Welcome to the latest Cushing's Newsletter!

Hi!

Happy Autumn! I hope everyone had a wonderful summer!

I hope you're enjoying these newsletters and learning something new about Cushing's and the websites by reading them.

If there is something you would like to see covered here, or if you would like to write an article, please let me know.  Your input and help are always welcome.

You may, of course, unsubscribe to this newsletter at any time.

Thank you!

Cushie Bloggers

Upcoming Interviews

Upcoming Meetings

Upcoming Cushing's Book

This project was started in June 2008 and put on hold due to several "life issues", one of them being the enormous amount of time it takes to apply for non-profit status.

Here are some of the thoughts and ideas that will be in the book when finished, hopefully by December 2009.

MaryO: some people have articles on the website like http://www.cushings-help.com/helpful_hints.htm and these:

• Kate's Family Letter
• Kate's Packing Suggestions For Surgery
• Kate's Pituitary Surgery Observations
• LindaP's Cushing's Tips

Spread the Word!

Cushing's on Facebook and Twitter

In Memory: Leader of OSU campus ministry dies at 49

By Ed Langlois

Sue Gifford

Want to Volunteer?

Book Project!

We always need people to be interviewed in the BlogTalk Interview series.  These interviews usually take place on Thursday nights at 7:30PM Eastern but you can do this at any time that's convenient for you. 

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> Start iGiving at: www.iGive.com/cushings & www.iSearchiGive.com/cushings Use iGive.com when you buy things online; buy books using the links on the book pages; tshirts and such from the giftstore. Then WEAR those tshirts!

Adrenal Glands

Anatomy
The adrenal glands are small, yellowish organs that rest on the upper poles of the kidneys in the Gerota fascia. The right adrenal gland is pyramidal, whereas the left one is more crescentic, extending toward the hilum of the kidney. At age 1 year, each adrenal gland weighs approximately 1 g, and this increases with age to a final weight of 4-5 g. The arterial blood supply comes from 3 sources, with branches arising from the inferior phrenic artery, the renal artery, and the aorta. Venous drainage flows directly into the inferior vena cava on the right side and into the left renal vein on the left side. Lymphatics drain medially to the aortic nodes.
Each adrenal gland is composed of 2 distinct parts: the adrenal cortex and the adrenal medulla. The cortex is divided into 3 zones. From exterior to interior, these are the zona glomerulosa, the zona fasciculata, and the zona reticularis.
Embryology
First detected at 6 weeks’ gestation, the adrenal cortex is derived from the mesoderm of the posterior abdominal wall. Steroid secretion from the fetal cortex begins shortly thereafter. Adult-type zona glomerulosa and fasciculata are detected in fetal life but make up only a small proportion of the gland, and the zona reticularis is not present at all. The fetal cortex predominates throughout fetal life. The adrenal medulla is of ectodermal origin, arising from neural crest cells that migrate to the medial aspect of the developing cortex.
The fetal adrenal gland is relatively large. At 4 months’ gestation, it is 4 times the size of the kidney; however, at birth, it is a third of the size of the kidney. This occurs because of the rapid regression of the fetal cortex at birth. It disappears almost completely by age 1 year; by age 4-5 years, the permanent adult-type adrenal cortex has fully developed.
Anatomic anomalies of the adrenal gland may occur. Because the development of the adrenals is closely associated with that of the kidneys, agenesis of an adrenal gland is usually associated with ipsilateral agenesis of the kidney, and fused adrenal glands (whereby the 2 glands join across the midline posterior to the aorta) are also associated with a fused kidney.
Adrenal hypoplasia occurs in the following 2 forms: (1) hypoplasia or absence of the fetal cortex with a poorly formed medulla and (2) disorganized fetal cortex and medulla with no permanent cortex present. Adrenal heterotopia describes a normal adrenal gland in an abnormal location, such as within the renal or hepatic capsules. Accessory adrenal tissue (adrenal rests), which is usually comprised only of cortex but seen combined with medulla in some cases, is most commonly located in the broad ligament or spermatic cord but can be found anywhere within the abdomen. Even intracranial adrenal rests have been reported.

Physiology
Adrenal Cortex
The adrenal cortex secretes 3 types of hormones: (1) mineralocorticoids (the most important of which is aldosterone), which are secreted by the zona glomerulosa; (2) glucocorticoids (predominantly cortisol), which are secreted by the zona fasciculata and, to a lesser extent, the zona reticularis; and (3) adrenal androgen (mainly dehydroepiandrosterone [DHEA]), which is predominantly secreted by the zona reticularis, with small quantities released from the zona fasciculata.
All adrenocortical hormones are steroid compounds derived from cholesterol (see Media file 3).
Cortisol binds to proteins in the blood, mainly cortisol-binding globulin or transcortin. More than 90% of cortisol is transported in the blood in this bound form. In contrast, only 50% of aldosterone is bound to protein in the blood. All adrenocortical steroids are degraded in the liver and predominantly conjugated to glucuronides, with lesser amounts of sulfates formed. About 75% of these degradation products are excreted in the urine, and the rest is excreted in the stool by means of the bile.
Mineralocorticoids
Aldosterone accounts for 90% of mineralocorticoid activity, with some activity contributed by deoxycorticosterone, corticosterone, and cortisol. The normal concentration of aldosterone in the blood ranges from 2-16 ng/dL supine and 5-41 ng/dL upright, although the concentration exhibits diurnal variation, and the secretory rate is generally 150-250 mcg/d.
Aldosterone promotes sodium reabsorption and potassium excretion by the renal tubular epithelial cells of the collecting and distal tubules. As sodium is reabsorbed, water follows passively, leading to an increase in the extracellular fluid volume with little change in the plasma sodium concentration. Persistently elevated extracellular fluid volumes cause hypertension. This helps minimize further increases in extracellular fluid volume by causing a pressure diuresis in the kidney, a phenomenon known as aldosterone escape. Without aldosterone, the kidney loses excessive amounts of sodium and, consequently, water, leading to severe dehydration.
As sodium is actively reabsorbed, potassium is excreted. Imbalances in aldosterone thus lead to hypokalemia and muscle weakness if levels are increased and to hyperkalemia with cardiac toxicity if levels are decreased. In addition to sodium being exchanged for potassium at the renal tubules, hydrogen is also exchanged, although to a much lesser extent. Therefore, with aldosterone excess, mild metabolic alkalosis may develop.
In addition to the effects of aldosterone on the renal tubules, a smaller but similar effect is noted on the sweat glands and salivary glands. Aldosterone stimulates sodium chloride reabsorption and potassium secretion in the excretory ducts, which helps prevent excessive salivation and conserve body salt in hot climates. Aldosterone also affects sodium absorption in the intestine, especially the colon. Deficiency may cause a watery diarrhea from the unabsorbed sodium and water.
Many factors affect aldosterone secretion, the most important of which involve the renin-angiotensin system and changes in the plasma potassium concentration.
Activation of the renin-angiotensin system: The juxtaglomerular apparatus senses decreased blood flow to the kidney secondary to hypovolemia, hypotension, or renal artery stenosis and releases renin in response. Renin is an enzyme that activates angiotensinogen to release angiotensin I. In the lung, ACE converts angiotensin I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone release by the adrenal gland.
Concentration of potassium in the extracellular fluid: Increases in the plasma potassium concentration stimulate the release of aldosterone to encourage potassium excretion by the kidney.
Concentration of sodium in the extracellular fluid: Decreases in sodium concentration also stimulate aldosterone release.
Adrenocorticotropic hormone (ACTH) secretion: ACTH secreted by the anterior pituitary primarily affects release of glucocorticoids by the adrenal but, to a lesser extent, also stimulates aldosterone release.
Glucocorticoids
Approximately 95% of glucocorticoid activity comes from cortisol, with corticosterone, a glucocorticoid less potent than cortisol, making up the rest. The normal cortisol concentration in the blood averages 12 mcg/dL, with a secretory rate averaging 15-20 mg/d. Cortisol release is almost entirely controlled by the secretion of ACTH by the anterior pituitary gland, which is controlled by corticotropin-releasing hormone (CRH) secreted by the hypothalamus. In normal situations, CRH, ACTH, and cortisol secretory rates demonstrate a circadian rhythm, with a zenith in the early morning and a nadir in the evening. Various stresses also stimulate increased ACTH and, thus, cortisol secretion. A negative feedback effect of cortisol on the anterior pituitary and the hypothalamus help control these increases and regulate plasma cortisol concentrations.
Cortisol has many effects on the body.
Cortisol stimulates gluconeogenesis in the liver by stimulating the involved enzymes and mobilizing necessary substrates, specifically amino acids from muscle and free fatty acids from adipose tissue. It simultaneously decreases glucose use by extrahepatic cells in the body. The overall result is an increase in serum glucose (ie, adrenal diabetes) and increased glycogen stores in the liver.
Cortisol decreases protein stores in the body, except in the liver, by inhibiting protein synthesis and stimulating catabolism of muscle protein.
Cortisol has clinically significant anti-inflammatory effects, blocking the early stages of inflammation by stabilizing lysosomal membranes, preventing excessive release of proteolytic enzymes, decreasing capillary permeability and, consequently, edema, and decreasing chemotaxis of leukocytes. In addition, it induces rapid resolution of inflammation that is already in progress.
Immunity is adversely affected. Eosinophil and lymphocyte counts in the blood decrease with atrophy of lymphoid tissue.
Adrenal androgens
The adrenal cortex continually secretes several male sex hormones, including DHEA, DHEA sulfate (DHEAS), androstenedione, and 11-hydroxyandrostenedione, with small quantities of the female sex hormones progesterone and estrogen. Most of the effects result from extra-adrenal conversion of the androgens to testosterone. All have weak effects, but they likely play a role in early development of the male sex organs in childhood, and they have an important role in women during pubarche. ACTH has a definite stimulatory effect on androgen release by the adrenal. Therefore, secretion of these hormones parallels that of cortisol.

Adrenal Medulla
The adrenal medulla is a completely different entity. Epinephrine (80%) and norepinephrine (20%), with minimal amounts of dopamine, are secreted into the bloodstream due to direct stimulation by acetylcholine release from sympathetic nerves. Preganglionic sympathetic nerve fibers pass from the intermediolateral horn cells of the spinal cord through the sympathetic chains and splanchnic nerves, without synapsing, into the adrenal medulla. These hormones are responsible for an increase in cardiac output and vascular resistance and for all the physiologic characteristics of the stress response.
Radiology of the Adrenal Gland
CT scanning is the imaging procedure of choice for the evaluation of adrenal lesions, although ultrasonography and, increasingly, MRI have their advantages.
Plain radiography has limited value but may reveal mass effect or calcifications that suggest possible neuroblastoma, previous hemorrhage, or chronic granulomatous disease.
Ultrasonography is often the first imaging study performed in children. It is safe and easy to perform without sedation. It can differentiate cystic from solid adrenal masses and is useful to assess for vascular involvement and liver metastases.
CT scanning most accurately defines the size, location, and appearance of adrenal lesions. In addition, it is useful for assessing local and vascular invasion, involvement of lymph nodes, or distant metastases. For certain lesions (eg, simple cysts, myelolipomas, often hemorrhage), CT scanning enables definitive diagnosis because the image is classic. For solid lesions, unenhanced or delayed–contrast enhanced CT scanning may help in distinguishing benign from malignant lesions by their attenuation. Benign lesions tend to have decreased attenuation because of an increased fat content. However, overlap is substantial; therefore, this finding is not always useful.
MRI is also an excellent study to define the full extent of an adrenal lesion, including its relationship to adjacent organs and major vessels. Its main benefit over CT is its improved ability, with gadolinium enhancement or with chemical shift imaging, to help in differentiating benign from malignant lesions. This is most important in adults with an incidentally discovered adrenal mass.
Radioisotope scanning can be helpful in some situations. Iodocholesterol-labeled analogs (eg, iodine-131 6beta-iodomethyl-19-norcholesterol [NP-59]) are used to detect primary adrenocortical adenomas, carcinomas, or metastases. Dexamethasone administered before the scan enhances sensitivity by suppressing normal ACTH-responsive adrenal tissue. Metaiodobenzylguanidine (MIBG) scans may be used to detect adrenal medullary tumors, pheochromocytomas, and neuroblastomas. This is especially useful in localizing such tumors in extramedullary sites, enabling the entire body to be imaged at once.
More recently positron emission technology (PET) scanning has been introduced in the evaluation of recurrent or metastatic adrenal tumors, especially neuroblastoma. Its role has yet to be fully defined.

Adrenal Pathology
Adrenal pathology can manifest in various ways, including the following:

• Ambiguous genitalia with or without salt wasting in the newborn

Now I know what it feels like to have a gun held to my own head: Ameera MacIntyre's battle with a brain tumour

Some husbands come home moaning that the boss doesn't appreciate them or that the train to work was delayed again. My husband Donal returns complaining about a crack dealer who pinned him to the floor, drilled a pistol into his temple and threatened to blow his brains out.

And now I know what it feels like to have a gun held to my own head.

I'm only 34, I work out, I don't smoke and I drink only socially. I normally enjoy excellent health. But suddenly, three years ago, I found myself waking up every day with what felt like a bad hangover. 

Rolling with the punches: Ameera with husband Donal MacIntyre

As each day progressed, the feeling of grogginess and a dull headache would coalesce into a mind-splitting migraine. Sometimes I would be violently sick.

Perhaps most frightening was the effect on my vision. I felt as if there were daggers behind my eyes. My eyesight seemed to be deteriorating rapidly and I was struggling to focus. By the end of each day I was exhausted.

Donal was working flat-out on various TV programmes at the time and I was struggling to look after our three-year-old daughter, Allegra, on my own. I went to see my GP. 'Most likely a hormone imbalance,' he announced airily, after examining me.

'Your periods are irregular and I would suggest that stress is the most likely explanation.' He sent me for blood tests, to reassure me, and he said that if the headaches got any worse I should try paracetamol.

Oh, and he suggested that I take some exercise. Well, we could all do with more of that but in my bones I knew that that wasn't the cause of the problem. Nor, I suspected, was stress.

Sharing my life with someone whose job involves mixing with violent criminals meant I did know a little something about stress. After all, Donal has moved house 50 times in the past decade to avoid the attentions of the criminals he specialises in exposing.

We have moved seven times since we married just three years ago.

I had also put on about 12lb. For someone whose weight had never changed in ten years, metamorphosing from a size six to a size ten in such a short period of time was profoundly worrying. 

Living with danger: Ameera and Donal have made efforts to spend more time together, along with daughters Tiger and Allegra, since her diagnosis

Then, even though it was nearly three-and-a-half years since I had given birth to Allegra, I started to lactate. My breasts just started leaking. It was difficult to go out without a change of bra or top because I could never tell when or where my breasts would discharge milk. It was uncomfortable and embarrassing.

My sister, Fareeda, is a consultant oncologist in Newcastle. Her first thought, when I described my symptoms, was that it could be a pituitary tumour.

Is there anyone who doesn't find the word 'tumour' terrifying? I knew that a tumour on the brain could be fatal. I was frightened for myself and for my family.

I contacted a consultant neurologist who set up an MRI scan without hesitation. Magnetic resonance imaging (MRI) works by taking a series of magnetic images of the brain and building them up into a 3-D picture.

Submitting to the scan is not a particularly enjoyable process for anyone, but is especially unpleasant for those who suffer from claustrophobia, as I do. It felt like being enclosed in a sterile white coffin. It took three attempts before I was able to stay in the machine for the required 20 minutes.

The radiologist entrusted me with the scan films and his report, in a large sealed envelope addressed to the neurologist. I opened it in the hospital waiting room, which I knew I wasn't supposed to do.

I felt the blood draining from my face as I read the words 'pituitary adenoma'. Despite the advance warning from my sister, I was still unprepared. It was one of those moments when a strange stillness descends. I knew nothing would ever be the same again.

I didn't tell Donal immediately because I didn't want to add to his stress levels. But once he knew his reaction was to scan the internet for any information on the condition. I had done the same, but the more I found out, the more the knowledge weighed me down. It didn't help that my father had died recently, leaving me feeling more vulnerable than ever.

Three days after the MRI, the neurologist slotted the scans on to the light box and explained what they showed. Our family's future, it seemed, now depended on a tiny nodule - an 'abnormality' - on my pituitary gland.

The bad news was that, yes, I had a tumour, but the good news was that it was small, treatable and manageable. The prognosis was very positive, although the threat will never go away. The neurologist compared it to having a loaded gun pointed at my head. That gun will always be present but drugs can hold the trigger in check.

Despite the neurologist's sugaring of the pill, I was literally shaking as Donal and I sat in his office. I was petrified. A tumour alert is less a diagnosis than an event - it is the end of one way of living and the beginning of a new lifestyle.

The first thing I did was return to my GP, who prescribed a short course of antidepressants to help me get through the day without being dragged down.

While I was dealing with my health issues, Donal was working for channel Five on a number of projects that required him, as ever, to spend a lot of time away from home. I wanted him around and he wanted to give up work and stay at home but, on the other hand, he had to earn a living and life has to go on.

'Don't imagine this means you can pack in the job and laze around the house watching sport,' I told him. We both knew I was trying to make light of something we were going to have to live with for a long time.

But I wasn't in despair. Donal's great friend and canoeing partner, Alexis Gohar, had lived with a pituitary gland tumour for a decade. His condition was chronic and much more severe than mine but his experience and encouragement gave us a great deal of hope.

Alexis had been a guinea pig for radical treatment at the Endocrine Unit at St George's Hospital in Tooting and although he lost sight in one eye, he remained an excellent canoeist, competing for many years after his diagnosis.

I was sent to see an endocrine specialistat Kingston Hospital in Surrey, just down the road from where Alexis lived.

The specialist told me more about the pituitary gland, a small ovalshaped gland found at the base of the brain, below the optic nerve. It helps control the other glands in the body and releases key hormones that affect growth and other body functions.

Pituitary gland tumours are mostly benign but they can grow and exert damaging pressure on the brain and the optic nerves. That was what had been affecting my vision, and causing the agonising headaches.

The tumour was also interfering with the regulating hormones that the gland produces, which was what was causing me to lactate.

I was prescribed a drug called bromocriptine to stabilise my tumour and to inhibit the production of excess hormones.

Researching this medication on the internet, Donal was fascinated to discover-that some men had used it for what one website delicately termed 'sexual enhancement'.

'Your wife's got a brain tumour and you've got one thing on your mind,' I scolded him.
Bromocriptine was a lifesaver. Within months, my symptoms were reduced. Soon the good days out-numbered the bad.

The deterioration of my eyesight was halted and after eight weeks my vision was back to normal. I returned to being a size six. Furthermore, because the treatment worked I escaped having to undergo radio or chemotherapy.

Finally one evening, I realised I had gone the whole day without a headache. I broke down and wept tears of relief.

At the same time, lactation ceased. And there was a wonderful 'side effect'. The consultant had said that the treatment might help with ovulation and could even help me conceive. And that's exactly what it did. The result is our gorgeous two-year-old girl, Tiger.

When I became pregnant, the consultant suggested I come off the drugs. The after-effect of the initial treatment kept the symptoms at bay but now, after two years without the drugs, some problems have returned.

My headaches are back and my periods have become irregular again. I recently put on some weight, just like before.

This has meant more scans and clinics with the endocrinologist and the neurologist.
Last time, these appointments gave me nightmares. This time I have been feeling much more confident and I am facing my uncertain future with fortitude, or endeavouring to at least.

We had been trying for another child without success and had considered IVF but that was on hold until we got the results of my most recent tests. They reaffirmed the previous condition and I am now back on the same medication and treatment.

Tragically, our friend Alexis was not so fortunate as I have been. He had what is called transsphenoidal surgery for his tumour - usually carried out by making a small incision on the inside of the roof of the nose or by making a small opening under the lip to be able to reach the pituitary gland. The singer Russell Watson underwent the same procedure to have a tumour 'the size of two golf balls' removed.

But Alexis didn't make it. He died last November at the age of just 46. His untimely death really brought home to Donal and me just what we are up against.

As a family we have now recalibrated our priorities. Wherever Donal works around the world, he tries to bring the children --school allowing - and me.

The world of television has never been particularly family friendly but we have decided to make the work fit around us, rather than vice versa.

It was me who decided - very much against Donal's will - that he should do the ITV show Dancing On Ice earlier this year, as I knew it would give him a chance to spend more time with me and the kids.

I don't think I've ever seen a man pushed so far outside his comfort zone, although he quickly grew to love it.

A tumour can change your life, and the lives of those around you, in ways you don't anticipate.

All the time Dancing On Ice was on air I was managing my reacquaintance with my old symptoms. At one stage during the last few weeks of the show, Donal considered dropping out to concentrate on looking after me but I wouldn't let him entertain the idea of quitting. It was a family experience we all shared and enjoyed, from baby Tiger to Allegra. Tiger would even hug the TV screen when Daddy appeared.

Because of my illness, Donal and I have become more spiritual. Donal is not particularly religious but he has always accepted that his Catholic heritage and Christian values are embedded in his DNA. In a way, he views religion as a celestial insurance policy - Pascal's Wager, the philosophers call it, after the French thinker who argued that there was much to gain and nothing to lose from believing in God.

I hesitate to say we have renewed faith, but we have decided to baptise the children into the Church. My family, who are Muslim, understand that we have to do what we feel is right for us. I am determined to be christened at the same time as the children.

Just recently Donal was attacked by thugs in a wine bar in Surrey. I was with him, having earlier in the day undergone another brain scan. I was punched and kicked during the attack and actually ended up with more bruises than my husband. But we're used to living with this kind of threat and now we are learning to cope with a different kind of danger.

My illness has changed us in ways we never expected - the arrival of Tiger, new directions in Donal's own career, a shift in our life philosophy. Surprisingly, the changes are almost all for the better. We know we will get through this. 

Centre for hormone production that's the size of a pea

The pea-sized pituitary gland sits in the centre of the brain, just above the back of the nose. It is linked by a stem to the hypothalamus and both are vital in producing essential hormones for the growth and functions of other glands in the body.

The most common problem with the pituitary is when a benign tumour develops. 

There are nearly 100 different types of brain tumour and about ten per cent of these are in the pituitary gland. More common in older people, they grow slowly and do not spread to other parts of the body.

There are six types of pituitary tumour, from tumours that produce growth hormones (which can cause acromegaly or gigantism) to prolactin-producing tumours (where the hormone stimulates a woman to lactate and disrupts her menstrual cycle).

Symptoms can also include headaches and visual problems caused by the tumour pressing on the optic nerve.

Treatment ranges from surgery to radiation therapy and drug therapy.

Read more: http://www.dailymail.co.uk/health/article-1205178/Now-I-know-feels-like-gun-held-head-Ameera-MacIntyres-battle-brain-tumour.html#ixzz0Nh9gw5SP

Addison's CD

This looks like this might be good for those of us with secondary Addison's, too!
 

2009 Conquering Addison's Disease - The Emp...
by PM Medical Health News
$25.00

This up-to-date and comprehensive set of two CD-ROM discs provides a superb collection of official Federal government documents on the subject of Addison's Disease. Your adrenal glands are just above your kidneys. The outside layer of these glands makes hormones that help your body respond to stress and regulate your blood pressure and water and salt balance. Addison's disease occurs if the adrenal glands don't make enough of these hormones. For patients, practical information is provided in clearly written patient education documents. For medical professionals, doctor reference tools and texts have detailed technical information and clinical background material. There is no other reference that is as fast, convenient, and portable - everything you need to know, from the federal sources you trust. This thoroughly researched collection presents vital information from many authoritative sources: Food and Drug Administration (FDA), Centers for Disease Control (CDC), National Institutes of Health (NIH) and the relevant institute for this disease, and others. In addition to the comprehensive disease-specific coverage, this disc set also includes our Medical Encyclopedia, a $19.95 value! The Encyclopedia presents a collection of official documents about a wide range of medical topics, diseases, illnesses, health and wellness. There is vital information from the National Institutes of Health (NIH), the Centers for Disease Control (CDC), National Cancer Institute, and more. Topics covered include: major diseases, including cancer, heart and vascular disease, stroke, blood diseases and disorders, lung diseases, and neurological disorders such as dementia and epilepsy * CDC Health Topics A to Z, Foodborne Illnesses, Infants and Children, Injuries, Occupational Health, Older Adults, Women * CDC Travelers' Health - Destinations, Vaccinations, Diseases, Mosquito, Tick, Food, Water, Clinics, Yellow Book, Children, Airplanes, Cruise Ships, Special Needs, Relief Workers, * Dietary Guidelines * NIH A to Z from abnormalities to X-rays. Since navigating the Internet to find additional non-governmental medical information can be confusing, we've also provided our exclusive "Guide to Leading Medical Websites" with updated links to 67 of the best sites for medical information! Built-in weblinks let you quickly check for the latest clinical updates directly from the government and the best commercial portals, news sites, reference/textbook/non-commercial portals, and health organizations.

This CD-ROM set has tens of thousands of pages reproduced using Adobe Acrobat PDF software. Advanced search and indexing features of the current version of Adobe Reader provide a complete full-text index. This enables the user to search all the files on the disc at one time for words or phrases using just one search command! The Acrobat cataloging technology adds enormous value and uncommon functionality to this impressive collection of medical documents and material. Our CD-ROMs are privately-compiled collections of official public domain U.S. government files and documents - they are not produced by the federal government. They are designed to provide a convenient user-friendly reference work, utilizing the benefits of the Acrobat format to uniformly present thousands of pages that can be rapidly reviewed or printed without untold hours of tedious searching and downloading. This book-on-a-disc makes a superb reference work and educational tool for patients and their families, physicians, and other medical professionals. (Information on this CD-ROM product is not a substitute for professional medical advice; of course, readers are urged to consult with a professional health care provider for any suspected illness.)

Pituitary Awareness Week

Pituitary Awareness Week takes place during the week of 20-26 September 2009. Lynda Lloyd, a volunteer for the Pituitary Foundation, has succeeded in securing a place on the plinth in Trafalgar Square to mark Pituitary Awareness Week. The plinth, the empty "Fourth Plinth" in Trafalgar Square, is currently a "living art monument" that will continue 24 hours a day for 100 days. Lynda will be on the plinth, wearing a Pituitary Foundation t-shirt, on Saturday, 26 September 2009 from 11:00 – 12:00. If you are in London or the surrounding area, please go to Trafalgar Square and give Lynda some support. For those of you not close to London, you can watch Lynda on the plinth live on the web at the link below.

There are plenty of other activities going on during Pituitary Awareness Week. For full details, visit the Pituitary Foundation website below.

Pituitary Foundation

The plinth (live link)

Pituitary Awareness Week 2009
20th – 27th September

 

It’s our 15th Anniversary this year and we have decided to mark this milestone in a big way by letting people know who we are, what we do and what issues matter to our community. Our campaign this year is called:

15 Years - 15,000 Letters - £15,000

and it consists of two stages.  Stage One is to send out Campaign Letters and Stage Two is aimed at raising funds.

Stage One – Campaign Letters

We need the pituitary community to band together and raise their voices (or lift their pens) to let the relevant people know the issues we face and what they can do to help us - so we’re asking you (and your partner, your family, your friends and your colleagues) to send campaign letters during Awareness Week to people who can make an immediate difference.

We have produced seven Campaign Letters to inform different people about important issues:

Pituitary Hydrocortisone Awareness – A&E
Pituitary Hydrocortisone Awareness – Ambulance Service
Promoting the Foundation - endocrinologists
Promoting the Foundation – endocrine nurses
Pituitary Disease Awareness – GPs
Pituitary Disease Awareness – Practice Nurses
Pituitary Disease Awareness - PCTs

All we are asking is for you to personalise the letters and send them to your GP, your GP practice nurse, your local PCT, your local A&E, your local ambulance service, your Endocrinologist, and your endocrine nurses.

Our aim is to send 15,000 letters and, once Awareness Week starts, we will be asking you all to let us know how many letters you have sent and we will publish a running total on our web site.

You will not be able to download the Campaign Letters until closer to the start of Awareness Week but you can download the Campaign Letters Guidelines now – this will enable you to plan your campaign and ensure that you mark the important dates on your calendar!

Download the Campaign Letter Guidelines.pdf (462 KB)

CAMPAIGN LETTERS CAN NOW BE DOWNLOADED !!

The seven Awareness Week Campaign Letters are now available for you to download.  Please remember, do not send out any letters until the start of Awareness Week (20th September).  Please send as many letters as you can and let us make this year's Awareness Week something special.  Thank You.

A&E letter.doc (24.00 KB)

Ambulance letter.doc (23.00 KB)

Endo Nurse letter.doc (29.00 KB)

Endocrinologists letter.doc (28.50 KB)

GP letter.doc (24.00 KB)

PCT letter.doc (28.50 KB)

Practice Nurse letter.doc (28.00 KB)

Stage Two – Organising Events to Raise Funds

Following the success last year of the Strawberry Line Walk (the walk between Yatton and Cheddar) we are organising it again this year but we really want to encourage you to organise local events to raise money for The Foundation – our target is £15,000.

Walks already arranged:

• The 3rd Annual Strawberry Line Walk (this year, Yatton to Winscombe) – 26 September. Registration and Sponsor Forms are now available to download - please click here.
• Cambridge Walk – Sunday 20th September (see Cambridge Group page for details)
• Derby/Nottingham Walk – Date TBC
• Aberdeen Walk – 20th September
• Liverpool - Walk Around Albert Dock on Liverpool Waterfront - Saturday 26th September
• Central Lancs - a 3-mile walk starting at Glasson Dock and ending with a pub lunch!  Saturday 19th September at 10.30am
• Aberdeen - Duthie Park, Sunday 20th September (click here for full details)
• Cardiff - a sponsored walk from Penarth to Cosmeston Park Lakes on Saturday September 26th. Walk between half to 3.5 miles. (Click here for more details)

We need you to do something in your local area

We aren’t asking for your walk to be 25 miles with 200 people participating – you can walk as far as you want with as many (or few) people as can do it with you.  Last year, the Salisbury Group organised a short, easy walk around a local landmark (Old Sarum Castle) and ten walkers raised £2000 between them – if every group could do something like this, we would easily exceed our £15,000 target!
Just get sponsorship to do it (and see if your employer will match it) and let your local paper know what you’re doing and why.

Not into walking?

Then swim, bike, climb, have a coffee morning, hold a quiz, ask friends to dinner but make them pay a tenner – do anything to raise cash and get the word ‘pituitary’ out and about as far as you can.

Be creative!

Not into asking for money?  Then do something like what the Sussex County Local Pituitary Support Group is doing.  They’ve booked awareness days (five of them!) at local shopping centres where they’ll be displaying leaflets and information and having a draw to ‘Name the Lion’ (winner gets the soft toy lion that’s been named).

We’ll provide you with sponsorship forms, example press releases and t-shirts!
[certain conditions apply for t-shirts – see the downloadable guidelines]

Download the Event Guidelines.pdf (545 KB)

Download the Sponsor Form.pdf (472 KB)

Please let us know what you’re doing so we can inform others how they can support you and we can monitor the impact our community is making!

Donations

We have created a dedicated page on the JustGiving website where you can make donations to the Awareness Week campaign (please enter on the Comment line the person/event you are sponsoring).  The 'money thermometer' on the page will let eveyone keep track of the money raised so far. Simply click on the £ button to go to the JustGiving web page:

Don’t ask what The Foundation can do for you…
…do something for yourself and get involved!

Together, we can make a statement, far and wide, loud and clear, to help you along your journey but also to help those who will be diagnosed in the years to come to have a better experience.

For more information or if you are planning a walk or other event:

e-mail helpline@pituitary.org.uk This e-mail address is being protected from spambots. You need JavaScript enabled to view it or phone 0845 450 0376.

 

 

 

To get your campaign letter pack, send an A5 SAE with two second class stamps to:

The Pituitary Foundation
15 Years – 15,000 Letters - £15,000
PO Box 1944
Bristol
BS99 2UB

[please note, we cannot send campaign packs without an SAE]

 

Endocrine Nurse Help Line - extra hours during Awareness Week

We are very pleased to announce that our endocrine nurse, Alison Milne, has offered to provide extended cover as her contribution to Awareness Week - well done Alison, many thanks!

The Nurse Help Line hours during Awareness Week will be:

• Monday 21st - 10am to 12noon; evening cover as normal
• Tuesday 22nd - 10am to 12noon
• Wednesday 23rd - 10am to 12noon
• Thursday 24th - 9am to 1pm (normal cover)
• Friday 25th - 10am to 12noon

Endo News: From isolated growth hormone deficiency to multiple pituitary hormone deficiency: an evolving continuum. A KIMS analysis

Marianne Klose, Bjorn Jonsson, Roger Abs, Vera Popovic, Maria Koltowska-Haggstrom, Bernhard Saller, Ulla Feldt-Rasmussen and Ione Kourides
M Klose, Endocrinology, Rigshospitalet, Copenhagen, 2100, Denmark
B Jonsson, Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
R Abs, Endocrinology, University of Antwerp, Wilrijk, Belgium
V Popovic, Neuroendocrine Unit, Endocrinology, Belgrade, Serbia
M Koltowska-Haggstrom, KIGS/KIMS/ACROSTUDY Medical Outcomes, Pfizer Endocrine Care, Sollentuna, Sweden
B Saller, Endocrine Care, Pfizer Ltd., Tadworth, United Kingdom
U Feldt-Rasmussen, Dept of Endocrinology P, Rigshospitalet, Copenhagen, Denmark
I Kourides, 7Global Endocrine Care, Pfizer Inc, New York, United States

Correspondence: Marianne Klose, Email: MCKlose@hotmail.com

Objective: To describe baseline clinical presentation, treatment effects, and evolution of isolated growth hormone deficiency (iGHD) to multiple pituitary hormone deficiency (MPHD) in adult-onset (AO) GHD.

Design: Observational prospective study.

Methods: Baseline characteristics were recorded in 4110 patients with organic AO-GHD, who were GH naïve prior to entry into KIMS (Pfizer International Metabolic Database)(283 (7%) iGHD, 3827 MPHD). The effect of GH replacement after two years was assessed in those with available follow-up data (133 iGHD, 2207 MPHD), and development of new deficiencies in those with available data on concomitant medication (165 iGHD, 3006 MPHD).

Results: iGHD and MPHD patients had similar baseline clinical presentation, and both groups responded similarly to 2 years of GH therapy, with favourable changes in lipid profile and improved QoL.

New deficiencies were observed in 35% of iGHD patients, which was similar to MPHD patients with one additional deficit other than GH. New deficiencies most often presented within the first year but were observed up to 6 years after GH commencement. Conversion of iGHD into MPHD was not predicted by etiology, baseline characteristics, surgery or radiotherapy, whereas in MPHD additional deficits was predicted by age (p<0.001) and pituitary disease duration (p<0.003).

Conclusion: Both AO-iGHD and -MPHD patients have similar baseline clinical presentation and respond equally well to 2 yrs of GH replacement. Hypopituitarism in adults seems to be a dynamic condition where new deficiencies can appear years from the initial diagnosis, and careful endocrine follow-up of all hypopituitary patients, including those with iGHD, is warranted.

Endo News: Disordered and Increased Adrenocorticotropin Secretion with Diminished Adrenocorticotropin Potency in Obese in Premenopausal Women

Ferdinand Roelfsema, Petra Kok, Marijke Frolich, Alberto M. Pereira and Hanno Pijl
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, 2333ZA Leiden, The Netherlands
Address all correspondence and requests for reprints to: Dr. Ferdinand Roelfsema, Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, The Netherlands. E-mail: f.roelfsema@lumc.nl.
 
Context: The pituitary-adrenal ensemble of obese humans is marked by increased urinary excretion of cortisol and its metabolites in the face of normal circulating cortisol levels. For better understanding of the (patho) physiological meaning of these changes, the mechanistic underpinnings need to be clarified.
 
Intervention and Methods: We investigated 17 obese women [body mass index (BMI) 30–39.4 kg/m2] and 14 normal women (BMI, 18.3–24.8 kg/m2) who underwent 24-h blood sampling at 10-min intervals, and plasma ACTH and cortisol concentrations were measured with sensitive assays. Data were analyzed with a new deconvolution program, approximate entropy (ApEn) analyses, and cosinor regression.
 
Outcome: ACTH and cortisol production rates were higher in obese women than in controls and correlated with BMI. Secretion of ACTH correlated with leptin (R = 0.63; P = 0.0001) and insulin (R = 0.67; P = 0.0001). ACTH ApEn and forward ACTH-cortisol cross-ApEn were diminished in obese women. The half-maximal effective concentration (ED50) of ACTH pulses vs. cortisol pulses was higher in obese women (38.3 ± 4.9 vs. 25.1 ± 3.7 ng/liter; P = 0.03), indicating decreased potency of ACTH. The diurnal properties of ACTH and cortisol secretion were unchanged in obese females.
 
Conclusion: Obese women exhibit enhanced ACTH and cortisol 24-h production compared with lean controls. The amplified ACTH drive is accompanied by decreased secretory regularity and diminished forward coupling between ACTH and cortisol. In addition, the potency of ACTH is decreased in obesity.

Endo News: Hypercoagulable State in Cushing’s Syndrome: A Systematic Review

Bregje Van Zaane, Erfan Nur, Alessandro Squizzato, Olaf M. Dekkers, Marcel (Th) B. Twickler, Eric Fliers, Victor E. A. Gerdes, Harry R. Büller and Dees P. M. Brandjes
Department of Internal Medicine (B.V.Z., E.N., V.E.A.G., D.P.M.B.), Slotervaart Hospital, 1066 EC Amsterdam, The Netherlands; Department of Vascular Medicine (B.V.Z., A.S., M.B.T., V.E.A.G., H.R.B.), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; Department of Clinical Medicine (A.S.), University of Insubria, 21100 Varese, Italy; Departments of Clinical Epidemiology (O.M.D.) and Endocrinology and Metabolic Diseases (O.M.D.), Leiden University Medical Center, 2333 ZA Leiden, The Netherlands; and Department of Endocrinology and Metabolism (E.F.), Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Address all correspondence and requests for reprints to: B. Van Zaane, Department of Internal Medicine, Slotervaart Hospital, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. E-mail: b.vanzaane@amc.uva.nl.

Context: It has been debated whether an increased risk of venous thromboembolism (VTE) exists in patients with Cushing’s syndrome.

Objective: We aimed to summarize published literature on the effects of endogenous hypercortisolism on coagulation and fibrinolysis, as well as on the clinical outcome of VTE.

Data Sources: We searched the MEDLINE and EMBASE databases up to July 2008. Review of reference lists further identified candidate studies.

Study Selection: Two investigators independently performed study selection and data extraction. Eligible studies had to include Cushing’s syndrome patients and either evaluate hemostatic parameters in comparison with control persons or posttreatment levels or describe the occurrence of VTE.

Data Extraction: The Newcastle-Ottawa Scale was used to assess study quality. A scoring system divided studies into categories of low, medium and high quality.

Data Synthesis: Of 441 identified publications, 15 reports were included. They contained information on eight cross-sectionals, two intervention, and eight cohort studies. No high-quality studies were identified. Hypercoagulability was suggested by high levels of factor VIII, factor IX, and von Willebrand factor and by evidence of enhanced thrombin generation. A risk of 1.9 and 2.5% was reported for VTE not provoked by surgery, whereas risk of postoperative VTE varied between 0 and 5.6%, with one outlier of 20%. VTE was reported as the cause of death in 0–1.9% of Cushing’s syndrome patients.

Conclusions: Available studies suggest a high risk of venous thrombosis in patients with Cushing’s syndrome. Glucocorticoid-induced hypercoagulability as well as surgery and obesity almost certainly contribute to this thrombotic tendency.

Endo News: Diminished and irregular thyrotropin secretion with delayed acrophase in patients with Cushing’s syndrome

F Roelfsema, A Pereira, N Biermasz, Marijke Frölich, Daniel Keenan, Johannes Veldhuis and J Romijn
F Roelfsema, Endocrinology and Metabolism, Leiden University Medical Center, Leiden, 2333ZA, Netherlands
A Pereira, Endocrinology and Metabolism, Leiden University Medical Center, Leiden, Netherlands
N Biermasz, Endocrinology and Metabolism, Leiden University Medical Center, Leiden, Netherlands
M Frölich, Endocrinology and Metabolism, Leiden University Medical Center, Leiden, Netherlands
D Keenan, Statistics, University of Virginia, Charlottesville, United States
J Veldhuis, Endocrine Research Unit, Mayo Clinic, Rochester, United States
J Romijn, Department of Endocrinology, C4-R, Leiden University Medical Center, Leiden, 2300 RC, Netherlands

Correspondence: F Roelfsema, Email: f.roelfsema@lumc.nl

Abstract

Context. The hypothalamo-pituitary-thyroid axis in Cushing’ syndrome may be altered.

Objective. We analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (n=16) or primary-adrenal origin (n=11) and after remission by pituitary surgery (n=7) in order to delineate aberrations in the hypothalamo-pituitary-thyroid system.

Intervention. Patients and controls (n=27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods and data were analyzed with a deconvolution program, approximate entropy (ApEn) and cosinor regression.

Results. Pulsatile TSH secretion, and mean TSH pulse mass, were diminished during hypercortisolism, independently of etiology (P<0.001). TSH secretion was increased in patients in remission only during day-time due to increased basal secretion (P<0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P<0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern-synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase-delayed in hypercortisolemic patients, but normal in cured patients (P<0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (P=0.003). Total 24-h TSH correlated negatively and linearly with log-transformed cortisol secretion (R=0.43, P=0.001).
 
Conclusion: Cortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated non-pulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic / annexin-1 control.

Endo News: Growth hormone replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies

Helena Filipsson and Gudmundur Johannsson

H Filipsson, Endocrinology, Göteborg, Sweden
G Johannsson, Endocrinology, Medicin, Gothenburg, SE-413 45, Sweden

Correspondence: Gudmundur Johannsson, Email: gudmundur.johannsson@gu.se

Severe growth hormone deficiency (GHD) in adults has been described as a clinical entity. Some of the features associated with GHD could, however, be due to unphysiological and inadequate replacement of other pituitary hormone deficiencies. This may be true for glucocorticoid replacement that lacks a biomarker making dose titration and monitoring difficult.

Moreover, oral oestrogen replacement therapy decreases insulin growth factor 1 (IGF-I) levels compared to transdermal route, which attenuates the responsiveness to GH replacement therapy in women. In addition, in untreated female hypogonadism, oral oestrogen may augment the features associated with GHD in adult women. Important interactions between the hormones used for replacing pituitary hormone deficiency occur. Introducing GH replacement may unmask both an incipient adrenal insufficiency and central hypothyroidism.

Therefore, awareness and proper monitoring of these hormonal interactions are important in order to reach an optimal replacement therapy. This review will focus on the complex hormonal interactions between GH and other pituitary hormones in GHD and in GH replacement.

Endo News: Temozolomide treatment of a pituitary carcinoma and two pituitary macroadenomas resistant to conventional therapy

Casper Hagen, Henrik Schroeder, Steinbjorn Hansen, Claus Hagen and Marianne Andersen
C Hagen, Department of Endocrinology, Odense University Hospital, Odense C, Denmark
H Schroeder, Department of Pathology, Odense University Hospital, Odense C, Denmark
S Hansen, Department of Oncology, Odense University Hospital, Odense C, Denmark
C Hagen, Department of Endocrinology, Odense University Hospital, Odense C, Denmark
M Andersen, Department of Endocrinology, Odense University Hospital, Odense C, Denmark
Correspondence: Casper Hagen, Email: casperhagen@gmail.com
Abstract

OBJECTIVE: Aggressive pituitary tumours may be difficult to treat. Temozolomide (TMZ) is an alkylating cytostaticum. In a small number of cases, TMZ therapy has been reported to reduce pituitary tumour size and hormone hypersecretion.

DESIGN: We present three patients with pituitary tumours treated with TMZ. One tumour was initially a macroprolactinoma that developed into a mixed GH and PRL- secreting carcinoma (patient A). To our knowledge, this is the first published in English literature. Two adenomas, a macroprolactinoma (patient B) and a clinically non-functioning pituitary adenoma (NFA) (patient C), were highly invasive. The three patients suffered from extensive tumour mass effects, and all tumours were resistant to conventional treatment.

METHOD: TMZ, 150-200 mg/m2 of body surface area was administered orally for 5 days during each 28 day cycle.

RESULT: During TMZ therapy, tumour sizes were significantly reduced, hormone levels normalized, and symptoms of mass effects decreased in all three cases. The carcinoma was treated from 2004 to 2006 (23 months). 3 years after terminating treatment, tumour has not regrown and hormone levels are normalized. Immunohistochemical staining for methylguanine DNA methyltransferase (MGMT) was negative in two patients (A and B), and in one patient (C) a few nuclei stained positive.

CONCLUSION: TMZ therapy significantly decreased tumour volume, hormone hypersecretion and symptoms in all three patients, corresponding to the pathological findings regarding MGMT. TMZ therapy may be a new option for the treatment of resistant pituitary adenomas.

In This Issue

Welcome to the latest Cushing's Newsletter!

Cushie Bloggers

Upcoming Interviews

Upcoming Meetings

Upcoming Cushing's Book

Cushing's on Facebook and Twitter

In Memory: Leader of OSU campus ministry dies at 49

Want to Volunteer?

Help Keep The Cushing's Sites Going

Adrenal Glands

Now I know what it feels like to have a gun held to my own head: Ameera MacIntyre's battle with a brain tumour

Addison's CD

Pituitary Awareness Week

Endo News: From isolated growth hormone deficiency to multiple pituitary hormone deficiency: an evolving continuum. A KIMS analysis

Endo News: Disordered and Increased Adrenocorticotropin Secretion with Diminished Adrenocorticotropin Potency in Obese in Premenopausal Women

Endo News: Hypercoagulable State in Cushing’s Syndrome: A Systematic Review

Endo News: Diminished and irregular thyrotropin secretion with delayed acrophase in patients with Cushing’s syndrome

Endo News: Growth hormone replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies

Endo News: Temozolomide treatment of a pituitary carcinoma and two pituitary macroadenomas resistant to conventional therapy