Distinguishing PCOS and Cushing's: Does testosterone tell the tale?

Cushing's Syndrome (CS) has been considered rare, but thoughts are changing about that. This article notes that fact, pointing out "most published articles on CS have examined patients with sustained and severe hypercortisolism." It also points out the increased recognition of the prevelance of "mild" and "episodic" CS which have both normal and high values with testing. (Image source)

CS and polycystic ovarian syndrome (PCOS) present similarly, but are treated much differently.

Both diseases can present with weight gain, hirsutism, acne, and irregular periods in women. However, CS usually includes symptoms such as easy bruising, sleep disturbances, decreased libido, a buff alo hump, and stretch marks, which are not present in PCOS. Women with mild and/or periodic CS, however, can be difficult to diagnose as they may lack classic manifestations of the disease and the diagnosis may require multiple hormonal measurements [4, 5, 7] . The treatment of CS is primarily the surgical removal of a pituitary, adrenal, or ectopic tumor. The treatment for PCOS is primarily medical and includes oral contraceptives, biguanides (metformin), thiazolidinediones (rosiglitazone or pioglitazone) or androgen antagonists (spirolactone or flutamide) [8] . Thus, distinguishing the two conditions is important.

This study used women who, under the 1990 NIH criteria, have PCOS. These were compared to women who had been diagnosed with mild CS due to a pituitary adenoma. The study goes into great detail about the criteria for each set.

The authors hypothesized "either total testosterone (TT) or bioavailable testosterone (BT) levels or the calculation of the free androgen index (FAI) would be low in patients with mild CS and elevated in patients with PCOS, and could help differentiate the two conditions." According to their statistical analyses:

Total testosterone gave the highest sensitivity, positive predictive value (PPV)and negative predictive value (NPV) while BT gave the highest specifi city for the diagnosis of CS. Determinations AUC demonstrate that use of a TT level gave “ good ” diagnostic accuracy, while BT and FAI gave “ fair ” diagnostic accuracy.

The authors emphasize "[m]ost commercial assays lack the accuracy and precision of assays when measuring testosterone in women, as recently reviewed in an Endocrine Society position statement [35]". They used mass spectroscopy analysis done at Esoterix Laboratories. They also determined there is overlap between the two groups when dexamethasone suppression is used due to the mild/cyclic nature of these CS patients. Most of all, the phenotypes between the two groups may be similar. Testosterone analysis, when using an accurate and precise assay at a validated laboratory, may be another tool to distinguish between the two.

Note: There are some great graphs and charts in the full-text article. It is well worth perusing. My previous post has some of them included in the first scribd presentation by Dr. Friedman.

Pall, M., Lao, M., Patel, S., Lee, M., Ghods, D., Chandler, D., & Friedman, T. (2008). Testosterone and Bioavailable Testosterone Help to Distinguish between Mild Cushing's Syndrome and Polycystic Ovarian Syndrome Hormone and Metabolic Research, 40 (11), 813-818 DOI: 10.1055/s-0028-1087186