Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders in which the enzymes the adrenal cortex needs to make cortisol are partly or completely inactive. Without enough cortisol, the normal negative feedback on the pituitary is lost, so the pituitary produces more adrenocorticotropic hormone (ACTH). Constant ACTH stimulation enlarges (hyperplasia) the adrenal cortex and diverts all the backed-up steroid precursors into the adrenal androgen pathway, causing marked androgen excess.
In dermatology and aesthetic medicine, the late-onset, non-classic form (NCCAH) is especially important. NCCAH usually shows up at puberty or in adulthood with cutaneous signs of androgen excess (severe, treatment-resistant acne, hirsutism, pattern hair loss) that look almost identical to polycystic ovary syndrome (PCOS). At Haute-Derma, accurately telling NCCAH apart from PCOS is the key to building a treatment plan that targets the root cause with correctly dosed glucocorticoid replacement.
Pathogenesis and Disordered Adrenal Steroid Synthesis
CAH arises from a break in the adrenal cortex's steroid production line:
- 21-hydroxylase (CYP21A2) deficiency: This accounts for more than 90–95% of all CAH cases. The enzyme converts 17-hydroxyprogesterone (17-OHP) to 11-deoxycortisol (a cortisol precursor) and progesterone to deoxycorticosterone (an aldosterone precursor).
- 17-OHP build-up and diversion to androgens: With 21-hydroxylation blocked, 17-OHP accumulates to very high levels in the blood. The excess is shunted into the adrenal androgen pathway via 17,20-lyase and 3β-HSD, producing large amounts of androstenedione, DHEA and testosterone.
- Raised ACTH and skin darkening: Low cortisol drives the pituitary to release ACTH in large amounts. ACTH comes from a precursor, POMC (pro-opiomelanocortin), which is also cleaved into alpha-melanocyte-stimulating hormone (alpha-MSH). High circulating alpha-MSH and ACTH directly stimulate MC1R receptors on melanocytes, darkening the skin in body folds (armpits, groin, neck), the mucous membranes and the areolae.
Classification of Congenital Adrenal Hyperplasia (CAH)
| Form / Enzyme Activity | Age of Onset and Systemic Features | Skin and Genital Features |
|---|---|---|
| Classic salt-wasting CAH (enzyme activity < 1%) | Onset in the newborn period (1–3 weeks). Acute salt loss, low blood pressure, low sodium, high potassium (life-threatening) | Clitoral enlargement / ambiguous genitalia in girls. Marked generalized skin darkening |
| Classic simple-virilizing CAH (enzyme activity 1–2%) | Onset in the newborn period or childhood. Virilized external genitalia in girls, early puberty in both sexes, early growth spurt but early growth arrest | Florid acne in childhood, early hirsutism, obvious skin darkening |
| Non-classic, late-onset CAH (NCCAH) (enzyme activity 20–50%) | Onset at puberty or in adulthood. No electrolyte disturbance or threat to life | Deep, treatment-resistant cystic acne, hirsutism (FG score > 8), pattern hair loss (AGA), menstrual irregularities |
Telling NCCAH from PCOS: Our Diagnostic Process at Haute-Derma
Because NCCAH and PCOS look so similar on the skin, Haute-Derma uses a three-step biochemical workup to confirm the diagnosis:
- Early-Morning 17-Hydroxyprogesterone (17-OHP)
- Blood is drawn at 8:00 a.m. in the follicular phase (days 2–4 of the menstrual cycle).
- 17-OHP < 2 ng/mL (6 nmol/L): NCCAH is ruled out (favoring PCOS).
- 17-OHP > 10 ng/mL (30 nmol/L): Confirms NCCAH due to 21-hydroxylase deficiency.
- 17-OHP between 2 and 10 ng/mL: An ACTH stimulation test is needed.
- ACTH (Synacthen) Stimulation Test
- 250 µg of synthetic ACTH (Synacthen) is given intravenously and 17-OHP is measured again after 60 minutes.
- A stimulated 17-OHP above 10 ng/mL (typically 15–30 ng/mL) confirms NCCAH. Patients with PCOS do not show this sharp rise in 17-OHP after ACTH.
- CYP21A2 Mutation Analysis and Extended Hormone Panel
- Molecular testing looks for heterozygous or homozygous mutations in the CYP21A2 gene.
- We also measure DHEAS (an androgen made specifically by the adrenal glands), total testosterone and SHBG, with a supporting ovarian ultrasound.
Multidisciplinary Treatment at Haute-Derma
Unlike PCOS, where the mainstay is oral contraceptives and spironolactone, the core treatment for NCCAH is suppressing pituitary ACTH secretion:
- Low-Dose Glucocorticoids to Suppress ACTH (Systemic Therapy)
- Physiological or sub-physiological doses of glucocorticoid restore negative feedback on the pituitary and lower ACTH, cutting off the source of excess adrenal androgens.
- Drugs of choice: dexamethasone (0.25–0.5 mg orally at bedtime) or hydrocortisone (10–15 mg/day in divided doses). Taking dexamethasone in the evening blunts the nighttime and early-morning ACTH peak most effectively.
- Adding Anti-Androgens and Oral Contraceptives
- During the first 3–6 months, while the glucocorticoid takes full effect, we add spironolactone (50–100 mg/day) or a combined oral contraceptive (containing drospirenone or cyproterone) to block androgen receptors in the sebaceous glands and hair follicles.
- Advanced Dermatologic and Aesthetic Procedures
- Acne and clogged pores: Chemical peels (salicylic acid 30%, azelaic acid) clear the follicular openings, combined with IPL/Biolight therapy to kill C. acnes.
- Hair removal for hirsutism: 808 nm diode laser destroys the androgen-overstimulated follicle bulbs.
- Restoring thinning hair: Exosome mesotherapy or PRP injections combined with topical minoxidil 5% to rebuild follicle density at the crown.
