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Atypical Cushing\'s And Xiao Yao San

by amymatthews - November 29, 2009

I was at your lecture on TCM and endocrine disease in September at the AHVMA meeting, interesting stuff! And now I have a patient who has developed atypical Cushing's with elevated 17-hydroxy progesterone and ZERO aldosterone (the internist involved with the case suspects deoxycorticosterone excess which is functioning as aldosterone given that her electrolytes are perfectly normal and aldosterone levels have been dropping with zero being the latest number). She has hypertension (~200-220), nonresponsive so far to meds or acupuncture (cases I've seen of Cushing's hypertension have responded best to treating the Cushing's). On ultrasound, both adrenals are enlarged and mass-like, so surgery isn't a good option. Ketoconazole has had no effect. We've talked about mitotane, but are worried how much it will screw up her system - take the normal corticosteroid levels down and cause an Addisonian crisis? Stop excess deoxycorticosterone production and cause an Addisonian crisis? The risk of death is a little high for our comfort, though the owner does an excellent job monitoring this dog.

To complete the picture, her tongue is dull pink with a reddish tip and sometimes sides; her pulse is thin and deep - hot and deficient. At her last appointment, her pulse was responsive to BL22-S, ovary point was active and TH5 was def.

Her history (since being rescued about 3 years ago, currently 10-12 years old) includes mammary carcinoma (surgically removed), masticatory myositis (treated with pred), bloat (after diet high in canola oil, which has been shown to be a risk factor), severe hip DJD (first pelvic adjustment literally GRATED; kept comfortable with acupuncture and chiropractic), thoracolumbar spondylosis, Anaplasmosis (we live in CT where it's common; treated with doxycycline), otitis (not common any more), and tendon injury just proximal to the accessory carpal bone (which healed with splinting, acupuncture, and laser). She's a busy girl!

I'd like to do a trial with Xiao Yao San. I was wondering if you have any knowledge about it's effect on the various hormones, or any thoughts in general? Do you have to adjust the dose to the clinical signs? How responsive have your patients been?

Thanks as always, looks busy on the forum after the holiday!

Amy

by naturevet

November 30, 2009

Whoa. This case is the first thing I looked at today, even before my morning coffee. Hell of a way to wake up. I almost had to go back to bed!

Anyway, after the fifth time reading it, I developed some ideas. Of course, the goal is always to try to find a thread that runs through everything, and that thread seems to be a 'pathogen in the Shao Yang'.

First off, it's the most likely cause of anything where there is the risk of sudden death. The Shao Yang is the deepest of the three Yang layers, so far as defense against external pathogens is concerned. There are plenty of diseases that through experience I've associated with that level of penetration, including of course problems like Anaplasmosis (can't get much deeper than the bloodstream); masticatory myositis; and GDV tendencies.

At the same time, we have 'stasis in the middle burner' as evidenced by the neoplasia. This is also typical of a Shao Yang pathogen.

We'd like a formula that can prevent an Addisonian crisis. You'll remember from the lecture that we rely on Xiao Chai Hu Tang for that, since it optimizes cortisol secretion and has mineralocorticoid effects. Yet we have a dog who despite having no aldosterone is somehow managing to be hypertensive. So we need to guard against that, which XCHT doesn't. Where is the hypertension coming from? I can only imagine it is insulin resistance from the high cortisol levels. So we might like herbs that promote insulin sensitivity. These are often bitter cold draining herbs.

From a TCM perspective, it's the extreme heat (evidenced in the tongue) that is causing the hypertension. So, again, something downbearing.

Putting that altogether, the first formula I'd go with is a modification of Xiao Chai Hu Tang, known as Chai Hu Jia Long Gu Mu Li Tang. It has all the benefits of the former, but with an overall cooling and Yang descending influence on top of it that will protect against hypertension. The core formula, XCHT, is a good anti-neoplastic formula.

So that's my best guess, given what you've presented. The only thing that I can't specifically and definitively tie in is the mammary tumor, but some of these are due to GB channel (Shao Yang) obstructions, as are musculoskeletal problems like hip dysplasia.

If you try the formula out, please come back to the forum (as you have in the past) and let us know how it went. This is a really interesting case.

Good luck!

P.S. The version of CHJLGMLT that you should use here is definitely Natural Path, because all other versions omit Ginseng, and you need it here for this dog.

Steve

by amymatthews

November 30, 2009

You make me laugh! I'm glad you persisted in reading her case through (and through, and through). So interesting to read your interpretation.

So, for clarity's sake, she doesn't have high corticosteroid to create hypertension, but the deoxycorticosterone (which is being hypothesized as present, but hasn't been measured; and which is a metabolite in the pathway to produce aldosterone) could replace aldosterone function (so she could be "functionally" normal with aldosterone, if this intermediate molecule is present in high enough concentration to replace aldosterone's function by binding to aldosterone receptors and even causing negative feedback to the aldosterone producing cells). When I talked to Dr. Oliver at the U.Tennessee endocrinology lab, he said that elevated sex hormones (this patient has high 17-hydroxy progesterone, which is an intermediate in the pathway of corticosterone production) could cause hypertension (but I haven't found the data to back that up -- perhaps he meant that they see hypertension in atypical Cushing's cases?).

So, I guess my concern is that herbs that support steroid and mineralocorticoid function when there is _functionally_ an excess (though a deficiency of aldosterone on labs) might worsen the situation.... Otherwise, the herb function sounds like a good fit. What do you think?

It's true that if these abnormal hormone levels decrease, her aldosterone will need to increase, but I suspect that it's negative feedback that is keeping aldosterone low and that her body might be capable of responding normally if we control the abnormal metabolites.

Her clinical signs have been primarily hypertension with proteinuria, but also ravenous appetite. No coat changes.

Thanks for the brain sweat!

by naturevet

November 30, 2009

Hi Amy,

I see your points. It sounds like we're speculating from a western medical perspective, so when there is doubt, I don't rely on the western actions of the herbs as much. Instead, I see if there is greater certainty when the case is looked at from another perspective. From the perspective of Chinese medicine, there's still a lot there to support the formula choice. So I'd go with it, and recheck the BP after a ten to fourteen days to ensure the BP is the same or lower.

Good luck!

Steve

by amymatthews

February 1, 2010

Hi Steve,

Update: she's been on CHJLGMLT (the "long name herb" at our clinic!) for 6 week, no significant changes (either clinically in appetite, urination, pot-belly, fat depostis) besides a mild electrolyte imbalance at this time (K slightly elevated). Tongue the same, pulse if anything is more distinctly deep and thin without being weak (the great majority of pulses that feel deep to me are also weak - not this girl). Her biggest change is that she will NOT eat cheese now, despite an increasingly ravenous appetite!

She is eating Taste of the Wild kibble and grain-free canned food. Owner tried raw food, but it's a price barrier for this owner.

I'm tempted to try Xiao Yao San still...in the face of lack of response. Our other thought to try lysodren, perhaps with florinef on board.

Thanks as always,
Amy

by naturevet

February 2, 2010

Please try the Xiao Yao San first before you hit her with Lysodren. My own perspective is that someday, fifty years from now, we'll look back at Western medicine, point fingers, and shake our heads at certain of our practices, and that Lysodren will be one of those that we pronounce as barbaric.

Harsh words. I guess that must be why people don't ask my opinion that often.

Steve

by amymatthews

February 22, 2010

Thanks, Steve. Her kidney values are starting to climb, blood pressure remains at 220 systolic despite western meds and CHJLGMLT, so we're trying Xiao Yao San as our last ditch effort before Lysodren. This chronic hypertension is not compatible with health!

by amymatthews

March 1, 2010

Well, your instincts seem to have been right. On XYS for one week her appetite has actually increased. I'm tempted to continue for another week or two before she goes down the lysodren path. Unless...can we combine this and CHJLGMLT? Or would they work against each other?

by naturevet

March 1, 2010

Hi Amy,

I'd continue to resist the urge to panic, and allow the XYS a couple more weeks to work. If the CHJLGMLT hasn't done anything for her, then I'd stick with the XYS for a while.

...and wasn't XYS your instinct?

S

by amymatthews

March 3, 2010

Hey Steve, what about Yi Guan Jian? For hypertension, hormonal imbalances (incl addison's, though her clinically important signs continue to be those of Cushing's). Might that help support her kidneys as well?

Just throwing it into the ring...

Amy

by amymatthews

March 3, 2010

Her tongue continues to be brickish, getting drier. Her pulse is weak and deep, hard to get any other details on.

by naturevet

March 3, 2010

Hi again,

There's no problem using YGJ if you feel XYS is close, but the dog is unstable. Maybe use them together, since specific efficacy of YGJ is less certain than for XYS.

S

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