Endoscopic endonasal approach for pituitary adenoma: surgical complications in 301 patients

Jackson A. Gondim, Joao Paulo C. Almeida, Lucas Alverne F. Albuquerque, Michele Schops, Erika Gomes, Tania Ferraz, Wladia Sobreira and Meissa T. Kretzmann

Pituitary

DOI: 10.1007/s11102-010-0280-1

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Abstract

The authors investigate the complications of transnasal transsphenoidal endoscopic surgery in the treatment of 301 patients with pituitary adenomas. A retrospective analysis of complications in 301 patients submitted to transsphenoidal transnasal endoscopic surgery at the General Hospital of Fortaleza, Brazil between January 1998 and December 2009. The complications were divided in two groups: anatomical (oronasofacial, sphenoid sinus, intrasellar, suprasellar and parasellar) and endocrinological complications (anterior and posterior pituitary dysfunctions). We observed a total of 81 complications (26.9%) in our series. Anatomical complications occurred in 8.97% (27 cases): 8 CSF postoperative leaks (2.6%), 6 cases (1.9%) of delayed nasal bleeding, 5 cases (1.6%) of sphenoidal sinusitis, 3 cases (0.9%) of carotid artery lesion, 2 cases of meningitis (0.6%) and one case (0.3%) of each of the uncommon following complications: intrasella-suprasella hematoma, pontine hematoma and chiasmaplexy. Endocrinological complications occurred in 17.9% (54 cases): additional postoperative anterior lobe insufficiency in 35 cases (11.6%), and postoperative diabetes insipidus in 19 cases (6.3%). In our series, 3 cases of deaths (not directly related to the procedure) were also observed. Endoscopic transsphenoidal surgery represents an effective option for the treatment of patients with pituitary tumor. Complications still occur and must be reduced as much as possible. Successful endoscopic pituitary surgery requires extensive training in the use of an endoscope and careful planning of the surgery. Additional improvement can be expected with greater experience and new technical developments.

Keywords  Pituitary - Adenoma - Transphenoidal - Endoscopy - Complications

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From http://www.springerlink.com/content/56w8617572673332/

Overactive Adrenal Glands

Adrenal glands are small glands located just on top of a person’s kidneys. These glands are just one of the many glands found in the endocrine system. Sometimes, these glands generate excessive amounts of hormones such as androgenic steroids, corticosteroids and aldosterone. They are then referred to as overactive adrenal glands, a condition also called Cushing's syndrome.

Here are some of the most common signs and symptoms of overactive adrenal glands:
1. Weight gain
One of the primary signs of Cushing’s syndrome is weight gain. A common sign of this condition is your face becoming rounder or more moon-shaped. In some cases, there will also be obesity in the upper body, particularly the upper back and the midsection. You may also begin to gain fat around the neck area.

2. Fragility
While you may be generally gaining weight, you will also experience a general thinning in both your arms and legs. Your fragile skin means that you may bruise easily and be more prone to sores and infection. Healing of bites and wounds take longer than usual. Acne breakouts might occur more frequently.

Red or purple stretch marks tend to develop on your buttocks, stomach, breasts, arms and thighs. In response to overactive adrenal glands, you will also probably experience severe fatigue, feeling very weak and tired most of the time. You may also feel muscle and bone weakness.

3. Reproductive system irregularities
Secreting hormones is just one function of the adrenal glands. Cushing’s syndrome can affect the sexual life and reproductive systems of both men and women. There may be a lower sex drive between both genders. Men may feel a drop in libido, as well as a decrease in fertility.  Women, on the other hand, may experience either irregular menstruation periods or may even stop menstruating. Other women may grow excessive amounts of hair on both the legs and face.

4. Psychological signs
Some individuals with overactive adrenal glands display psychological signs and symptoms. Increased irritability, depression and anxiety are common emotions in people with this condition. These emotions may be displayed for no particular reason. This tends to be an effect of a hormonal imbalance that you are probably experiencing.

Treatment for overactive adrenal glands depends on several factors, including the person’s overall health and medical history.

At times, Cushing’s syndrome can be the result of various medical conditions, such as tumors that have grown on the adrenal or pituitary glands. Remember that the symptoms and signs of overactive adrenal glands vary per person, as well as by the extent to which the glands malfunction. Of course, these signs and symptoms may resemble other medical problems and conditions. It would be best to consult with a medical professional immediately.

 

From http://www.testcountry.org/4-signs-of-overactive-adrenal-glands.htm

Seven Lots of Dexamethasone Injection Recalled

Robert Lowes

Authors and Disclosures

December 27, 2010 — American Regent is voluntarily recalling 7 lots of dexamethasone sodium phosphate injection (USP 4 mg/mL, 30 mL multiple-dose vials) because some vials either contain particulates or have the potential to do so before their expiration dates, the US Food and Drug Administration (FDA) announced today.

A corticosteroid, dexamethasone is used to treat a wide variety of conditions such as severe allergic reactions, arthritis, blood diseases, certain cancers, and breathing disorders. Clinicians also use it to test for Cushing's syndrome and prevent nausea and vomiting in chemotherapy patients. The injectable form of the drug is used when a similar drug cannot be taken orally, or when a patient in a medical emergency needs a rapid response.

The recall pertains to the lots of the product listed in the table.

Table. Recalled Lots

Lot	Expiration Date (Month/Year)
8811	12/2010
9093	02/2011
9195	03/2011
9296	04/2011
9419	06/2011
9505	07/2011
9649	09/2011

American Regent issued the recall on December 20. Hospitals, infusion centers, clinics, and other healthcare facilities should not use any of the recalled lots but should instead quarantine them for return to the company. Anyone with questions about the return process or any other issue can call American Regent at 1-800-645-1706.

The company reminds clinicians that as a matter of standard practice, they should visually inspect parenteral drugs for particulate matter and discoloration before administration, whenever the solution or container permits.

More information about today's announcement is available on the FDA Web site.

To report adverse events related to injectable dexamethasone, contact MedWatch, the FDA's safety information and adverse event reporting program, by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to MedWatch, FDA, 5600 Fishers Lane, Rockville, Maryland 20852-9787.

From http://www.medscape.com/viewarticle/734851

Pegylated Long-Acting Human Growth Hormone Possesses a Promising Once-Weekly Treatment Profile, and Multiple Dosing Is Well Tolerated in Adult Patient

Esben Søndergaard, Marianne Klose, Mette Hansen, Birgit Sehested Hansen, Marianne Andersen, Ulla Feldt-Rasmussen, Torben Laursen, Michael Højby Rasmussen*, and Jens Sandahl Christiansen

Aarhus University Hospital (E.S., T.L., J.S.C.), DK-8000, Aarhus C, Denmark; Rigshospitalet (M.K., U.F.-R.), Copenhagen University, DK-2100, Copenhagen, Denmark; Odense University Hospital (M.H., M.A.), DK-5000, Odense, Denmark; and Global Development (B.S.H., M.H.R.), Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark

* To whom correspondence should be addressed. E-mail: mhr@novonordisk.com.

Background: Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc injections for several years or lifelong, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed for once-weekly administration.

Objectives: Our objective was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of NNC126-0083 in adult patients with GH deficiency (GHD).

Subjects and Methods: Thirty-three adult patients with GHD, age 20–65 yr, body mass index 18.5–35.0 kg/m2, and glycated hemoglobin of 8.0% or below. Fourteen days before randomization, subjects discontinued daily rhGH. NNC126-0083 (0.01, 0.02, 0.04, and 0.08 mg/kg) was given sc once weekly for 3 wk (NNC126-0083 for six subjects and placebo for two subjects). Blood samples were collected up to 168 h after the first and up to 240 h after the third dosing. Physical examination, antibodies, and local tolerability were assessed.

Results: NNC126-0083 was well tolerated with no difference in local tolerability compared with placebo and with no signs of lipoatrophy. A more than dose-proportional exposure was observed at the highest NNC126-0083 dose (0.16 mg protein/kg). Steady-state pharmacokinetics seemed achieved after the second dosing. A clear dose-dependent pharmacodynamic response in circulating IGF-I levels was observed [from a predose mean (SD) IGF-I SD score of -3.2 (1.7) to peak plasma concentration of -0.5 (1.3), 1.6 (1.3), 2.1 (0.5), and 4.4 (0.9) in the four dose groups, respectively].

Conclusion: After multiple dosing of NNC126-0083, a sustained pharmacodynamic response was observed. NNC126-0083 has the potential to serve as an efficacious, safe, and well-tolerated once-weekly treatment of adult patients with GHD.


From http://jcem.endojournals.org/cgi/content/abstract/jc.2010-1931v1

UK guidelines for the management of pituitary apoplexy

Authors: Rajasekaran, Senthil¹; Vanderpump, Mark²; Baldeweg, Stephanie³; Drake, Will⁴; Reddy, Narendra¹; Lanyon, Marian⁵; Markey, Andrew⁶; Plant, Gordon⁵; Powell, Michael⁷; Sinha, Saurabh⁸; Wass, John⁹

Source: Clinical Endocrinology, Volume 74, Number 1, January 2011 , pp. 9-20(12)

Publisher: Wiley-Blackwell

Abstract:

Summary

Classical pituitary apoplexy is a medical emergency and rapid replacement with hydrocortisone maybe life saving. It is a clinical syndrome characterized by the sudden onset of headache, vomiting, visual impairment and decreased consciousness caused by haemorrhage and/or infarction of the pituitary gland. It is associated with the sudden onset of headache accompanied or not by neurological symptoms involving the second, third, fourth and sixth cranial nerves. If diagnosed patients should be referred to a multidisciplinary team comprising, amongst others, a neurosurgeon and an endocrinologist. Apart from patients with worsening neurological symptoms in whom surgery is indicated, it is unclear currently for the majority of patients whether conservative or surgical management carries the best outcome. Post apoplexy, there needs to be careful monitoring for recurrence of tumour growth. It is suggested that further trials be carried out into the management of pituitary apoplexy to optimize treatment.

Document Type: Research article

DOI: 10.1111/j.1365-2265.2010.03913.x

Affiliations: 1: Churchill Hospital, Oxford 2: Royal Free Hospital, London 3: University College Hospital, London and Trustee and member of the Medical Committee -The Pituitary Foundation 4: St. Bartholomew's Hospital, London and Society for Endocrinology 5: University College Hospital, London 6: The Lister Hospital, London 7: National Hospital for Neurology, London and Society of British Neurosurgeons 8: Royal Hallamshire Hospital, Sheffield 9: Churchill Hospital, Oxford and Royal College of Physicians

From http://www.ingentaconnect.com/content/bsc/cend/2011/00000074/00000001/art00002

Happy Holidays!

 

No matter what your beliefs may be,
we wish the very best holiday season,
full of family, friends and better health.

Help Give Back to Cushing’s Help – At No Cost to You!

From iGive.com:

We're celebrating with a challenge for Cushings Help!

What are we celebrating?
    1) The end of a tough year;
    2) Our web search is new and improved (using Microsoft Bing) and;
    3) iGive members have helped donate over $5,000,000 to causes so far.

You are invited to participate in our celebration --  it's free and definitely easy.

Here's the challenge:

iGive.com is going to attempt to donate $5,000 in just 27 hours to Cushings Help and other causes.

For each person who joins iGive using the special link below and does just one qualified web search on our site between Thursday at 9.a.m. CST and 12:00 Noon CST Friday, we'll give Cushings Help a dollar. 5,000 new members, $5,000 donated.  No purchase necessary.

 

Of course, if they search more (or buy something) they'll earn even more money for Cushings Help.  Right now, we're donating $.02 per search and a bonus $5 for a new member's first purchase (plus the usual percentage).

Here's where you come in.  The only way Cushings Help will get new supporters and that free $1 (or more) is if they're invited.  Send your supporters, friends, family, and colleagues the following link in an e-mail, tweet it, chirp it, do a Facebook posting, put up posters, shout from mountain tops (you know the drill) and let the world know you think Cushings Help is pretty cool and deserves their support, especially since it's free!  You can even just forward this e-mail.

This is the link:

http://www.igive.com/welcome/warm_reg_promo.cfm?c=17825

We're really proud of our improved search capability, powered by Bing.  We want lots of people to try it out and see if they like it as much as we do.  If they keep on searching or shopping after checking us out, so much the better for Cushings Help and iGive.com.

The details:

• Offer active between 9 a.m. Thursday, December 9, 2010 and 11:59 a.m., Friday, December 10, 2010 (Chicago time).
  
• New members only (never have been an iGive member previously).  All the normal rules of membership, searching, and  purchasing apply, our site has the details. 
  
• Real people only, who sign themselves up. (It's not fair to hire a room full of elves who sign people up, the new member has to sign him or herself up.)
  
• Once we've given away $5,000, the offer ends.  That's $5,000 to all causes, not just yours, so it's a bit of a race.
  
• The special link is important.  No link, no $1.
  
• A web search is a search from the WEB tab on our site.  Qualified searches are explained on our site, but basically means NOT a search for a store or a site name.

Thanks so much for reading and helping out!

 

Successful treatment of Lt. Adrenocortical Tumor or Cushing's syndrome

Successful treatment of Lt. Adrenocortical Tumor or Cushing's syndrome (+ Enlarge)

Mohini Nayak the two year old female child was brought to Apollo Hospital with H/O gaining excessive weight and became obese since 1 yr. She was treated by different doctors in multiple hospitals in Bhubaneswar and Cuttack. After investigation in S.C.B. Medical College, Cuttack, it was found that the baby is suffering from Lt. Adrenocortical Tumour. Cushing Syndrome in Pediatric age group, particularly less than 2 years old child is a very rare condition, the incidence being 0.3 – 0.4 in one million child below 15yrs of age. Cushing’s syndrome may occur either due to Pituitary tumor or Adreno cortical tumor, said Dr. B N Mishra, Sr. Pediatric Surgeon, Apollo Hosipitals, Bhubaneswar. The baby had adreno cortical; tumor on left side, informed Dr. Mishra. Adrenal glands are present in our body just above and adjacent (Superiorly) to kidneys on both sides.

She had a very large tumor of left adrenal gland of size 10x6x3 cm size and such type of large tumors is usually malignant and rarely seen. However the biopsy does not show features of malignancy, but needs to be observed for a long time. Dr. Mishra informed that, her obesity will take time to reduce, may be six months to one year. Mohini got admitted on 12th November 2010.

Mohini comes from a very low socio-economic status. The child is the youngest of the three siblings and her parents in spite of their poverty tried their limited resources to provide the best medical treatment. Hopeless slum dwellers finally had a smile. Victory of life over death prevailed. Ashok Naik a low paid sweeper and his wife Jyotsna a domestic help sacrificed what ever little earning they did to save their youngest girl child of 2 years old, Mohini.

The girl became about 20kg within 1 year 2months. Finally parents lost all hope. Some couple of weeks back the heart touching story of the girl and her parents, featured in a local daily. The story dragged few social activists of Lions Club Bhubaneswar met the parent and resolved to take an attempt. After initial checkup, Apollo decided for operation with financial assistance from corporate houses and government of odisha.

It was risky and expensive. A group of expert doctors led by Dr. B.N. Mishra successfully operated the massive tumor after a long operation of three hours. The baby is now free of danger.

From http://www.odisha360.com/news/720/successful-treatment-of-lt-adrenocortical-tumor-or-cushings-syndrome

40 Days of Thankfulness: Days Thirty-one through Thirty-five

Day 31, November 14: Dr. Roberto Salvatori and Johns Hopkins. I found Dr Salvatori to be wonderfully kind, interested and knowledgeable. He listened thoughtfully to my complaints and never suggested that I was simply "fat and depressed". In the first visit, I learned things about my diagnosis that my previous endo had completely skipped. I feel confident that he will take care of any future endocrine issues. It didn't hurt that he was showing my website and bio around to other staff when I went for an appointment!

Day 32, November 15: Facebook. What can I say? FB has brought me closer to people I might not have otherwise known.

Day 33, November 16: Bells. I love playing handbells. Nearly any bells but I really like the lower octave, the G3-B3 area.I'm not so good with 4-in-hand or shelley ringing. For more info about handbell techniques, there's a good article here.

Day 34, November 17: Computers. When the first computer came into this house I wasn't a happy camper. It cost far too much and I couldn't see any value in it at all. There was a tiny grey/yellow monitor, no hard drive. What good can come of this?

Things changed a bit over the years!

Day 35, November 18: Today is the first annversary of my one and only zipline experience. I’ve been thinking about since my kidney cancer surgery 3 years earlier. Since then, I figure I have “extra years” and I wanted to do something kinda scary, yet fun. So, somehow, I decided on ziplining.

What I wrote then:

Day Four, November 18, 2009: Belize City, Honduras

Today's Schedule!

From http://www.belizecruiseexcursions.com/BelizeCaveTubingZipLineExcursion.htm

Belize Enjoy two of the most exciting tours offered in Belize today, cave tubing and the canopy zip line excursions on your one day visit to Belize!

Your Zip Line adventure begins from the First Platform where you will "jump" from the first Platform to zip to the next Platform found 150ft away. Flying through the air surrounded by nature is the most exhilarating feeling ever encountered, the birds and Howler Monkeys found onsite will be at eye level making you one with the prolific nature Belize is famous for.

The Zip Line Adventure consists of 8 Zip Line Platforms each strategically located within the Rainforest canopy. Double cables (each capable of withstanding 2,000 pounds of weight, the requirement for this tour truly has nothing to do with weight but with the size of the safety equipment) are used for the ultimate safety. All landing Platforms are equipped with safety gear, handrails and Guides to meet your next landing as well as to ensure your personal safety throughout the tour. The Platforms are as high as 85ft into the Canopy and as far apart as 250ft!

On the second part of your exciting excursion you will then reach the Cave Branch System Welcome Area where you will be fitted with your life vest, (if you would like one) cave lamp and your tube.

The walk to the beginning of the first Cave Entrance is an easy gentle 30 to 40 minute stroll through the beautiful Belizean Rainforest. Your guide will take you through two dry caves where many stalagmites and stalactites can be admired along the way. Once we have reached our access point for your Cave Tubing adventure, you will be able to enter the crystal clear, refreshing river and enter the first cave. A picture of the first cave can be seen on our website but unfortunately the picture does not do the area justice as the cave entrance and color of the water is simply spectacular!

You will visit 1 full underground cave system (2 caves) within the Cave Branch System, you will also be guided to underground dry caves within the cave system, a treat only offered by our outfit, X-Stream Cave Tubing! As you approach the end of your cave tubing experience you will float through small fun rapids where you will pickup some speed and end the cave tubing ride in style, bringing you right back to the starting point of your Cave Tubing adventure. Tropical Fruits are offered following your excursion.

If a picture is worth a thousand words the following pictures should give you a great description of both tours.

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Trekking in the Belizean Rain Forest, an easy 30 minute walk with your tube cave tubing entrance

Walking through a cave on the way to the river for the cave tubing

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In the Rain Forest, an easy 30 minute walk with your tube to the river tubing entrance

Off we go on our Xtreme Cave Tubing Adventure

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Regular Cave-Tubing entry and our guides assist you if you need help

Floating through the Belizean underworld

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Exploring the cave system and various formations by the glow of the cave lights (head lights?)

The famous cave wave

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The short walk through the rainforest to reach the first platform.

The Guides instruct the Zip method and explain the cables, platforms and itinerary. You can see the double cables.

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Getting ready for the first jump to the first platform 85ft in the air!

Zip lining away!!!!

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One of the many platforms found high in the canopy

Wayyy up!

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At the end of the Zip Line Excursion you will repel from the last platform back down to Earth.

Easy does it. This is the experience of a lifetime!

Up and at ‘em early this morning.

This is finally the zipline day I’ve been thinking about since my kidney cancer surgery 3 years ago. Since then, I figure I have “extra years” and I wanted to do something kinda scary, yet fun. So, somehow, I decided on ziplining. Tom wouldn’t go with me but Michael would so I set this up almost as soon as we booked this cruise.

Our tour left first so after breakfast, Michael and I got on the tender for Belize. Tom’s tender was about 45 minutes later. Even though the tender went zipping along, it was about 20 minutes to shore.

We got on our bus with about 30 other brave and not-so-brave folks and our guide, Eddie, told us a bit about Belize City, Belize in general and what to expect on our tour.

Belize City used to be the capital of British Honduras (as Belize was formerly named) but it’s 2 feet below sea level and prone to hurricanes so the capital was moved to the other city – Belmopan in 1970. It was almost entirely destroyed in 1961 when Hurricane Hattie swept ashore on October 31.

Because of the altitude, graves are all above ground.

The main languages are English (the official language), Spanish and Kriol. Eddie said the kids learned English in school but, as soon as they were out, it was back to the Kriol. They wear uniforms to school.

Bordering on Mexico, Guatemala and the Caribbean, Belize is the second smallest country in Central America (after El Salvador), with an area of approximately 9,000 square miles that includes numerous small islands off the coast known as cayes.

More than half of the mainland is covered with dense forests, and at its longest point Belize is 174 miles long while its greatest width is 68 miles. Long a strong advocate of environmental protection, the government has set aside approximately 20% of its land as nature reserves.

There are also several important Mayan sites situated on the mainland such as Altun Ha and Xunantunich that make for excellent day trips and are included on shore excursions by most cruise ships. As a matter of fact, Belize has the highest concentration of Mayan sites of all the countries in Central America.

Eddie tried to tell us that our tour would be scary – but FUN, it would be hard – but FUN. He himself had done the zipline only once, because he had to for this job. He said that the caves might have things brushing up against us but they would be leaves and twigs. The caves might have “log-gators” in them, too.

We travelled along the 37-mile drive along the Western Highway – the scenery changed from city to suburbs, to a settlement called Hattieville where hurricane survivors met to life after the country was destroyed, to the beginnings of the rain forest.

We turned down a road to a jaguar preserve – yes, they have them here! then, finally, to our destination, Caves Branch National Park.

Eddie handed out water (which we had to leave on the bus). A bathroom break, then off to the zipline area.

Each person had a harness around their legs with attached pulleys and carabiners. Women had them on their chests as well. In addition, we had leather construction gloves and hard hats.

We climbed to the top of the first platform and were given brief instructions and off we went. Because of the heavy gloves, I couldn’t get any pictures. I had thought that they would take some of us on the hardest line to sell to us later but they didn't. They also didn’t have cave pictures or T-Shirts. What a missed opportunity!

This was so cool, so much fun. I thought I might be afraid at first but I wasn’t. I just followed instructions and went.

Sometimes they told us to break. We did that with the right hand, which was always on the upper cable.

After the second line, I must have braked too soon because I stopped before I got to the platform. Michael was headed toward me. The guide on the end of the platform wanted me to do some hand over hand maneuver but I couldn’t figure out what he was saying so he came and got me by wrapping his legs around me and pulling me to the platform.

After that, no more problems with braking!

The next platform was very high – over 70 feet in the air – and the climb up was difficult. It was very hot and the rocks were very uneven. I don’t know that I would have gotten to the next platform if Michael hadn’t cheered me on all the way.

We zipped down the next six lines up to 250-feet between platforms and 85-feet high in the trees, at canopy level. It seemed like it was all over too soon.

But, I did it! No fear, just fun.

Here we are, after getting our gear off. The people behind Michael are just starting out on their zipline adventure. I thought maybe we could go again…?

Next stop was lunch in the trees. It was a buffet similar to those in Barbados – a jerk chicken (Eddie had said it would taste like chicken – might be egret, road kill, log-gator or even…chicken!), peas and rice, a pasta salad, cake, fruit salad, the usual fare.

Next up, cave tubing! This is the event I got my new waterproof camera for. Thanks again, Alice! If you're interested in reading the cave tubing part, it's here: http://www.cushingsonline.com/cruise/cruise2009.htm

Posted via email from Cushings Help

40 Days of Thankfulness: Days Twenty-Two through Thirty

I haven't been too great on keeping this list up online but I have been keeping up on my computer so there will be a few catchup posts like this one.

Day 22 (November 5): Jack Canfield's book Chicken Soup for the Surviving Soul: 101 Healing Stories About Those Who Have Survived Cancer.  There is a great piece in there called The Best Day of my Life.  I've written about it before on http://cushingshelp.blogspot.com

Day 23 (November 6): Lou Argow.  She's been my counselor for many years, starting with my terrifyingly real dreams of death. Thanks, Lou!

Day 24 (November 7): SusanM on the message boards.  She did something so wonderful for me a few years ago, words can't even describe it.  Fortunately, I have described it before. :)  Read more here!  People on the message boards can check this thread out.  Thanks again, Susan!

Day 25 (November 8): Travel.  I've been fortunate to be able to travel to several interesting places.  Some, like Iceland, we just lucked in to.  We' wanted to go to Ireland but the travel agent couldn't get us in at any time over that summer.  She did get us a deal where, if we flew Iceland Air, they'd give us a free week in a hotel in Iceland before flying us to London.  Duh!  Wonderful trip.

Day 26 (November 9): My dear friend, and sister I never had, Alice.  We've only met twice in person but we talk for several hours about every other day.  We're closer than any of my local friends.  Happy Birthday, Alice!

Day 27 (November 10): TiVo.  I love that I can fast forward through commercials and have all my favorite shows waiting for me when I lie down on the sofa (and fall asleep!)  I probably wouldn't have gotten one of these when we did but our son got us one for Christmas.  He had it all set up and ready to go on Christmas morning.  At that time, I had no idea of its capabilities but now, I don't think I could live without it!

Day 28 (November 11): Veteran's Day.  I am thankful for those who have served and are serving now.  My husband served during the Vietnam-era although he never had to go to Vietnam.

Day 29 (November 12): Crockpot.  Yay!

Day 30 (November 13): Rainbows. I have a special affinity for them.  To me, a rainbow is a sign that things are going to be ok.  Years ago, our little family was in Florida.  I felt guilty about going because my dad was terminally ill with his second bout of colon cancer.  I was worried about him and said a little prayer for him.  I was lying on the beach while DH and our son were in the ocean and I looked up and saw a rainbow.  It was a perfectly clear, sunny afternon.   I even called the people out of the water, in case it was something I wanted to see that didn't really exist.  They saw it, too.

Where in the world did that rainbow come from, if it wasn't a sign?

Cyclical Cushing's

zhen posted this for us on the message boards

There are many good articles published on cyclical Cushing's. You wouldn't want to restrict your search to NIH.

Dr. Stratakis of NIH published the following paper:
Cyclical Cushing Syndrome Presenting in Infancy: An Early Form of Primary Pigmented Nodular Adrenocortical Disease, or a New Entity?

NIH published the following paper concerning screening tests with author Dr. Nieman and others.

Specificity of Screening Tests for Cushing’s Syndrome in an Overweight and Obese Population

I found the following publications for you using PubMed for the search. BTW, Google is not your friend for starting these medical topic searches. Google will lead you in too many directions and information that hasn't been peer reviewed often has mistakes.
Search on PubMed. If you find an interesting title that only has the abstract, you can often find the full text by pasting the full title into google. Weed through the paid document providers and you'll often find a free full .pdf document later in the list.

Sometimes you can do a search directly on a publisher's web site for even more articles.

Here are some articles for you. I encourage you/your friend to spend s few evenings searching and reading.

The prevalence and characteristic features of cyclicity and variability in Cushing’s disease

A case of cyclical Cushing's disease associated with corticosteroid-binding globulin deficiency: a rare pitfall in the diagnosis of Cushing's disease.

Cyclical Cushing's syndrome: an update.

Cyclical Cushing’s syndrome due to an atypical thymic carcinoid
There's also lots of valuable information on Dr. F.'s (Theodore C. Friedman, M.D., Ph.D.) website.

www.goodhormonehealth.com.

I recommend you spend an entire evening reading on Dr. F.'s web pages. His work integrates clinical experience that's lacking in much of the other work. Then read everything Dr F. published by using www.pubmed.com with an author search. On pubmed you do an author search by typing F. T [au] in the search box.
When you find a useful article on pubmed, click on the authors name in the author list below the title. That will bring up a listing of their other publications. Often these authors have a special interest in the topic you're searching and have published many other papers. If there is a "free text" icon shown to the upper right, you can read the full article by following the link. If the free icon isn't there, copy and paste the article title into google. You may get lucky if you spend some time.

Concerning testing, the endocrine society has published a guideline that represents current practice.

The Diagnosis of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline

You have the right approach. An educated patient can get through the diagnostic maze by understanding the limitations of the classical tests. A patient who doesn't know the research is likely to be screened out and never get the necessary care.

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staticnrg added this on the CushieWiki

Cyclic Cushing's is a controversial subject among endocrinologists. Other terms used for it are "episodic" and "intermittent". Tumors which cause Cushing's disease can intermittently secrete hormones which cause increased cortisol.

Pituitary tumors will secrete ACTH intermittently while adrenal tumors secrete cortisol periodically. This leads to a cycle of Cushing's symptoms which may repeat over the period of hours, or days, or weeks, and sometimes even years. Because of this, it is difficult to diagnose for some patients.

To review some articles which include cyclic/episodic/intermittent Cushing's, see the links below:

Staticnrg's Delicious Bookmarks

What causes Cushing’s syndrome and Cushing’s disease?

Cushing’s syndrome can be caused by medication or by a tumor. Sometimes, there is a tumor of the adrenal gland that makes too much cortisol. It may also be caused by a tumor in the pituitary gland (a small gland under the brain that produces hormones that in turn regulate the body’s other hormone glands).

Some pituitary tumors produce a hormone called adrenocorticotropic hormone (ACTH ), which stimulates the adrenal glands and causes them to make too much cortisol. This is termed Cushing’s disease. ACTH -producing tumors can also originate elsewhere in the body and these are referred to as ectopic tumors.

It is important to note that pituitary tumors are almost never cancerous.

 

From http://www.medicaltoday.net/what-causes-cushing%E2%80%99s-syndrome-and-cushing%E2%80%99s-disease.html

Cushing’s syndrome and chronic venous ulceration

From the International Wound Journal…

Cushing’s syndrome is a condition caused by high levels of glucocorticoids, or most commonly as a result of prolonged exposure to exogenous steroids. Clinical features include diabetes, hypertension, obesity, skin atrophy, immune suppression and delayed wound healing. We report a patient with iatrogenic Cushing’s syndrome, in whom long-term topical steroid therapy was used to treat varicose eczema, which contributed to the development of type 2 diabetes, morbid obesity, sleep apnoea and chronic wound sepsis. In this case, repeated hospital admissions and systemic antibiotics were associated with considerable comorbidity. Aggressive local treatment, consisting of potassium permanganate soaks and irrigating gels, was highly effective in reducing the amount of exudate, pain and preventing from further deterioration of the patient’s legs.

.:: Original Article Here ::.

1. Moushmi Biswas^1,*,
2. Owain Gibby²,
3. Tzvetanka Ivanova-Stoilova³,
4. Keith Harding⁴

 

From http://www.thewoundcareblog.com/2010/11/cushings-syndrome-and-chronic-venous-ulceration-%E2%80%93-a-clinical-challenge/

In Vivo and In Vitro Glucocorticoid Sensitivity in Obese People With Cushingoid Appearance

Obesity (2008) 16 10, 2374–2378. doi:10.1038/oby.2008.346

Akheel A. Syed¹, Christopher P.F. Redfern² and Jolanta U. Weaver^3,4

1. ¹Department of Endocrinology, Newcastle University Teaching Hospitals, Newcastle upon Tyne, UK
2. ²Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
3. ³School of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
4. ⁴Department of Diabetes and Endocrinology, Queen Elizabeth Hospital, Gateshead, UK

Correspondence: Christopher P.F. Redfern (chris.redfern@ncl.ac.uk)

Received 21 September 2007; Accepted 10 March 2008; Published online 24 July 2008.

Abstract:

Clinical similarities between Cushing's syndrome and obesity/metabolic syndrome have led to speculation of a role for glucocorticoids (GCs) in the etiopathogenesis of obesity. People with idiopathic obesity have normal circulating cortisol concentrations. However, there may be considerable interindividual variation in GC sensitivity. The objective of this study was to determine whether enhanced GC sensitivity in the absence of GC excess was a characteristic of obese people with cushingoid features. We studied 12 obese subjects with cushingoid features in the absence of Cushing's syndrome and six slim control participants. Data recorded included BMI, waist-to-hip ratio, blood pressure, glucose and insulin response to 75 g oral glucose challenge, and low-dose (0.25 mg) overnight dexamethasone (DEX) suppression test (ODST-0.25 mg). To study GC-sensitivity in vitro, we performed dose–response studies of DEX-induced suppression of interleukin-6 (IL-6) secretion in skin fibroblast cultures. Seven obese subjects were normosensitive and five subjects hypersensitive to GCs in vitro. ODST-0.25 mg resulted in a median suppression of cortisol from baseline of 32% in normosensitive and 60% in hypersensitive obese subjects (P < 0.004). No other clinical or biochemical measures were discriminatory between these two groups. These data from two independent measures of GC sensitivity suggest that enhanced GC sensitivity may characterize a substantial proportion of obese people with cushingoid appearance.

The role of glucocorticoids (GCs) in promoting and maintaining positive energy balance, a function that is exaggerated in Cushing's syndrome, has been suspected in the etiopathogenesis of simple obesity. People with idiopathic obesity have normal circulating cortisol concentrations that are independent of fat stores but an augmented cortisol turnover rate (1,2) and enhanced hypothalamic–pituitary–adrenal (HPA) axis reactivity (3,4,5,6). There is considerable interindividual variation in GC sensitivity in health (7,8). This is also evident in some patients who develop Cushing's syndrome on low-dose GC therapy for conditions such as asthma, whereas others appear to be resistant to much higher doses. Thus, it has been speculated that obesity with Cushingoid appearance is a state of enhanced responsiveness to GCs. The aim of this study was to test the hypothesis that adiposity was associated with enhanced GC-sensitivity in vitro and in vivo in obese individuals with a cushingoid appearance.

Participants and Methods

We studied 12 obese subjects (10 women) aged 18–53 (median 29.5) years who had cushingoid features such as central obesity and skin striae on clinical assessment, suggestive of enhanced GC activity; none had Cushing's syndrome (at least two normal 24-h urinary free cortisol measurements) or a history of treatment with steroids, hypothyroidism, or any major illness. For comparative analysis, we studied six healthy control participants (four women) aged 33–49 (median 40) years with BMI <25 kg/m². All participants gave informed signed consent and the local research ethics committee approved the study. Data recorded included age, gender, weight, height, BMI, waist circumference, hip circumference, waist-to-hip ratio, blood pressure, and bioimpedance analysis of body composition. A 75-g oral glucose tolerance test was performed after an overnight fast with measurements of fasting and 2-h glucose and insulin levels. Insulin resistance was computed by homeostasis model assessment (9). An overnight dexamethasone (DEX) suppression test (ODST) was performed on a subsequent day with 0.25 mg DEX administered at 2300 hours and serum samples collected at 0900 hours the following morning. Cortisol, corticosteroid-binding globulin, prolactin, adiponectin, resistin, leptin, interleukin-6 (IL-6), testosterone, sex hormone binding globulin, luteinizing hormone, follicle-stimulating hormone, and estradiol concentrations were measured at baseline (0900 hours fasting sample of oral glucose tolerance test); cortisol, prolactin, adiponectin, resistin, leptin, and DEX concentrations were also measured following ODST-0.25 mg. Free cortisol index, calculated as total cortisol (nmol/l)/corticosteroid-binding globulin (mg/l), was used as a surrogate for serum-free cortisol (10). The proportional change in concentrations before and after ODST-0.25 mg was used in analyses. Study participants were not on estrogenic or cytochome P450-metabolized drug therapies and gonadal hormone profiles in menstruating women subjects indicated that they were in the follicular phase of the menstrual cycle when biochemical tests were carried out.

GC-sensitivity in vitro

We developed a novel bioassay for determining GC-sensitivity in vitro by quantifying DEX-induced suppression of unstimulated, natural state IL-6 secretion in cultured human skin fibroblasts (HSFs). Forearm skin biopsies were taken with a 3 mm Stiefel disposable punch. Primary cultures were set up on Matrigel (BD Biosciences, Oxford, UK) bathed in MEM-Alpha with Glutamax-I (50%), fetal bovine serum (50%), penicillin (5,000 units), streptomycin (5,000 g), and amphotericin 0.1% (all from Invitrogen, Paisley, UK) at 37 °C in an atmosphere of 5% CO₂. HSFs were propagated in 90% DMEM with Nutrient Mixture F-12 with Glutamax-I (Invitrogen) and 10% fetal bovine serum and passaged by trypsinisation. HSFs harvested at Passage 5–8 were grown to full confluence in 96-well culture plates. The wells were exposed to DEX in doses ranging from 10^–11 to 10^–4 M for 1 h followed by rinsing and incubation in serum-free media overnight for 12 h. Cell supernatants were aspirated and analyzed in duplicate for IL-6 using a human IL-6 ELISA (Bender MedSystems, Vienna, Austria) as per the manufacturer's instructions. Control solutions containing high and low concentrations of IL-6 were used in every batch. A coefficient of variation <20% was accepted for reproducibility of the assay (11), and the overall mean coefficient of variation was 4.58% in this study. Under these conditions, DEX produced a clear dose–response decrement in the IL-6 content of culture supernatants and the IC₅₀ (median inhibitory concentration) was computed by four-parameter nonlinear regression sigmoidal dose–response with variable slope curve fitting. The lower-bound value of the 97% confidence interval of the median IC₅₀ in controls was used as the cutoff for classifying obese subjects as normosensitive (IC₅₀ 4.4 nmol/l) or hypersensitive (IC₅₀ < 4.4 nmol/l) to GCs. Statistical analyses were performed with Prism v4 (GraphPad Software, San Diego, CA), SPSS v11 (SPSS, Chicago, IL), and Systat v10 (Systat Software, San Jose, CA). We used conservative, nonparametric statistics (Mann–Whitney U-test, asymptotic two-tailed significance) for comparative analysis. For testing the association of cortisol response to ODST-0.25 mg and in vitro GC sensitivity, stepwise backward multiple regression analysis was performed with an F-ratio probability of 0.15 as the criterion for removal or inclusion of explanatory variables in the model. Pearson's correlation coefficient was determined as a measure of correlation between variables. Receiver operating characteristic analysis was used for defining sensitivity and specificity of cortisol response to ODST-0.25 mg in relation to GC-sensitivity in vitro. A P value <0.05 was accepted as significant.

Results

GC-sensitivity in vitro

GC-sensitivity in vitro was represented by the IC₅₀ of DEX-induced inhibition of IL-6 secretion in HSFs (Figure 1a). The median IC₅₀ for controls was 9.7 nmol/l (97% confidence interval, 4.4–22.3 nmol/l). Seven obese subjects were normosensitive (obese normosensitive, ONS; Figure 1b) with median IC₅₀ 12.6 nmol/l (compared to controls, P = 0.09). The remaining five obese subjects were hypersensitive (obese hypersensitive, OHS); the median IC₅₀ was 0.5 nmol/l and significantly different from control participants (P < 0.006) and ONS subjects (P < 0.004). There were no significant differences in clinical measures including the degree and distribution of adiposity, blood pressure, fasting and 2-h glucose during oral glucose tolerance test, homeostasis model assessment of insulin resistance, and lipid profiles between ONS and OHS subjects (Table 1).

Figure 1.

Glucocorticoid (GC)-sensitivity in vitro and in vivo. (a) GC- sensitivity in vitro. Dose–response curves showing fall in IL-6 concentration (y-axis; percentage of baseline value) plotted against increasing dexamethasone (DEX) concentrations (x-axis; log scale); thick solid line, median dose–response curve for control participants (CON), flanked by 95% confidence intervals of the curve (gray shaded area) for illustration (97% confidence interval of the median was used for determining the reference range); thin solid lines, dose–response curves for obese-hypersensitive (OHS) subjects; broken lines, dose–response curves for obese-normosensitive (ONS) subjects; IC₅₀ is marked by dotted horizontal line. (b) Median inhibitory concentration. IC₅₀ values for DEX-induced interleukin-6 (IL-6) suppression in vitro (y-axis; log scale), grouped by participant type. (c) GC-sensitivity in vivo. Percent suppression in cortisol concentration from baseline after overnight 0.25 mg DEX suppression test (y-axis), grouped by participant type. (d) Correlation of in vivo and in vitro GC sensitivity. Linear regression of cortisol response to overnight 0.25 mg DEX suppression test (y-axis) against IC₅₀ values of DEX concentration (x-axis; log scale) confirmed significant correlation (Pearson's r = 0.6, P < 0.009). Open circles, female; filled circles, male; horizontal lines, median value.

Full figure and legend (20K)

Table 1 - Clinical measures in participants.

Full table (55K)

Overnight 0.25 mg DEX suppression test (ODST-0.25 mg)

There were no significant differences between the groups in serum DEX concentrations after ODST-0.25 mg (Table 1). Although there were no significant differences in baseline serum total cortisol concentrations or free cortisol index, the median-cortisol response to ODST-0.25 mg was 24.1% in control participants, 32.4% in ONS and 60.0% in OHS subjects (Figure 1c). The cortisol responses in OHS subjects were significantly different compared to ONS subjects (P < 0.004). Stepwise backward multiple regression performed to further test the relationship of cortisol response (dependent variable) to in vitro GC sensitivity in obese subjects with age, BMI, waist-to-hip ratio, baseline cortisol, corticosteroid-binding globulin, and serum DEX concentration after ODST-0.25 mg as additional explanatory variables confirmed a significant association (P < 0.001; Table 2). The IC₅₀ of DEX-induced inhibition of IL-6 secretion in HSFs correlated significantly with cortisol response to ODST-0.25 mg (Pearson's r = 0.6, P < 0.009; Figure 1d). On receiver operating characteristic analysis, a cutoff of 50% suppression in cortisol from baseline in response to ODST-0.25 mg gave a sensitivity of 100% and specificity of 92% for distinguishing OHS from ONS subjects.

Table 2 - Multiple regression of cortisol responses to ODST-0.25 mg.

Full table (27K)

Insulin, prolactin, adipokines, and gonadal hormones

Insulin resistance was greater in obese subjects (1.55) than in controls (0.5; P < 0.04), but there was no significant difference between the ONS (1.8) and OHS (1.1) subgroups (P > 0.51). Median basal concentrations in control participants compared to obese subjects of leptin were 7.68 ng/ml vs. 118.06 ng/ml (P < 0.001), resistin 3.60 ng/ml vs. 7.51 ng/ml (P < 0.025), and IL-6 0.70 pg/ml vs. 1.98 pg/ml (P < 0.002). However, there were no significant differences between ONS and OHS subjects in leptin (99.61 ng/ml vs. 140.24 ng/ml, P > 0.46), resistin (8.24 ng/ml vs. 6.78 ng/ml, P > 0.68), or IL-6 (1.70 pg/ml vs. 2.18 pg/ml, P > 0.93). There were no significant differences in basal concentrations of prolactin and adiponectin between any of the groups and there were no significant differences in the responses of leptin, resistin, adiponectin, IL-6, or prolactin to ODST-0.25 mg across the groups. After taking gender into account, there were no differences in serum concentrations of luteinizing hormone, follicle-stimulating hormone, sex hormone binding globulin, total and calculated bioavailable (free) testosterone, and estradiol between groups.

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Discussion

Obesity with cushingoid appearance, by sharing some clinical features of Cushing's syndrome, raises the possibility of hypersensitivity to normal circulating levels of endogenous GCs. Various bioassays have been described for measuring cellular GC sensitivity (8,12). Most rely on GC-induced suppression of cell proliferation or mitogen-stimulated cytokine release in peripheral blood cells, which may be affected by exposure to circulating GCs in vivo before harvesting, or by the stimulation process itself. We therefore developed a bioassay based on GC-induced suppression of IL-6 secretion in HSFs to measure GC sensitivity. This is unaffected by in vivo circulating GCs and reflects a stable, heritable property of the HSFs derived from each participant. We studied a sample of obese subjects who were preselected on clinical suspicion of GC hypersensitivity (cushingoid appearance with no evidence of GC excess) of which two-fifths manifested evidence of tissue GC hypersensitivity. Furthermore, the hypersensitive obese subjects were indistinguishable from normosensitive obese subjects by routine objective clinical measures such as body weight, BMI, waist circumference, or waist-to-hip ratio in this small sample. Thus, conventional clinical features alone are inadequate at identifying GC-hypersensitive individuals.

Although ODST-1 mg is often used as a screening test in clinical investigation of Cushing's syndrome, in people without Cushing's syndrome, it results in too much suppression of the HPA axis to allow detection of individual differences in feedback sensitivity. However, ODST-0.25 mg results in a broad range of cortisol concentrations, giving a good insight into feedback sensitivity (7) and low-dose DEX can distinguish a finely regulated HPA axis from a poorly regulated one (13). Earlier population studies employing low-dose overnight DEX suppression tests have reported considerable variation in GC sensitivity of the HPA axis, but have been unable to reliably identify enhanced GC sensitivity in obesity. By selecting subjects with morphological features suggestive of GC excess in the absence of true Cushing's syndrome, we have shown that there is a clear difference in regulation of cortisol concentration in vivo between normosensitive and hypersensitive obese people, thus maintaining circulating cortisol levels within normal limits. This autoregulation is also reflected by GC sensitivity at a cellular level. Whereas measurement of serum-free cortisol is technically difficult, expensive, and not widely available, free cortisol index has been shown to correlate strongly with measured free cortisol (10). Moreover, percent-cortisol response (proportional change from baseline) to ODST, as used in this study, is unaffected by whether total cortisol or free cortisol index is used. The results of this study on a small sample of obese individuals suggest that percent-cortisol response to ODST-0.25 mg may be used to identify those who are likely to have underlying enhanced GC sensitivity. However, this conclusion will need independent replication in larger cohorts before warranting incorporation as a test for GC sensitivity into standard clinical practice.

Leptin, an adipokine hormone involved in negative feedback regulation of food intake, is inducible by GCs both in normal weight and obese individuals (14). Conversely, it can directly inhibit GC secretion in the adrenal gland (15). Thus, it has been suggested that feedback loops exist at the tissue level regulating cortisol concentrations within the intraindividual physiological range, resulting in reduced negative feedback tone higher up in the HPA axis (16). Basal leptin, resistin, and IL-6 concentrations were significantly higher overall in obese subjects compared to control participants, but there was no statistical difference between ONS and OHS subjects in our small sample. Similarly, although obese subjects had greater insulin resistance overall, there was no statistical difference between ONS and OHS subjects. This suggests that insulin resistance is more a function of obesity per se rather than GC sensitivity, but study in a larger sample is warranted. A previous study has demonstrated evidence of variation in cortisol response to ODST-0.25 mg depending on the phase of the menstrual cycle in women (17). However, this is unlikely to have influenced the outcome of this study as the women were assessed in the same phase of the menstrual cycle. A reduction in the sensitivity of the HPA axis to GC feedback inhibition has been demonstrated in 70-year-old compared to 26-year-old subjects (18). Although the median age of control participants was 10 years greater than of obese subjects in our study, there was no difference in age between the ONS and OHS subgroups. Moreover, intraindividual GC sensitivity has been shown to be constant with aging (7).

In conclusion, we suggest that enhanced sensitivity to GCs may characterize excess adiposity in a proportion of obese people with cushingoid appearance. As clinical assessment alone may not have sufficient discriminatory value, an ODST-0.25 mg may be used as a screening test to identify people with GC hypersensitivity for future research.

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Disclosure

The authors declared no conflict of interest.

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References

REFERENCES

1. Dunkelman SS, Fairhurst B, Plager J, Waterhouse C. Cortisol metabolism in obesity. J Clin Endocrinol Metab 1964;24: 832–841. | PubMed | ChemPort |
2. Hautanen A, Adlercreutz H. Altered adrenocorticotropin and cortisol secretion in abdominal obesity: implications for the insulin resistance syndrome. J Intern Med 1993;234: 461–469. | PubMed | ChemPort |
3. Marin P, Darin N, Amemiya T et al. Cortisol secretion in relation to body fat distribution in obese premenopausal women. Metabolism 1992;41: 882–886. | Article | PubMed | ChemPort |
4. Weaver JU, Kopelman PG, McLoughlin L, Forsling ML, Grossman A. Hyperactivity of the hypothalamo-pituitary-adrenal axis in obesity: a study of ACTH, AVP, beta-lipotrophin and cortisol responses to insulin-induced hypoglycaemia. Clin Endocrinol (Oxf) 1993;39: 345–350. | Article | PubMed | ChemPort |
5. Rosmond R, Dallman MF, Bjorntorp P. Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab 1998;83: 1853–1859. | Article | PubMed | ISI | ChemPort |
6. Pasquali R, Ambrosi B, Armanini D et al. Cortisol and ACTH response to oral dexamethasone in obesity and effects of sex, body fat distribution, and dexamethasone concentrations: a dose-response study. J Clin Endocrinol Metab 2002;87: 166–175. | Article | PubMed | ChemPort |
7. Huizenga NA, Koper JW, de Lange P et al. Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals. J Clin Endocrinol Metab 1998;83: 47–54. | Article | PubMed | ChemPort |
8. Chriguer RS, Elias LL, da Silva IM Jr, Vieira JG, Moreira AC, de Castro M. Glucocorticoid sensitivity in young healthy individuals: in vitro and in vivo studies. J Clin Endocrinol Metab 2005;90: 5978–5984. | Article | PubMed | ChemPort |
9. Levy JC, Matthews DR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 1998;21: 2191–2192. | Article | PubMed | ISI | ChemPort |
10. le Roux CW, Sivakumaran S, Alaghband-Zadeh J, Dhillo W, Kong WM, Wheeler MJ. Free cortisol index as a surrogate marker for serum free cortisol. Ann Clin Biochem 2002;39: 406–408. | Article | PubMed | ChemPort |
11. Rosner B. Fundamentals of biostatistics. 2006; Thomson-Brooks/Cole: Belmont, CA.
12. Vermeer H, Hendriks-Stegeman BI, Verrijn Stuart AA, van Buul-Offers SC, Jansen M. A comparison of in vitro bioassays to determine cellular glucocorticoid sensitivity. Eur J Endocrinol 2004;150: 41–47. | Article | PubMed | ChemPort |
13. Rosmond R, Bjorntorp P. The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke. J Intern Med 2000;247: 188–197. | Article | PubMed | ChemPort |
14. Dagogo-Jack S, Selke G, Melson AK, Newcomer JW. Robust leptin secretory responses to dexamethasone in obese subjects. J Clin Endocrinol Metab 1997;82: 3230–3233. | Article | PubMed | ChemPort |
15. Bornstein SR, Uhlmann K, Haidan A, Ehrhart-Bornstein M, Scherbaum WA. Evidence for a novel peripheral action of leptin as a metabolic signal to the adrenal gland: leptin inhibits cortisol release directly. Diabetes 1997;46: 1235–1238. | Article | PubMed | ISI | ChemPort |
16. Syed AA, Weaver JU. Glucocorticoid sensitivity: the hypothalamic- pituitary-adrenal-tissue axis. Obes Res 2005;13: 1131–1133. | Article | PubMed | ChemPort |
17. Altemus M, Redwine L, Leong YM et al. Reduced sensitivity to glucocorticoid feedback and reduced glucocorticoid receptor mRNA expression in the luteal phase of the menstrual cycle. Neuropsychopharmacology 1997;17: 100–109. | Article | PubMed | ISI | ChemPort |
18. Wilkinson CW, Peskind ER, Raskind MA. Decreased hypothalamic- pituitary-adrenal axis sensitivity to cortisol feedback inhibition in human aging. Neuroendocrinology 1997;65: 79–90. | Article | PubMed | ChemPort |

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Acknowledgments

Funding for this study was provided by Gateshead NHS Research and Development Fund and the Queen Elizabeth Hospital Diabetes Charitable Fund. We are grateful to Lorna Ingoe (Queen Elizabeth Hospital and Newcastle University) for assisting in the conduct of clinical assessments, John Barker (Queen Elizabeth Hospital) for clinical biochemistry services, and Penny Lovat (Newcastle University) for helpful discussions on tissue culture technique.

From http://www.nature.com/oby/journal/v16/n10/full/oby2008346a.html

Medical Apps, Part 2: FindER

smilez133 posted this on the message boards here

Massachusetts General Hospital Launches iPhone App to Locate Emergency Rooms

FindER Connects Users to the Most Complete Database of ERs in the U.S.

BOSTON—Researchers at Massachusetts General Hospital’s (MGH) Emergency Medicine Network (EMNet) announced today the launch of EMNet findER™, a free iPhone application designed to help users locate the closest emergency room to their current location, as well as provide directions and additional information with a touch of the screen. FindER uses the iPhone’s global positioning system to quickly direct patients to emergency rooms anywhere within the United States.

“FindER is designed to provide key information to people experiencing health emergencies,” says Carlos A. Camargo MD, of MGH’s Department of Emergency Medicine and EMNet director. “FindER uses information from EMNet’s own database of emergency departments, which is the most complete and accurate in the nation.”

Along with directions and general information, findER is designed for quick phone calls to both the care-center itself and in cases where necessary, 911 emergency services.

“EMNet researchers maintain a database of nearly 5,000 emergency rooms in the United States. Unlike a simple Google search where the results may include many emergency centers that have closed or moved, or even veterinary hospitals, findER’s results are based on an aggregation of emergency room listings from multiple sources that have been confirmed by researchers at EMNet,” says Camargo. “FindER is designed to help patients get to emergency rooms in the shortest amount of time.”

FindER is ideal for travelers, especially those suffering chronic medical conditions, or those traveling with friends or relatives with health problems. FindERis available now as a free download in the iTunes app store. Simply click this link or search "EMNet findER," to download. For a short demonstration video, users can visit YouTube.

From http://www.massgeneral.org/about/pressrelease.aspx?id=1248

MaryONote: Just as info - the iTunes store said that there was nothing called FindER when I did a search. I found it only by typing EMNet findER. I have the app - looks great - and I hope I never need it again!

Radiosurgery for pituitary adenomas: evaluation of its efficacy and safety

Object: To assess the effects of radiosurgery (RS) on the radiological and hormonal control and its toxicity in the treatment of pituitary adenomas.

Methods: Retrospective analysis of 42 patients out of the first 48 consecutive patients with pituitary adenomas treated with RS between 1999 and 2008 with a 6 months minimum follow-up. RS was delivered with Gamma Knife as a primary or adjuvant treatment.

There were 14 patients with non-secretory adenomas and, among functioning adenomas, 9 were prolactinomas, 9 were adrenocorticotropic hormone-secreting and 10 were growth hormone-secreting tumors. Hormonal control was defined as hormonal response (decline of more than 50% from the pre-RS levels) and hormonal normalization.

Radiological control was defined as stasis or shrinkage of the tumor. Hypopituitarism and visual deficit were the morbidity outcomes.

Hypopituitarism was defined as the initiation of any hormone replacement therapy and visual deficit as loss of visual acuity or visual field after RS.

Results: The median follow-up was 42 months (6 -109 months). The median dose was 12,5 Gy (9 - 15 Gy) and 20 Gy (12 - 28 Gy) for non-secretory and secretory adenomas, respectively.

Tumor growth was controlled in 98% (41 in 42) of the cases and tumor shrinkage ocurred in 10% (4 in 42) of the cases. The 3-year actuarial rate of hormonal control and normalization were 62,4% and 37,6%, respectively, and the 5-year actuarial rate were 81,2% and 55,4%, respectively.

The median latency period for hormonal control and normalization was, respectively, 15 and 18 months. On univariate analysis, there were no relationships between median dose or tumoral volume and hormonal control or normalization.

There were no patients with visual deficit and 1 patient had hypopituitarism after RS.

Conclusions: RS is an effective and safe therapeutic option in the management of selected patients with pituitary adenomas. The short latency of the radiation response, the highly acceptable radiological and hormonal control and absence of complications at this early follow-up are consistent with literature.

Author: Douglas CastroSoraya CecilioMiguel Canteras
Credits/Source: Radiation Oncology 2010, 5:109

From: http://7thspace.com/headlines/364042/radiosurgery_for_pituitary_adenomas_evaluation_of_its_efficacy_and_safety.html

Corticotrophin-releasing factor mediates hypophagia after adrenalectomy, increasing meal-related satiety responses

Ernane Torres Uchoa, Lilian Eslaine Costa Mendes da Silva, Margaret de Castro, Jose Antunes-Rodrigues and Lucila Leico K. Elias

a Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil

b Department of Internal Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil

Adrenalectomy-induced hypophagia is associated with increased satiety-related responses, which involve neuronal activation of the nucleus of the solitary tract (NTS). Besides its effects on the pituitary–adrenal axis, corticotrophin-releasing factor (CRF) has been shown to play an important role in feeding behaviour, as it possesses anorexigenic effects. We evaluated feeding-induced CRF mRNA expression in the paraventricular nucleus (PVN) and the effects of pretreatment with CRF₂ receptor antagonist (Antisauvagine-30, AS30) on food intake and activation of NTS neurons in response to feeding in adrenalectomised (ADX) rats. Compared to the sham group, ADX increased CRF mRNA levels in the PVN of fasted animals, which was further augmented by refeeding. AS30 treatment did not affect food intake in the sham and ADX + corticosterone (B) groups; however, it reversed hypophagia in the ADX group. In vehicle-pretreated animals, refeeding increased the number of Fos and Fos/TH-immunoreactive neurons in the NTS in the sham, ADX and ADX + B groups, with the highest number of neurons in the ADX animals. Similarly to its effect on food intake, pretreatment with AS30 in the ADX group also reversed the increased activation of NTS neurons induced by refeeding while having no effect in the sham and ADX + B animals. The present results show that adrenalectomy induces an increase in CRF mRNA expression in the PVN potentiated by feeding and that CRF₂ receptor antagonist abolishes the anorexigenic effect and the increased activation of NTS induced by feeding in the ADX animals. These data indicate that increased activity of PVN CRF neurons modulates brainstem satiety-related responses, contributing to hypophagia after adrenalectomy.

Research Highlights

►Primary adrenal insufficiency increases meal-related satiety responses.

►Adrenalectomy-induced hypophagia is associated with increased CRF mRNA expression in the hypothalamic paraventricular nucleus (PVN) and increased NTS neuron activation in the brainstem. ►The increased activity of PVN CRF neurons modulates brainstem satiety-related responses. ►CRF type 2 receptor mediates CRF suppressing effect on food intake after adrenalectomy.

Keywords: Glucocorticoids; Food intake; Corticotrophin-releasing factor; Paraventricular nucleus of the hypothalamus; Nucleus of the solitary tract

Article Outline

Introduction

Experimental procedures

Animals

Intracerebroventricular (icv) surgery

Perfusion, tissue preparation and immunohistochemistry

Microdissection, total RNA isolation and quantitative real-time PCR

Experimental protocols

Experiment 1: effects of ADX and B replacement on CRF mRNA expression in the PVN in the fasting–refeeding regimen

Experiment 2: effects of pretreatment with CRF₂ receptor antagonist on food intake in sham, ADX and ADX + B animals

Experiment 3: effects of pretreatment with CRF₂ receptor antagonist on NTS neuron activation in sham, ADX and ADX + B animals in the fasting–refeeding regimen

Statistical analysis

Results

Experiment 1: effects of ADX and B replacement on CRF mRNA expression in the PVN in the fasting–refeeding regimen

Experiment 2: effects of pretreatment with CRF₂ receptor antagonist on food intake in sham, ADX and ADX + B animals

Experiment 3: effects of pretreatment with CRF₂ receptor antagonist on NTS neuron activation in sham, ADX and ADX + B animals in the fasting–refeeding regimen

Discussion

Acknowledgements

References

Fig. 1.

Relative CRF mRNA expression in the PVN of fasted and refed sham, ADX and ADX + B animals (n = 5–8 rats/group). Data are shown as mean ± SEM. *P < 0.05.

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Fig. 2.

Food intake (g/100 g) after 4 h of refeeding (n = 5–7 rats/group) for sham, ADX and ADX + B animals pretreated with vehicle or d-Phe¹¹,His¹²-Sauvagine 11–40 (Antisauvagine-30, AS30; 5 μg/5 μL icv). Data are shown as mean ± SEM. *P < 0.05.

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Fig. 3.

Number of Fos-immunoreactive (A) and Fos/TH-immunoreactive (B) neurons in the NTS (n = 4–8 rats/group) of fasted and refed sham, ADX and ADX + B animals pretreated with vehicle or d-Phe¹¹,His¹²-Sauvagine 11–40 (Antisauvagine-30, AS30; 5 μg/5 μL icv). Data are shown as mean ± SEM. ND: not detectable. *P < 0.05 vs. respective fasted group. #P < 0.05 vs. refed sham/vehicle, refed ADX + B/vehicle and refed ADX/AS30 groups.

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Fig. 4.

Representative photomicrographs (40× magnification) of coronal sections showing Fos/TH immunoreactivity in the NTS of refed sham, ADX and ADX + B animals pretreated with vehicle or d-Phe¹¹,His¹²-Sauvagine 11–40 (Antisauvagine-30, AS30; 5 μg/5 μL icv). Each inset depicts at 20× magnification the area where the photomicrograph was taken. Scale bar, 100 μm.

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Table 1. Number (means ± SEM) of TH-immunoreactive neurons and percentage of Fos/TH double labelled neurons in the NTS of fasted and refed sham, ADX, and ADX + B animals, pretreated with vehicle or AS30.

Data are expressed as means ± SEM (n = 4–8 rats/group). NTS, nucleus of the solitary tract; TH, tyrosine hydroxylase.

^a P < 0.05 vs. respective fasted group.
^b P < 0.05 vs. refed sham/vehicle, refed ADX + B/vehicle and refed ADX/AS30 groups.

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Corresponding author. Avenida Bandeirantes, 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil. Fax: +55 16 3633 0017.

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Hormones and Behavior
Volume 58, Issue 5, November 2010, Pages 714-719

From http://www.sciencedirect.com/science