dromlakhani Measure serum androstenedione or other steroid intermediates when atypical features suggest adrenal pathology
STEP 1 — Gather Information
Collect hirsutism score (Ferriman–Gallwey), menstrual history, signs of virilization (clitoromegaly, deepened voice, increased muscle), family history of adrenal disease or congenital adrenal hyperplasia, ethnicity (high‑risk groups), and baseline serum total and free testosterone levels. If total and free testosterone are normal but atypical features are present, proceed to rule‑in/out adrenal pathology.
STEP 2 — Rule In / Rule Out
Are atypical features suggestive of adrenal pathology present (e.g., rapid progression of hirsutism, virilization signs, family history of CAH, high‑risk ethnicity)?
- Yes: Proceed to measure steroid intermediates.
- No: No further steroid intermediate testing indicated; consider alternative etiologies or routine management.
STEP 3 — Classify or Stratify
Classify the patient as suspected adrenal androgen excess when atypical features are present despite normal testosterone. This warrants measurement of adrenal pathway precursors such as androstenedione, DHEAS, or 17‑hydroxyprogesterone.
STEP 4 — Decide
Order a morning serum androstenedione level (and optionally DHEAS or 17‑hydroxyprogesterone). If results are elevated, consider ACTH stimulation testing or genetic workup for nonclassic congenital adrenal hyperplasia; if normal, look for other sources of androgen excess (e.g., ovarian tumors, medication effects).
Clinical Guardrails / Mimics / Pitfalls
Do not rely on androstenedione alone; interpret in the context of clinical presentation and other steroid levels. Avoid testing in low‑risk patients without atypical features to prevent false positives. Remember that mildly elevated DHEAS with normal testosterone rarely changes management. Ensure assays are performed in a reliable specialty laboratory, as routine immunoassays may be inaccurate at low female levels.
Concrete Clinical Example
A 24‑year‑old woman presents with worsening hirsutism over 3 months, new clitoromegaly, and a sister diagnosed with nonclassic CAH. Her serum total and free testosterone are normal. According to the algorithm, atypical features prompt measurement of serum androstenedione, which returns markedly elevated, leading to ACTH stimulation testing and confirmation of 21‑hydroxylase deficiency.
Source: Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline, Endocrine Society, 2018, DOI:10.1210/jc.2018-00241