 5. Not a disease — but… Cortexolone 17α-propionate (Breezula)
- A topical anti-androgen drug derived from cortexolone.
- Used for androgenetic alopecia (hair loss).
- Has no systemic hormonal effect, but locally blocks DHT at hair follicles.
🧬 Summary Table:
| Condition | Cortexolone Level | Mechanism |
| 11β-Hydroxylase CAH | ⬆️ Elevated | Blocked conversion to cortisol |
| Adrenal tumors | ⬆️ Elevated | Overproduction from adrenal mass |
| HPA axis dysfunction | Variable | Altered ACTH signaling |
| Normal physiology | 🟰 Moderate | Precursor in cortisol pathway |