Friday, 13 January 2012

New origin(?) and New methodology(!) - Reassessing Cushing's syndrome

Because I am having trouble respecting the schedule I presented myself earlier this week (loads of stuff going on in the lab, questions without answers and optimising procedures), I decided to, at least, offer my audience a few of the advances science made concerning Cushing's syndrome since I last presented my BSc thesis. Not that I think my thesis offered a brand new perspective to the world, possibly the only persons who read it were the ones who had to assess it and myself; in addition, rarely (in my perspective) an undergraduate studying a case-study will ever produce scientific roller-coasters. However, I'd like to know what has changed concerning this topic since the last time I deliberately "sat" on top of the ideas I was studying back in 2007. 

Possibly, if time and responsibilities allow me, then during the weekend I will finally post my BSc presentation and wait for the comments of those who know a lot more on the subject than I do. I'd also like to invite whoever studies or works in the fields of Toxicology, Endocrinology, Molecular Microbiology or similar areas, to just share their BSc presentations with us, it is a good way of making knowledge ever more accessible and show other people what you've been working on. Sometimes it might help others progress on their own research fields. No knowledge should ever be wasted.

Now! Focusing on two nice papers I recently found concerning this whole topic. The first one comes from Spain, more precisely from the Institute for Biomedical Research and the National Biotechnology centre, both in Madrid, also with the participation of the Asturian Oncology Universitary Institute, in Oviedo. They recently published an article concerning the growing role of DNA methylation on endocrine function where they briefly touch Cushing's syndrome:

This research group states that "The pro-opiomelanocortin [a precursor polypeptide involved in expressed in both lobes of the pituitary gland and once mutated is related to early onset obesity and adrenal insufficiency - tipical of the Cushing's pattern of symptoms I think],  gene plays an important role not only in the regulation of the HPA axis [hypothalamic-pituitary-adrenal] and adrenal development but also in obesity". [1] 

These researchers say that pro-opiomelanocortin gene is functional in "ACTH-dependent Cushing’s syndrome" [1]. The POMC promoter that shows normal features "normal non-methylation" in sane tissues is, therefore, "specifically demethylated in expressing tissues and tumors". [2] The methylation biomolecular and biochemical consequences can be found in the article, it wouldn't be respectful to disrispect copyrights, nevertheless they suggest that different levels of methylation can occur which will ultimately affect appetite and obesity [2]. The ideas might not be completely new as they even subliminally assume by referring very frequently the works of Newell-Price published in 2003. However, it does have significance especially for those who in the 90s underwent surgery and even though found themselves with recurrent Cushing's episodes, thus looking for another possible explanation to their problem. The later is but a personal hypothesis!
A second paper that I will very briefly touch concerns a new method for measuring cortisol in Cushing's syndrome patients. Length of exposure to glucocorticoids define how harsh Cushing's can be, thus representing a fine indicator for endocrinologists. I remember that back in 2007 I worked with around 15 years of data from one single patient; the data I analysed contained levels for salivary, serum and urinary cortisol... amongst other indicators. But very recently, a research team from Ontario, Canada, found a brand new perspicacious way of measuring and comparing past/present levels of glucocorticoids. Simply by adapting a salivary kit and testing for hair. Exactly, for hair!!! As they say in their abstract:

"The severity of Cushing's Syndrome (CS) depends on the duration and extent of the exposure to excess glucocorticoids... Current measurements of cortisol in serum, saliva and urine reflect systemic cortisol levels at the time of sample collection, but cannot assess past cortisol levels. Hair cortisol levels may be increased in patients with CS, and, as hair grows about 1 cm/month, measurement of hair cortisol may provide historical information on the development of hypercortisolism". [3], thus suggesting "that hair cortisol measurement is a novel method for assessing dynamic systemic cortisol exposure and provides unique historical information on variation in cortisol...", but has they say this is just too recent and better understanding of the limitations and advantages associated to this technique are necessary.

These are two simple ideas in a world of research; fresh principles that when thoroughly studied might provide a much better understanding of the ways to prevent Cushing's syndrome expressing, and even the methodology to comprehend how successful treatment is through time.

[1] Garcia-Carpizo, V., Ruiz-Llorente, R., Fraga, M., Aranda, A. (2011). "The growing role of gene methylation in endocrine function". Journal of Molecular Endocrinology, 47, R75-R89.

[2] Newell-Price, J. (2003). "Proopiomelanocortin gene expression and DNA methylation: implications for Cushing’s syndrome and beyond". Journal of Endocrinology, 177, pp. 365–372. 

[3] Thomson, S., Koren, G., Fraser, L. A., Rieder, M., Friedman, T. C., Van Hum, S. H. M. (2010). "Hair Analysis Provides a Historical Record of Cortisol Levels in Cushing's Syndrome"Exp Clin Endocrinol Diabetes, 118(2), pp. 133-138.

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