Polycystic ovarian syndrome (PCOS) is often a convenient diagnosis for many actually suffering with other endocrine disorders. Cushing's patients are frequently misdiagnosed with PCOS. It is an easy diagnosis (in layman's terms) and avoids the multiple tests and confusion which suspicion of Cushing's seems to bring. In a previous post, I wrote about 4 cases of Cushing's misdiagnosed as PCOS. Once treated for the Cushing's, all symptoms which had been attributed to PCOS resolved.A new article in the New England Journal of Medicine, Inactivating PAPSS2 Mutations in a Patient with Premature Pubarche, the authors show that "PAPSS2 deficiency should be added to the list of defined causes of androgen excess that must be ruled out before diagnosing the polycystic ovary syndrome."
There are two isozymes encoded by genes located on chromosome 4 (PAPS synthase 1) and chromosome 10 (PAPS synthase 2, also abbreviated as PAPSS2) which are important in the sulfation of DHEA to DHEAS. DHEA is a precursor to androgens, and when the sulfation to DHEAS can not take place, the authors hypothesize this leads to androgen excess. They present the case of an 8 year-old girl with "premature pubarche, hyperandrogenic anovulation, very low DHEAS levels, and increased androgen levels." They determined she had a genetic defect which caused a loss of PAPSS2 activity. It is still unclear why the PAPSS1 enzyme did not compensate for that.
The article is well-written, very thorough, and full of graphs, pictures, and diagrams. It explains how they followed this young lady for several years, the studies they did, and the testing that was done. It also begs the question of diagnosing PCOS due to androgen excess. PAPSS2 deficiency appears to be a genetic adrenocortical cause of androgen excess.
Noordam C, Dhir V, McNelis JC, Schlereth F, Hanley NA, Krone N, Smeitink JA, Smeets R, Sweep FC, Claahsen-van der Grinten HL, Arlt W. (2009). Inactivating PAPSS2 mutations in a patient with premature pubarche New England Journal of Medicine, 360 (22), 2310-2318 PMID: 19474428
To read more:
Distinguishing PCOS and Cushing's: Does testosterone tell the tale?
Cushing's Syndrome in Women With Polycystic Ovaries and Hyperandrogenism
Gosh PCOS seems to be the diagnosis du jour! I'm just beginning to investigate Cushing's after feeling that something wasn't quite right about my PCOS diagnosis - my androgens are low, I'm ovulating, and I have no evidence of insulin resistance. But my increasing cortisol serum readings and elevated nightime saliva collection meant nothing to my docs! Shees!
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