What is the initial approach to diagnosis and management in a patient with elevated DHEA, low SHBG, and high Free Testosterone, with a pending Pelvic Ultrasound to rule out PCOS?

Initial Diagnostic Approach for Suspected PCOS with Elevated DHEA, Low SHBG, and High Free Testosterone

Based on your laboratory findings showing elevated DHEA (298), low SHBG (19), and high free testosterone (1), you have biochemical hyperandrogenism that strongly suggests PCOS, but you must first exclude other causes of androgen excess before confirming this diagnosis. 1

Immediate Diagnostic Steps

Complete the Hormonal Evaluation

Your current labs already show the pattern most consistent with PCOS (low SHBG with elevated free testosterone), but you need additional testing to exclude other conditions:

• Measure 17-hydroxyprogesterone (17-OHP) to rule out non-classical congenital adrenal hyperplasia (NCCAH), particularly if levels exceed 2 ng/mL; values above this threshold warrant ACTH stimulation testing 1, 2

• Check TSH and prolactin levels to exclude thyroid disease and hyperprolactinemia, which can present with similar menstrual irregularities and hyperandrogenism 1, 2

• Obtain LH and FSH levels (ideally averaged from three samples taken 20 minutes apart between cycle days 3-6); an LH/FSH ratio >2 supports PCOS diagnosis, while LH/FSH ratio <1 suggests functional hypothalamic amenorrhea 1

• Measure mid-luteal progesterone (day 21 of a 28-day cycle) to assess ovulatory status; levels <6 nmol/L indicate anovulation 1

Assess for Cushing's Syndrome

If you have any signs of hypercortisolism (buffalo hump, moon facies, hypertension, abdominal striae, centripetal fat distribution, easy bruising, or proximal myopathy), perform screening tests 1, 2:

• Overnight dexamethasone suppression test or 24-hour urinary free cortisol
• This is critical because Cushing's syndrome can present with identical features to PCOS, including low SHBG and hyperandrogenism 3

Rule Out Androgen-Secreting Tumors

If you have rapid onset of symptoms, severe virilization (clitoromegaly, deepening voice, male-pattern baldness), or extremely elevated androgens, imaging is mandatory 1, 2:

• Total testosterone >2.5 nmol/L or androstenedione >10.0 nmol/L should prompt evaluation for ovarian or adrenal tumors 1
• Your DHEA level of 298 ng/mL needs age-specific interpretation: abnormal if >3800 ng/mL (age 20-29) or >2700 ng/mL (age 30-39) 1

Interpreting Your Pelvic Ultrasound

Ultrasound Criteria for PCOM

When your pelvic ultrasound is performed, PCOS diagnosis requires (using modern 8MHz transvaginal ultrasound) 1:

• ≥20 follicles per ovary measuring 2-9mm in diameter, OR
• Ovarian volume ≥10 mL on either ovary
• Ensure no corpus luteum, cysts, or dominant follicles ≥10mm are present

Important Caveat About Ultrasound

If you have irregular menstrual cycles AND biochemical hyperandrogenism (which you do), the ultrasound is not necessary for PCOS diagnosis—it only identifies the complete phenotype 1. However, completing it helps exclude other pathology and confirms the full syndrome.

Metabolic Screening (Essential)

PCOS carries significant metabolic risks that require immediate assessment 1:

• 2-hour oral glucose tolerance test with 75g glucose load (fasting glucose followed by 2-hour glucose) to screen for diabetes and glucose intolerance 1

• Fasting lipid panel including total cholesterol, LDL, HDL, and triglycerides, as insulin resistance causes dyslipidemia even in lean PCOS patients 1

• Calculate glucose/insulin ratio: values >4 suggest reduced insulin sensitivity; calculate HOMA-IR for insulin resistance assessment 1, 4

• Measure BMI and waist-hip ratio as obesity exacerbates all PCOS features 1

Differential Diagnosis Considerations

Functional Hypothalamic Amenorrhea (FHA)

This is a critical alternative diagnosis to consider, particularly if you have 1:

• History of excessive exercise, caloric restriction, stress, or low body weight
• Low gonadotropins (especially LH)
• LH/FSH ratio <1 (seen in 82% of FHA patients)
• Normal or low insulin levels with normal insulin sensitivity (opposite of PCOS)

The key distinguishing feature: PCOS patients have LOW SHBG due to insulin resistance, while FHA patients typically have higher SHBG levels 1. Your low SHBG of 19 strongly favors PCOS over FHA.

Confirming PCOS Diagnosis

PCOS requires two of three criteria 5, 4:

1. Chronic anovulation/ovulatory dysfunction (oligomenorrhea or amenorrhea)
2. Hyperandrogenism (clinical OR biochemical)—you already have biochemical hyperandrogenism
3. Polycystic ovaries on ultrasound or elevated AMH

Since you already have biochemical hyperandrogenism (elevated free testosterone, low SHBG, elevated DHEA), you only need ONE additional criterion—either menstrual irregularity OR polycystic ovaries on ultrasound 1.

Management Framework Once PCOS is Confirmed

If Not Seeking Pregnancy

• Combined oral contraceptives are first-line therapy, suppressing ovarian androgen production and increasing SHBG 1, 5
• Consider adding spironolactone (anti-androgen) for hirsutism or acne if OCPs alone are insufficient 5
• Metformin for insulin resistance, particularly if glucose intolerance is present 5

Endometrial Protection

With chronic anovulation, you require endometrial protection to prevent endometrial hyperplasia and cancer 1:

• Either cyclic progestins (medroxyprogesterone) or continuous OCPs
• The optimal progestin regimen is not definitively established, but protection is mandatory 1

Lifestyle Modification

• Weight loss and regular exercise are first-line interventions before pharmacotherapy for dyslipidemia 1
• Even modest weight loss (5-10%) significantly improves metabolic and reproductive outcomes

Common Pitfalls to Avoid

• Do not diagnose PCOS in adolescents <2-3 years post-menarche without persistent oligomenorrhea and clear biochemical hyperandrogenism, as menstrual irregularity is physiologic early after menarche 5

• Do not use ultrasound for PCOS diagnosis if gynecological age <8 years due to high prevalence of multifollicular ovaries 1

• Do not rely on total testosterone alone; free testosterone (calculated or measured by equilibrium dialysis) is more sensitive for detecting hyperandrogenism 1, 5

• Do not assume PCOS without excluding other causes of hyperandrogenism, particularly NCCAH, Cushing's syndrome, and tumors 2