New Treatment for Pituitary Adenomas

[Guest Rose Marie]

We heard last summer that this drug can help with Cushings Disease.

 

It seems that this drug is also shows promise for managing patients harboring GH- and PRL-secreting pituitary tumors, which are unresponsive to dopamine agonists and somatostatin receptor analogues.

 

"Three researchers at the Cedars-Sinai Institute at UCLA recently announced they managed to halt the growth of pituitary tumor tissue with a drug recently approved for treatment of type 2 diabetes mellitus. The research team tested the substance known as rosiglitazone on lab mice and human pituitary tissue, but not on live human subjects.

 

The team of Anthony Heany, Manory Fernando, and Shlomo Melmed wrote that rosiglitazone worked by linking with a receptor called the PPAR-gamma. When rosiglitazone was introduced to the human pituitary cells, those cells reduced hormone output, and the drug shrank tumors in mice. Rosiglitazone is sold under the name Avandia and is sold in tablet form by GlaxoSmithKline.

 

The authors noted that the PPAR-gamma receptor is present on cells that secrete both prolactin and growth hormone as well as on non-functioning tumor cells. This line of therapy, should it prove useful, would be the first effective pharmaceutical weapon against non-functioning tumors, and would add to the arsenal physicians now have for fighting acromegaly and hyperprolactinemia.

 

According to the authors, the effect of the drug might not be seen at dose levels ordinarily prescribed for Type 2 diabetes. This type of diabetes mellitus involved resistance to insulin, requiring treatment that compensates for the problem (type 1 diabetes mellitus involves inadequate secretion of insulin)."

 

Reference Link

 

Copyright ? 2003, American Society for Clinical Investigation

J Clin Invest. 2003 May 1; 111 (9): 1381?1388

DOI: 10.1172/JCI200316575

 

PPAR-? receptor ligands: novel therapy for pituitary adenomas

Anthony P. Heaney, Manory Fernando, and Shlomo Melmed

 

Cedars-Sinai Research Institute, University of California Los Angeles School of Medicine, Los Angeles, California, USA

 

Address correspondence to: Anthony Heaney, Division of Endocrinology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, B-126, Los Angeles, California 90048, USA. Phone: (310) 423-6648; Fax: (310) 423-0440; E-mail: HeaneyA@csmc.edu.

 

Received August 2, 2002; Accepted February 11, 2003.

 

Abstract  

 

Pituitary tumors cause considerable morbidity due to local invasion, hypopituitarism, or hormone hypersecretion. In many cases, no suitable drug therapies are available, and surgical excision is currently the only effective treatment. We show here abundant expression of nuclear hormone receptor PPAR-? in all of 39 human pituitary tumors. PPAR-? activating thiazolidinediones (TZDs) rosiglitazone and troglitazone induced G0-G1 cell-cycle arrest and apoptosis in human, rat somatolactotroph, and murine gonadotroph pituitary tumor cells, and suppressed in vitro hormone secretion. In vivo development and growth of murine somatolactotroph and gonadotroph tumors, generated by subcutaneous injection of prolactin-secreting (PRL-secreting) and growth hormone?secreting (GH-secreting) GH3 cells, luteinizing hormone?secreting (LH-secreting) L?T2 cells, and ?-T3 cells, was markedly suppressed in rosiglitazone-treated mice, and serum GH, PRL, and LH levels were attenuated in all treated animals (P < 0.009). These results demonstrate that PPAR-? is an important molecular target in pituitary adenoma cells and PPAR-? ligands inhibit tumor cell growth and GH, PRL, and LH secretion in vitro and in vivo. TZDs are proposed as novel oral medications for managing pituitary tumors.

 

You can see the full text article here!

http://www.pubmedcentral.nih.gov/article....2727930

[GoodIdeaLady]

:exclaim:  Can I blame you, Rose Marie, for the fact that I cancelled my Nov 10m 2003 second pit surgery date to go instead to a Dec 3, 2003 appt with Dr. Heaney to discuss if Avandia would be successful for me?     I have to apologize to MaryO...   :B:   I had PLANNED on the surgery, and she had posted it, and now I'm listed as "recovering"    since it is now Nov 14th.... ooops!   :wow:   Bad girl, Tamara!  I am going to email her now....       hehe.gif    I promise to be good about keeping y'all updated on how it goes, etc.    

[Kristy]

The research has only been done in animals, not in humans. I found this in a news wire a few weeks ago. I think you need to move forward Tammy.

 

Diabetes Drugs May Cause Heart Failure.

 

Tuesday, September 9, 2003 Posted: 10:15 AM EDT (1415 GMT)

WASHINGTON (Reuters) -- Two popular drugs used to treat type-2 diabetes can cause fluid buildup and heart failure in some patients, U.S. doctors said on Tuesday.

 

The drugs, sold under the brand names Avandia and Actos, caused heart failure and a buildup of fluid in the lungs in six men with poor kidney or poor heart function, the researchers said.

 

The findings, published in the Mayo Clinic Proceedings, are another potential blow to the newest class of diabetes drugs, the thiazolidinediones or glitazones.

 

The first drug in the class, Rezulin, was pulled from the market in March 2000 after about 100 people who took it died from acute liver failure or had to have liver transplants.

 

Pfizer Inc., which owns Rezulin as part of its purchase of Warner-Lambert company, is fighting off thousands of lawsuits alleging that Warner-Lambert failed to inform the public of the drug's health risks.

 

Tuesday's report from a team at the University of Texas Southwestern Medical Center at Dallas may support lawsuits by other patients against GlaxoSmithKline Plc, which makes Avandia, known generically as rosiglitazone.

 

The six men whose cases are detailed in the report took either Avandia or Actos, known generically as pioglitazone and jointly marketed by Japan's Takeda and Eli Lilly Co. Inc.

 

An estimated 6 million Americans take one or the other of the drugs. About 16 million Americans have type-2 or adult-onset diabetes.

 

Many do not need to take insulin but can take a variety of drugs including metformin and drugs in a class called sulfonylureas. The glitazones are gaining in popularity because they restore the body's ability to respond to insulin.

 

High-risk patients

"Many physicians are prescribing these drugs in patients with chronic renal insufficiency because a first-line diabetes drug, metformin, is not recommended for them," said Dr. Abhimanyu Garg, a professor of internal medicine at UT Southwestern who worked on the study.

 

"These new data suggest that such patients may be at particularly high risk of developing heart failure. These are newer agents, and we need to become more familiar with their side effects so that we can use them judiciously."

 

All six patients showed up at the Veterans Affairs Medical Center in Dallas with shortness of breath, weight gain and swelling in the legs. "These are the signs and symptoms of congestive heart failure and pulmonary edema," Garg said in a telephone interview.

 

Pulmonary edema is a potentially fatal condition in which fluid builds up in the lungs because the heart is not working efficiently.

 

"All physicians are aware that these drugs can cause swelling of the legs. But whether they could cause this serious complication was not very clear," Garg said.

 

The drugs increase blood volume, and doctors are told not to use them in patients with the most advanced heart dysfunction. But Garg said these six men all had mild to moderate heart and kidney problems.

 

"It seems to me these drugs may not be safe in such patients. They may not be able to tolerate fluid overload induced by such drugs," he said.

 

Luckily, he said, the patients were treated, taken off the glitazone drugs and all recovered.

 

In June, 32 diabetes patients in Texas and California sued GlaxoSmithKline, claiming the company failed to warn them of serious side-effects of Avandia.

 

But a spokeswoman for GlaxoSmithKline said Avandia's U.S. label warns that the drug can cause fluid retention that can cause heart failure or worsen it.

[GoodIdeaLady]

I saw Heaney Weds, Dec 3rd. ?Argued with him to let me try the Avandia. ?He kept the 2 recent MRI's on CD's, before and after photos, and gave me a thick form to read and sign before he will agree to let me do so --- and ONLY if I have a definite surgery date set so no delay if it doesn't seem to be working / or side effects make me quit.

 

I was so upset I drug my HEAVY rolling case with the 25+ pounds of MRI FILMS that he hadn't even looked at back to my motel [ten blocks?] and cried; called my son in San Diego, who drove 2.5 hours to come get me. ?I am at his place now [sun, 2am]. ?Fly back to Oregon on Monday. ?Might take these MRI's to Scripps or "?" while here to request a 2nd opinion before the 2nd pit surgery.

 

Heaney DID comment that "someday there WILL be a pill to cure Cushing's... there are things 'in the pipeline'...but that Avandia is probably not it [the definitive, PRIOR to surgery, solution]." ?He is only at his clinical desk on Weds, so you can guess that I will be calling him them to ask just what he was referrring to. ?I mentioned CRH Receptor Antagonists, and his expression had changed, "Oh, yes, those, too...." so that hadn't been what he was thinking about.

 

I think that he and my 2 OHSU endo's think I'll die prior to "better than surgery" solutions are available, but I am not bedridden yet, nor in a wheelchair, nor having to make trips to the Emergency Room or even Urgent Care Centers... I can travel by myself, etc. ? The brain fog and fatique makes working impossible, and pain most of my waking hours is unpleasant, but so many have had NUMEROUS surgeries with parts we do NOT yet replace, that I am still holding out for a better answer. ? ?Even medical documents now state that Cushing's is NOT curable [now if I can just remember where I read that ---- and it was just earlier tonight!]

[Kristy]

Tammy,

 

The research on what Cushings does to the brain is what got me... I am on medication, but the doctors are keeping a really close eye on me.

 

I was on Avandia three years ago - It didn't help. I had horrid edema - I gained weight. I was miserable.

 

If the medication experiment does not work for me, and if there is still no cure...

 

I've got too much to live for  :eh:

 

So do you.