Saturday, April 27, 2013

Exposure To Low Doses Of Multiple Xenoestrogens Found To Strongly Distort Hormone Action

Endocrine disruptors. Patients with hormonal imbalances of unknown origin cringe when they hear these words. 

A recent study on the pituitary cells of rats show the unfavorable results of our complicated chemical-laden daily environments. 

If this doesn't scare you, read more.


Exposure To Low Doses Of Multiple Xenoestrogens Found To 
Strongly Distort Hormone Action

Summary:
"These things are all over the environment, and we need to know what they do so we can start figuring out what we need to change," Watson said. "They're probably disrupting and confusing hormones in people, and it's important to find a way to prevent that as soon as we can. We need to test these compounds for their hormone-disrupting activities before they are put into products, so we can redesign for safety very early in the process." 


Read article here: 

SIGNIFOR - New Product Releases


Signifor is a new pharmacological treatment of adult patients with Cushing's disease for whom pituitary surgery is not an option or has not been curative.


Wow-- another potential medical therapy for patients like me.

Pituitary Stalk Lesions: The Mayo Clinic Experience


Context: Pituitary stalk lesions have various etiologies, often not clinically apparent. Pathological samples from these lesions are rarely obtained, because of the critical location and function of the hypophyseal stalk.

The Journal of Clinical Endocrinology & Metabolismjc.2012-4171

15-yo Katie Rozena battles Cushing's and wins



Katie, brave Katie.

Thank you for sharing your story. 
It is so important for those who come after you.

Have fun in your disease-free, non-judgmental, forgiving life. 
Enjoy every day and live.

Sincerely, 

Melissa


Katie's transformation from 2006 to 2008:









*******************************************

My battle with Cushing's disease
By Katie Rozenas

You may not know by looking at me now, but I recently fought a battle. All my troubles started in January 2007, when I was 15 years old, and I began gaining weight. As the year went on, it only got worse and my weight gain became more and more noticeable with every passing week. Over the summer, I tried different weight-loss programs but nothing worked. It got to the point where none of my clothes fit me anymore. A red flag went up in July 2007 when I stopped getting my menstrual cycle. I went to the doctor, but she said it was probably from my rapid weight gain, and that once I lost some weight I would get it back, but just in case she referred me to a gynecologist. In December I started Weight Watchers and ran on the treadmill for one to two hours religiously, but I still was disappointed when I got on the scale. Every week I would only either gain or lose a little, then gain again. I didn't know what I was doing wrong, since I was following my points and filling up on water. I knew then that I was fighting a battle within my body for my health and self-esteem.

I told the gynecologist my symptoms and she said I might have either polycystic ovarian syndrome or something wrong with my endocrine system, so she referred me to Dr. Madeline Fay, an endocronoligist in Worcester. Finally, after several tests, in March of 2008 Dr. Fay told me I had Cushing's disease. After a long and frustrating year of not knowing what was wrong with me, I finally had an answer. I was so relieved to find out that the weight gain wasn't my fault that I couldn't stop smiling.

Despite my happiness at knowing what was causing my symptoms, Cushing's is a rare and difficult disease. It's characterized by obesity, an inability to lose weight, a buffalo hump, stretch marks, a moon face, masculine qualities such as more facial and body hair, patches of dark brown or black skin on the neck, arms, breasts, or thighs and loss of menstrual cycle. I was very skinny before I started showing the symptoms. I had a fast metabolism and could eat whatever I wanted and not gain a pound. In all I gained 75 pounds in the course of a year. I went from 125 pounds to 200 pounds (at my heaviest). I had blamed myself for gaining the weight, thinking I had overeaten because of stress and my metabolism had slowed. So I was relieved when I found out I actually had a medical reason, but the "answer" to my problems was not simple. It is very tough having Cushing's because it's caused by a non-cancerous tumor on the pituitary gland, which is located in the brain. The only treatment for it is brain surgery. It was at this point that I knew I was facing my biggest battle ever.

The most painful thing was what my weight gain caused people in and out of school to say about me. It was so hard to wake up every morning and get dressed in clothes that would hide my body. My family thought I was eating excessively and blamed me for my weight gain. My classmates said things like, "I don't blame her for not wanting to go swimming. If I was like her, I wouldn't either" and "What, does she have diabetes?" and "Look at that girl, she's such a chunky monkey". It got to the point where I didn't eat or jump or run in front of people. I knew people were talking about me behind my back and that was bad. But if I found out what someone said about me, I was not only hurt, I also started to hold a grudge against that person. But the second I found out I had Cushing's, I told all my friends with a text message. I told people I knew, especially the big mouths in school. I did everything I could to spread the word. My parents told everyone they knew and I told everyone I knew. I would work it into a conversation, and say "Oh, you didn't know, I have a brain tumor. That's why I put on so much weight." I tried to keep my head up, but it was hard when I felt like the world was against me and time was passing me by.

The biggest challenge I had to overcome was not the physical pain—even though that was very difficult—it was the emotional and mental pain. Although my parents were physically with me the whole time, I still always felt alone. My friends looked at me differently after I gained the weight and shied away from me. They treated me as an outcast. Guys stopped flirting with me and they hardly talked to me. Once my friends found out that "Katie Rozenas had a brain tumor" it was a whole different ballgame. Some were compassionate, some were scared, some were apprehensive and some stayed the same. People became my best friend after they found out. People I hadn't really had the best relationships with in years. I felt as if no one knew what kind of pain I was going through. No one else knew what was going on inside my head and I was always very emotional because of my elevated hormones. I overcame these challenges by looking to the future and what I wanted to accomplish. There was nothing I could do about my physical state. Until the surgery, no matter how hard I tried; I couldn't lose any significant amount of weight because of the tumor. It was extremely frustrating and depressing for me to be so helpless, but I had anchors. I had the perseverance to do well in school even though I was often absent to attend doctor's appointments. Although it got to be a hassle, I knew I had to keep my grades up. I wanted so badly to stay on National Honor Socaiety and to make First Honors again. I managed to maintain an overall A average throughout the year, and I did well in my AP U.S. History class. I didn't want this illness to beat me academically as well as physically. I also kept going to Girl Scouts, until I got very sick. All through this battle, I continued on my Girl Scout Gold Award, and continued to do service projects and volunteer work for my community.

"You have a brain tumor and the only solution is brain surgery to remove it". Imagine hearing that when you're 16 years old and have never broken anything and have only gone to the hospital two or three times in your life. That was my reality in March of 2008. I knew what was in store for me, but I wanted to get better so badly I was willing to do anything to get back to normal. My parents and the rest of my family were scared.

The night before my surgery, my friend Jordan instant messaged me telling me how great I was going to do and that I was such a strong person. She said she would see me Sunday when she was supposed to come visit me and then I signed off. I was so scared that that was the last time I would ever talk to her.

So on May 16, 2008 I woke up at 4 am and was brought to Children's Hospital Boston, walked into pre-op, was taken up to the 6th floor, given a hospital johnny, given anesthesia and wheeled into the operating room to have brain surgery. Everything went well, but I woke up with a terrible headache and a sore throat. It was horrible, but I got through it. I think now about what it was exactly that I "got through" and certain aspects come up in my mind. I think about the fear of going into the operating room alone without my parents, and the fear I had of something going wrong. I truly thought I was going to die. Then I think about how I stayed strong because I knew I wasn't the only one scared. My parents were in the waiting room with my aunt and uncle clenching each other's hands. After waking up from the anesthesia, I was so tired and my throat hurt so bad that I just wanted to sleep but when I heard my surgeon, Dr. Ed Smith, say he was going to talk to my parents, I told him to tell my parents that I loved them. When they heard that, they knew I was okay I think about my small veins, how hard it is to get an IV in, and how many I had; so many that my arms and hands were bruised. I didn't like seeing my blood on the outside of me and the IVs got so sore. Then I think it's only made me braver. So when I hear someone say I have to go get blood drawn today I just laugh to myself and think about how many times I had my blood drawn.

And I wonder, why me? Then I think about those kids at Children's who won't get better and I count my lucky stars that my disease was curable. I think about the 5-year-olds with cancer and I wonder why I am so selfish.

I think about how the ridicule of others has taught me not to judge others and to be more understanding because you don't know the real story. If there is one thing I want people to take away from my story, it is that you never know why the person sitting next to you on the bus is obese or what the rash is on that person who you always pass at the grocery store. I don't want people to feel sorry for me. I just want them to take from my story this moral and treat other people better. I have eyes that are less judgmental and a mind that is more open. When someone walks by me I think maybe it's not their fault. And that is one thing many people, not only 16 year olds, don't think about as they go through life.

I have lost 65 pounds since my surgery and I am feeling better. I am still on a lot of medicines but I am almost back to the way I was before. My old clothes fit me again and I feel more confident. However, every time I think about what I "got through" I think about and glance down at the battle scars that Cushing's left me that will never go away, for they will only fade in time except for when the blood pulses through my veins.

To read Katie's journal project for her junior year, click here:

My Very Own "CSI: Cyclical Cushing's"



HAS AN ENDOCRINOLOGIST EVER TOLD YOU THAT CYCLICAL CUSHING'S WAS NEW OR RARE?

For the past six years or 2,190 days, my battle with Cushing's has been a lopsided fight. As a new patient, I went in totally unarmed, with only my patient history, medical knowledge, lab protocals, medical literature, etc. We all know, facts, stories, labs, and witnesses weren't enough to corroborate this bizarre tale of strange physical deformities and an emotional roller coaster ride.  We were completely unarmed against the MDs who stood before us.  

I have spent my time in the chat room trenches with our Cushie platoon, breaking down all the information, developing hypotheses, discussing theories, and offering help. It's very difficult to move beyond that when we, the patients, have critical information about our peers yet it goes unpublished by our doctor friends in the endocrinology.

For example, many endocrinologists I know tell me that cyclical Cushing's is very rare, fairly new, and poorly defined. Cyclical Cushing's is not well understood in the medical literature. Although I respond with a "Well, we have a lot of friends on the message boards with Cyclical Cushing's, so that doesn't do much good for me," it is undoubtedly a conversation killer. My having no come back to that questionable remark about the RARITY of Cyclical Cushing's has always bothered me to the core.

Well, I've complained about that before, but TODAY what is chapping my hide is this article I found after a simple Google search for the keywords Cyclical Cushing's.

First, you will read in the abstract that more than five cases were cyclical. By the end, there are more.


Second, I was really beside myself in a FIT when I reviewed the dates for these articles in the Selected References.  I will highlight some below. You will see some medical journal articles cited from 1956 and later.  Cyclical Cushing's has been studied and written on 50 years before I sought diagnosis and treatment in 2007. Why did these endocrinologist bozos act like they didn't know anything about cyclical Cushing's? What are these teachers teaching these endocrinologists in medical school? Why did they all treat me like there was just NO POSSIBLE WAY I had cyclical Cushing's and thereby must just be depressed, fat, extra body-haired, bruised, forgetful but rageful person. I am so furious that I always pressed for more information about cyclical Cushing's, and few had a comprehensivie answer explaining what we DO know about the matter.

Please take the time to read this article below, as my flabbergasted mind and I sit here wondering how these countless endiots could not remember even ONE of the 13 articles referenced in the article alone that studies fluctuating or cyclical cortisol when I questioned them about cyclical cushing's.


Another choice bit: the referenced articles below were published in 1956, 1958, 1961, 1973, 1975, 1976 (2), 1979 (3), 1980, 1982, and 1985. Any one of these show researchers had already discovered the distinct subset of cyclical Cushing's patients and tried to determine the best way to diagnose and treat patients.  From what I have seen 30 to 55 years later to the present, it seems that garden-variety endocrinologists and even well renowned pituitary centers have been riding on the diabetes bus (obesity! heart attacks! exercise! insulin!) all the while totally neglecting data that others clearly have shown us so long before. 


Does anyone coming out of medical school know how to research and prepare a proper literature review? Do they just ignore the clankiness of old articles and focus on single-hospital data studies?  I am mean, come on, people!  Do I have to do everything?  


When I cool down, I'll begin to read the articles post below (with links). I am truly interested to figure out who knew what and when.  This is my own CSI: Cyclical Cushing's.   

******************
PMCID: PMC1418075


Five cases of cyclical Cushing's syndrome.

A B Atkinson, A L Kennedy, D J Carson, D R Hadden, J A Weaver, and B Sheridan


British Medical Journal (Clinical Research Ed) . 1985 November 23; 291(6507): 1453–1457.

Abstract

Reported cases of cyclical Cushing's syndrome are rare. Of 14 successive patients with Cushing's syndrome nine collected sequential urine samples for the estimation of cortisol:creatinine ratio. Five had cyclical Cushing's syndrome while two had considerable variation in urinary cortisol excretion without a cyclical pattern being established. Two of the five patients with a cyclical syndrome had paradoxical responses to dexamethasone. In only one patient with a cyclical pattern did the cortisol:creatinine ratio fall after treatment with bromocriptine or cyproheptadine, or both. The high incidence of the cyclical form of Cushing's syndrome has important clinical implications. A high index of suspicion of the syndrome is required in patients with symptoms or signs of Cushing's syndrome but with normal cortisol values, in patients with fluctuating cortisol values, and in patients with anomalous responses to dexamethasone. Because of possible variations in steroidogenesis the results of drug studies in Cushing's syndrome must be interpreted cautiously.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article(989K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References
These references are in PubMed. This may not be the complete list of references from this article.
  • Bailey RE. Periodic hormonogenesis--a new phenomenon. Periodicity in function of a hormone-producing tumor in man. J Clin Endocrinol Metab. 1971 Mar;32(3):317–327.[PubMed]
  • Brown RD, Van Loon GR, Orth DN, Liddle GW. Cushing's disease with periodic hormonogenesis: one explanation for paradoxical response to dexamethasone. J Clin Endocrinol Metab. 1973 Mar;36(3):445–451. [PubMed]
  • BIRKE G, DICZFALUSY E. Fluctuation in the excretion of adrenocortical steroids in a case of Cushing's syndromeJ Clin Endocrinol Metab. 1956 Feb;16(2):286–290. [PubMed]
  • Chajek T, Romanoff H. Cushing syndrome with cyclical edema and periodic secretion of corticosteroids. Arch Intern Med. 1976 Apr;136(4):441–443. [PubMed]
  • Liberman B, Wajchenberg BL, Tambascia MA, Mesquita CH. Periodic remission in Cushing's disease with paradoxical dexamethasone response: an expression of periodic hormonogenesis.J Clin Endocrinol Metab. 1976 Oct;43(4):913–918. [PubMed]
  • Oates TW, McCourt JP, Friedman WA, Agee OF, Rhoton AL, Thomas WC., Jr Cushing's disease with cyclic hormonogenesis and diabetes insipidus. Neurosurgery. 1979 Nov;5(5):598–603. [PubMed]
  • Cook DM, Kendall JW, Jordan R. Cushing syndrome: current concepts of diagnosis and therapy. West J Med. 1980 Feb;132(2):111–122. [PMC free article] [PubMed]
  • Schteingart DE, McKenzie AK. Twelve-hour cycles of adrenocorticotropin and cortisol secretion in Cushing's diseaseJ Clin Endocrinol Metab. 1980 Nov;51(5):1195–1198.[PubMed]
  • Jordan RM, Ramos-Gabatin A, Kendall JW, Gaudette D, Walls RC. Dynamics of adrenocorticotropin (ACTH) secretion in cyclic Cushing's syndrome: evidence for more than one abnormal ACTH biorhythm. J Clin Endocrinol Metab. 1982 Sep;55(3):531–537. [PubMed]
  • Crapo L. Cushing's syndrome: a review of diagnostic tests. Metabolism. 1979 Sep;28(9):955–977. [PubMed]
  • Riad-Fahmy D, Read GF, Gaskell SJ, Dyas J, Hindawi R. A simple, direct radioimmunoassay for plasma cortisol, featuring a 125I radioligand and a solid-phase separation technique. Clin Chem. 1979 May;25(5):665–668. [PubMed]
  • Cook JG. Factors influencing the assay of creatinine. Ann Clin Biochem. 1975 Nov;12(6):219–232. [PubMed]
  • Atkinson AB, Chestnutt A, Crothers E, Woods R, Weaver JA, Kennedy L, Sheridan B. Cyclical Cushing's disease: two distinct rhythms in a patient with a basophil adenoma. J Clin Endocrinol Metab. 1985 Feb;60(2):328–332. [PubMed]
  • Scott RS, Espiner EA, Donald RA. Intermittent Cushing's disease with spontaneous remission.Clin Endocrinol (Oxf) 1979 Nov;11(5):561–566. [PubMed]
  • PASQUALINI RQ, GUREVICH N. Spontaneous remission in a case of Cushing's syndrome. J Clin Endocrinol Metab. 1956 Mar;16(3):406–411. [PubMed]
  • BASSOE HH, EMBERLAND R, STOA KF. Fluctuating steroid excretion in Cushing's syndromeActa Endocrinol (Copenh) 1958 Jun;28(2):163–168. [PubMed]
  • Aber CP, Cheetham HD. Cyclical Cushing's SyndromeBr Med J. 1961 Feb 4;1(5222):336–338.[PMC free article] [PubMed]
  • Blau N, Miller WE, Miller ER, Jr, Cervi-Skinner SJ. Spontaneous remission of Cushing's syndrome in a patient with an adrenal adenoma. J Clin Endocrinol Metab. 1975 Apr;40(4):659–663. [PubMed]
  • Green JR, van't Hoff W. Cushing's syndrome with fluctuation due to adrenal adenoma. J Clin Endocrinol Metab. 1975 Aug;41(2):235–240. [PubMed]
  • Bochner F, Burke CJ, Lloyd HM, Nurnberg BI. Intermittent Cushing's diseaseAm J Med.1979 Sep;67(3):507–510. [PubMed]
  • Halberg F, Engeli M, Hamburger C. The 17-ketosteroid excretion of a healthy man on weekdays and weekends. Exp Med Surg. 1965;23(1):61–69. [PubMed]
  • Costello RT. Subclinical Adenoma of the Pituitary Gland. Am J Pathol. 1936 Mar;12(2):205–216.1. [PMC free article] [PubMed]
  • Burrow GN, Wortzman G, Rewcastle NB, Holgate RC, Kovacs K. Microadenomas of the pituitary and abnormal sellar tomograms in an unselected autopsy series. N Engl J Med. 1981 Jan 15;304(3):156–158. [PubMed]
  • Spark RF, Dickstein G. Bromocriptine and endocrine disorders. Ann Intern Med. 1979 Jun;90(6):949–956. [PubMed]
  • Lamberts SW, Klijn JG, de Quijada M, Timmermans HA, Uitterlinden P, de Jong FH, Birkenhäger JC. The mechanism of the suppressive action of bromocriptine on adrenocorticotropin secretion in patients with Cushing's disease and Nelson's syndrome. J Clin Endocrinol Metab. 1980 Aug;51(2):307–311. [PubMed]
  • Kennedy AL, Sheridan B, Montgomery DA. ACTH and cortisol response to bromocriptine, and results of long-term therapy, in Cushing's disease. Acta Endocrinol (Copenh) 1978 Nov;89(3):461–468. [PubMed]
  • Krieger DT, Amorosa L, Linick F. Cyproheptadine-induced remission of Cushing's disease. N Engl J Med. 1975 Oct 30;293(18):893–896. [PubMed]
  • Grant DB, Atherden SM. Cushing's disease presenting with growth failure: clinical remission during cyproheptadine therapy. Arch Dis Child. 1979 Jun;54(6):466–468. [PMC free article][PubMed]
  • Hsu TH, Gann DS, Tsan KW, Russell RP. Cyproheptadine in the control of Cushing's disease.Johns Hopkins Med J. 1981 Aug;149(2):77–83. [PubMed]

Nocturnal Salivary Cortisol May Prove to be an Additional Option or Replacement for Early Morning Urine in Detecting Cyclical Cushing's Syndrome

Ireland, well done you!  Doctors continue to confirm the legitimacy of nighttime cortisol saliva samples in diagnosing Cushies. By now, this should totally be a given, but I am always please to see it repeated. Also, I find it interesting that the Irish use early morning cortisol-to-creatinine urine samples to diagnose. Hmm. Don't think I've heard of that being used in the USA. Nice to see the give the patient the opportunity to show high cortisol results in 28 days, not a few point-in-time tests that don't "catch" the high cortisol.  

*********
A comparison of the use of urinary cortisol to creatinine ratios and nocturnal salivary cortisol in the evaluation of cyclicity in patients with Cushing's syndrome.

J Clin Endocrinol Metab. 2013 Jan; 98(1):E72-6. doi: 10.1210/jc.2012-2925. Epub 2012 Nov 12.  

Graham UMHunter SJMcDonnell MMullan KRAtkinson AB. 


Source
Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BA, United Kingdom. qublbc8@hotmail.com

Abstract

CONTEXT:
Cyclical Cushing's syndrome is detected in our center by collecting sequential early morning urine (EMU) samples for cortisol to creatinine ratio over 28 d. The Endocrine Society suggests that nocturnal salivary cortisol (NSC) may be used to assess patients for cyclical Cushing's. However, there is only very limited evidence that it correlates with early morning urine testing or that it demonstrates cycling over 28 d.

OBJECTIVE:
We sought to correlate nocturnal salivary cortisol with early morning urine results collected the following morning and to determine whether nocturnal salivary cortisol could be used to detect cyclical Cushing's.

DESIGN AND SETTING:
An observation study of 28-d collections for nocturnal salivary cortisol and early morning urine was performed in a tertiary referral center over 1 yr. Patients: A 28-d collection of nocturnal salivary cortisol and early morning urine was performed in 10 patients with confirmed or suspected Cushing's syndrome.

MAIN OUTCOME MEASURE:
The main outcome of the study was the correlation of salivary and urinary cortisol with graphical assessment of results for cycling.

RESULTS:
Eleven collections were performed. One patient with cyclical Cushing's completed the collection before and after cabergoline therapy. Two hundred seventy matched salivary and urinary results were correlated (r = 0.79; P < 0.001). In two patients with cyclical Cushing's, early morning urine and nocturnal salivary cortisol followed a similar cyclical pattern. In one patient with recurrent cyclical Cushing's, cortisol was elevated in both saliva and urine but with more prominent cycles in saliva.

CONCLUSION:
Nocturnal salivary cortisol correlated well with early morning urine. Nocturnal salivary cortisol detected all cases of cyclical Cushing's. Therefore, nocturnal salivary cortisol may prove to be an additional option or replacement for early morning urine in detecting cyclical Cushing's syndrome. [blogger emphasis]

PMID:  23150688 [PubMed - indexed for MEDLINE]

NOTE: Blogger changed all abbreviations for EMU and NSC to early morning urine and nocturnal salivary cortisol. This Cushie brain can’t remember what these mean half way down the article.