Wednesday, December 01, 2010

My new blog

If you came here, you're viewing my old blog, several years out-of-date. My new blog is on TypePad. I no longer recall the reasons for the move!

Please see for my latest-and-greatest posts.

Thank you for visiting!

Tuesday, October 03, 2006

Why I don't believe in Adrenal Fatigue

There's a lot of talk about "Adrenal Fatigue". The claim is, that, due to the stresses of modern living, the adrenal gland can get tired or burned out, and lose the ability to produce enough cortisol. This can result in major fatigue and other symptoms.

Basically, I believe the patients, but I don't believe the doctor's explanation. Here's why.

Among other hormones, the adrenal gland produces cortisol, often termed "the stress hormone". (This is a big misleading -- it has a much broader role in regulating glucose metabolism and the immune system). Cortisol production is regulated by the hypothalamus in the brain, which releases a hormone called CRH, which tells the pituitary to release another hormone called ACTH, which tells the adrenal gland to make cortisol. Long and complicated! But this chain of command is called the HPA Axis -- HPA = Hypothalamus, Pituitary, Adrenal.

The adrenal gland actually atrophies if it does not receive stimulation. This is seen, for example, in patients who take steroids such as prednisone for asthma for an extended time. (Prednisone is a stronger synthetic modification of cortisol). The high levels of prednisone suppress ACTH production, and the adrenal gland will eventually atrophy, making it difficult or impossible to stop the prednisone.

At the other end of the range, some tumors produce high levels of ACTH. This is where, if stress caused the adrenal glands to overwork, we'd see burned out adrenal glands. These high levels of ACTH should produce adrenal fatigue on steroids, so to speak.

But no, instead we get Cushing's Disease, a serious condition defined by high cortisol levels.

So we should dismiss the "fatigue" explanation. I have seen no evidence to support it, nor even a suggested mechanism at a cellular level. Instead, the explanation seems to draw on the intiuitive notion that working hard makes you tired, and that things wear out. A better analogy is muscles -- if you don't use them, they wither away, but if you lift weights and use your muscles, they gain in strength!

But let's not dismiss the patient's complaints! There really are cases where the adrenal glands can't make enough cortisol under stress conditions, or make a bit too little under normal conditions. In addition, there can be problems at the hypothalamus or pituitary.

And let's not dismiss stress as a contributor. There are many things that cause alterations in the behavior of the HPA axis. Prolonged stress and depression are two.

But if we work from the wrong explanation, we can't interpret test results sanely. And it is important to not treat with steroids, without testing first and verifying that there is a problem. If you treat a cortisol deficiency that doesn't exist, you can create the very problem you're treating! (Remember the part about the adrenal gland atrophying if it doesn't receive ACTH stimulation).

I won't discuss adrenal testing in this post. It's a hot topic for me, as I've had it done wrong a couple times, and I want to do it justice. But I will say that single cortisol tests aren't that meaningful, and stimulation tests are needed to understand how the adrenal gland reacts to stimulation. A normal cortisol result can mask an adrenal gland that can't handle the high demands of a major stressor, such as illness or injury.

And what results to consider a problem that should be treated can be an interesting question. Risks vs benefits, with quality of life now often hanging in the balance against long-term risks.

Serious deficiencies in cortisol (Addison's Disease or Adrenal Insuficiency) are life-threatening, and should always be treated.

Unfortunately, some doctors put people on cortisol replacement without adequate testing, or they have patients "try" some hydrocortisone to see if that helps. This creates a lot of problems, not the least of which is that once you're on steroids, it alters the test results, so you can't get the information you need for a real diagnosis.

Monday, October 02, 2006

How Blood Pressure Works, Part 1

On one level, blood pressure is pretty simple:

Squeeze in more blood volume into the body, and blood pressure goes up.

If the heart works harder, blood pressure goes up.

If it's harder to get the blood through all those pipes, blood pressure goes up.

All blood pressure medications work on one (or more) of these three principles.

But when we look deeper, to see what these medications are actually doing and how they work, we find that evolution has worked out an very complex system to regulate our blood pressure within a narrow range.

Why so complex? To keep the blood flowing to our brains, and everything else, as we go from laying, to sitting, to standing, to running and and jumping. And all the while, keeping the pressure low enough to not break anything -- all those delicate fine blood vessels in the kidneys, eyes, brain, and elsewhere.

And that's why it's important to intervene when things go wrong, and our blood pressure gets too high or too low.

Our story covers everything from the kidneys and adrenal glands to the bloodstream to the lungs, the brain, the heart -- even the little blood vessels in our feet play a role.

So let's look at blood volume, first. Blood is mostly water, and regulating blood volume means adjusting how much water we hold in our bloodstreams. This is done through a complex network of mechanisms.

We'll start with one that's a bit indirect -- the renin-angiotensin-aldosterone loop. It's indirect, but as we'll see, it's in the middle of everything, so it's hard to talk about the rest without covering this one first.

The body's main sensor for blood pressure is the kidney. When the blood pressure or the difference in pressure between the inlet and outlet of the kidney is too low, the kidney increases its output of renin (pronounced "reenin").

Renin in the bloodstream splits a protein in the blood called angiotensingen. One piece of this is called angiotensin I.

Angiotensin I doesn't do much, but in the lungs, it encounters Angiotensin Converting Enzyme (ACE). And already, we find a drug target. So-called ACE inhibitors block the action of this enzyme, so it cannot convert angiotensin I to angiotensin II.

But there's another pathway that can convert angiotensin I to angiotensin II, so sometimes these drugs stop working. We have an alternative to solve that problem, that we will get to in a minute. And ACE inhibitors in a minority of people, can cause a dry cough. Blocking angiotensin conversion leads to production of bradykinin and substance P in the lungs, which irritate the vagus nerve, leading to the cough. So if you're in that minority, or have asthma, you may need that alternative, too.

Angiotensin II is the nasty stuff. It causes thirst, higher cardiac output, cardiac hypertrophy (the heart gets bigger), increased vascular resistance (the pipes resist the flow of blood).

All of these things cause the blood pressure to rise.

But there are two things it does in particular that are noteworthy. One, it tells the pituitary (at the base of the brain) to release a hormone known as either AVP (arginine vasopressin) or ADH (anti-diuretic hormone). This tells the kidneys to hold onto water.

The other is that it tells the adrenal glands to make aldosterone. Aldosterone is a steroid hormone that regulates the balance between potassium and sodium in the blood. Water follows the sodium, through osmosis. If the kidneys let sodium escape, a good deal of water will follow it, and blood pressure will drop.

Aldosterone tells the kidneys to readsorb sodium, in exchange for potassium. That helps keep the blood volume up. Without enough blood volume, we may not have enough to reach the brain when we stand up, and can feel dizzy or even pass out on standing. But retaining too much sodium raises our blood pressure.

Angiotensin Receptor Blockers (ARBs) help put a stop to all that nonsense. They block the action of angiotensin II.

The actions of aldsterone can be blocked with a drug called spironolactone, which blocks the adlosterone receptors

For some of us, sodium (as in salt) gets retained, often because of an excess of aldosterone, often due to too much angiotensin II. (There's another hormone, ANP, produced by the heart, that tells the kidneys to get rid of sodium.) For these people, with salt-sensitive hypertension, reducing the sodium in their diet will lower blood pressure. (The rest of us just get rid of any excess in our urine).

Regulation of blood volume all comes back to the kidneys. The pressure is sensed by the kidneys, and the kidneys are responsible for both the water balance and managing potassium and sodium (and a good deal more).

Some have more problem with too much blood volume, so diuretics are used. These come in two main flavors -- ones that get rid of potassium, and ones that don't ("potassium sparing"). Restricting sodium also helps these people. There are even drugs which oppose the action of aldosterone -- helping let sodium escape. (Some people make too much aldosterone even without the angiotensin II signal).

It's important to choose one that maintains potassium levels within range, because potassium being too low or high can cause heart arrythmias, or even a heart attack.

ACE inhibitors have been shown to help protect the kidneys from diabetes damage. It's likely that ARBs do this as well, but this isn't as well-studied as the benefits from ACE inhibitors, so those are often what's recommended to diabetics.

And one of the causes of high blood pressure is kidney damage. The goal is to stop high blood pressure before it becomes a downward spiral toward a bad end.

We've covered blood pressure regulation by adjusting the blood volume. Next time we'll talk about some of the other medications and affecting how hard the heart works and the pipes resist. And we'll see some more about how why angiotensin II is such an important player.

DMV update

I never did get around to filling in subsequent events with the CA DMV...

The DMV finally granted me a phone interview, after leaving me hanging in the wind for 6 weeks or so.

Seems that because I was rear-ended a few months earlier, but the SFPD didn't report the nature of the accident, they felt they needed to determine if it was diabetes related. Duh. Asking the wrong driver -- was SHE hypoglycemic when she plowed into me and sent me to the hospital? No, much more likely she was talking on her cell phone.

"But the light was green!" (Yes, direct quote). I guess she never learned that it is traditional to allow the car ahead of you to proceed through the intersection first, without ballistic assistence.

Anyway, after the interview, "no problem" -- but they gratuitously make you wait for the US mail to deliver a letter. And then they gratiutously made the effective date ONE DAY LATER than the letter was delivered. Gratiutous punishment for what -- being honest and attempting to follow their rules?

Wednesday, August 23, 2006

You CAN Learn Medicine!

I've not been posting to my blog much lately (!!), but I've got an idea. I'm considering moving (or copying) my postings of various medical explanations (endocrinology, mostly -- diabetes, Addison's Disease, etc.).

The idea is to build an "introduction to medicine" for patients -- you too can learn Medicine. (As opposed to learning to be a Doctor -- an entirely different problem).

And just to be clear: I am NOT a doctor, and if I WERE a doctor, I am not YOUR doctor, and even if I were YOUR doctor, I'm posting general info on the internet, and not examining you. Anything you learn here should be a starting point for a conversation with your doctor.

I have strong opinions about the importance of patient involvement in medical care. To do that, we need to educate ourselves, in order to be able to participate in and direct our care.

I post a lot of diabetes-related stuff on the forum at, which is a good place for support. I also post on several forums and lists on Addison's Disease.

Wednesday, January 04, 2006

My FURL archive gets top page ranking!

ORD IRD deiodinase cortisol - Google Search

I guess it must be useful -- I was researching a question from someone else. I learn more from other people's questions!

Cortisol is the most essential of the adrenal hormones.

ORD, IRD, and deiodinase relate to the process of turning the main hormone released by your thyroid gland, called T4 for the number of iodine atoms it has, into T3, which is what's actually active in your tissues.

So if you want to know what effect taking cortisol (hydrocortisone, Cortef) would have on your thyroid hormones, then my Furl archive is considered by Google's PageRank algorithm to be your best starting point.

(Or other glucocorticoid steroids -- prednisone, prednisolone, methylprednisolone (Medrol), dexamethasone, etc.)

The irony, of course, is that most of the articles in my Furl archive I found via Google searches.


My comments on my mother's blog can be found here:

Curiosity Did Not Kill the Cat

Lawyers everywhere, but can't find one when you need one

... because they're all on holiday.

So I went to the law library today. Needed references on writs of mandate. I told the librarian what I needed, and he looked at the clock. "Not two hours into the new year, and Murphy's Law has struck twice!"

I gave him a sort of puzzled, expectant look.

He led me over to a shelf and pointed to an empty binder that had what I needed. HAD what I needed -- until some theiving lawyer had stolen it. "Shocking! Theives among lawyers! Our dark secret; nobody knows better than us there are thieves among lawyers!".

So he gets me a more advanced pair of large binders, entitled "Administrative Mandamus".

I've made it through the first couple chapters so far. I've got to get back there somehow tomorrow. Hard to do around here when the DMV has said you can't drive until THEY get around to renewing your license, SOMEDAY!

I'll write more on this what all this is about another day, but for now: if you have diabetes, and you live in California, and you renew your license -- ignore anything they tell you at the counter. The Driver Safety Office makes their own rules, and ignores anything they do for you at the main license-renewal counter -- and those rules are based on the assumption that you are an imminent danger to society, and if they can catch you up in their rules, you're screwed. And your only route of appeal is a writ of mandate from a Superior Court Judge.

And school starts today, so I've lost my newly-licensed teenager as driver.

Oh, and there's no point in renewing early.

Sunday, December 11, 2005

Life is a lesson

Really, just signed up so I could post a comment on my mom's blog. Came up with this blog title a while back, but never really did anything with it.

So often, solutions to problems hinge on finding the right approach -- the right way to think about the problem. Or, rather, a right way. Each approach gives us certain insights, and opens up certain vistas.

Math, science, family, politics, medicine, society -- they all provide examples, and all are things I'm prone to ponder -- and perhaps pontificate upon.

The downside of the title, of course, is that one might think I'm going to tell you what to think, or at least what approach to use. Nope -- it's life that's the teacher -- and if I were the teacher, I'd expect you to be doing the thinking...