Clinical Assessment
When an adolescent girl is referred for hyperandrogenism, the first visit must include a thorough record of history and a careful physical examination.

Although infrequent, some clinical symptoms must be carefully searched for, since they draw the clinician’s attention toward a severe disease: (a) rapidly growing hirsutism, with other signs of virilization such as clitoromegaly, temporal balding, voice deepening, and increasing muscle mass, which are indicative of an adrenal or ovarian tumor; (b) symptoms of hypercorticism (Cushing syndrome), and (c) galactorrhea, indicative of a prolactinoma.

In the other situations, symptoms of hyperandrogenism are mild and consist in: (a) hirsutism, whose degree should be quantified according to the Ferriman- Gallwey score; (b) acne, indicative of hyperandrogenism when it occurs early, is inflammatory, and mainly localized in chin, neck and thorax, and (c) alopecia, indicative of hyperandrogenism when it affects the vertex.

Some clinical features are predictive of PCOS: (a) family history of hyperandrogenism and menstrual disorders; (b) history of precocious adrenarche; (c) history of menstrual disorders, mainly oligomenorrhea, persisting more than 2y ears after menarche; (d) obesity (body mass index (BMI) >25 kg/m2) or abdominal adiposity, with increased waist/hip ratio (WHR), and (e) presence of an acanthosis nigricans.

First Laboratory Assessment
After the first visit, a minimal laboratory screening is mandatory, unless the clinical findings lead to search at once for adrenal or ovarian tumor, or a prolactinoma. Blood sampling must be performed early in the morning, certainly before 10:00 h. This will avoid false negative results due to the circadian decrease in adrenal steroids, mainly 17-hydroxyprogesterone (17-HP), that parallels the one in cortisol and ACTH and occurs later in the day. Second, patients must be investigated in the early follicular phase. This will avoid false positive results due to the steroid production from the corpus luteum. In amenorrheic or oligomenorrheic patients, blood sampling should be performed after a short sequence of progestin treatment.

This laboratory screening must include the assay of total T, DHEAS and 17-HP. Other assays are less useful (e.g., the A assay) or not robust enough (e.g., the free T assay) to fulfill the reliability needed for this first step.

Further Investigations
According to these preliminary results, the diagnostic strategy can follow the flow chart indicated in

figure 1:

(a) If an adrenal or ovarian tumor is suspected, adrenal computed tomography or pelvic MRI is indicated, respectively.

(b) If NCAH is suspected (basal 17-HP >2ng/ml), an ACTH test should be performed. For some authors, the ACTH test is mandatory as soon as the first visit to ascertain the diagnosis of NCAH. However, there is no evidence that its sensitivity in detecting 21-OHD is higher than the one of basal 17-HP determination, providing that the above-mentioned rules are respected.

Therefore, the ACTH test is only useful when the morning follicular unsuppressed 17-HP level falls between 2 and 5 ng/ml (6 - 15 nmol/l), which is the case in approximately 6% of all patients referred for hyperandrogenism.

(c) If the patient is suspected of having PCOS, pelvic ultrasound imaging and metabolic work-up are indicated, in complement to other hormonal assays (see below).