Should a dexamethasone (Dex) suppression test be performed to differentiate between adrenal disorders and Polycystic Ovary Syndrome (PCOS), or a stimulatory test with 17-hydroxyprogesterone to distinguish between PCOS and adrenal pathology in a 47-year-old female with elevated androstenedione, Dehydroepiandrosterone Sulfate (DHEAS), and 17-hydroxyprogesterone levels?

From the Guidelines

A dexamethasone suppression test is the most appropriate initial step to differentiate between adrenal causes and PCOS in this patient. The laboratory values provided, including a slightly elevated 17-hydroxyprogesterone (90 ng/dL) and normal ACTH (20 pg/mL) with high-normal cortisol (19.4 μg/dL), suggest possible mild adrenal hyperfunction that needs to be evaluated 1.

Key Considerations

• The overnight 1mg dexamethasone suppression test would help determine if there is autonomous cortisol production or if the HPA axis responds normally to negative feedback.
• For this test, the patient should take 1mg of dexamethasone at 11pm and have cortisol measured at 8am the following morning.
• Cortisol suppression below 1.8 μg/dL would rule out Cushing's syndrome, as per the latest guidelines on Cushing's disease diagnosis and management 1.

Androgen Profile and PCOS Evaluation

• The androgen profile (testosterone 32 ng/dL, DHEAS 346 μg/dL) is not markedly elevated, and the FSH:LH ratio (15.6:9.2) doesn't show the typical LH predominance seen in PCOS.
• The normal DHEAS level makes adrenal hyperandrogenism less likely as the primary cause.
• If the dexamethasone test is normal, further evaluation for PCOS could follow based on clinical features like menstrual irregularities, hirsutism, or ovarian ultrasound findings, considering the diagnostic challenges and variations in androgen measurement methods 1.

Diagnostic Approach

• The choice between a dexamethasone suppression test and a STIM test with 17 hydroxyprogesterone for differentiating between PCOS and adrenal causes should be based on the clinical presentation and initial laboratory findings.
• Given the patient's profile, starting with a dexamethasone suppression test aligns with recommendations for suspected Cushing's syndrome or adrenal hyperfunction 1.

From the FDA Drug Label

Following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including fever, myalgia, arthralgia, and malaise Phenytoin, phenobarbital, ephedrine, and rifampin may enhance the metabolic clearance of corticosteroids, resulting in decreased blood levels and lessened physiologic activity, thus requiring adjustment in corticosteroid dosage. These interactions may interfere with dexamethasone suppression tests which should be interpreted with caution during administration of these drugs False negative results in the dexamethasone suppression test (DST) in patients being treated with indomethacin have been reported. Thus, results of the DST should be interpreted with caution in these patients

Dexamethasone Suppression Test may be done to differentiate between adrenal and PCOS disorders, but the results should be interpreted with caution due to potential interactions with other medications.

• The patient's hormone levels, including ACTH, cortisol, androstenedione, DHEAS, estrogen, progesterone, testosterone, LH, FSH, and 17 hydroxyprogesterone, should be considered when deciding which test to perform.
• A STIM test with 17 hydroxyprogesterone may also be considered for PCOS vs adrenal disorders, but the FDA drug label does not provide direct information on this test 2.

From the Research

Diagnostic Approach

To determine the source of androgen excess in the given patient, the following diagnostic approaches can be considered:

• A dexamethasone suppression test to differentiate between adrenal and PCOS causes of hyperandrogenism 3, 4, 5, 6
• A STIM test with 17 hydroxyprogesterone to evaluate PCOS vs adrenal causes 3, 4

Dexamethasone Suppression Test

The dexamethasone suppression test can be used to diagnose and differentiate causes of hyperandrogenism, including:

• Congenital adrenal hyperplasia (CAH) 5
• Polycystic ovary syndrome (PCOS) 4, 6
• Androgen-secreting tumors 7, 6
• Cushing's syndrome 7

STIM Test with 17 Hydroxyprogesterone

The STIM test with 17 hydroxyprogesterone can be used to evaluate:

• Ovarian function and androgen production 3, 4
• Adrenal function and androgen production 3, 4

Key Findings

• The patient's laboratory results show elevated androgen levels, including androstenedione, DHEAS, and testosterone 3, 4, 6
• The patient's 17 hydroxyprogesterone level is elevated, which may indicate CAH or adrenal hyperandrogenism 3, 5
• The patient's LH and FSH levels are within normal limits, which may suggest PCOS or other causes of hyperandrogenism 3, 4

Diagnostic Considerations

• The diagnosis of PCOS requires the exclusion of other causes of hyperandrogenism, including CAH, androgen-secreting tumors, and Cushing's syndrome 3, 4, 6
• The dexamethasone suppression test and STIM test with 17 hydroxyprogesterone can be used to differentiate between these causes and diagnose PCOS or adrenal hyperandrogenism 3, 4, 5, 6