Cushing's Syndrome in Women With Polycystic Ovaries and Hyperandrogenism

P. Gerry Fegan; Derek D. Sandeman; Nils Krone; Deborah Bosman; Peter J. Wood; Paul M. Stewart; Neil A. Hanley


Nat Clin Pract Endocrinol Metab. 2007;3(11):778-783. 

In This Article

Discussion of Diagnosis

Diagnosis of Polycystic Ovarian Syndrome

PCOS is a multifactorial complex genetic disorder with dysregulated steroidogenesis.[1] The initial diagnosis of PCOS in this patient was made owing to the presence of its hallmark clinical features of hyperandrogenism, anovulation and polycystic ovaries: the three diagnostic criteria included in the Rotterdam Consensus Statement on PCOS.[2,3] At presentation to the clinic 7 years later, however, the case bore cardinal features of Cushing's syndrome, which were inconsistent with PCOS; namely, plethoric round facies, supraclavicular fat pads and violaceous striae.[4] The hypercortisolism had probably existed during the preceding 7 years and was certainly present immediately before the correct diagnosis was made when the patient was under active PCOS treatment. It is interesting that during this period the patient carried a pregnancy to term, when, potentially, the cortisol excess was temporarily attenuated by placental type 2 11β-hydroxysteroid dehydrogenase.[5]

All definitions of PCOS make reference to infrequent or absent ovulation and clinical or biochemical features of hyperandrogenism.[1,2,3] The Rotterdam Consensus Statement adds polycystic ovaries as a third criterion, with a diagnosis of PCOS requiring two out of three factors.[2,3] In addition, serum estradiol should be detectable in cases of PCOS[6] and, unlike in this case, in our experience serum estradiol is usually more than 150 pmol/l (40.9 pg/ml).

Most importantly, all definitions of PCOS require the exclusion of other causes of hyperandrogenism; failure to do so increases the potential for misdiagnosis.[1,7] Although the present case illustrates this risk on its own, we know of three other cases in which an original diagnosis of PCOS became revised to that of Cushing's syndrome ( Table 1 ). Upon curative treatment, all symptoms, originally attributed to PCOS, resolved. The diagnosis, treatment and management of Cushing's syndrome have been the subject of recent discussion in this journal.[4] Here, we address the importance of correctly distinguishing Cushing's syndrome from PCOS to minimize the risk of misdiagnosis.

How Common Might This Scenario Be and Is it Important?

PCOS is one of the commonest endocrine conditions and affects up to 10% of women of reproductive age.[8] Accordingly, PCOS is a frequent presentation to primary care. By contrast, classical Cushing's syndrome is considered rare, yet unlike PCOS it is curable.[4,9] Screening 340 referrals for hirsutism found only 1 case of Cushing's syndrome.[10] Where clinical features overlap to a greater extent, however, rates of detection of Cushing's syndrome are much higher. Screening individuals with type 2 diabetes, which is associated with PCOS, detects cortisol excess in 2-5% of patients.[9]

These findings imply that beneath the classical, rare presentation of Cushing's syndrome with specific but insensitive features (e.g. purple striae)[4] there exists an undercurrent of more prevalent subtle cortisol excess,[9] which reinforces the importance of careful history taking, examination and (potentially repeated) investigations in order to exclude Cushing's syndrome. A recent survey, however, found that only 17% of endocrinologists and 6% of gynecologists screened 'PCOS referrals' for Cushing's syndrome,[11] and Table 1 illustrates cases in which the diagnosis of Cushing's syndrome was initially missed. In Case B only written advice on PCOS management was issued by the initial referral center. Case D presented with primary amenorrhea, the false diagnosis of PCOS being made on the basis of ultrasonography findings and hyperandrogenism.

The ability to distinguish between PCOS and Cushing's syndrome is important because Cushing's syndrome, which is more frequent in women than men, increases age-adjusted and sex-adjusted mortality fivefold; yet--as shown by the case described here--once identified can be cured.[9] By contrast, PCOS is a heterogeneous disorder that can be managed but not eliminated.[1]


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