Cancerous Pituitary Brain Tumor after CJC-1295 use

[dak290]

About a year ago I used the CJC-1295 peptide. Two month before that I had gotten a concussion playing football and had an initial CAT scan then a follow up MRI (with and without contrast). Everything was normal (no tumor or abnormalities of any kind). About three months ago, after some abnormalities in my blood work, my endo Doc sent me for some additional testing. The results of that testing led him to do another MRI (with and without contrast) which showed a massive pituitary tumor this last Tuesday. He told me this growth must have taken years to develop. I told him about my recent brain scans and he said then may have missed it. He order the previous scans and looked over it and said that nothing was missed and that he had never seen a pituitary tumor grow so fast. He refered me to a oncologist and he also said the same thing. I know CJC-1295 acts directly on the pituitary gland which is roughly the size of a pea (mine now is the size of a baseball). I do not know if the CJC-1295 is the cause of, or even related to my tumor, but I thought I would post this information. All of this is unknown. Just sharing my thoughts.

Dak

[Dukkit]

wow, what is the treatment for that? like will you be able to get it back to normal?

[dak290]

My oncologist said that the treatment course is as follows: Chemo and Radiation to reduce its size then surgery to remove it. I kinda freakin out right now and so is my family.

Dak

[Dukkit]

well keep us posted and youll be in my thoughts bro!

[dak290]

Thanks bro. I will keep everyone updated on my progress.

[binder]

That is very weird. For the pituitary glad to get to the size of a baseball that would have to break the sella turcica. I don't know where that would even fit in there.

That is very odd for something to grow that fast in 3 months. I would look into other environmental factors. Your use of CJC-1295 could have an effect on this but I wouldn't be sure this would effect it as a sole reason. You could have had a genetic predisposition that was unknown and this triggered it. Your head injury could have also damaged something that wouldn't show up but caused it to develop into something serious after a month. Damage at a microscopic cellular level might not be a physical damage that is seen on an MRI scan, but enough to alter DNA.

That really sucks. I hope the best for you. With the advancement in tumor treatments you should keep your head up.

[dak290]

I wasn't saying that the CJC-1295 caused the tumor but I don't believe it is just happen stance either. The tumor has spread and is pushing into other parts of my brain because of its size. My endo (is a really good friend of mine) thinks that the CJC may have spark off something because it constantly stimulates the pituitary to produce growth hormone which never happens normally. I don't know. I guess I never will. But no matter the outcome I will always have this conclusion lingering in the back of my mind. I guess it can be expected for putting untested compounds into your body.

Thanks for all the repsonses,

Dak

That is very weird. For the pituitary glad to get to the size of a baseball that would have to break the sella turcica. I don't know where that would even fit in there.

That is very odd for something to grow that fast in 3 months. I would look into other environmental factors. Your use of CJC-1295 could have an effect on this but I wouldn't be sure this would effect it as a sole reason. You could have had a genetic predisposition that was unknown and this triggered it. Your head injury could have also damaged something that wouldn't show up but caused it to develop into something serious after a month. Damage at a microscopic cellular level might not be a physical damage that is seen on an MRI scan, but enough to alter DNA.

That really sucks. I hope the best for you. With the advancement in tumor treatments you should keep your head up.

[binder]

I'm curious to find out. Find out all you can on the pathology report when they do a biopsy or remove it.

Hopefully they'll find out what caused it. That way you will know if it was your body going rouge or an outside source.

[jg42058p]

thats really sad, I honestly hope the tumor shrinks and dies off and you get better.

I have heard that steroids and forms of growth hormone can cause the enlargement of tumors/cancers in the body...

cjc1295 might have plaid a role

Good luck man!

[widowmaker2]

wishin you the best of luck dak...hope all goes well for you bro!

[CrazyHorse89]

damn bro, i hope your okay, Im not to happy about reading this cause im taking cjc-1295 with HGH now.

[dak290]

damn bro, i hope your okay, Im not to happy about reading this cause im taking cjc-1295 with HGH now.

I wouldn't be alarmed. I just think taking the CJC-1295 didn't help the issue maybe. I will know more in the next few weeks I guess. Thanks all for your thoughts.

Dak

[BG]

That is very weird. For the pituitary glad to get to the size of a baseball that would have to break the sella turcica. I don't know where that would even fit in there.

I agree, you would think if it grew to that size there would be many side effects caused by that alone??

[legobricks]

Im also with BG and others when i say that is strange... a gland the size of a pea to grow to the size of a baseball in 3 months would surely cause motor function disabilaty in SOME way, headaches, etc.... lots of things/sides effects from that rapid of growth in your brain. What side effects did u have?
Also your in my thoughts and prayers dude, hope you pull thru

[Kale]

Thats bad news dude, and good luck with the surgery. From my research on this and other tumors (my daughter died from a BT when she was three years old, not a Pituitary tumor), the Pituitary type tumors are treatable and have a reasonable prognosis. Have the Dr's given you a long term prognosis yet ?

[gangers]

having a slightly larger pitituary gland can be a good thing but not if its the size of a baseball.

pitituary gigantism is caused by a tumar on the pitituary gland and the guys who have pitituary gigantism are all over 7ft plus very strong.

but yours is way to big i wish u the best of luck with surgerry.

[datbtrue]

Written by: M.M. a/k/a DatBtrue
Copyright 2008 by M.M. a/k/a DatBtrue
All rights reserved.

No part of this article may be reproduced in any form without the written permission of the copyright owner.

Does GHRH result in Pituitary Over-stimulation?

Has that type of concern ever been raised in regard to long-lasting analogues of Growth Hormone Releasing Hormone?

Yes but not directly in a study itself or by one of its authors.

In a fairly recent editorial in the New England Journal of Medicine in which the results from a clinical trial for Tesamorelin, a long-acting analogue of growth hormone releasing hormone (GHRH) were also reported, several questions were raised by the editor. Among them "Would such a regimen...overstimulate the pituitary gland...with an increased risk of pituitary neoplasms?" - Manipulation of the Growth Hormone Axis in Patients with HIV Infection, Marc R. Blackman, M.D., NEJM Volume 357:2397-2399 December 6, 2007

I should point out that the referenced study, Metabolic Effects of a Growth Hormone–Releasing Factor in Patients with HIV, Julian Falutz, M.D, et al. administered 2 mg per day of tesamorelin by subcutaneous injection for 26 weeks to study participants without any indication whatsoever of pituitary problems or for that matter any other problems.

Yet it is a valid concern and one we should seek to understand.

Before we preceed to see if we can create a better understanding for ourselves...we need to clarify exactly the type of things that most concern us regarding potential pituitary damage since the phrase "overstimulate the pituitary gland" is not used in any other journal article.

Reviewing the actions of GHRH on the pituitary & reviewing the literature leads me to focus on two primary areas of concern: pituitary hyperplasia/somatotroph hyperplasia and tumors/adenomas.

THE NATURAL ORDER OF THINGS

In non-diseased people of all ages there exists very large amounts of growth hormone (in various isoforms) stored in the pituitary. While this store of growth hormone accounts for ten percent (10%) of the pituitary's dry weight only a very small portion (1-2ng/mL) of it is found in the circulation. No other pituitary hormone is stored in such high amounts. In fact the quantity of growth hormone stored in the pituitary is 800 times larger then the stored quantity for any other pituitary hormone. - Lewis UJ. Growth hormone: what is it and what does it do? Trends Endocrinol Metab 1992;3:117–121

From this simple understanding alone we can fairly accurately surmise that asking the pituitary to release some of that store of growth hormone so that we can achieve youthful levels or double the amount of youthful levels shouldn't "overstimulate it" or tax it in such a way as to force it to unduly expand the somatotroph population.

Only a portion of the population of cells within the pituitary are called upon to secrete growth hormone and this is not static. It is controlled by the three hormones that govern this process - Growth Hormone Releasing Hormone (GHRH), Ghrelin (of which GHRPs are mimetics) and Somatostatin.

GHRH and Ghrelin (i.e. GHRPs) appear to act on different somatotrope subpopulations. GHRP has been shown to increase the number of somatotropes releasing GH, without altering the amount of hormone released by each individual cell. On the other hand, GHRH stimulates both the number of cells secreting GH and the amount of GH secreted per cell.

Somatostatin (the GH inhibiting hormone) has been shown primarily to decrease the number of cells secreting GH without affecting the amount of GH secreted per cell.

In very general terms GHRP increases, while Somatostatin decreases, the number of active GH secreting somatotropes.

On the other hand GHRH does both, but acts primarily by stimulating the amount of secreted GH within the active somatotropes.

So fluctuations in somatotrope populations and secretion activity is a natural occurrence.

SOMATOTROPH HYPERPLASIA

But when we see references in journals and in the medical community to somatotroph hyperplasia and the very rare pituitary hyperplasia they are referring to an abnormal increase in the number of cells with consequent enlargement of tissue.

From an article titled "Pituitary Hyperplasia" in the May 1999 issue of the journal Pituitary we see that "Somatotroph hyperplasia is rare; it is limited to cases of GHRH overproduction by extrapituitary endocrine neoplasms and sporadic examples of gigantism."

For the reason that we may be supplying GHRH beyond what is naturally occurring in our body which subsequently binds to receptors on somatotrophs in the pituitary and act on them we need to consider if the amount of GHRH we are supplying is on par with the level of overproduction that can bring about hyperplasia. But first let's examine our other concern.

TUMORS/ADENOMAS

If we were to somehow bring about somatotroph hyperplasia will this result in tumors?

It doesn't appear to be likely. From the 2008 edition of Diagnosis and Management of Pituitary Disorders, Edited by Brooke Swearingen, MD, et al.:

"It is a common clinical observation that ectopic overproduction of releasing hormones, such as GHRH or corticotropin-releasing hormone (CRH), results in proliferation of the target cells. However, the vast majority of sporadic pituitary tumors do not show hyperplasia in the surrounding tissue. Although these data suggest that hormonal stimulation is not a primary etiologic mechanism in pituitary tumorigenesis, it is worth noting that aggressive GH-secreting adenomas frequently express high intrapituitary amounts of GHRH (45)."

If we follow up that footnote (45) we discover that the overexpression of GHRH referred to comes from the tumor itself. In other words like a lot of tumors the hormone in question is locally produced and locally used by the tumor within. - Thapar K, Kovacs K, Stefaneau L, et al. Overexpression of the growth-hormone-releasing hormone gene in acr*****ly associated pituitary tumors. An event associated with neoplastic progression and aggressive behavior, Am J Pathol 1997;151:769–84.

Let's take a look at someone who had a tumor that hyper-secreted GHRH. This type of overproduction is known as ectopic GHRH hypersecretion. From the autopsy:

"In this report we describe the functional and morphological features of the pituitary removed from a patient with a 10-yr history of a disseminated bronchial carcinoid producing GHRH.
...
Although somatotroph proliferation was widely evident, there was no evidence of adenomatous transformation.
...
We conclude that sustained exposure to ectopic GHRH leads to somatotroph hyperplasia, but, at least in this case, was not sufficient for adenomatous transformation." - Somatotroph hyperplasia without pituitary adenoma associated with a long standing growth hormone-releasing hormone-producing bronchial carcinoid , S Ezzat, SL Asa, L Stefaneanu, R Whittom, HS Smyth, E Horvath, K Kovacs, and LA Frohman, J. Clin. Endocrinol. Metab., Mar 1994; 78: 555 - 560

The general conclusion drawn from similar case studies is that GHRH induced hyperplasia does not bring about tumors.

WHAT DOES BRING ABOUT TUMORS?

From another case study:

"...it is still not known whether hypothalamic hormones have a role in tumorigenesis in human pituitary adenomas.
...
Despite extremely high local levels of hypothalamic releasing hormone, adenoma formation did not occur in our patient. This study provides further evidence that although hypothalamic hormone excess may be important in cellular proliferation, the pathogenesis of pituitary adenoma formation may be mediated by other factors including new oncogenes and suppressor genes that are as yet uncharacterized." - A Growth Hormone-Releasing Hormone-Producing Pancreatic Islet Cell Tumor Metastasized to the Pituitary Is Associated with Pituitary Somatotroph Hyperplasia and Acr*****ly, N. Sanno, A. Teramoto, R. Y. Osamura, S. Genka, H. Katakami, L. Jin, R. V. Lloyd, and K. Kovacs, J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2731 - 2737

Eventually though we get to the one study that was able to bring about tumor formation in mice after a year of bombardment. What they found was that GHRH hyperstimulation was not sufficient without other factors to bring about adenomas. In fact GHRH by itself was not sufficient to bring about hyperplasia. They highlighted a codependence between GHRH and GH/IGF-I on pituitary cell proliferation.

Tumor formation was likely dependent on other factors relevant to GH signaling. What was most interesting was the process:

"Although supraphysiological levels of hGHRH were present in pituitaries and hypothalami of both GHR+,hGHRH and GHR-/-,hGHRH mice, the appearance of pituitary adenomas was not preceded by a progressive increase in pituitary size. In fact, tumor formation was preceded by a static pituitary growth phase in which mean pituitary weight remained constant for a minimum of 4 months, and in 8% of 12-month-old mice expressing the hGHRH transgene, pituitary weights and gross morphology were indistinguishable from those observed at 2 months of age." - The Effect of GHRH on Somatotrope Hyperplasia and Tumor Formation in the Presence and Absence of GH Signaling, R. D. Kineman, L. T. Teixeira, G. V. Amargo, K. T. Coschigano, J. J. Kopchick, and L. A. Frohman, Endocrinology, Sep 2001; 142: 3764.

This leads us into understanding that the pituitary has defense mechanisms that protect it from such dangers. Nothing happens overnight. The speculation on the actual defense mechanism which resisted adenoma formation for 4 months in mice is as follows:

"...adult somatotropes may become desensitized to the proliferative actions of GHRH. Alternatively, the normal somatotrope may be capable of only a finite number of divisions regardless of the time of onset and duration of GHRH hyperstimulation. Finally, GHRH hyperstimulation could result in an increase in somatotrope proliferation independently of age, but the increase in the rate of proliferation is counterbalanced by an increase in the rate of cell death in the adult gland. Although the exact mechanisms involved in the maintenance of pituitary mass in the presence of elevated GHRH remains to be determined, it is clear that sustained supraphysiological levels of GHRH secondary to expression of the hGHRH transgene ultimately led to a loss of these protective mechanisms in select cells (presumably caused by somatic mutations), thereby allowing for clonal expansion and adenoma formation."

Continued Below

[datbtrue]

Continued from Above

Written by: M.M. a/k/a DatBtrue
Copyright 2008 by M.M. a/k/a DatBtrue
All rights reserved.

No part of this article may be reproduced in any form without the written permission of the copyright owner.

HOW MUCH GHRH IS TOO MUCH?

First it is not clear that too much leads to tumor formation. For the most part it doesn't. We really just have the mouse study. While it is comforting to know that somataotroph hyperplasia is reversible and does not result in tumor formation it is important to understand that huge amounts of unchecked chronic GHRH may possibly in some cases play a secondary role in tumor formation.

The body has mechanisms to protect itself from unchecked somatotroph proliferation. The everyday mechanism of most import is the inhibiting hormone somatostatin.

Somatostatin acts as a sweeper. It comes into the pituitary and declares "enough is enough" and it reduces the number of cells secreting growth hormone . In the traditional model it played a primary role in growth hormone pulsation. In the present model it must share this role with Ghrelin.

If we completely antagonize somatostatin we likely do away with the biologically significant pulsatile nature of growth hormone release. But just as unfortunate we eliminate our continual check on chronic growth hormone release. While it may be fun to speculate about using Acetylcholinesterase inhibitors to eliminate somatostatin's inhibitory effect and let GHRH exert its action unrestrained and on a continual basis, it probably isn't a terribly wise or healthy way to go about effecting higher GH levels.

What is interesting about CJC-1295 is that despite its long-lasting nature the pulsatility of growth hormone release is maintained. In other words sure GHRH is continually available but its actions are not unchecked. Somatostatin is still able to give our pituitary the break it needs so that we don't end up with somatotroph hyperplasia.

We don't want to put our pituitary in any danger of having to rely on those "fourth quarter" defense mechanisms touched on in the mice study. So that brings us back to the question we previously raised "is the amount of GHRH we are supplying on par with the level of overproduction that can bring about hyperplasia?" Again keeping in mind that hyperplasia may not be such a bad thing but it nonetheless is a step in a direction we don't want to take.

Our best available comparison is to look at the quantities of GHRH that tumors that bring about giantism and acr*****ly produce and see how the medical practioners in this field define excess. This is not really fair to us to do it this way because they look to the presence of plasma GHRH levels in a particular range in conjunction with such factors as high levels of growth hormone and other hormones in patients with visibly identifiable characteristics of gigantism or acr*****ly.

We don't have those factors that would indicate mutations & processes gone awry. Nor are we necessarily sustaining high levels of unchecked GHRH for periods measured in years.

The following from, "Ectopic GRH syndromes" In: Robbins RJ, Melmed S, eds. Acr*****ly: a century of scientific and clinical progress, Frohman LA, Downs TR. 1987, New York: Plenum Press; pp 115-125 serves as our benchmark.

"It is suggested that peripheral plasma GHRH-IR levels greater than 300 ng/L are pathognomonic of an ectopic tumoral source of GHRH, even though levels in most patients exceed 1000 ng/L."

This benchmark was used in other studies as a standard, such as the study, Congenital gigantism due to growth hormone-releasing hormone excess and pituitary hyperplasia with adenomatous transformation, D Zimmerman, et al., J. Clin. Endocrinol. Metab., Jan 1993; 76: 216 - 222.

So it is these types of patients that demonstrate pituitary/somatotroph hyperplasia and their plasma levels usually exceed 1000ng/L. When the GHRH plasma level exceeds 300ng/L the medical community views this as potentially symptomatic of a GHRH secreting tumor.

HOW DOES THIS STANDARD COMPARE TO CJC-1295?

I am going to use the CJC-1295 pulsatility study * for the reason that the study participants were normal non-GH deficient people and they report the plasma concentration numbers in ng/ml whereas the clinical CJC-1295 trial reports the plasma concentration numbers in nmols. I have found conversion factors for somatostatin, IGF-1 and growth hormone but not for GHRH. So I have no way to equate that study to the system used in the studies cited above.

The GHRH analogue CJC-1295 levels circulating in plasma was found to be between 1 and 2 ng/ml or 1000-2000ng/L one week after injection.

The doses injected were either 60 or 90 mcg/kg of CJC-1295. In a 100kg man that is a 6mg or 9mg per week dose that brought about circulating GHRH levels of 1000-2000ng/L.

If we extrapolate to a 2mg per week dose that equates to 330 to 660ng/L of circulating GHRH in plasma.

If we further extrapolate down to 700mcg per week dose (i.e. 100mcg per night) that equates to 110 to 220ng/L of circulating GHRH in plasma.

Keep in mind that ectopic hypersecretion of GHRH averages 1000ng/L from tumors that cause somatotroph hyperplasia and that 300ng/L is a threshold upon which the medical community begins to look for further symptoms.

* - Pulsatile Secretion of Growth Hormone (GH) Persists during Continuous Stimulation by CJC-1295, a Long- Acting GH-Releasing Hormone Analog, Madalina Ionescu and Lawrence A. Frohman, The Journal of Clinical Endocrinology & Metabolism 2006 91(12):4792–4797

IN CONCLUSION

This is not the type of analysis that is meant to have a tidy conclusion. It is what it is.

DISCLAIMER

I am not a licensed practitioner of medicine. I am not a trained professional in the area discussed herein. I am not qualified to give medical advice of any kind. Nothing that I write should be construed as anything other than free expression of thought.

[lovbyts]

Wherent you using HIGH doses of the CJC01295?
Quote
I upped my CJC-1295 dosage to 1000mcgs

That seems like a LOT to me but I may be wrong. How many iu is that?

[OH REALLY]

brow what happend are you ok

[oc pitbull]

**** man i hope everything works out for you

[chitownhoker]

it was my understanding that pitutary tumors are non cancerus....the doc's thought i might have one from high prolactin levels and he said not to worry that it couldn't be cancerus

[chitownhoker]

i just read up on it and it says that it is very rare to ever get one on the pitutary gland....that must suck man

[celticd]

**** that,i hope everything goes ok for you and youre family
i believe the use of any peptide can excelerate any cancer one may have
my prayers are with you for a speedy recovery
dave

[dak290]

Thanks everyone for your kind thoughts. Progress is slow at the moment. To answer everyone's questions yes I experienced a lot of neural /motor symptoms before the discover of my tumor. And now because of the pressure being exerted on my optic nerve I now have no vision in my left eye. I am also having tremors and loss of muscle control thought out my body. Radiation has had some success at shrinking the tumors size. But my latest MRI shows that the tumor has begun to encapsulate part of my brain stem. Given this data, my doctor has opted to remove the tumor earlier then expected because of the fear that it may damage my brain stem and kill me. This surgery is not expected to remove the complete tumor as the tumor has penetrated part of my temporary lobe and part of my cerebellum. The jist is to remove as much as they can and try to separate the tumor from my brain stem (the tricky part that can kill me) and place chemo wafers around the remain parts of the tumor in hopes that it may prevent it from growing /spreading. From what I understand this is pretty much as bad as it gets. My doc told me that they is a fair chance I will not survive the surgery and to plan for that. So this may be my last post for a while. My surgery is scheduled for next Tuesday the 11th. I may have time to respond before then but I have a few things I wanna do before Tuesday.

Again thanks for everyone's thoughts,

DAK

[OH REALLY]

good luck i will pray for you

[F4iGuy]

Focus your thoughts on the best possible outcome. I'll say a prayer.

[takincareofbusiness]

Yeah bro, focus. You'll do good.

[binder]

Good luck. I hope everything turns out and expect to hear the results as soon as you get the strength to get back on here and post.

[petethemanc]

Shit man, i sincerely hope everything goes fine and the docs work their magic. My thoughts go out to you and your family.

[legobricks]

thoughts and prayers are out to you and your loved ones bro.

Good luck and i hope the doctors get you through this. As new as you may be or the little posts you may have, ANY members here at AR are definatly thought of in times like these and the staff here wants you to know that. Hope to see you back posting soon with a full recovery!

[956Vette]

Look forward to your comeback story dak

[OH REALLY]

Look forward to your comeback story dak

Thats whats up

[chriswhat]

Any updates for us Dak?

[GORILA-UNIT]

any news

[XD40]

Raw deal. Shit man, i hope all is well..anyone heard from him?

[The Punnisher]

I googled his screen name a few weeks ago and any of the sites I found him in, his activity stopped around the same time as here. I hope he's just too caught up in getting well to answer rather than the alternative.

[juicy_brucy]

Hopefully we'll hear from him soon. He may still be recovering from that surgery/chemo/stress, etc.
Until then, we can only wait and hope to hear about his recovery.
Sorry to bump this thread after three weeks, but i've been following this one...
HOPE YOU ARE OK DAK.

[dak290]

Well my procedure was what my medical team deemed a successful failure. I am alive and there is much to be said of that. I am very greatful of everyone's support and well wishes in my absence. In some weird way you get to know the guys on here by reading there posts and somehow it feels like a family community. My doctor was able to remove a significant portion of the tumor and relieve its pressure on my brain stem. During that process there was some slight damage to my nerve tract leading to my spinal cord. As a result I am essentially paralyzed on the left side of my body. But hope lingers on and my doctor thinks this condition is only temporary. As for the pathology of my tumor my doctors are dumbfounded. The tumor consisted of primary anterior pituitary cells (which further inspection relieved them to be pathologically normal). It is being defined as a "extremely aggressive" benign pituitary anterior adenoma with the posterior of the pituitary remaining completely intact. The report also revealed that the abnormality had no apparent ability to spread to other cells. In short my original diagnosis of cancer was not accurate. They really have no idea what it is I guess. So I am still alive. Thanks everyone for your thoughts and concerns. I will try and keep everyone updated on my life.

thanks,

DAK

[FallenWyvern]

This is horribe, I hope for the best. Get well.