Cushing's Syndrome after Hemodialysis for 21 Years

Koki Mise, Yoshifumi Ubara, Keiichi Sumida, Rikako Hiramatsu, Eiko Hasegawa, Masayuki Yamanouchi, Noriko Hayami, Tatsuya Suwabe, Junichi Hoshino, Naoki Sawa, Masaji Hashimoto, Takeshi Fujii, Hironobu Sasano and Kenmei Takaichi

- Author Affiliations

Nephrology Center (K.M., Y.U., K.S., R.H., E.H., M.Y., N.H., T.S., J.H., N.S., K.T.), Surgical Gastroenterology (M.H.), Pathology (T.F.), and Okinaka Memorial Institute for Medical Research (Y.U., K.T.), Toranomon Hospital, 1058470 Tokyo, Japan; and Department of Pathology (H.S.), Tohoku University Graduate School of Medicine, 9800872 Sendai, Japan

Address all correspondence and requests for reprints to: Koki Mise, M.D., Nephrology Center, Toranomon Hospital Kajigaya, 1-3-1, Kajigaya, Takatu-ku, Kawasaki-shi, Kanagawa-ken, 213-0015, Japan. E-mail: kokimise@yahoo.co.jp.

Abstract

Context: Hyperkalemia and weight loss are critical clinical problems for hemodialysis patients. There have been no documented reports of adrenal Cushing's syndrome with central obesity and hypokalemia in a hemodialysis patient.

Objective: The aim of the study was to report a patient with Cushing's syndrome after chronic hemodialysis, review the published literature, and discuss the significance of hypokalemia and obesity in anuric hemodialysis patients from the perspective of cortisol metabolism.

Patient: A 61-yr-old woman who had been on hemodialysis for 21 yr presented with persistent hypokalemia and central obesity. In 2002, her dry weight was 48.1 kg, but thereafter she gained weight to 60 kg.

Results: Adrenal Cushing's syndrome was diagnosed from endocrinological findings such as increased cortisol secretion without a circadian rhythm and suppression of plasma ACTH. Spironolactone was administered (25 to 50 mg/d), and her serum potassium became normal. Then, left adrenalectomy was performed by laparoscopic surgery. The resected specimen contained a well-circumscribed adrenal adenoma expressing P450c17. After surgery, hypokalemia improved gradually without medication, and her weight gain stopped.

Conclusions: This is the first documented case of adrenal Cushing's syndrome in a patient on long-term hemodialysis, although several authors have reported a relation between hypokalemia and primary hyperaldosteronism in hemodialysis patients.

From The Journal of Clinical Endocrinology and Metabolism

Happy Thanksgiving!

What are YOU thankful for this year?

Evaluation of depression, quality of life and body image in patients with Cushing’s disease

Nilufer Alcalar, Sedat Ozkan, Pinar Kadioglu, Ozlem Celik, Penbe Cagatay, Baris Kucukyuruk and Nurperi Gazioglu

 

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Abstract

The aim of this study was to evaluate patients with Cushing’s disease (CD) who had undergone transsphenoidal surgery in terms of depression, quality of life (QoL), and perception of body image in comparison to healthy controls.

Forty patients with CD and 40 healthy controls matched for demographic characteristics were included in the study. The subjects were evaluated with the Beck depression inventory (BDI), the health survey-short form (SF-36) and the multidimensional body-self relations questionnaire (MBSRQ). Subgroups of the patients with CD were formed on the basis of remission status and BDI scores. In this study, QoL in the general health category and body image were lower in the patients with CD than in the healthy subjects. However, no differences in depression scores were found between the two groups.

When the CD group was evaluated according to remission rate, the mean BDI score was significantly higher in the CD patients without remission than in both the CD patients with remission and the healthy subjects (p = 0.04). However, the physical functioning, bodily pain and general health scores of the CD patients without remission on the SF-36 questionnaire were lower than in the CD patients in remission and the healthy subjects (p = 0.002, p = 0.04, p = 0.002, respectively). Fitness evaluation, health evaluation and body areas satisfaction scores of the MBSRQ were significantly different in the three groups (p = 0.003, p = 0.009 and p = 0.001, respectively). In this study, patients with CD were found to have lower QoL, lower body image perception and higher levels of depression compared to healthy controls, particularly if the disease is persistant despite surgery.

Keywords  Cushing’s disease – Pituitary surgery – Depression – Quality of life – Body image

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Share Your Cushing's Story on TV

A new series on Lifetime TV's daily morning talk show, The Balancing Act is featuring Cushings Syndrome.

Producers are looking for patients to share their stories in the comments of their landing page for Unveiling the Mystery: Rare and Genetic Diseases!

http://www.thebalancingact.com/rare/

Robotic versus laparoscopic adrenalectomy in obese patients

Surgical Endoscopy, 10/23/2012 Clinical Article

Aksoy E et al. – The aim of this study is to compare perioperative outcomes of RA versus LA in obese patients. The study did not show any difference in perioperative outcomes between RA and LA in obese patients. These results suggest that the difficulties in maintaining exposure and dissection in obese patients nullify the advantages of robotic articulating versus rigid laparoscopic instruments in adrenal surgery.

Methods

• Between 2003 and 2012, 99 obese (BMI ≥ 30 kg/m2) patients underwent adrenalectomy at a tertiary academic center.
• Of these, 42 patients had RA and 57 had LA. The perioperative outcomes of these patients were compared between the RA and LA groups.
• Data were collected from a prospectively maintained, institutional review board approved database.
• Clinical and perioperative parameters were analyzed using Student t and χ2 tests.
• All data are expressed as mean ± standard error of the mean.

Results

• The groups were similar in terms of age, gender, and tumor side.
• Body mass index was lower in the robotic versus laparoscopic group (35.4 ± 1.0 vs. 38.8 ± 0.8 kg/m2, respectively, p = 0.01).
• Tumor size (4.0 ± 0.4 vs. 4.3 ± 0.3 cm, respectively, p = 0.56), skin–to–skin operative time (186.1 ± 12.1 vs. 187.3 ± 11 min, respectively, p = 0.94), estimated blood loss (50.3 ± 24.3 vs. 76.6 ± 21.3 ml, respectively, p = 0.42), and hospital stay (1.3 ± 0.1 vs. 1.6 ± 0.1 days, respectively, p = 0.06) were similar in both groups.
• The conversion to open rate was zero in the robotic and 5.2 % in the laparoscopic group (p = 0.06).
• The 30–day morbidity was 4.8 % in the robotic and 7 % in the laparoscopic group (p = 0.63).

From MDLinx

A Quarter of a Century

I had my one, and only, pituitary surgery on this date in 1987.  Of course, I was trying to get a diagnosis for several years before that.

I know it's hard to get a diagnosis now - imagine how hard it was over 30 years ago - before the Internet, Facebook, Twitter, message boards, chatrooms.  No online support - no support anywhere. 

Finding any information possible at the Public Library.  Days that you feel like death warmed over, heading out to the library to Xerox medical articles you don't understand, poring over them at home, trying to find any kernel of hope for what you have.  Then trying to convince doctors when your family doesn't even believe you.

Finally, a doctor believes you...but he's the wrong kind of doctor so he sends you away.  Another year goes by.  The endo recommends surgery but there are only 3 possibilities anywhere.  NIH - close by and free, Montreal - they speak French - and San Francisco.  

After a diagnosis, 6 weeks of inpatient testing at the NIH.

From my bio at http://www.cushings-help.com/maryos_story.htm

 

There were about 12 of us there and it was nice not to be alone with this mystery disease. Many of these Cushies (mostly women) were getting bald, couldn't walk, having strokes, had diabetes. One was blind, one had a heart attack while I was there. Towards the end of my testing period, I was looking forward to the surgery just to get this whole mess over with. While I was at NIH, I was gaining about a pound a day!

The MRI still showed nothing, so they did a Petrosal Sinus Sampling Test. That scared me more than the prospect of surgery. (This test carries the risk of stroke and uncontrollable bleeding from the incision points.) Catheters were fed from my groin area to my pituitary gland and dye was injected. I could watch the whole procedure on monitors. I could not move during this test or for several hours afterwards to prevent uncontrolable bleeding from a major artery. The test did show where the tumor probably was located. Also done were more sophisticated dexamethasone suppression tests where drugs were administered by IV and blood was drawn every hour (they put a heplock in my arm so they don't have to keep sticking me). I got to go home for a weekend and then went back for the surgery - the Transsphenoidal Resection. I fully expected to die during surgery (and didn't care if I did) so I signed my will and wrote last letters to those I wanted to say goodbye to. During the time I was home just before surgery, a college classmate of mine (I didn't know her) did die at NIH of a Cushing's-related problem. I'm so glad I didn't find out until a couple months later!

November 3, 1987, the surgeon, Dr. Ed Oldfield, cut the gum above my front teeth under my upper lip so there is no scar. He used tiny tools and microscopes. My tumor was removed successfully. In some cases (not mine) the surgeon uses a plug of fat from the abdomen to help seal the cut. Afterwards, I was in intensive care overnight and went to a neurology ward for a few days until I could walk without being dizzy. I had some major headaches for a day or two but they gave me drugs (morphine) for those. Also, I had cotton plugs in my nostrils. It was a big day when they came out. I had diabetes insipidus (DI) for a little while, but that went away by itself - thank goodness!

I had to use a foam product called "Toothies" to brush my teeth without hitting the incision. Before they let me go home, I had to learn to give myself an injection in my thigh. They sent me home with a supply of injectible cortisone in case my level ever fell too low (it didn't). I was weaned gradually off cortisone pills (scary). I now take no medications. I had to get a Medic Alert bracelet. I will always need to tell medical staff when I have any kind of procedure - the effects of my excess cortisone will remain forever.

I went back to the NIH for several follow-up visits of a week each where they did all the blood and urine testing again. After a few years NIH set me free. Now I go to my "outside" endocrinologist every year for the dexamethasone suppression test, 24-hour urine and regular blood testing.

As I get further away from my surgery, I have less and less chance that my tumor will grow back. I have never lost all the weight I gained and I still have the hair on my chin but most of my other symptoms are gone. I am still and always tired and need a nap most days. I do not, however, still need to take whole days off just to sleep.

I consider myself very lucky that I was treated before I got as bad as some of the others on my floor at NIH but think it is crazy that these symptoms are not taken seriously by doctors.

 

 

Use of ketoconazole in the treatment of Cushing's syndrome

An older, but still useful, abstract:

J Clin Endocrinol Metab. 1986 Dec;63(6):1365-71.

 

Loli P, Berselli ME, Tagliaferri M.

Abstract

The therapeutic value of ketoconazole for long term treatment of patients with Cushing's syndrome was studied. Seven patients with Cushing's disease and one with an adrenal adenoma received 600-800 mg/day ketoconazole for 3-13 months. Plasma ACTH, cortisol, and dehydroepiandrosterone sulfate levels and urinary cortisol, 17-ketosteroid, and tetrahydro-11-deoxycortisol excretion were determined periodically during the treatment period.

Plasma ACTH and cortisol responses to CRH stimulation were determined before and during treatment. Rapid and subsequently persistent clinical improvement occurred in each patient; plasma dehydroepiandrosterone sulfate and urinary 17-ketosteroid and cortisol excretion decreased soon after the initiation of treatment, subsequently remaining normal or nearly so throughout the treatment period. Urinary tetrahydro-11-deoxycortisol excretion increased significantly. Plasma cortisol levels decreased. Plasma ACTH levels did not change, and individual plasma ACTH and cortisol increments in response to CRH were comparable before and during treatment. The cortisol response to insulin-induced hypoglycemia improved in one patient and was restored to normal in another.

The seven patients tested recovered normal adrenal suppressibility in response to a low dose of dexamethasone during ketoconazole treatment. Ketoconazole is effective for long term control of hypercortisolism of either pituitary or adrenal origin. Its effect appears to be mediated by inhibition of adrenal 11 beta-hydroxylase and 17,20-lyase, and it, in some unknown way, prevents the expected rise in ACTH secretion in patients with Cushing's disease.

From http://www.ncbi.nlm.nih.gov/pubmed/3023421

 

Cushing's, The "Gift" that Keeps on Giving

I had an eye doctor appointment yesterday. No problems, just a routine check, maybe update my contacts to a newer version.

I was completely not ready when the doctor said "cataracts" to me. Say what? I'm not that old.  He mentioned a few other things like macular degeneration but that was less distressing to me somehow than the Cataract Word.

They're not bad yet.  They're slow growing.  I won't need to do anything about them for 7-8 years.  AARRGGHH!

My mother is waiting for her cataract surgery.  Maybe we can do this together, a bonding thing.

When I got home and all the eye drops had worn off, I looked at the brochures he had given me.  One of the symptoms was light insensitivity.  So that explains why I have trouble first thing in the morning and it hurts to open my eyes and other bright lights can be painful.  It's nice to be validated but...

Then, I turned the page to find contributing factors and came upon the word STEROIDS.  Not again!  Almost all the problems in my life start with the word steroids.  I did a search of the Cushing's Help boards for "Cataracts" and came up with 84 entries.  How could I have missed this?

From Cigna.com:

The eye conditions glaucoma and cataracts also may occur in Cushing's syndrome. In Cushing's disease (tumors on the pituitary gland), your field of vision can be affected. You may have loss of side, or peripheral, vision.

Metro Area Cushie Lunch (or Dinner)

A Cushie from Maryland is coming to the Metro DC area for lunch on Wednesday, October 24 in Falls Church.  If anyone else is interested, she's willing to come for dinner instead.

If you're interested, please let me know.  :)

Surgical Versus Medical Treatment for Cushing Disease, the New and the Old

Surgical Versus Medical Treatment for Cushing Disease the New and the Old

Novartis launches pasireotide for Cushing’s disease

Cushing’s disease patients for whom surgery is not a viable option have a new treatment alternative, in the form of the orphan medicine pasireotide.

Launched by Novartis as Signifor, the drug is a somatostatin analogue that blocks the release of excessive adrenocorticotropic hormone, thus reducing cortisol levels.

Pasireotide is available as a solution for injection that should be self-administered by the patient twice a day. Patients should be informed how to inject the drug under the skin and that using the same injection site for two consecutive injections is not recommended.

After two months of treatment, patients’ blood cortisol levels are measured to determine whether treatment should continue, and at what dose (see Panel).

Patients who experience adverse reactions may need to temporarily lower their twice-daily dose, with decrements of 0.3mg suggested in the summary of product characteristics.

Pasireotide is indicated for adults only and is contraindicated for use by patients with severe liver impairment. It should be used with caution by patients who are taking medicines that prolong the QT interval, and clinical monitoring of heart rate is recommended for patients receiving pasireotide concomitantly with bradycardic drugs.

Dose adjustments of ciclosporin, insulin and antidiabetic medicines may be required if these are taken concomitantly with pasireotide.

The EMA granted marketing authorisation for pasireotide in April 2012 on the basis that, although the proportion of patients who responded to treatment in clinical trials was small (around 15 per cent), a partial response may be of benefit to patients whose condition cannot be managed with surgery.

Product information

Class: Somatostatin analogue

Dose: 0.6mg by subcutaneous injection twice daily. After two months of treatment, patients whose urinary free cortisol levels have reduced can continue treatment for as long as they experience a benefit. The dose can be increased to 0.9mg as long as the 0.6mg dose is well tolerated. Patients who have not responded after two months of treatment should be considered for discontinuation. The recommended twice-daily dose for patients with moderate liver impairment is 0.3mg initially, up to a maximum of 0.6mg.

NHS list price: 60 x 0.3mg/ml, £2,800; 60 x 0.6mg/ml, £3,240; 60 x 0.9mg/ml, £3,240

Legal category: POM 

From PJOnline

 

Interview with Dr. Amir H. Hamrahian

Amir H. Hamrahian, MD, is a Staff member in the Department of Endocrinology, Diabetes and Metabolism at Cleveland Clinic's main campus, having accepted that appointment in 2005. Prior to that appointment, he was also a clinical associate there for nearly five years. 

His clinical interests include pituitary and adrenal disorders.

Dr. Hamrahian received his medical degree from Hacettepe University in Ankara, Turkey, and upon graduation was a general practitioner in the provinces of Hamadan and Tehran, Iran. He completed an internal medicine residency at the University of North Dakota, Fargo, and an endocrinology fellowship at Case Western Reserve University and University Hospitals, Cleveland.

In 2003, he received the Teacher of the Year award from Cleveland Clinic's Department of Endocrinology, Diabetes and Metabolism. Dr. Hamrahian speaks three languages -- English, Turkish and Farsi -- and is board-certified in internal medicine as well as endocrinology, diabetes and metabolism. He is a member of the Endocrine Society, Pituitary Society and the American Association of Clinical Endocrinologists.

Some of the questions answered in this interview October 1, 2012 include (not in this order):

 

• Can you tell me a little about you endocrine practice and your experience with Cushing’s as part of your practice?
• What are some of biggest challenges you have in treating Cushing’s?
• How do you test cyclical/episodic Cushing's?
• Can someone with cyclical/episodic Cushing's take Korlym?
• I know that Cushing's patients (those that currently have it and/or are cured/in remission can have healthy pregnancies with the right care. How do doctors support this process? Through an endocrinologist and a high-risk ob/gyn? And what sort of treatment is given throughout the pregnancy to prevent hypercortisolism.
• While many patients have a successful long term result from surgery, there are just as many that don’t. Do you find that there are any particular challenges treating patients with Cushing’s disease when pituitary surgery has already failed?
• As I understand, you were an investigator in the clinical trial for Korlym, and I think you treated 4 patients. Did these patients all have a previous surgery that had failed?
• Many Cushing’s patients are trying to understand if they might be candidates for Korlym treatment, can you tell me a little history about the types of patients you treated with Korlym?  I hear that not all patients can take Korlym. Which type of patient should not take it?
• Every past treatment for Cushing’s has always had the goal of lowering cortisol levels, but Korlym doesn’t lower cortisol levels, can you explain how it works?
• So, how do you judge success for a Cushing’s patient on Korlym?
• I lost copious amounts of hair while on Korlym, is this a known side effect?
• Are there any long term reproductive implications due to use of Korlym?

Listen to this interview at http://www.blogtalkradio.com/cushingshelp/2012/10/01/dr-amir-hamrahian-answers-our-questions or to the podcast by searching for Cushings in the iTunes podcast area or click here: http://itunes.apple.com/podcast/cushingshelp-cushie-chats/id350591438

 

 

Dr. Redmond, Johns Hopkins Pituitary Day

MEETING NOTES : Dr. Redmond, Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 12:07 PM

Baltimore

radiotherapy

indications

• recurrence
• persistent hormone secretion
• inoperable

tumors repair more slowly than normal cells

IMRT Intensity modulated radiation therapy

stereotactic radiosurgery

more radiation beams, greater precision

very small tumors 1-5 treatments

larger 5-6 weeks

150-300 radiation beams target area

Synergy machine

for divided course of radiation

cyberknife for 1-5 treatments

short-term

fatigue

hair loss

tearful or dry eye

headache

nausea

long-term

cataracts

decreased hormones

damage to vision (rare)

second tumor (rare)

tumor control 90%

hormone normalization 60%

Dr. Ishii, Johns Hopkins Pituitary Day

MEETING NOTES : Dr. Ishii, Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 11:41 AM

Baltimore

patient participation is most important

waiting for other doctor's computer

________________________

nasal issues pst-op

nose is good corridor to pituitary, endoscope

nose: smells, filters air, air flow

instruments

post-op care

problems

pain

smell

activity

CSF leak

tired

Dr. Gary Gallia, Johns Hopkins Pituitary Day

MEETING NOTES : Dr. Gary Gallia, Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 11:11 AM

Baltimore

pituitary lesions, surgery

micro

macro

large

giant

confined to sella, outside sella

surgical risk

CSF leak

damage

incomplete

DI

recovery variable

29 YO f with Cushing's

cheerio is 13mm

cortisol below 2 after surgery

Dr. Barbara Craven, Johns Hopkins Pituitary Day

MEETING NOTES : Dr. Barbara Craven, Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 10:49 AM

Baltimore

Cushing's, cyclical

dietician

started noticing problems early 1990s

1993 people told her she had a red face, 3 little kids

mood swings, depression

gaining weight

1997, Christmas, puffy face, tired, red face, no energy

internist, bloodwork

Epstein-barr virus high, mono.

bone biopsy - rule out cancer. bones too soft, fractured hip in 2 places falling from horse

1998, mole growing on back, removed.  then more and more, every 2 weeks mole removed, all pre-cancerous, melanoma

immune system compromised

2000, racing heart, aching in chest, cardiologist, testing for heart, beta blocker for BP

2001, getting pudgier, weight increasing, tai kwondo, still couldn't lose weight.  800 calories per day, still gaining, shrunk, hair started falling out

dermatologist, no problem.  blood test.  took cortisol and DHEA

endocrinologist (not pituitary), dex suppression test positive

MRI of pit and adrenals.

Dr. Salvatori

hard to diagnose, 9 more months of testing, UFCs, blood, symptoms but not positive tests, salivary was positive

swollen feet, chest hurting, sleeping in recliner, memory became terrible, 

depressed, anxiety, panic attacks, miserable, couldn't fly due to anxiety. Agreed to surgery

removed whole pituitary, only found soft spots.  didn't find pituitary tumor.  found 3mm ACTH tumor

hormones still messed up even though in remission

2006 feeling better

even now hormones can get out of balance. DI.  DDVAP

sodium got low. stopped DDVAP.  drink a lot of water now.

stick with it, don't give up.

Dr. Craven was our guest in the Guest Speakers Interview series.

Dr. Subramarnian, Johns Hopkins Pituitary Day

MEETING NOTES : Dr. Subramarnian, Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 10:28 AM

Baltimore

neuro-opthalmology

diseases and surgery of the eye

vision loss

peripheral field loss

double vision

kinetic perimetry

5 case studies

craniopharingioma

can find pituitary tumor through vision

Johns Hopkins Pituitary Day

MEETING NOTES : Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 10:04 AM

Baltimore

Dr. Gary Wand

pituitary slides, growth hormone, ACTH

prolactin, breast milk

anterior, Oxytocin

ADH, vassopressin, sodium, diabetes insipidus

micro/macro adenoma

secretory vs nonfunctional

normal MRIs compared to tumors

compression of pituitary

• thyroid: energy, weight, mental function, skin, temp
• sex hormones, drive and function
• adrenal: light-headed, fatigue, appetite, weight, GI

Compression of surrounding structures like optic nerve

Excess hormones: prolactin, GH or cortisol

34% prolactin

36% nonfunctioning

nonfunctioning

signs from compression

diminished pituitary: sex hormones, thyroid, adrenal

visual defects

headaches

no medication

no hormone excess

surgery

prolactinoma

medication

some surgery

rarely radiation

growth hormone - acromegaly

surgery

medication

radiation

cortisol, Cushing's

symptoms

surgery

medications

tsh tumor, similar symptoms to Grave's

surgery

meds

other pit disorders

Johns Hopkins Pituitary Day

MEETING NOTES : Johns Hopkins Pituitary Day

Meeting Created:September 29, 2012, 10:00 AM

Chantilly

Patient Education Day Agenda:

9:30 - 10:00 AM REGISTRATION AND BREAKFAST
10:00 - 10:20 AM What is the pituitary, and what can go wrong Gary Wand, MD
10:25 - 10:45 AM Vision problems in pituitary patients Prem Subramanian, MD, PhD
10:50 - 11:10 AM Pituitary Disease: a patient’s prospective Barbara Craven, PhD
11:15 - 11:35 AM Surgery for Pituitary tumors: what to expect Alfredo Quinones-Hinojosa, MD and Gary Gallia, MD, PhD
11:40 - 12:00 PM Nose problems before and after pituitary surgery Masaru Ishii, MD, PhD
12:05 - 12:25 PM When is radiotherapy needed for pituitary tumors Kirsten Redmond, MD
12:30 - 1:25 PM Lunch
1:30 - 3:00 PM Breakout sessions
1) Medical therapy (Wand/Salvatori)
2) Surgical therapy (Gallia)
3) Radiation therapy (Redmond/Lim)
4) Vision issues (Subramanian)
5) Nose issues (Ishii)
*This schedule is subject to change

Transsphenoidal Microsurgery for Cushing’s Disease: Initial Outcome and Long-Term Results

Transsphenoidal Microsurgery for Cushing’s Disease: Initial Outcome and Long-Term Results