What investigations should be ordered for a patient presenting with Polycystic Ovary Syndrome (PCOS) as indicated by ultrasound?

Investigations for PCOS with Ultrasound Findings

Order comprehensive hormonal and metabolic testing including total testosterone (preferably by LC-MS/MS), TSH, prolactin, 2-hour oral glucose tolerance test, and fasting lipid panel to complete the diagnostic workup and assess metabolic complications. 1, 2

Essential Hormonal Testing

First-Line Androgen Assessment

• Measure total testosterone using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the single best initial biochemical marker, with 74% sensitivity and 86% specificity for PCOS diagnosis 2
• Calculate free testosterone using the Vermeulen equation from high-quality total testosterone and SHBG measurements, which demonstrates the highest sensitivity at 89% with 83% specificity 1, 2
• LC-MS/MS is mandatory over direct immunoassays because it shows superior specificity (92% vs 78%) 2

Second-Line Androgen Testing (if total/free testosterone normal but clinical suspicion remains high)

• Measure androstenedione (A4), which has 75% sensitivity and 71% specificity 1, 2
• Measure DHEAS to evaluate adrenal androgen production, particularly valuable in women <30 years, with 75% sensitivity and 67% specificity 1, 2

Exclude Other Endocrine Disorders

• Measure TSH to rule out thyroid disease as a cause of menstrual irregularity 1, 2
• Measure prolactin using morning resting serum levels to exclude hyperprolactinemia (levels >20 μg/L considered abnormal) 2
• Measure 17-hydroxyprogesterone if DHEAS is elevated to rule out non-classic congenital adrenal hyperplasia 1, 2

Mandatory Metabolic Screening

All women with PCOS require metabolic screening due to increased risk of type 2 diabetes, dyslipidemia, and cardiovascular disease. 1, 2

Glucose Metabolism Assessment

• Perform 2-hour oral glucose tolerance test with 75g glucose load to screen for glucose intolerance and type 2 diabetes 1, 2
• Measure fasting glucose and insulin levels; a glucose/insulin ratio >4 suggests reduced insulin sensitivity 2

Lipid Assessment

• Obtain fasting lipid panel including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides 1, 2

Anthropometric Measurements

• Calculate BMI to assess obesity (BMI >25 considered obese) 2
• Measure waist-hip ratio to identify central obesity (WHR >0.9 indicates truncal obesity) 2

Optional Ovulatory Function Assessment

• Measure LH and FSH between days 3-6 of menstrual cycle; an LH/FSH ratio >2 suggests PCOS, though this is abnormal in only 35-44% of women with PCOS, making it a poor standalone diagnostic marker 2
• Measure progesterone in mid-luteal phase to confirm anovulation (levels <6 nmol/L indicate anovulation) 2

Critical Diagnostic Considerations

When Ultrasound Alone is Sufficient

If the patient has both irregular menstrual cycles AND clinical/biochemical hyperandrogenism, ultrasound is not necessary for PCOS diagnosis, though it will identify the complete PCOS phenotype 3

AMH Testing Not Recommended

Do not use AMH levels as an alternative for detecting polycystic ovarian morphology or as a single test for PCOS diagnosis due to lack of standardization, no validated cut-offs, and significant overlap between women with and without PCOS 3, 1, 2

Age-Specific Ultrasound Limitations

• Ultrasound should not be used for PCOS diagnosis in those with gynecological age <8 years (<8 years after menarche) due to high incidence of multifollicular ovaries in this life stage 3
• In adolescents (<20 years, at least 1 year post-menarche), avoid ultrasound as primary diagnostic tool due to high false-positive rate; rely more heavily on clinical and biochemical hyperandrogenism plus menstrual irregularity 1

Conditions to Exclude

High-Priority Exclusions

• Screen for Cushing's syndrome if patient has buffalo hump, moon facies, hypertension, abdominal striae, central fat distribution, easy bruising, or proximal myopathies 1, 2
• Consider androgen-secreting tumors if rapid onset of symptoms, severe hirsutism, or very high testosterone levels (androstenedione >10.0 nmol/L) 1, 2

Additional Differential Diagnoses

• Primary ovarian failure (check FSH levels) 1, 2
• Acromegaly if coarse facial features or enlarged hands/feet are present 1, 2

Common Pitfalls to Avoid

• Normal testosterone does not exclude PCOS: Total testosterone is abnormal in only 70% of women with confirmed PCOS, meaning 30% have normal testosterone levels despite having the condition 2
• Clinical hyperandrogenism alone is sufficient: A woman can be diagnosed with PCOS based solely on clinical hyperandrogenism (hirsutism, acne, or alopecia) plus irregular menstrual cycles, without any abnormal laboratory values, per Rotterdam criteria 2
• Do not test hormones while on hormonal contraception: Biochemical hyperandrogenism testing requires testing in the absence of hormonal contraception, including progestin-only implants like Implanon, which suppress the hypothalamic-pituitary-ovarian axis and make hormone levels unreliable 1