More on taking Ketoconazole to lower cortisol

Well, the past week has been very interesting with the Ketoconazole.  I've learned some things by taking it:

• I definitely cycle. 
• I have very low cortisol in the mid-afternoon (worse on Keto) and it is difficult to function without some additional hydrocortisone.  I come home from work and crash each day.
• Even taking the keto in the evenings, I still get more "wired" and less tired around 9 p.m., so my body/tumor is producing more ACTH/cortisol then.  And it gets even more wired around midnight or so.
• Taking the Keto makes me low in cortisol most of the time, and I have to replace some right now in the morning by taking hydrocortisone.  But I don't think I'm low enough at night. However, this is working to simulate a normal diurnal pattern.  Thus, I'm sleeping better.

I haven't lost much weight, but I have lost inches in my stomach area.  I go up and down in weight, so it's hard to know if what I have lost is from cycling or from the keto. 

This isn't easy. I'd be lying if I said it was.  On Wednesday, I posted this on the Cushing's Help message boards:

Oh man...whew.... this is hard on a person. I definitely know what my lows feel like. From 3-9 (I'm assuming I'll do the same around 9 tonight) I feel like I just can't walk another step or even stay awake. I absolutely had to go to the grocery store after work, and I just did not think I'd make it. My cupboards and refrigerator were bare. It was so hard to do, but I did it. Once I got home, I thought I'd never unload the minimum amount I managed to get. And only the cold stuff is put away. The rest are on the table or right inside the door where they were dropped.

I took another 2.5 [of hydrocortison] at 1 p.m. today because I had such a hard time standing up. I felt it coming. Every joint, every muscle hurts. My knees are horrible. If I stay awake 'til 9, I'll let you know how it goes. I suspect I'll perk up then.

I think I feel my cycle even more on the keto...not less.

Nausea is also bad in the afternoon/evening, but then I get really hungry around the 8-9 time.   It's really the only time of day I'm hungry.  Eating at night and not during the day is not a good habit.  I'm trying to eat something in the mornings and then at lunch.  Actually, lunch is ok if I eat it early enough before I start feeling bad.  And if I eat dinner (called supper around here), I am eating something light and low-carb because it's late when I do want to eat.

Again, I sure wish I had a "cortisolometer" to be able to monitor my cortisol levels.  That sure would help me know whether to take hydrocortisone and how much to take in the mornings and early afternoon.  I don't want to take it if I don't need it because then I'm just replacing what I'm trying so hard to block.  I do want to emulate a normal diurnal level all day long.

---

I've started Ketoconazole...

...and it's a crap-shoot....

Well, I bit the bullet and started a course of Ketoconazole to see how I do. Keto works by blocking the secretion of cortisol by inhibition of adrenal 11 beta-hydroxylase. Since no two people respond the same, it's a guessing game at first.


My endo started me on 200 mg of the Keto at 6 p.m. and another 200 mg at 10 p.m. In a "normal" person, cortisol is the highest around 8 a.m. and decreases to about half that value around 4 p.m. By midnight (give or take an hour each way), cortisol should be about zero or close to it with blood and salivary levels. This is a normal diurnal variation. It is also called the circadian rhythm.


When one has Cushing's, this circadian rhythm is lost, and the normal diurnal variation changes. Cushing's patients have "flat" diurnal levels of cortisol, or even higher levels at night instead of in the morning. So, taking the keto at those "high" times lowers it to more natural levels, which is what I want.


But, the flip side of this is I don't produce the normal levels in the morning. So, I essentially have a type of "morning sickness" a lot of mornings with low cortisol until my body (aka...tumor) kicks in and makes some. (Read more about the Cushing's diurnal variation here.) So, I already don't make it in the mornings (or very well), and now I'm lowering it in the afternoon and evening.


Here is where the guessing game comes in. If I need to replace/add "cortisol" in the form of hydrocortisone in the morning, I also have a prescription of that. But how do I know? It varies by day, and there is no meter to help me. I so wish there was. I'd give my eyeteeth for a meter similar to a glucometer so I could figure out how much I need. The only thing I have to go by, except for regular serum cortisol checks which can't be done daily , is how I feel.


And what is so concerning about that? Cortisol is a corticosteroid hormone produced by the adrenal cortex, the outer layer of the adrenal glands which are essentially lying on top of the kidneys. Without it we die. It is the hormone that responds to "stress", both good and bad. It affects levels of multiple other hormones and electrolytes, and is very important in the homeostasis of the body. I need ENOUGH. Not too much and not at the wrong times. If I don't have enough, I'll end up with adrenal insufficiency, which is life-threatening.


Why this instead of other treatment? We are working toward a long-term solution for me. I explained it in the Medscape interview with Dr. Colin Son. It's not an easy choice.


I don't know how this is going to go. I'll let you know. I hope I can read my body right.

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Blech...

....

I haven't done a "personal" post in a while, and debated about doing this one. However, I think it's important to document what honestly goes on in the life of a person who deals with the repercussions of Cushing's on a daily basis.

As a quick recap, I had transsphenoidal endoscopic surgery to remove a pituitary adenoma almost 2 years ago. Prior to the surgery, I had a very Cushie body with numerous symptoms, and had most of those for a very long time (over 20 years). I was already suffering from hypothyroidism, multiple low hormones, and was probably growth hormone deficient, but I didn't test for that prior to surgery.

Since surgery, I have been diagnosed with adult growth hormone deficiency along with my hypothyroidism, plus my anti-TPO keeps going up and up indicating an auto-immune problem with my thyroid. I have very low levels of estradiol, LH, FSH, and testosterone. Also low are potassium, vitamin D, and ferritin. After surgery I had a problem with diabetes insipidus, but that gradually decreased. I still have days when I think I may have a bit of that, but not often.

Right after surgery, I made so little cortisol on my own that it was next to nil. ACTH was also under the testing limits. I was on 20 mg of cortef in the a.m. and 5 in the p.m as a replacement. Gradually, my levels have come up and a few months ago I was able to wean down to 5 mg a day. I was able to maintain that for the most part. Except....

Yes, the big "EXCEPT".... except when stressed in any way physically, emotionally, or mentally. Normal folks (I'm speaking biologically) don't have to even worry about the body producing enough cortisol to handle stress. The pituitary and adrenal glands have a feedback loop that works with the hypothalamus to produce what is needed when it is needed. But those of us who deal with the aftereffects of Cushing's don't have that. In fact, those who have cyclical Cushing's don't have it, either. The body does not regulate itself well, and can go through major "high" and "low" swings in ACTH and/or cortisol. This can lead to adrenal insufficiency (AI).

What is AI? Basically, it is the body's inability to produce enough cortisol. The body can also go into "shock" with AI symptoms when a drastic reduction of cortisol happens. This can happen with someone who still has Cushing's and who cycles drastically. AI symptoms include being extremely cold, inability to reason/think, shivering/shaking or just being "out of it", nausea/vomiting, muscle weakness, and much more. I listed these because they are the ones which affect me the most.

Which leads me to my life lately. I'm playing a guessing game each day of how much cortef my body needs. I tend to the least amount because I really, really want off the stuff. And I've quit losing weight although I've done all I can to keep losing short of going on a starvation diet. I'm contemplating that next. My GH replacement has helped tremendously with muscle strength which allows me to do more walking when I'm not dealing with AI.

A few weeks ago I had a scare, thinking I was getting "Cushie" again. My face got rounder/fatter, I gained 7 pounds in one week, and I hadn't changed a thing. Now, a few weeks later, I'm again AI most of the time and guessing how much cortef I need to "get by" for the day. The 7 pounds are gone (thankfully), and I feel like ...ahem... crud. I wake up sometimes not able to get out of bed due to extreme muscle weakness. I have to take cortef (on my bedside table) in order to get up. Nausea is often my companion until the cortef works, and often even then. But the worst part is the "walking through mud" part. And the shivering. Everyone else is shedding jackets and I'm piling them on. My hands stay cold. I feel like ice is running through my veins.

Why? Now, that's a good question. I've been fighting sinus infections and pyelonephritis (kidney infection) for months. The sinuses seem to be clear now, but the kidneys are another story. I'm tired of taking antibiotics. I saw an urologist last week, had a CT scan done (I'm allergic to the IVP dye), and will see him again on Tuesday. Just the office visit with the procedures done there threw me into adrenal insufficiency. Naively, I didn't think it would stress me like it did (I wasn't expecting to be catheterized, either), and between the bladder spasms and the catheterization, my body rebelled. I guess it was good he got to see it first-hand, because he realized the implications of my problems beyond the norm. The bad thing is, I broke out in hives and a rash, again.

Oh, I forgot that part. It seems when I go extremely AI, I get hives and a rash. I spent two weeks miserably trying not to "dig" during the prior episode. (There ought to be a commercial in that somewhere!)

Thus, my life is a rollercoaster. And it is for most folks trying to figure out hormone replacements "manually" instead of being on autopilot like normal people. Just one hormone replacement is not so bad. But factor in several, and it's a different story. Both GH and thyroid replacements need enough cortisol to work correctly. They can cause an already "low" person to go into AI without sufficient cortisol replacement. Too much cortisol replacement, and one is back into being "Cushie". Working one-and-a-half jobs while riding it isn't easy.

Damned disease. I hate it. I used to love a good rollercoaster ride.

The Altered Adrenal Axis and Treatment With Glucocorticoids During Critical Illness

From the article:

Critical illness is generally hallmarked by activation of the hypothalamic- pituitary-adrenal axis. The development of very high levels of cortisol has been associated with severe illness and a raised risk of death. Likewise, a response that is inadequate relative to the degree of stress, termed relative adrenal insufficiency (also known as critical-illness-related corticosteroid insufficiency) has been associated with increased mortality.

...Both very high and very low cortisol levels have been associated with increased mortality from critical illness.^[21] This finding suggests that appropriate activation of the HPA axis is a determining factor for survival. High cortisol levels reflect severe stress, whereas low levels, at baseline and/ or upon ACTH stimulation, could point to an inability to sufficiently respond to stress.^[22] This effect is termed relative adrenal insufficiency (also known as critical-illness-related corticosteroid insufficiency)...

To read more:
The Altered Adrenal Axis and Treatment With Glucocorticoids During Critical Illness

Is it AI or just electrolytes? Or thyroid? Or an infection?

Well, durn-it-all, I had to take an extra 5 mg of hydrocortisone again tonight. That's twice this week, and actually three times if I count last Sunday when I was flying across the country coming home. I'm trying so hard to wean off of the hydro but my body just won't let me. I don't know if it's because my pituitary still isn't making enough ACTH after my surgery 18 months ago or if it's cantankerous sometimes. Or is it my adrenal glands? Have they given up the ghost?

Between the nausea, being freezing cold in a 76 degree room, the fatigue, and the headache that comes with it, there was no way around my need for the drug I both love and hate. I fought for years to get rid of the bugger that was causing my body to be overrun with the steroid only now to be dependent on it. But I never want a repeat of a couple of episodes I've had with AI. No way, no how.

So, are my electrolytes off, or do I need more cortisol? And if I do, why? Do I have an infection? That's usually my first indication of an infection, but that's not the only reason I get AI. In fact, I'm still fighting that sinus infection and see my ENT on Wednesday. The last few times other than with sinuses, it's been UTI's. I didn't even know I had them until they got so bad and became Pyelonephritis. You know, it's all relevant and we "Cushies" tend to ignore signs others don't just because we've tolerated so much for so long. It's hard to know when one is sick outside of the endocrine disease itself.

I know, I know...time to go get some blood work done. I've been putting it off for too long. I spent the week with my daughters this past week, so really need to get on the ball and go. But, I can't go in the morning. Since I have to have the serum cortisol and ACTH done at 8 a.m. and I'm supposed to withhold my hydrocortisone for 24 hours prior...well....I blew that.

I know that my pituitary has quit making a lot of things, but the tumor did that. Surely it will make ACTH again. I hope it will, but yet, I'm afraid it will, too. The chance of a recurrence within 5 years is high, and since my tumor went into my cavernous sinus and had to be scraped off the wall there, just one cell can cause it to regrow. Most of the time I don't think about that, but every now and again....like tonight....I do.

Why would my pituitary start making ACTH and not the GH or TSH I need? Oh, I've read all the research and supposition that goes with a pituitary tumor and the hormones it affects. But think about it. The pituitary has a posterior and anterior section. It also leads into the hypothalamus. The anterior section is responsible for the majority of the hormones, and those are the hormones I'm missing. All of them. TSH, GH, FSH, LH, etc. So, why would I not produce them but still produce ACTH? Yeah, you see why I'd worry if I did produce enough ACTH? Why won't I produce all the other ones?

Oh, I know, as we get older there are a lot of other things that happen in our bodies that cause the GH and estrogen to fall. And I know there are feedback mechanisms that fail, too. In fact, the hypothalamus directs a lot of the action with the anterior pituitary, including GH production.

The hypothalamus is a very small portion of the brain, but wow, is it ever busy! I'll have to do a piece on it sometime. In fact, there is some new research involving the hypothalamus and obesity. It's very interesting. If the hypothalums is damaged, a lot of the hormone production of the body goes haywire or stops. You can read more about it in Testing 101: An introduction. So, is my hypothalamus damaged? Ok, y'all....I know some of you are saying "she's dain bramaged for sure!" ;) Yeah, yeah.... I'm just curious!

So, I'm still cold, my nausea has abated to a tolerable level, and my headache is tolerable, too. Maybe I can sleep again. At least my polar fleece blanket will feel good tonight!

Oh, my sore Cushie bum....but the view is gorgeous!

As my British friends would say, "Oh my aching bum!" I think too much sitting is as hard on the body as too much walking or running. I tried to walk a lot yesterday in between my flights (and oh, I had the time...as you read yesterday), but sitting for 5 hours straight is just hard on a body.

It sure is nice here where I am. Breezy and low 70's. I'm actually sitting by the pool right now and FREEZING! The sun feels good, but I may have to go get my polar fleece blanket. I don't lack in insulation, so what is it that keeps me so cold? The only time I got warm (not hot) yesterday was when I was wearing my jacket and lugging my wannabe-a-totebag purse along with my laptop and hoofing it through the terminal. And that was short-lived because as soon as I stopped, I was cold again.

I guess I need to go get bloodwork done to check my free T3 and free T4 levels so my endo can figure out what's going on there. The last time I had them checked my endo had to increase my Levoxyl dosage. And my anti-TPO was up, again. I know I freeze with AI, but that's a different kind of cold. It's a cold-from-the-inside-out chill. The bloodwork will have to wait 'til I get back home, though!

My suite where I'm staying is beautiful! This part-time job has its perks, that's for sure. I have two bedrooms and bathrooms, a living area with dining area, full kitchen with stainless steel appliances, LCD TV, wireless internet, and an empty refrigerator. Oops...that last one doesn't sound like a perk, does it? HA! Nah, I could get a cab and go get stuff to stock it or the staff here will go for me, but several of us are going out to eat tonight, so why bother? Plus, I ordered from a local restaurant who delivers last night and got a half-a-chicken (smallest plate they had!) with steamed veggies and a salad and ate the leftovers for lunch today. There is breakfast served for all the guests, so I'm covered. I'll be wined and dined all week. Who needs food? (Oh, I brought my coffee...I'm 'tic'lar!)

So, I sound like I'm bragging, but trust me, I'm not. I really, really enjoy this, and I love what I do to earn it. I get to meet and work with people from all over the world, plus I get to teach something I love: database design and programming. That keeps it from being a "job". And there have been some very tough times in my life where I was wondering how I was going to feed myself and my girls. You know what I mean. So, I know I've been blessed with this "not-a-job" and I'm thankful.

I have a spare bedroom...who's coming to visit? The view is gorgeous.

Fast forward...

.....

I meant to get back here before now to add more information. Right now, all I can do is try to not get sick from the sinus infection that is pulling me down. Yep, went to the doctor, got the antibiotic, and you'd think it would be simple as that. Not.

Since the removal of my pituitary adenoma involved transsphenoidal endoscopic surgery which went through said sinuses to the base of my brain, it is a tad worrisome. Not mention the fact that any stress on the body (good, bad, or indifferent) causes some degree of adrenal insufficiency (AI). This includes infections. In fact, it often is the first indication I have of any infection.

Back to the doctor. My doctor. She is a sweet person. In fact, she was the only one in all these years of suffering with Cushing's Disease who realized I had something "endocrine" going on until I saw Dr. Friedman in Los Angeles. However, that's about as far as she went with the understanding of the disease. Since she is willing to listen and work with me, I don't hold it against her. I do hold it against medical schools who don't teach their doctors enough about this disease. She doesn't understand AI. She doesn't understand what the tumor did or how it messed up my system even beyond removal. She doesn't get "stress dosing" to combat the AI. But she does understand a sinus infection. Just not how bad it can be. At least she now asks "what works" and then prescribes it. And she cares. There's a lot to be said for that. A whole lot.

I wish I could get rid of the headache. It won't go away.

A horse of a different color

Or should I say zebra? In med school, potential doctors are told ""When you hear hoofbeats, think horses, not zebras". Well, what about those of us who are zebras? What does that say to those who don't fit any mold of illness or have multiple illnesses which paint stripes?

As I said earlier, my primary care doctor sees horses, but every now and then she does notice a stripe. The thing is, she tries to get rid of the stripe instead of looking at what caused it. And she's not alone. Frankly, I'm wondering if there really are any horses out there? Ok...ok....I guess there are. Maybe.

Diabetes, you say, is a horse. Nope.... Did you know that endocrine disease can cause it? And that it is just a secondary symptom? You didn't know that? Don't worry. Most endocrinologists don't seem to, either. Thankfully, I never had that particular stripe.

Ok, how about thyroid function/disease? Nope, not that one either. It's actually a stripe in the zebra of endocrine disease, especially a pituitary tumor. Secondary/central hypothyroidism is linked to a pituitary tumor suppressing the pituitary, and hyperthyroidism can be linked to a TSH producing tumor.

Low hormones? Oh, that must be early menopause or pre-menopause with females, right? Wrong. Just stripes of another color in the zebra of pituitary tumors.

How about high hormones? Well, guess what? Do I need to say it? More stripes...... Pituitary adenomas are famous for growth hormone and ACTH overproduction.

PCOS and metabolic syndrome are often the horses with which a Cushing's patient is diagnosed. Too often, it's just too easy to camouflage the stripes with those diagnoses.

Oh, and my favorite. Obesity. "You need to eat less and get more exercise." How many people do you know who want to be extremely overweight? Those doctors who don't listen, ignore the stripes (some literal ones called striae) and keep repeating that mantra need a A Swift Kick in the ASP. They don't know that fat is an endocrine organ. They also don't know it is actually possible to literally starve while remaining obese.

I do not know the answers. I do know there is a problem. Instead of heading to the dude ranch, maybe med schools ought to take their future doctors on a safari.