Midnight Salivary Cortisol Versus Urinary Free and Midnight Serum Cortisol as Screening Tests for Cushing’s Syndrome

Posted on October 2, 2016 by MaryO

From PubMed

Gafni RI, Papanicolaou DA, Nieman LK.
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1862, USA.

OBJECTIVE: There is currently no optimal test to screen for endogenous Cushing’s syndrome (CS) in children. Traditional 24-hour urine or midnight serum cortisol values may be difficult to obtain or elevated by venipuncture stress. We hypothesized that salivary cortisol measurement is a reliable way to screen for CS in children.

STUDY DESIGN: Sixty-seven children (5-17 years) were studied: 24 obese volunteers, 29 non-obese volunteers, and 14 children with CS. Saliva was obtained at 7:30 AM, bedtime, and midnight for measurement of free cortisol by radioimmunoassay.

RESULTS: Salivary cortisol was detectable in all morning and evening samples from patients with CS but was frequently undetectable in healthy children at bedtime (66%) and at midnight (90%). With cut points that excluded healthy children, a midnight salivary cortisol value of 7.5 nmol/L (0.27 microg/dL) identified 13 of 14 patients with CS, whereas a bedtime value >27.6 nmol/L (1 microg/dL) detected CS in 5 of 6 patients. The diagnostic accuracies of midnight salivary cortisol and urinary free cortisol per square meter were the same (93%).

CONCLUSION: Salivary cortisol measurement at bedtime or midnight rules out CS in nearly all cases. Nighttime salivary cortisol sampling is thus a simple, accurate way to screen for hypercortisolism in children. PMID: 10891818 [PubMed – indexed for MEDLINE]

THE PRINCIPLE RESEARCHER FOR SALIVARY CORTISOLS IS HERSHEL RAFF AT THE UNIVERSITY OF WISCONSIN. HE IS A RESEARCH SCIENTIST, NOT A DOCTOR. YOU CAN CONTACT HIM DIRECTLY FOR ORDERING INFO.

Salivary Cortisol: A Screening Technique

By: Dr. Hershel Raff

Cushing’s syndrome – endogenous hypercortisolism – is characterized by a loss of circadian rhythmicity. In normal patients, cortisol levels peak in the early morning hours and decrease to substantially lower levels at night. Rather than the normal decrease in late evening cortisol, patients with Cushing’s syndrome of any cause fail to decrease cortisol secretion in the late evening. Therefore, the measurement of elevated late evening cortisol is helpful in the diagnosis of Cushing’s syndrome. Obtaining a late night, unstressed plasma cortisol is virtually impossible in most clinical practices. Salivary cortisol is in equilibrium with the free, biologically active portion of cortisol in the plasma. Therefore, if one obtains a saliva sample in patients at bedtime in their homes under unstressed conditions, one can make the diagnosis of endogenous hypercortisolism.

A simple way to sample saliva is by using a Salivette made by the Sarstedt Company (Newton, NC). This device consists of a cotton tube and plastic tubes. The patient only has to chew the cotton tube for 2-3 minutes and place it in the plastic tube. The tube is then transported to our lab for analysis.

Late-evening salivary cortisol is not intended to replace the current standard screening test – measurement of a 24 hr urine free cortisol. However, the salivary cortisol test can be extremely useful for patients suspected of having intermittent Cushing’s syndrome. Due to the convenience of sample collection, the patient can sample saliva several evenings in a row. In fact, our clinical endocrinologists routinely order 2-3 consecutive late-evening salivary cortisol samples.

Our research (Raff H, Raff JL, Findling JW. 1998 LATE-NIGHT SALIVARY CORTISOL AS A SCREENING TEST FOR CUSHING’S SYNDROME. J Clin Endocrinol Metab. 83:2681-2686) has shown that the combination of late-evening salivary cortisol and urine free cortisol is very accurate in diagnosing Cushing’s syndrome in most patients. Doctors can obtain a kit by contacting ACL Client Services at 1-800-877-7016.

Editor’s Note: DR. HERSHEL RAFF, PH.D. IS A PROFESSOR OF MEDICINE AND PHYSIOLOGY AT THE MEDICAL COLLEGE OF WISCONSIN’S ENDOCRINE RESEARCH LABORATORY AT ST. LUKE’S MEDICAL CENTER IN MILWAUKEE, WISCONSIN.

Filed under: Cushing's, Diagnostic Testing | Tagged: , , , , , , | Leave a comment »

A Single-Center 10-Year Experience with Pasireotide in Cushing’s Disease: Patients’ Characteristics and Outcome

Posted on April 30, 2016 by MaryO

Pasireotide is the first pituitary-directed drug approved for treating patients with Cushing’s disease (CD). Our 10-year experience with pasireotide in CD is reported here.

Twenty patients with de novo, persistent, or recurrent CD after pituitary surgery were treated with pasireotide from December 2003 to December 2014. Twelve patients were treated with pasireotide in randomized trials and 8 patients with pasireotide sc (Signifor®; Novartis AG, Basel, Switzerland) in clinical practice. The mean treatment duration was 20.5 months (median 9 months; range, 3-72 months).

Urinary free cortisol (UFC) levels mean percentage change (± SD) at last follow-up was-40.4% (± 35.1; range, 2-92%; median reduction 33.3%) with a normalization rate of 50% (10/20). Ten patients achieved sustained normalized late night salivary cortisol (LNSC) levels during treatment. LNSC normalization was associated with UFC normalization in 7/10 patients. Serum cortisol and plasma ACTH significantly decreased from baseline to last follow-up. Body weight decrease and blood pressure improvement during pasireotide treatment were independent from UFC response. Glucose profile worsening was observed in all patients except one. The frequency of diabetes mellitus increased from 40% (8/20) at baseline to 85% (17/20) at last follow-up requiring initiation of medical treatment only in 44% of patients.

Pasireotide treatment was associated with sustained biochemical and clinical benefit in about 60% of CD patients. Glucose profile alteration is a frequent complication of pasireotide treatment; however, it seems to be easy to manage with diet and lifestyle intervention in almost half of the patients.

From http://www.ncbi.nlm.nih.gov/pubmed/27127913

Filed under: Cushing's, Diagnostic Testing, Treatments | Tagged: , , , , , , , , , , , , , | Leave a comment »

Cushing’s: Update on signs, symptoms and biochemical screening

Posted on October 11, 2015 by MaryO

10.1530/EJE-15-0464

  1. Lynnette Nieman⇑

+Author Affiliations


  1. L Nieman, RBMB, NIH, Bethesda, 20817-1109, United States
  1. Correspondence: Lynnette Nieman, Email: niemanl@mail.nih.gov

Abstract

Endogenous pathologic hypercortisolism, or Cushing’s syndrome, is associated with poor quality of life, morbidity and increased mortality. Early diagnosis may mitigate against this natural history of the disorder.

The clinical presentation of Cushing’s syndrome varies, in part related to the extent and duration of cortisol excess. When hypercortisolism is severe, its signs and symptoms are unmistakable. However, most of the signs and symptoms of Cushing’s syndrome are common in the general population (e.g. hypertension and weight gain) and not all are present in every patient.

In addition to classical features of glucocorticoid excess, such as proximal muscle weakness and wide purple striae, patients may present with the associated co-morbidities that are caused by hypercortisolism. These include cardiovascular disease, thromboembolic disease, psychiatric and cognitive deficits, and infections. As a result, internists and generalists must consider Cushing’s syndrome as a cause, and endocrinologists should search for and treat these co-morbidities.

Recommended tests to screen for Cushing’s syndrome include 1 mg dexamethasone suppression, urine free cortisol and late night salivary cortisol. These may be slightly elevated in patients with physiologic hypercortisolism, which should be excluded, along with exogenous glucocorticoid use. Each screening test has caveats and the choice of tests should be individualized based on each patient’s characteristics and lifestyle.

The objective of this review was to update the readership on the clinical and biochemical features of Cushing’s syndrome that are useful when evaluating patients for this diagnosis.

Read the entire manuscript at http://www.eje-online.org/content/early/2015/07/08/EJE-15-0464.full.pdf+html

Filed under: Cushing's, Diagnostic Testing, Rare Diseases | Tagged: , , , , , , , , , , , , , , , , , , , , , , | Leave a comment »

Interview with Fabiana October 21

Posted on September 29, 2015 by MaryO

Fabiana had transsphenoidal surgery (pituitary) July 30th 2004.  She had a recurrence after seven years of being Cushing’s free.  A second pituitary surgery on 10/26/2011 was unsuccessful.

Another Golden Oldie, this bio was last updated 9/12/2015

interview

Fabiana will be our guest in an interview on BlogTalk Radio  Wednesday, October 21 at 6:00 PM eastern.  The Call-In number for questions or comments is (657) 383-0416.

The archived interview will be available after 7:00 PM Eastern through iTunes Podcasts (Cushie Chats) or BlogTalkRadio.  While you’re waiting, there are currently 88 other past interviews to listen to!

~~~

Well it has taken me a year to write this bio…and just to give some hope to those of you just going thru this process…I have to say that after surgery I have not felt better! I am back to who i always knew I was….the depression and anxiety is gone and I am living life like a 24 year old should!

I guess it all started when i was sixteen (hindsight is 20-20 i guess). My periods stopped i was tired all the time and the depression started. We all kind of just chalked it up to being sixteen. But my mom insisted something was not right. we talked with my gyno…who said nothing was wrong, I had a fungus on my head (my hair was getting really thin) and sometimes girls who had normal periods (in my case three years of normal periods) just go awry.

My mom wasnt hearing that and demanded a script for an endo. I went….he did blood work…and metioned cushings. But nothing came back definitive…so they put me on birthcontol and gave me some hormones and the chushings was never mentioned again because that all seemed to work.

As time went on my depression got worse, the shape of my body started to change-my face and stomach was the most noticeable- and my energy level kept going down. I kept going back to the doctors asking to be tested for mono..or something. I went to a psycologist….but i knew there was no reason for my depression. Two of them told me “i had very good insight” and that I didnt need them. I started getting more anxiety..especially about going out socially.

High school ended and my typical optimistic personality started to decline. I put on a good act to my friends but my family was seeing me break down all the time. I went away for college (all the while gaining weight). My sophmore year I had a break down..I called my family crying that i needed help. I couldnt beat my depression. I didnt drink in college because i knew that would mean instant weight gain, i barely went out…i exercised everyday..hard….i joined weight watchers…i stuck with it. I was at 103 lbs….that crept up to 110…that crept up to 117…each time my weight goal would be “ohh if i could just get back to 108..112…115” with each weight gain my original weight goal would get higher and higher.

Internally i felt like I was constantly under a black cloud..i knew there was no reason why i shoudl feel this way..i was doing great in school, i had a supportive family, an amazing boyfriend and great friends…why was i depressed? I was becoming emotionally draining to the people closest to me…I would go home a lot on the weekends…i was diagnosed with PMDS….like severe PMS..and was given an antidepresant…i hated it it made me feel like a zombie…i stopped taking it and just made it apoint to work on fighting the depression….and the weight gain.

When i was done college i was about 120 lbs. My face was getting rounder and rounder..i was noticing more hair on my face and arms…and a hump between my shoulder blades and the bottom of my neck. My mom saw a tv show about Polycystic ovarian syndrome and felt that maybe that was what was going on with me…i went to my PCP with this and she said it was possible and that i should to talk to my gyno….I am 4’8 and at the time weighing close to 125..i talked to my gyno and she said I was not heavy..that i was just “itailan” ..i told her my periods were getting abnormal again even w/the birthcontrol and that i was so tired all the time and my arms and legs ached. I also told her that i was bruising very easily…and that the weight gain would not stop despite my exercising and following the atikins diet very strickly for over 6 weeks. My boyfriend and I decided to try the diet together..he lost 35 llbs in 6 weeks..i lost NOTHING! I went back to my PCP who ordered an ultra sound of my ovaries…..NOTHING.(i kept thinking i was going crazy and that it was all in my head)….she also decided to do some blood work…and as i was walking out the door she said..”you know what..i am going to give you this 24hr urine test too. Just so that we cover everything”. I just kept thinking please let something come back ….please dont let this be all my fault…please dont let this be all in my head…..please dont let me be crazy. When i got the test results back it turned out that the 24hr urine test was the one test i needed to get on the right track to finding what was wrong. My cortisol level was 3x’s the normal.

I went to an endo…by the time i got to the endocronoligist i was up to 130…i could not work a full day without needing a full day of sleep and my body was aching beyond description. I was crying all the time…in my room…and was becoming more and more of a recluse…i would only hang out with my boyfriend in our houses. I looked my symptoms up on the internet and saw cushings…that was it! I went to the endo and told him..i think it is cushings….he said he had only saw it one other time and that he wanted to do more tests. I got CAT scans, x-rays, MRI’s….my adrenals my pituitary my lungs….he did a CRH stimulation test which was getting blood work done every fifteen minutes for 90minutes….it took weeks to get that test scheduled..no one had ever heard of it and therefore did not know how to do it…..finally after 3 months of tests my dr. felt he had enough evidence to diagnos me with cushings disease (tumor on my pituitary) I was diagnosed in March of 2004. By this time i was about 137 lbs i had to work part time (i am an occupational therapist for children..i do home visits….i could not make it thru a whole day)

In April i had to change to office work…i could not lift the children and i could barely get up off the floor. I have to say i was one of the lucky people who worked for people who were very supportive and accomidating…my boss was very willing to work with me and willing to hold my job for me.

July 30th 2004 i finally had transphenodial surgery to remove my tumor (they went thru my lip and nose because they felt my nose was too small). It is now over 1 year later….i am down to 108 lbs, i have so much energy…no depression….and i dont mind looking at myself in the mirror…i am enjoying my friends and my boyfriend…(who stayed with me thru it all) And my family. I feel healthy mentally, emptionally, and physically. And i just got back into my size 2 jeans!!!

It was a crappy time…(as i am sure you all can atest to) but i learned a lot…..most importantly i was bombarded by good wishes and prayers….friends requested masses for me…a nun in brazil prayed for me…people who i never thought i touched their lives…took the time to wish me well…send an email..or call….I got to experience the wonderful loving nature of human beings and i was lucky to be supported by my family (my mom, dad, and two younger brothers) and my boyfriend throughout this entire tough journey.

This experience taught me to realize the strength i have as well as to appreciate the good and the bad in life. I was on hydrocortizone for about 8 months…i was lucky that my tumor was in its own little sack so my pituitary gland was not touched. In the end in took about 7 years to diagnose me..i think that if the dr. at 16 would have pursued the cushings idea nothing would have been found because it took so long for my symptoms to really peak…needless to say i love my PCP and my endo ..and that i changed gyno’s…

I just want to let anyone out there going thru this disease to know..you are not alone….and to take each day is stride…when you need help ask for it….and that this road can lead to a happy ending. God Bless!

ps- it is ok to feel bad about what you are going thru…it is a tough thing to endure…and when the docotors tell you there is noting wrong…..follow your gut…and you keep searching for the doctor that will listen… If there is anyone in the philadelphis of south jersey area who needs someone to talk to please feel free to email me…fapadula@hotmail.com…i will help you out the best i can!

Update November 6, 2011

Well- here is an update, after seven years of being Cushings free it has returned.

With in those seven years I married my college boyfriend and we now have a son- Nicholas who will be 2 in Decemeber. It has been a blessed and wonderful seven years. However right around when my son was turning 1 I started to notice symptoms again. Increase facial hair, the whole “roundness” of my body, buffalo hump. I decided I was going to work out hard, eat right, and see – I didnt just want to jump to any conclusions. I stuck to it- and nothing…..my hair started thinning again and the acne was coming back and then the missed periods…..so I went to my PCP- told them i needed the 24hr urine and wouldnt you know…..427 cortisol level (on that 0-50 scale)……here we go again.

So back to endo- now at Penn Pituitary Center…..it was another journey b/c the tumor wasnt definative on MRI, and it seems to be cycling…..but I was diagnosed with Cushings again- with the option of 2nd pit surgery or BLA…….after some months of trying to make a decision I went with the 50/50 chance of the second pituitary surgery on 10/26/2011.

It didnt work- my levels never came down in the hospital and I went home w/ out of range cortisol levels and no need for medication……BLURG……Sooooo on to the next step…..after I recover from this surgery I will most likely have the BLA- with the hopes of not having to deal with Cushings ever again. This time around has been a little more difficult just with being a mom and feeling sick- but I still continue to be amazingly blessed with a supportive family and husband and we are surrounded by love and support and for that I am beyond greatful.

I keep all of you in my prayers for relief and health- as I ( we all) know this no easy journey.

Many Blessings!

Fabiana

Update September 12, 2015

So to bring this up to date. My second pituitary surgery in 2011 was unsuccessful. January of 2012 I had both of my adrenal glands removed. Going to adrenal insufficiency was a very difficult transition for me. It took me nearly 2 years before I felt functional. As time went on I felt more human, but I haven’t felt healthy since that day. I can and do function, but at a lower expectation of what I used to be capable of….my “new normal”.

My husband and I decided to try for a second child…my pituitary was damaged from the second surgery and we needed fertility…after 8 months of fertility I got pregnant and we had our second son January of 2015.

In April of 2015 we discovered that my ACTH was increasing exponentially. MRI revealed a macroadenoma invading my cavernous sinus. The tumor is sitting on my carotid artery and milimeterrs away from my optic chasim. I was not a candidate for another surgery due to the tumors proximity to.both of those vital structures.

So September 1st of this year I started daily radiation treatments. I spent my 34th birthday getting my brain zapped. I am receiving proton beam therapy at the Hospital of the University of Pennsylvania. I am so lucky to live so close to an institute that has some of the rarest treatment options.

Again Cushing’s is disrupting our life, my husband goes with me every night to radiation while family takes turns watching the kids….I am now on my 18th year of fighting this disease. I never imagined it would get to this point.

But here we all are making the best of each day, fighting each day and trying to keep things as “normal” as possible. Blessings to all of you fighting this disease…my new go to saying is” ‘effing Cushing’s”! For you newbies…Fight, Advocate for yourselves, and find a doc who doesn’t dismiss you and hang on to them for dear life.

HOME | Sitemap | Adrenal Crisis! | Abbreviations | Glossary | Forums | Donate | Bios | Add Your Bio | Add Your Doctor | CushieWiki

Filed under: Cushing's, Interview, pituitary, Rare Diseases, Treatments | Tagged: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , | Leave a comment »

Metopirone effective treatment for hypercortisolemia in Cushing’s syndrome

Posted on September 15, 2015 by MaryO

Hypercortisolemia in Cushing’s syndrome can be controlled with Metopirone therapy, according to recent study findings published in The Journal of Clinical Endocrinology & Metabolism.

John Newell-Price, PhD, FRCP, of the University of Sheffield in the United Kingdom, and colleagues evaluated 195 patients with Cushing’s syndrome to determine the effect of Metopirone (metyrapone, HRA Pharma) on the control of excess cortisol. Cushing’s syndrome was most commonly Cushing’s disease (n = 115), followed by ectopic adrenocorticotropic hormone (ACTH; n = 37), benign adrenal disease (n = 30), adrenocortical carcinoma (n = 10), ACTH-independent macronodular adrenal hyperplasia (n = 2) and primary pigmented nodular adrenal hyperplasia (n = 1).

The biochemical parameters of activity of Cushing’s syndrome were measured by mean serum cortisol day-curve (target, 150-300 nmol/L), early morning serum cortisol and 24-hour urinary free cortisol.

Most participants received monotherapy (n = 164) and had significant improvements in excess cortisol during treatment. Significant improvements were revealed from first to last review for cortisol day-curve, early morning cortisol and 24-hour urinary free cortisol.

At last review, 55% of participants who had cortisol day-curve, 43% who had urinary free cortisol, 46% who had early morning cortisol less than 331 nmol/L and 76% who had early morning cortisol less than the upper limit of normal/600 nmol/L achieved control.

The median final dose of metyrapone was 1,375 mg among those with Cushing’s disease, 1,500 mg among those with ectopic ACTH, 750 mg among those with benign adrenal disease and 1,250 among those with adrenocortical carcinoma.

Twenty-five percent of participants experienced adverse events, with the most common being mild gastrointestinal upset and dizziness. Most of the adverse events occurred within 2 weeks of initiation or dose increase and were reversible.

“Overall more than 80% of patients showed an improvement in levels of circulating cortisol with over 50% achieving biochemical eucortisolemia when on monotherapy when assessed by the stringent criterion of control on a [cortisol day-curve],” the researchers wrote. “It is likely that additional therapies were added because of the severity of disease and clinician preference, but the retrospective and multicenter nature of our study precludes a formal assessment of this. Furthermore, our data support that metyrapone monotherapy is an effective treatment for hypercortisolemia either before or after surgical intervention to the primary cause of [Cushing’s syndrome].” – by Amber Cox

Disclosure: Newell-Price reports various financial ties with HRA Pharma and Novartis. Please see the full study for a list of all other authors’ relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B067ff9a2-dbce-428f-be94-849e1f466150%7D/metopirone-effective-treatment-for-hypercortisolemia-in-cushings-syndrome

HOME | Sitemap | Adrenal Crisis! | Abbreviations | Glossary | Forums | Donate | Bios | Add Your Bio | Add Your Doctor | CushieWiki

Filed under: adrenal, Cushing's, pituitary, Treatments | Tagged: , , , , , , , , , , | Leave a comment »

« Previous Page — Next Page »