I knew it.

[kickaha]

Remember how my endocrinologist dismissed Addison's out of hand because I don't exhibit hyperpigmentation?

Pigmentation in all non-redheads is the production of eumelanin by melanocytes, triggered by the gene MC1R which is expressed in binding melanotropin to the melanocyte.

ACTH and melanotropin are both products of the proopiomelanocortin (POMC; 176830) gene.[1] Leftover ACTH can be broken down in the blood, and one of the pieces is free melanotropin, ready to bind to the MC1R,[2] which is why excessive ACTH in primary Addison's disease causes hyperpigmentation.[3]

BUT...

Redheads don't express eumelanin, but pheomelanin[4, 5, 6], which is NOT produced by the above chain, in fact, pheomelanin production is turned *off* by the triggering of eumelanin[6], and the MC1R receptor site in redheads is generally dead of any activity. [4][5] Therefore the presence of melanotropin won't activate the melanocytes. It's the whole reason we *ARE* redheads.

So excess ACTH *won't* cause hyperpigmentation in redheads.

Dipshit.




Great. I'm still doing homework for the slow ones. Twenty minutes with Google, skimming articles and putting the pieces together. It took me longer to write this.

Biblio:
1) http://www3.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=155555
2) Nat. Genet. 11: 238, 1995
3) http://www.emedicine.com/DERM/topic761.htm
4) J. Inv. Derm. 117: 1314, 2001
5) Hum. Mol. Genet. 9: 2531, 2000
6) Barsh, G.S. (1996) The genetics of pigmentation: from fancy genes to complex traits. Trends Genet., 12, 299–305.

Comments

[morgyne.livejournal.com]

He's a doctor, duuuuh.

[jinasphinx.livejournal.com]

Jesus. Just another example of how we have to work so damn hard to jolt them out of their stupid decision tree. I hope you can find a smart endo.

[ginkgo.livejournal.com]

Indeed. I'm glad I sent you the article yesterday which kicked this off. Quite a good summary.

And we've found a backup guy in case he isn't better next time, which makes me happier. :)

[tealynx.livejournal.com]

I, also a redhead, had no pigmentation. Though I wonder now if I had more feckles while I was sick... I seem to have fewer now. I also had what seemed to be normal electrolight levels, which my (now ex) GP told me ment that I didn't have any kind of adrenal condtion.

Oh, and FYI, given what I've seen on the addision's mailing list, at least a third (and possibly as much as 3/4th) of all endos are idiots. And even my good endo totally blew me off and was completely convinced I wasn't sick (it was all in my mind after all) until the timed stim test came back. Then it was all "well, of course you do seem to have it. I knew it all the time" on the phone.

In good news, the drugs are helping... mostly. *hugs*

[hetaera15.livejournal.com]

God, if only your doc was more like the vets I've worked for...they're always like "Symptoms of Addison's(or Cushing's)? Do an ATCH stim right now!"
Or at least they were before the price of cortrosyn incresed about 500%.

[gwywnnydd.livejournal.com]

Can't help much with finding a decent endo, all the ones I've been sent to stare at me blankly until they realize I should be seeing a nephrologist, not an endo...

OTOH, I *can* commiserate with you on "Knowing more about your condition than the medical staff around you". BTDT all my life.
For some reason, doctors don't *like* being told "I know what's wrong with me and you don't." By a 10 year old.

[jason0x21.livejournal.com]

Research on Redheads is still rather new, we both know that from experience. Keep working the books and teaching the docs. Or find a redhead doc, like we did.

[babbleon1.livejournal.com]

I've been asking nurses I know whether our experiences were common, and three of four have now said, "patients have to manage their own care." Doctors are so busy they focus on the the easy answers to the exclusion of everything else.