Late-Onset Congenital Adrenal Hyperplasia (CAH) - a Great Mimicker of PCOS

Irregular ovulation is one of the most common endocrine disorders affecting women of reproductive age leading to abnormal bleeding and infertility. Causes vary, but by far the largest culprit is a condition called polycystic ovary syndrome (PCOS) especially when the irregular ovulation is accompanied by signs of excessive male hormone production such as upper lip hair or acne. The prevalence of PCOS is approximately 6-8% in the general population. Because PCOS is so prevalent, clinicians often overlook the fact that other medical conditions, some with severe health risks, can lead to a similar presentation.

Mutations in 21-hydroxylase exist among Caucasians at a frequency as high as 1 in 1000 to 1 in 100. The prevalence is even higher among Mediterraneans, Hispanics, and Eastern European Jews. As mentioned before, men with late-onset CAH are typically asymptomatic. Women can present with a symptom profile that is indistinguishable from that of PCOS: infrequent or absent ovulation and excessive androgen. These are the patients with the risk of being misdiagnosed. Depending on the patient’s ethnicity, the chances of having late-onset CAH in those who present with apparent PCOS range between <5% in the U.S. and up to 10% in some European countries. In a specific region of Turkey, the prevalence of late-onset CAH in PCOS-like patients is reportedly to be as high as 60%.

Why is it important to make the right diagnosis when the treatment for menstrual irregularities and androgen excess is the same for PCOS and late-onset CAH? After all, hormonal birth control is still the first line therapy for both symptoms. In severe cases of facial hair, other pharmacologic agents can be added. However, it is vitally important to make the right diagnosis because many women desire conception. If a woman with late-onset CAH has a partner who happens to be also a carrier of a more severe mutation (carriers are asymptomatic), their child may inherit two different mutations that in combination can lead to the classic form of CAH. Classic CAH can be lethal at birth. Preconception genetic testing of both parents and appropriate counseling are essential to minimize the risks of classic CAH in the offspring. A simple blood test to differentiate late-onset CAH from PCOS can make the world of difference.

- Liyun Li, M.D.

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