Differential Diagnosis for a 27-Year-Old Woman with Hirsutism, Acne, Irregular Menses, Hypercholesterolemia, Insulin Resistance, and Anemia with Eosinophilia
Polycystic ovary syndrome (PCOS) is the most likely diagnosis, accounting for 70-80% of hirsutism cases in young women and directly explaining the constellation of hyperandrogenism (acne, hirsutism), menstrual irregularity, insulin resistance (elevated HOMA index), and dyslipidemia (elevated LDL cholesterol). 1
Primary Diagnosis: Polycystic Ovary Syndrome (PCOS)
PCOS is a hyperandrogenic chronic anovulation disorder affecting 4-6% of women in the general population, characterized by acceleration of pulsatile GnRH secretion, insulin resistance, hyperinsulinemia, and downstream metabolic dysregulation. 2 The pathophysiology involves hypersecretion of luteinizing hormone, ovarian theca stromal cell hyperactivity, and hypofunction of the FSH-granulosa cell axis, resulting in hyperandrogenism, hirsutism, follicular arrest, and ovarian acyclicity. 2
Clinical Features Supporting PCOS in This Patient:
Hyperandrogenism manifestations: Acne and hirsutism (hairy hands) are classic presentations of androgen excess in PCOS. 1, 3
Menstrual irregularity: Irregular cycles indicate chronic anovulation, a hallmark of PCOS. 4, 5
Insulin resistance: Elevated HOMA index directly indicates insulin resistance, which is present in 65-80% of women with PCOS and plays a crucial role in the pathophysiology. 2, 4
Dyslipidemia: Women with PCOS frequently have elevated LDL cholesterol levels, disproportionately elevated compared to other lipid fractions, due to insulin resistance. 2 The insulin resistance is associated with elevated triglyceride levels, increased small dense LDL cholesterol, and decreased HDL cholesterol. 2
Age: At 27 years old, this patient is in the typical age range for PCOS presentation. 5
Important Differential Diagnoses to Exclude
Non-Classical Congenital Adrenal Hyperplasia (NCAH)
NCAH (21-hydroxylase deficiency) can present with hirsutism, acne, and menstrual irregularity similar to PCOS. 1
Key distinguishing test: Measure DHEAS levels (age 20-29: >3800 ng/ml is abnormal) and androstenedione (>10.0 nmol/l suggests adrenal pathology). 2
NCAH may cause modest elevation of testosterone but typically has more pronounced DHEAS elevation than PCOS. 2
Androgen-Secreting Tumors (Ovarian or Adrenal)
Critical red flag: Total testosterone >200 ng/dL or very rapid onset of virilization suggests tumor. 1
Measure total testosterone or bioavailable/free testosterone (>2.5 nmol/l is abnormal for PCOS range). 2
Androstenedione >10.0 nmol/l warrants investigation to rule out adrenal/ovarian tumor. 2
Cushing's Syndrome
Look for coexisting signs: buffalo hump, moon facies, hypertension, abdominal striae, centripetal fat distribution, easy bruising, or proximal myopathies. 2
Screen with appropriate testing if these features are present. 2
Thyroid Disease and Hyperprolactinemia
Measure thyroid-stimulating hormone to exclude thyroid disease as a cause of menstrual irregularity. 2
Measure prolactin levels (>20 μg/l is abnormal) to rule out hyperprolactinemia, which can cause menstrual irregularity. 2 Note that prolactin may be mildly raised in patients with epilepsy, and drugs may impact prolactin levels. 2
Functional Hypothalamic Amenorrhea (FHA)
FHA is characterized by low gonadotropin levels (especially LH <7 IU/ml), history of weight loss, vigorous exercise, or stress, and negative progesterone challenge test. 2
FHA patients typically have low insulin levels and normal insulin sensitivity, which contrasts with this patient's elevated HOMA index. 2
Addressing the Anemia with Eosinophilia
The anemia with eosinophilia does not fit the typical PCOS presentation and requires separate investigation. This finding is unusual and suggests:
- Parasitic infection: Most common cause of eosinophilia with anemia
- Allergic conditions or drug reactions
- Hematologic disorders: Including eosinophilic syndromes
- Autoimmune conditions: Though less likely to present with isolated eosinophilia
This component requires independent workup including complete blood count with differential, peripheral smear, stool examination for ova and parasites, and consideration of other systemic causes.
Recommended Diagnostic Workup
Hormonal Evaluation:
LH and FSH: Measure between day 3-6 of cycle; LH/FSH ratio >2 supports PCOS. 2
Total testosterone or free testosterone: Levels >2.5 nmol/l suggest PCOS; levels >200 ng/dL suggest tumor. 2, 1
DHEAS: Age-specific cutoffs to rule out NCAH (age 20-29: >3800 ng/ml abnormal). 2
Androstenedione: >10.0 nmol/l warrants tumor investigation. 2
Prolactin: Morning resting levels >20 μg/l are abnormal. 2
TSH: To exclude thyroid disease. 2
Metabolic Evaluation:
Two-hour oral glucose tolerance test with 75-gram glucose load: All women with PCOS should be screened for type 2 diabetes and glucose intolerance due to demonstrated increased risk. 2
Fasting lipid panel: Including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. 2
Mid-luteal progesterone: <6 nmol/l indicates anovulation. 2
Imaging:
- Pelvic ultrasound (transvaginal or transabdominal, day 3-9 of cycle): >10 peripheral cysts 2-8 mm diameter in one plane with thickened ovarian stroma indicates polycystic ovaries. 2, 1
Clinical Pitfalls to Avoid
Do not confuse isolated polycystic ovaries with PCOS: Polycystic ovaries on ultrasound alone (without symptoms or hormonal abnormality) occur in 17-22% of normal women. 2
Timing matters for hormone testing: LH, FSH, and testosterone should be measured on days 3-6 of the menstrual cycle for accuracy. 2
Do not measure prolactin post-ictally: If the patient has epilepsy, ensure prolactin is not measured after a seizure. 2
Consider medication effects: Certain antiepileptic drugs (valproate, carbamazepine, phenobarbital, phenytoin) can affect sex hormone levels and may trigger or worsen PCOS features. 2, 1