dromlakhani Assess response to cosyntropin stimulation to exclude rare congenital adrenal hyperplasia
STEP 1 — Gather Information
Collect menstrual history, family history of congenital adrenal hyperplasia, ethnicity (especially high-risk groups such as Ashkenazi Jewish, Mediterranean, Middle Eastern, Hispanic), baseline early morning total and free testosterone, and 17-hydroxyprogesterone (follicular phase or random if amenorrhea). Review medications that could affect adrenal steroids (e.g., glucocorticoids, recent ACTH exposure).
STEP 2 — Rule In / Rule Out
If the patient has high-risk features for nonclassic congenital adrenal hyperplasia (positive family history or high-risk ethnicity) and presents with clinical hyperandrogenism (moderate/severe hirsutism, oligomenorrhea, progression despite therapy) despite normal baseline total and free testosterone, proceed to cosyntropin stimulation testing. Otherwise, rule out rare CAH and pursue other etiologies of androgen excess.
STEP 3 — Classify or Stratify
Administer 250 µg cosyntropin (ACTH) intravenously and draw serum for 17-hydroxyprogesterone, DHEA, 17-hydroxypregnenolone, and 11-deoxycortisol at baseline and 60 minutes post-stimulation. A positive test is defined by a post-stimulation 17-hydroxyprogesterone ≥ 1000 ng/dL (≥ 30 nmol/L) or a disproportionate rise in other precursors suggestive of a specific enzyme block (e.g., 11-deoxycortisol for 11β-hydroxylase deficiency).
STEP 4 — Decide
If the stimulation test is positive, refer the patient for genetic counseling and confirmatory CYP21A2 genotyping to establish the diagnosis of nonclassic congenital adrenal hyperplasia. If negative, exclude rare CAH and continue the workup for other causes of androgen excess (e.g., ovarian/adrenal tumors, Cushing syndrome, exogenous androgen exposure).
Clinical Guardrails / Mimics / Pitfalls
Do not rely on a single baseline 17‑OHP level; mild enzyme variants may yield false‑negative results. Avoid testing in patients receiving glucocorticoids or within 24 hours of ACTH exposure, as this can blunt the response. Ensure the assay used is specific for 17‑OHP (e.g., LC‑MS/MS) to prevent cross‑reactivity with related steroids that could mimic elevation.
Concrete Clinical Example
A 28‑year‑old woman of Ashkenazi Jewish descent presents with a Ferriman–Gallwey score of 12, oligomenorrhea, and normal baseline testosterone and 17‑OHP. She reports a cousin with classic CAH. Cosyntropin stimulation shows 17‑OHP rising from 80 ng/dL at baseline to 1250 ng/dL at 60 minutes, prompting CYP21A2 genotyping that confirms two pathogenic alleles consistent with nonclassic 21‑hydroxylase deficiency.
Source: Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2018, 10.1210/jc.2018-00241