What is the appropriate management for a patient with hyperandrogenism, normal DHEA, and normal FSH and LH levels, presenting with skin discoloration?

Management of Hyperandrogenism with Elevated Testosterone, Normal DHEA-S, and Normal Gonadotropins

This patient most likely has polycystic ovary syndrome (PCOS) and should be evaluated with pelvic ultrasound, fasting glucose/insulin, lipid panel, and TSH/prolactin levels, followed by first-line treatment with combined oral contraceptives. 1, 2

Diagnostic Interpretation

Hormone Pattern Analysis

• Elevated testosterone (57 ng/dL) with normal FSH and LH strongly suggests ovarian androgen excess rather than adrenal or pituitary pathology 1, 2
• Normal DHEA-S effectively rules out adrenal causes including non-classical congenital adrenal hyperplasia and adrenal tumors, as DHEA-S >2700 ng/mL (age 30-39) would indicate adrenal pathology 1, 3
• Normal gonadotropins (FSH/LH) exclude primary ovarian failure and suggest functional ovarian hyperandrogenism rather than hypothalamic-pituitary dysfunction 1

Most Likely Diagnosis

• PCOS is the most common cause of this hormonal pattern in women of reproductive age, affecting 4-6% of the general population 1, 2
• The combination of elevated testosterone with normal gonadotropins is characteristic of PCOS, where ovarian theca cells produce excess androgens despite normal pituitary function 1

Essential Additional Testing

Confirm Hyperandrogenism

• Repeat morning testosterone measurement using LC-MS/MS if available, as this is the gold standard method with superior accuracy compared to immunoassay 1, 2
• Measure free testosterone or calculate free androgen index (FAI) to assess bioavailable androgen, as SHBG fluctuations can affect interpretation 1, 2

Rule Out Alternative Diagnoses

• Measure serum prolactin to exclude hyperprolactinemia, which can cause menstrual irregularity and hirsutism 1, 2
• Check TSH levels to rule out thyroid disease, which can present with similar symptoms 1, 2
• Perform pelvic ultrasound (transvaginal preferred, day 3-9 of cycle) looking for >10 peripheral cysts (2-8 mm diameter) and thickened ovarian stroma characteristic of PCOS 1, 2

Assess Metabolic Complications

• Obtain fasting glucose and 2-hour oral glucose tolerance test to screen for diabetes and insulin resistance, which are common in PCOS 1, 2
• Check fasting lipid panel to assess cardiovascular risk 2
• Calculate glucose/insulin ratio if fasting insulin is measured; ratio >4 suggests reduced insulin sensitivity 1

Evaluate Skin Discoloration

• Examine for acanthosis nigricans (dark, velvety patches typically in neck, axillae, groin), which indicates insulin resistance and is common in PCOS 2
• If skin changes are atypical, consider dermatology referral to exclude other causes 1

Critical Red Flags Requiring Urgent Evaluation

When to Suspect Androgen-Secreting Tumor

• Testosterone >150-200 ng/dL (>5.2-6.9 nmol/L) warrants immediate imaging for ovarian or adrenal tumor 1, 3
• Rapid onset of virilization (clitoromegaly, voice deepening, increased muscle mass) suggests tumor rather than PCOS 4, 5
• Very elevated DHEA-S (>600 μg/dL) would indicate adrenal adenoma, though this patient's DHEA-S is normal 3

When to Refer to Endocrinology

• Persistently elevated prolactin on repeat testing requires pituitary MRI and endocrinology referral 1
• Testosterone <150 ng/dL with low/normal LH should prompt pituitary MRI regardless of prolactin to exclude non-secreting adenomas 1

First-Line Treatment Approach

Combined Oral Contraceptives (COCs)

• COCs are first-line therapy for hyperandrogenism in PCOS, effectively regulating menstrual cycles and reducing androgen levels 2, 6
• COCs work by suppressing ovarian androgen production, increasing SHBG (which lowers free testosterone), and directly antagonizing androgen effects on skin 6
• Formulations containing progestogens with antiandrogenic activity (such as cyproterone acetate, drospirenone) are preferred for treating hirsutism and acne 6

Lifestyle Modifications

• Weight loss through diet and exercise is crucial for overweight/obese patients, as it improves insulin sensitivity and reduces androgen levels 2
• Even 5-10% weight reduction can significantly improve hormonal and metabolic parameters in PCOS 2

Adjunctive Antiandrogen Therapy

• Spironolactone (100-200 mg/day) can be added if COCs alone are insufficient for controlling hirsutism 1, 6
• Cyproterone acetate in higher doses (25-100 mg/day) may be used for severe hirsutism or acne, with improvement expected after 6-12 months 6
• Antiandrogens require contraception due to teratogenic risk in male fetuses 6

Common Pitfalls to Avoid

Laboratory Interpretation Errors

• Do not rely on single testosterone measurement, as levels can fluctuate; confirm with repeat testing 2, 3
• Avoid direct immunoassay for free testosterone, as it has poor accuracy at low concentrations typical in women 1, 2
• Consider SHBG effects: obesity, metabolic syndrome, and insulin resistance lower SHBG, increasing free testosterone even when total testosterone appears normal 6, 3

Diagnostic Oversights

• Do not confuse isolated polycystic ovaries on ultrasound with PCOS; diagnosis requires both hyperandrogenism and ovulatory dysfunction 1, 2
• Normal testosterone does not exclude hyperandrogenism if clinical signs are present; measure androstenedione and DHEA-S as second-line tests 1, 2
• Screen for non-classical congenital adrenal hyperplasia with 17-hydroxyprogesterone if family history or ethnic background suggests risk 1

Treatment Considerations

• Address psychological impact of hirsutism and skin changes as part of comprehensive care 2
• Monitor for metabolic syndrome development, as PCOS increases long-term cardiovascular and diabetes risk 1, 2
• Counsel about fertility preservation if patient desires future pregnancy, as some treatments may affect reproductive potential 1