Thursday, May 19, 2011

Glimmer of Hope: Delayed Remission

Thank you to my Cushie friend Debra for sharing this article.  You gotta believe. ~m

Delayed Remission after Transsphenoidal Surgery in Patients with Cushing’s Disease

Full text available for free in pdf here.


Background: Transsphenoidal surgery (TSS) is the treatment of choice for Cushing’s disease (CD). Postoperative hypercortisolemia mandates further therapy.

Objective: The aim of the study was to characterize patients without immediate postoperative remission who have a delayed decrease to normal or low cortisol levels without further therapy.

Design and Setting: A retrospective case series was conducted at three tertiary care centers.

Patients and Intervention: We reviewed the records of 620 patients (512 females, 108 males; mean age, 38 ± 13 yr) who underwent transsphenoidal pituitary surgery for CD between 1982 and 2007.

Results: Outcomes were classified into the following three groups based upon the postoperative pattern of cortisol testing: group IC (immediate control) included 437 of the 620 patients (70.5%) with hypocortisolism and/or cortisol normalization throughout the postoperative follow-up; group NC (no control) included 148 of 620 patients (23.9%) with persistent hypercortisolism; and group DC (delayed control) included 35 of 620 patients (5.6%) who had early elevated or normal UFC levels and developed a delayed and persistent cortisol decrease after an average of 38 ± 50 postoperative days. The total rate of recurrence was 13% at a median follow-up time of 66 months after TSS; the cumulative rate of recurrence at 4.5 yr was significantly higher in group DC vs. group IC (43 vs. 14%; P = 0.02).

Conclusions: Hormonal assessment in the immediate postoperative period after TSS for CD may be misleading because delayed remission can occur in a subset of patients. Expectant management and retesting may spare some patients from unnecessary further treatment. Optimal timing to determine the need for further therapy after TSS remains to be determined.

  • Received August 5, 2009.
  • Accepted November 23, 2009.

- Author Affiliations

  1. Neuroendocrine Unit (E.V., B.M.K.B., A.K.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Chair of Endocrinology (E.V., F.P.G., F.C.), Universita’ di Milano, Ospedale San Luca, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico, 20149 Milan, Italy; Department of Neurosurgery (M.L., P.M.), Universita’ Vita-Salute, Istituto Scientifico San Raffaele, 20132 Milan, Italy; and Biostatistics Center (D.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
  1. Address all correspondence and requests for reprints to: Anne Klibanski, M.D., Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, Bulfinch 457B, Boston, Massachusetts 02114. E-mail:

Why Obesity Is A Disease

Wednesday, May 18, 2011

Dumb da Dumb Dumb..... DUMB!!!!

This is what it sounds like when the President of the National Honor Society cries.
Whaaaaa waaaaaaaaaa whaaaaaa waaaaaaaaaa

"Cognitive function, reflecting memory and executive functions, is impaired in patients despite long-term cure of Cushing’s disease. These observations indicate irreversible effects of previous hypercortisolism on cognitive function and, thus, on the central nervous system."

Subtle Cognitive Impairments in Patients with Long-Term Cure of Cushing’s Disease

Journal of Clinical Endocrinology & Metabolism. June 2010.|Tiemensma et al. 95 (6): 2699

Jitske Tiemensma,Nieke E. Kokshoorn,Nienke R. Biermasz,Bart-Jan S. A. Keijser,Moniek J. E. Wassenaar,Huub A. M. Middelkoop,Alberto M. Pereira andJohannes A. Romijn


Context and Objective: Active Cushing’s disease is associated with cognitive impairments. We hypothesized that previous hypercortisolism in patients with Cushing’s disease results in irreversible impairments in cognitive functioning. Therefore, our aim was to assess cognitive functioning after long-term cure of Cushing’s disease.

Design: Cognitive assessment consisted of 11 tests, which evaluated global cognitive functioning, memory, and executive functioning.

Patients and Control Subjects: We included 74 patients cured of Cushing’s disease and 74 controls matched for age, gender, and education. Furthermore, we included 54 patients previously treated for nonfunctioning pituitary macroadenomas (NFMA) and 54 controls matched for age, gender, and education.

Results: Compared with NFMA patients, patients cured from Cushing’s disease had lower scores on the Mini Mental State Examination (P = 0.001), and on the memory quotient of the Wechsler Memory Scale (P = 0.050). Furthermore, patients cured from Cushing’s disease tended to recall fewer words on the imprinting (P = 0.013), immediate recall (P = 0.012), and delayed recall (P = 0.003) trials of the Verbal Learning Test of Rey. On the Rey Complex Figure Test, patients cured from Cushing’s disease had lower scores on both trials (P = 0.002 and P = 0.007) compared with NFMA patients. Patients cured from Cushing’s disease also made fewer correct substitutions on the Letter-Digit Substitution Test (P = 0.039) and came up with fewer correct patterns on the Figure Fluency Test (P = 0.003) compared with treated NFMA patients.

Conclusions: Cognitive function, reflecting memory and executive functions, is impaired in patients despite long-term cure of Cushing’s disease. These observations indicate irreversible effects of previous hypercortisolism on cognitive function and, thus, on the central nervous system. These observations may also be of relevance for patients treated with high-dose exogenous glucocorticoids. 

- Author Affiliations

  1. Departments of Endocrinology and Metabolism (J.T., N.E.K., N.R.B., B.-J.S.A.K., M.J.E.W., A.M.P., J.A.R.) and Neurology (H.A.M.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands
  1. Address all correspondence and requests for reprints to: J. Tiemensma, MSc., Department of Endocrinology and Metabolic Diseases C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail:

Monday, May 16, 2011

CUSHING’S: Relentless and Nefarious

I am 27 days post op for my second pituitary surgery. I had blood work done on post op day 16 after withholding for 24 hours, aka skipping my afternoon dose of hydrocortisone the day before.  Late last Friday, I received some terrible news from my lab results.  My body is making too much cortisol and ACTH so soon after pituitary surgery.

04/24/2011 post op day 5 @ 8 am (withheld pm dose on previous day)
cortisol 13.6 (4-22)
acth 24 (5-27)
glucose 96 (65-99)
sodium 142 (135-146)

05/06/2011 post op day 16 @ 8 am (withheld pm dose on previous day)
cortisol 17.1 (4-22)

acth 59 (5-27)
glucose 102 (65-99)
sodium 142 (135-146)

       My cortisol increased to 17.1 in the am, and ACTH is more than twice normal. I did capture some high ACTH values prior to my first pituitary surgery, with one high ACTH during the day, and that was 125 baseline for IPSS. Some daytime values were in the high 20s but not like this. My 4 am ACTH in 2007 were 78 and 105.

 ** ** ** ** ** ** ** **

       My friend Debra reminded me that a cure for Cyclical Cushing’s is very uncertain, often as low as 30% for the first pituitary surgery. She reviewed the medical literature and read every single study she could find on remission after pituitary surgery for Cushing’s. The highest cortisol value she could find that indicated remission was 14 (post op day 5 cortisol level while withholding HC dose for 24 hours). Mine are 13.6 and 17.1.  Debra pointed to this European Journal of Endocrinology article entitled The Prevalence and Characteristic Features of Cyclicity and Variability in Cushing's Disease, which was published in 2009.
       The second pituitary surgery did not cure my Cushing's.  There is no other conclusion. I am just heartbroken and devastated about this medical development, even though I have known it was a possibility since 2007.
Cushing’s patients whose bodies will not stop producing cortisol must remove both adrenal glands in order to ultimately stop all cortisol production at the source. Since high cortisol breaks down many body systems, it just not an option to let Cushing’s keep going.  So, we trade Cushing’s and high cortisol for Addison’s and low cortisol. REPEAT: I will trade the terribly relentless and rollercoaster cortisol levels of Cyclical Cushing's disease for the unpredictable make-no-cortisol-at-all and hope-there-is-no-emergency-or-trauma Addison's.  I am now making plans to have both adrenal glands removed in a procedure called a bilateral adrenalectomy (BLA). NYU’s Department of Surgery posted information on the adrenalectomy procedure.
       Last month, I posted a list of Cushie Warriors – 50 people from around the world who have had to have multiple surgeries in an attempt to rid themselves of Cushing’s. I wish we could get a restraining order for this Cushing’s menace.
       My current dose of hydrocortisone is 15 mg at 8 am and 5 mg at 1 pm.  I will taper that dose responsibly but quickly after speaking to my Cushing’s endocrinologist this Wednesday. 
       That’s all I have to say about that.

Saturday, May 7, 2011

Obesity Research: Consequences vs. Causes

Obesity is bad, we get that
The Guardian
"People tend not to believe that a medical condition can cause weight gain, but the little-known – and devastating – Cushing'sdisease is one such cause, alongside more well-recognised but not yet fully understood illnesses including hypothyroidism and..." 

 "The greatest distress for patients is that nobody is sympathetic, including many healthcare professionals. There is a lot to do in terms of challenging perceptions."

Thursday, May 5, 2011

This is your Life.


Cushing’s Syndrome during Pregnancy


Cushing’s Syndrome during Pregnancy: Personal Experience and Review of the Literature

Cushing’s syndrome (CS) occurs rarely during pregnancy. We investigated and treated four patients with pituitary-dependent Cushing’s syndrome during pregnancy over a 15-yr period at the National Institutes of Health. Except for preservation of menses before conception, our patients presented with typical clinical features, increased urinary free cortisol, and loss of diurnal variation of cortisol. The diagnosis was facilitated, without complications, by the use of CRH testing and inferior petrosal sinus sampling in three women. Transsphenoidal pituitary surgery achieved remission in three women, but there were two fetal/neonatal deaths. This experience and review of 136 previous reports suggest that: 1) urinary free cortisol in CS patients overlaps the normal pregnant range; 2) ACTH levels are not suppressed in adrenal causes of CS, which may be identified by the 8-mg dexamethasone test; 3) inferior petrosal sinus sampling and transsphenoidal pituitary surgery, the optimal diagnostic test and treatment for nonpregnant patients with pituitary-dependent Cushing’s syndrome, can safely facilitate the management of pregnant patients; and 4) surgery may achieve remission during pregnancy, but the prognosis for the fetus remains guarded. It is likely that earlier recognition and treatment would improve outcome. There is a need for development of criteria for interpretation of diagnostic tests and increased consideration of CS in pregnancy.

Check out this original article.

John R. Lindsay, Jacqueline Jonklaas, Edward H. Oldfield, and Lynnette K. Nieman

Reproductive Biology and Medicine Branch (J.R.L., L.K.N.), National Institute of Child Health and Human Development,
and Surgical Neurology Branch (E.H.O.), National Institute of Neurologic Disorders and Stroke, National Institutes of
Health, Bethesda, Maryland 20892-1109; and Georgetown University Medical Center (J.J.), Washington, DC 20057

J. Clin. Endocrinol. Metab. 2005 90:3077-3083 originally published online Feb 10, 2005; , doi: 10.1210/jc.2004-2361

Wednesday, May 4, 2011

Addison's Disease Poses Risks To Patients

I am so happy to see this article.  Addison's is the opposite of Cushing's. Addison's results from low cortisol levels, and Cushing's results from high cortisol.  When a Cushing's patient has a pituitary tumor removed, s/he can suffer from Addison's while the body's hypothalamus-pituitary-adrenal axis regulates itself again.  Also, a Cushing's patient who will not stop producing cortisol ultimately has to remove both adrenal glands in order to ultimate stop all cortisol production.  This makes the Cushing's patient an Addison's patient for the rest of his/her life.  These diseases are inextricably linked, and I am glad that doctors are realizing how life threatening cortisol can be. Patients know it.  European doctors know it. Let's hope US doctors will learn quickly, too.  ~m

Greater Awareness Needed On Risks That Addison's Disease Poses To Patients

Main Category: Endocrinology
Also Included In: Infectious Diseases / Bacteria / Viruses
Article Date: 03 May 2011 - 0:00 PDT

Two new studies presented at the European Congress of Endocrinology in Rotterdam show the possible dangers facing patients with Addison's disease are higher than previously thought. The new research shows that Addison's patients, who have low levels of cortisol produced by the adrenal glands, are more likely to get infections which may provoke life-threatening adrenal crises.

Addison's disease is caused by low levels of the hormone cortisol, produced by the adrenal glands. Without treatment, the condition can be fatal. Patients with Addison's disease can suffer a range of symptoms, including fatigue, dizziness, weight loss, muscle weakness, mood changes and the darkening of regions of the skin if they don't receive treatment. The most famous Addison's disease sufferer was John F Kennedy, but it is a comparatively rare condition, affecting about 1 person in 15,000.

Dr Stefanie Hahner, working at University of Würzburg, Germany, looked at the incidence of adrenal crisis in 472 German patients with Addison's disease. An adrenal crisis is a potentially life-threatening condition which occurs when cortisol levels fall dangerously low, requiring an immediate injection of hydrocortisone. Dr Hahner found that 62 of the patients had an adrenal crisis over the two-year period of the prospective study, with almost two-thirds of those needing to be hospitalised and 9.5% being treated in intensive care. Two patients died from adrenal crises during the study. The study also found that many patients were unprepared to deal with the threat to life presented by crises and further patient education programmes may be warranted.

Researcher Dr Stefanie Hahner said:

"The number of adrenal crises was higher than we expected from previous studies. Infectious disease provoked 39% of the crises, with psychological stress also causing problems. Ninety-five percent of the patients were aware of the dangers of an adrenal crisis, but only 28% had the emergency injection set. This shows that these crises are largely caused by infectious diseases and stress, but also that patients need to be better prepared to respond to the crises when they arise and that infectious disease has to be treated early and aggressively in this patient group."

In another study presented at the European Congress of Endocrinology from the University of Utrecht, The Netherlands, Dr Lisanne Smans showed that patients with Addison's disease were more at risk of suffering infections than the rest of the population.

She identified 390 Addison's patients from pharmacy records and compared the risk of infections and hospital admissions. Dr Smans found that the risk of infectious disease was 1.5 times that of a control population, (overall incidence rate of 59.2/100 person-years). In addition, Addison's patients were significantly more likely to be hospitalised for infectious disease than control groups (3.8/100 person years for Addison's patients, versus 0.8/100 person years for control groups).

Researcher Dr Lisanne Smans commented:

"We need to raise awareness amongst doctors and patients of the risk of infections in Addison's patients compared to the general population. We now want to move on to see whether influenza vaccinations can help this patient group."

Commenting on the two papers, Professor Peter Trainer, Chair of the European Congress of Endocrinology Programme Organising Committee, said:

"These studies reinforce our knowledge of the risks that infections pose to patients with Addison's disease and serious consequences that can arise. We need to look at ways of making both the medical community and patients more aware of the appropriate medical action needed to treat an adrenal crisis. This really is a case where quick action can save lives. All patients with Addison's disease should carry an emergency kit containing a hydrocortisone injection that can be given immediately if they fall ill."

Sources: European Society of Endocrinology, AlphaGalileo Foundation.

Hair Samples: Better Testing

My endocrinologist in Los Angeles has been working on a similar study here in the US.  I hope that patients in the future will not have to undergo the ridiculous rigmarole that I faced (four years of testing).  I continue to grow my hair out in hopes that I can contribute a hair sample to some study... one day.  ~mm

New Method To Measure Cortisol Could Lead To Better Understanding Of Development Of Common Diseases

Main Category: Endocrinology
Also Included In: Anxiety / Stress;  Heart Disease;  Preventive Medicine
Article Date: 03 May 2011 - 0:00 PDT

A new method to measure the amount of the stress hormone cortisol found in the body over the long term could lead to new research avenues to study the development of common conditions, such as heart disease, diabetes and depression. In results announced at the European Congress of Endocrinology, researchers found that hair can be used to create a retrospective timeline of exposure to cortisol. Cortisol is implicated in the development of many common conditions and this new technique could allow us to study its role better.

Cortisol is a hormone produced by the adrenal glands and its primary role is to help maintain body metabolism. If the body is put under (psychological or physical) stress, cortisol levels increase to allow the body to respond to the situation. Currently the standard method to measure cortisol levels is to take a blood or saliva sample. However, since cortisol is released in a circadian rhythm and with pulses throughout the day, levels can fluctuate considerably, meaning it is difficult to estimate an individual's long-term exposure to cortisol through blood and saliva tests alone. Finding a new non-invasive method to measure long-term cortisol exposure could have a major impact on our ability to determine the role of cortisol in the development of many common diseases, such as cardiovascular disease, diabetes and depression.

Dr Laura Manenschijn and her team from Erasmus MC in The Netherlands collected scalp hair samples from 195 healthy individuals and from 11 patients with Cushing's syndrome (a condition where the adrenal glands produce too much cortisol) and 3 patients with Addison's disease (a condition where the adrenal glands are unable to produce cortisol) and tested their cortisol levels. All participants filled out a questionnaire to assess what products and treatments they used on their hair. A subset of 46 participants also had their waist and hip measurements taken.

The team found that hair cortisol levels correlated positively with waist to hip ratio (r=0.425, p=0.003) and waist circumference (r=0.392, p=0.007), meaning people with higher exposure to cortisol showed higher abdominal obesity. In individuals with Cushing's syndrome the levels of cortisol in hair were significantly higher than in healthy individuals (p<0.0001). In long hair of individuals with Cushing's syndrome and Addison's disease, the levels of hair cortisol corresponded with clinical records of the amount of cortisol they had been exposed to. Additionally, in long hair of healthy women, the team were able to record alterations in cortisol exposure due to psychological stress over time. Hair cortisol levels were not influenced by gender (p=0.353), hair colour (p=0.413), frequency of hair wash (p=0.673) or hair products (p=0.109), although there was a slight, borderline significant, decrease in cortisol levels in hair that was treated (dyed/bleached) (p=0.08).

This is the first time that cortisol measurements taken from hair have been shown to correlate with known tissue effects of cortisol, such as abdominal obesity, and to provide a retrospective timeline of exposure to this hormone. The next step is to use this technique in larger studies to examine the role of long-term cortisol exposure in the development of cardiovascular disease and depression. Ultimately, this could lead to a better classification of individuals at risk of common conditions and novel approaches to prevent these.

Researcher Dr Laura Manenschijn from Erasmus MC said:

"We have suspected for a while that cortisol may be implicated in the development of many common conditions, such as heart disease, diabetes and depression. However, until now, doctors have not been able to accurately measure cortisol exposure over the long-term and so research into this has been limited.

"Our results are very exciting as they show that measuring the amount of cortisol in hair can potentially be used to monitor a person's long-term exposure to cortisol. This technique could lead to many potential uses in clinical research and has the additional benefit that it is easy to use and non-invasive.

"The results of this study show that hair cortisol is a reliable measure of long-term cortisol exposure. Now, we would like to use this tool in larger studies to examine the role of cortisol in the development of conditions such as cardiovascular disease and depression."

Sources: European Society of Endocrinology, AlphaGalileo Foundation.

Cushing's Disease: Unraveling a Medical Mystery

I found this video tonight when doing some research online. You know you will be sick a while when your disease is called a "medical mystery."

Cushing's Disease: Unraveling a Medical Mystery

The goal of the program is to educate viewers on the mysterious condition known as Cushing's disease. We will discuss why the diagnosis is often delayed: many patients can have it for five or-ten years before they are correctly diagnosed. The reason is the symptoms of Cushing's Disease are similar to those of other conditions. But as viewers will hear from experts Cushing's Disease can be treated and in some cases a full recovery is possible. In this program we will also explore the history of Cushing's Disease which is named for Harvey Cushing considered by many to be "the father of modern neurosurgery".

See 26 minute video, "Cushing's Disease: Unraveling a Medical Mystery."


Recovery: Post Op Day 14

Hi everyone.  I felt pretty good up until yesterday.  Luckily, I had a follow up appointment with my endocrinologist who diagnosed me with Cushing's. He's a Cushing's specialist. I always feel so relieved after speaking with him.

I thought I would share my questions and his responses. It may help others figure things out post op. ~m

Complications from surgery -- diabetes insipidus. Sodium levels in the hospital were 150, so they gave me DDVAP. Sodium levels dropped to 145 before I was discharged from hospital (post op day 3).

Improvements after surgery
Buffalo hump feels less rigid, skin not pulled so tight.
Belly fat is loose and jiggly. Stomach feels deflated.  Before surgery, belly tight as a drum from excess cortisol. Doc says this is a good sign.

Lab work -- 13.6 cortisol, 24 ACTH  (post op day 5 after withholding hydrocortisone dose in day 4 pm)

Concerned that I’m feeling bad now. I am 14 days post op pituitary surgery. Felt OK before yesterday. Not cartwheels but not in pain either. Yesterday, I woke up with a mild headache and stiffness in my neck and shoulders. I went to the chiropractor but it didn't offer much relief. I took a 4 hr nap and had 9 hours of sleep, but my symptoms remain. Today, my symptoms are the same, even after a 2 hour nap.

  • Mild burning/itching in sinus
  • Headache
  • Pressure in head, upside down
  • Overall body aches
  • Stiff neck and shoulders
  • Sore back
  • Preference for dark rooms, no noise
  • No drainage in throat so probably not a cerebrospinal fluid leak (CSF leak) 
Doc said feeling bad was a great sign. He is concerned because I am showing signs of hypoatremia, or low sodium levels.  This is common after pituitary surgery, especially for those of us who experienced diabetes insipidus which leads to hyperatremia, or high blood sodium levels. He said he often sees these symptoms happen right around this time (days 7-14 post op). At 8 am on Friday, I will have blood drawn for an electrolyte panel (includes sodium) with cortisol and ACTH after withholding 1 pm dose on Thursday. He suggests that when I drink fluids, I drink Gatorade only, no water, for the next two days. This will help rebalance my electrolytes.
University of California at San Francisco's Pituitary Center mention this in their post surgical instructions:
Some patients develop disorders of salt and water metabolism following pituitary surgery. Headache, nausea, vomiting, confusion, impaired concentration, and muscle aches might be due to hyponatremia (low blood sodium levels). This disorder typically occurs 7 to 10 days after surgery and is more common in patients who have had surgery for Cushing's disease. If you develop these symptoms, contact us immediately. Excessive urination, thirst, and the need to ingest large quantities of fluids might be related to the onset of diabetes insipidus or diabetes mellitus. These disorders put you at risk for dehydration. These symptoms require urgent evaluation and determination of the underlying cause so that appropriate treatment may be given.

I’m taking 10 mg Ambien sleeping pills at night. I tried a few nights without them and I didn’t sleep.
Doc asked if I had any other Cushing’s symptoms, as perhaps too much hydrocortisone was keeping me up at night. I told him I had no other symptoms, and I had lost 6 pounds. A person doesn’t lose weight with Cushing’s!  So, Doc suggested I move dose my 2 pm dose to 1 pm. This will hopefully allow the cortisol levels to be low enough for me to sleep at night.

Dose schedule – can I reduce my hydrocortisone dose now, 14 days post op or wait a few days until the weekend?  What are the next dose levels?
  • Do not drop more than 2.5 mg of cortef at a time.
  • Currently on 20 / 5
  • Stay at 20 / 5 -- next few days, get through the next 8 am blood draw this Friday
  • 17.5 / 5  -- stay at this dose for 10-14 days
  • 15 / 5  -- stay at this dose for 10-14 days
  • Appointment with Doc before dropping dose any lower

When do I need to have an overall hormone lab panel done? How far post op?  I haven’t done my labwork scheduled for after my appointment in January 2011.
Do this 6 weeks post op, or June 1, 2011.

When do I test?  Do I need to test 17-OHS or 8 am cortisol or 24hr UFC when dropping dose of Cortef?

~Moxie Melissa

93 Years Old and Still Dancing

I found this while researching low sodium levels. I like this lady. This made me smile.

New York Times' article: Doctors Say Don't, and the Patient Says Do 

''You see,'' she said, ''we patients are not just statistics. We don't always behave the way studies predict we will.''
 Remember, you know your body best. Don't let anyone tell you otherwise.

Cushing's in the News

This beautiful and sweet gal had the same pituitary surgery as I did two weeks ago.

Dramatic difference in appearance. She gained 70 pounds. I've gained 100. Stupid Cushing's disease.

~Moxie Melissa