February 27, 2008

They Grow Up So Fast These Days: Is a Fungal Toxin Involved?

ResearchBlogging.orgFungi are amazing biochemical factories. They produce a bewildering array of unusual compounds, including quite a few that qualify as toxins. These range from deadly amanitins to psychotropics. Moreover, some of these compounds are close mimics for human hormones. Because of this, my interest was quite high when I saw reports of a paper entitled High Growth Rate of Girls with Precocious Puberty Exposed to Estrogenic Mycotoxins in the Journal of Pediatrics. The idea that Fusarium, a common pathogen of certain grains, might have a role in inducing the early onset of puberty in girls is certainly an intriguing thought. After reading this paper, though, I'm not convinced that the authors have added anything to our body of knowledge regarding this possibility.

The study begins with two cohorts of girls who have sought treatment for central precocious puberty (CPP) in northwestern Italy. 17 are from Viareggio and 15 are from Pisa. Serum samples are taken and a variety of Fusarium-originated mycotoxins are sought. Out of the 32 girls diagnosed with CPP, only 6 of them test positively for two compounds, namely zearalenone (ZEA) and α-zearalanol (α-ZOL), one of its metabolites. All 6 of these girls were from the Viareggio cohort; none of the girls from Pisa were positive for any mycotoxin at all. Over the course of twelve months of treatment with triptorelin (Decapeptyl), the six girls with CPP and mycotoxins form one group and those with CPP but no mycotoxin (26) form a second. The changes to estrogen levels, height, weight and bone age, etc. are charted and compared to the control group of girls without CPP.

Herein lies my first problem with this study; there is no data on the effect of triptorelin on prepubescent children. Triptorelin itself is a gonadotropin inducer. According to the Mayo Clinic's Drugs & Supplements page, for example:

Triptorelin is similar to a hormone normally released from the hypothalamus gland...

Studies on this medicine have been done only in adult patients, and there is no specific information comparing use of triptorelin in children with use in other age groups.
The researchers are introducing a confounding factor from the outset.

Secondly, the researchers never appear to check whether any of their control subjects have mycotoxins in their blood. Considering that only 6 of the 32 girls presenting with CPP had the toxins, it would have been a good control to rule out the presence of ZEA and α-ZOL in the girls who didn't have CPP at all. A lack of controls is a problem throughout this study; however, forcing the investigators to admit in their closing discussion that
...ZEA pollution could not explain the epidemic CPP data of the Viareggio area, suggesting that other environmental factors such as dioxin and pesticides may be involved.
What the investigators demonstrate, in the end is that girls with CPP who are positive for the mycotoxins grow a bit faster than girls with CPP but no mycotoxin, and both groups get taller faster than those girls who don't have CPP at all.

That the first two groups grow faster than the control group is unsurprising; that's what one would expect with early puberty. Moreover, the differential growth between the two CPP groups is shown to occur only after therapy with injections of triptorelin has been ongoing for three and twelve months. There is no investigation of whether the treatment itself may be causing this effect. We don't even see a statiscally significant change in estrogen levels between the groups. At best we can say, then, that there may be evidence here that an interaction of triptorelin and Fusarium-derived 17β-estradiol mimics may cause an increased rate of growth in girls diagnosed with CPP. Even that is rather tenuous, though, as the sample size is so small and no controls have been put in place for other potential interactions.

Despite this, the authors go on to discuss the similarities between the mycotoxins found in the six girls from Viareggio and growth promoters fed to livestock in the United States but which have been banned in Europe since 1985. These compounds are similar, but they aren't the same as the compounds isolated from the mycotoxin-positive cohort. The language that follows strikes me as being a bit alarmist and speculative in terms of the phenomenon that the researchers had set out to study.

All in all, I don't see much of value in the results from this study. It remains possible, of course, that Fusarium might play a role in some instances of CPP, perhaps in combination with other factors. Then again, it might not. Without more information about the effects of the drug being given to these girls in the course of treatment and about other environmental contaminants, not to mention some genetic background, the authors haven't given us much to go on.

Massart, F., Meucci, V., Saggese, G., Soldani, G. (2008). High Growth Rate of Girls with Precocious Puberty Exposed to Estrogenic Mycotoxins. The Journal of Pediatrics DOI: 10.1016/j.jpeds.2007.10.020

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