Investigational drugs may expand medical treatment of Cushing’s syndrome

We Cushies hope that in 2012, we will see success as more patients to try these drugs. 

As you know, my pituitary continues to produce excess ACTH, a hormone that causes my Cushing's. Even after two tumors were removed during two pituitary surgeries, abnormal cells persist. Medication may be a real possibility for Cushies like me. If medication can stop this ACTH production, there will be no need for a life-changing bilateral adrenalectomy (BLA).  Click here to see the December 2011 cover story for Endocrine Today.

Investigational drugs may expand medical treatment of Cushing’s syndrome

Endocrinologists face many challenges when treating patients with Cushing’s syndrome. Diagnosis can be difficult because many of the disease’s characteristics, such as obesity, depression and hypertension, are also common in the general population. Treating the disease presents hurdles as well. With its potential for total cure, transsphenoidal surgery remains the first-line treatment. However, the problems of achieving permanent remission in all cases demonstrate the need for medical therapies for this condition. Laurence Katznelson, MD, of Stanford University, Hospital and Clinics, said pasireotide could possibly prevent pituitary tumor growth and promote tumor shrinkage in patients with Cushing’s syndrome. Photo by: Steve Gladfelter, Visual Arts at Stanford University Currently, endocrinologists use several medical therapies to treat hypercortisolism, although none have FDA approval for that particular indication. Two new investigational drugs — mifepristone (Korlym, Corcept Therapeutics) and pasireotide (SOM230, Novartis) — have the potential to meet those unmet needs, according to experts interviewed by Endocrine Today. “Recently completed research studies, which involved innovative medical therapeutic strategies that target the corticotroph adenoma itself or block the effects of cortisol in the periphery, should bring new treatment options in the future,” Maria Fleseriu, MD, associate professor, director of the Northwest Pituitary Center at Oregon Health & Science University, said in an interview. Manufacturers of both new medications have submitted new drug applications to the FDA. Corcept expects to hear from the FDA on Feb. 17, according to a spokesperson for the company. Mifepristone has a unique mode of action in that it blocks the cortisol receptor, Robert L. Roe, MD, president of Corcept Therapeutics, said in an interview. “With that receptor blocked, many of the problems associated with Cushing’s syndrome can be greatly improved, including: obesity, diabetes, insulin resistance, high blood pressure, quality of life and depression,” Roe said. The SEISMIC trial, a 24-week, multicenter, open-label study, included 50 patients with persistent or recurring Cushing’s disease, metastatic adrenal cortical carcinoma or ectopic adrenocorticotropic hormone (ACTH) syndrome that was not amenable to surgery, according to Fleseriu, who was an investigator on the study. There were two primary endpoints: blood sugar improvement in patients with glucose intolerance and an improvement in BP in patients with a diagnosis of hypertension but without abnormal blood sugar levels. The key secondary endpoint looked for global clinical improvement as determined by a three-member independent data review board. Results from the phase 3 study showed that, overall, mifepristone yielded significant clinical and metabolic improvement in patients with refractory Cushing’s syndrome, Fleseriu said. Of the glucose-intolerant patients, 60% responded, and BP improved in 38% of patients. The global clinical endpoint was positive in 87% of patients, Roe said. Maria Fleseriu “In addition, out of 34 patients who completed the main study, 30 elected to continue in the long-term extension study,” Fleseriu said. She said mifepristone “offers a new approach for the treatment of Cushing’s syndrome that [has] failed other therapies. Keeping in mind that biochemical parameters will not be available for monitoring these patients, close clinical observation is recommended.” Yet, there are aspects of mifepristone that are still unknown. “There will be a learning curve with this drug on how to dose it and use it properly to get a good response,” said James Findling, MD, professor of medicine, Endocrinology Center and Clinics, Medical College of Wisconsin, Milwaukee, who was the principal investigator of the study. James Findling Also on the horizon is the investigational agent pasireotide, a multiligand somatostatin analogue with a high affinity for the somatostatin receptor type 5, which is often expressed by corticotroph adenomas in Cushing’s disease. Pasireotide blocks the secretions from ACTH-secreting pituitary tumors. “Pasireotide works by attacking the pituitary tumor to reduce the ACTH level,” according to Laurence Katznelson, MD, professor of medicine and neurosurgery at Stanford University and medical director of the pituitary program at Stanford Hospital and Clinics. “Possibly, this drug could prevent tumor growth or lead to tumor shrinkage, although we await data to support that.” Results of the multicenter, phase 3 PASPORT-CUSHINGS trial, presented at the Endocrine Society’s 93rd Annual Meeting & Expo in June, included 162 patients with persistent/recurrent or newly diagnosed Cushing’s disease who were ineligible for surgery. Researchers randomly assigned participants to receive twice-daily subcutaneous pasireotide injections of 600 mcg or 900 mcg. The primary endpoint was urinary-free cortisol levels at 6 months without dose up-titration. Of the patients in the 900-mcg dose group, 26.3% had normal urinary-free cortisol levels at 6 months; at 12 months, 25% maintained normal levels. The median reduction from baseline in urine-free cortisol after 6 months of treatment was 47.9% for both dose groups. The researchers noted significant clinical benefit in most patients, including lower BP and total cholesterol, as well as weight loss, Fleseriu said. “It is noteworthy that while urinary-free cortisol normalization was seen in just a subset of patients, the rate of normalization was higher in patients with lower baseline urinary-free cortisol, making it, in my opinion, an attractive treatment for patients with mild elevations in urinary-free cortisol,” Fleseriu, who was also an investigator for this trial, told Endocrine Today. Pasireotide was well tolerated in the studies, she added. “Adverse events were comparable to the other somatostatin analogues, with the exception of a much higher incidence of hyperglycemia,” Fleseriu said. “Patients treated with this drug will require strict monitoring and prompt treatment of hyperglycemia.” The reasons for hyperglycemia are related to inhibition of insulin release from the pancreas by this multiligand somatostatin analogue. The type 5 receptor is abundant on pancreatic insulin secreting cells of the pancreas. Timely diagnosis, treatment critical Cushing’s syndrome is the result of chronic exposure to high levels of cortisol. Cortisol, typically released in stressful situations, controls how the body uses carbohydrates, fats and proteins. In addition, it helps decrease the immune system’s response to inflammation. Untreated, Cushing’s syndrome can have serious consequences, including significant mortality and morbidity. Timely diagnosis and appropriate treatment are critical for this rare disorder, according to Fleseriu, who is also associate professor of medicine/endocrinology and neurological surgery at Oregon Health & Science University. The endocrinologist uses the following tests to diagnose the disorder: 24-hour urinary-free cortisol levels; late-night salivary cortisol measurements; and low-dose dexamethasone suppression test. After making the diagnosis of hypercortisolism, the next step is to determine the cause of excess cortisol secretion. There are several tests available for this purpose: corticotropin-releasing hormone (CRH) simulation test; direct radiologic visualization of the pituitary and adrenal glands; and inferior petrosal sinus sampling for ACTH. The most common cause is long-term synthetic steroid use to treat inflammatory illnesses such as asthma or rheumatoid arthritis, according to Katznelson. In these cases, gradually reduction of the glucocorticoid will reverse the disorder. Another cause is an ACTH-secreting pituitary adenoma. The excess stimulates the adrenals to produce and secrete excess cortisol release, Katznelson said. This is also known as Cushing’s disease. Pituitary adenomas are responsible for 70% of Cushing’s syndrome cases, according to information from the National Institute of Diabetes and Digestive and Kidney Diseases. Surgery is first-line treatment John Carmichael First-line therapy for Cushing’s disease is transsphenoidal adenomectomy, in which the surgeon approaches the pituitary through the nose and, using either a microscope or endoscope by trained neurosurgeons, according to John Carmichael, MD, assistant professor of medicine, The Pituitary Center, Cedars-Sinai Medical Center, Los Angeles. The procedure boasts an excellent cure rate. “In good hands, with a small tumor, you can get cure rates of about 85%,” Carmichael said. “It depends on a number of factors: the skill of the surgeon, the size of the tumor and the level of invasiveness.” If surgery is curative, the patient will require cortisol replacement. “Once you remove the tumor, the normal tissue has been suppressed by the activity of the tumor for so long that it takes a long time for patients to recover and start making cortisol on their own,” Carmichael said. “It can take as long as 6 to 12 months for patients to completely recover their normal cortisol secretion once they’ve been cured.” David M. Cook However, the surgery is associated with risks, including bleeding and infection, although they are “pretty rare,” according to Carmichael. One of the most common risks is a pituitary injury that can cause diabetes insipidus, which is almost always transient. Other postoperative problems include possible cerebrospinal fluid leaks and the possibility of recurrence, said David M. Cook, MD, an endocrinologist in the department of medicine, Oregon Health & Sciences University. Sometimes the tumor is hard to find during the first surgery, Katznelson said. “The problem is, in 40% to 50% of patients who have Cushing’s disease, the tumor is very small, if not almost invisible, on the MRI scan,” he said. As a result, the surgeon may remove normal gland or possibly the entire pituitary, resulting in hypopituitarism. The patient would require hormone replacement and would still have Cushing’s syndrome. Radiation is a possible treatment for these cases. “The role of radiation is in the patient who has already had surgery for Cushing’s syndrome. The tumor is visible but cannot be completely removed. Radiation is most useful when there is a target to irradiate,” Katznelson said, adding that even in these cases, radiation cannot promise 100% efficacy. Unfortunately, radiation takes a significant amount of time to work. “People are a little reluctant to use radiation because it takes years to help,” Cook said. “It is not curative and patients can relapse from radiation also; it is not foolproof.” Ectopic ACTH syndrome Sometimes, tumors located outside the pituitary can produce ACTH, resulting in the ectopic ACTH syndrome. The tumors are usually malignant. In more than half of the cases, the tumors are found in the lungs, according to information from the NIDDK. “You would need surgery in that location to get rid of the tumor,” Carmichael said. If an adrenal tumor is stimulating an overabundance of cortisol, the definitive cure is adrenalectomy. “If we do adrenalectomy, all of the [symptoms of] Cushing’s syndrome go away, but the primary pituitary tumor, which may have been microscopic, can start to become more aggressive and grow and become more difficult to treat in the long run,” Katznelson said. “That is Nelson’s syndrome.” The adrenal insufficiency that follows adrenalectomy is serious, Cook said. “It is dangerous to not have your adrenals; it is the most dangerous disease that endocrinologists treat,” he said. “A number of sudden deaths have been reported in patients without adrenals.” Katznelson also said that managing these patients can be challenging. “Management of primary adrenal insufficiency is sometimes difficult, because not only does the patient lack cortisol, but will also lack aldosterone, which is important for maintaining electrolytes and volume status,” he said. “Patients often find it quite challenging to manage primary adrenal insufficiency.” Medical therapies for Cushing’s syndrome Besides surgery and radiation, endocrinologists can use several medical therapies to treat Cushing’s syndrome; however, to date, none has obtained FDA approval to treat the disorder. The medical treatment used most often in the United States is ketoconazole, an antifungal agent that blocks the enzymes in the adrenal glands that produce steroids, Findling toldEndocrine Today. Ketoconazole, administered two to three times daily, is generally successful. “It is an effective therapy,” Findling said. “Probably 50% to 70% of patients will have a response.” However, this drug is not the optimal choice for long-term use. “Ketoconazole has been associated with some toxicity; liver function abnormalities can occur and, in fact, liver failure can occur,” he said. Another medical treatment option is mitotane (Lysodren, Bristol-Myers Squibb), which blocks adrenal steroid enzymes, Findling said. This toxic agent takes considerable time to work; in fact, it may require roughly 3 or 4 months for cortisol levels to normalize. It is used rarely in the United States. “Mitotane has a limited future as a therapy for Cushing’s syndrome, except for in patients who have adrenal cancer, at least in the US,” Findling said. Metyrapone (Metopirone, Novartis), another agent, effectively blocks adrenal steroid enzymes; however, it is not commercially available in the United States, Findling said. Etomidate is an anesthetic agent that also inhibits adrenal steroidogenesis and is employed successfully in patients with very severe hypercortisolism who are not ready for surgery. “If etomidate were available in a pill, it would be an excellent medical treatment for Cushing’s syndrome,” Findling said. “With subhypnotic doses, etomidate lowers the cortisol level smoothly down into the normal range. … It is well tolerated, but has to be given as a continuous IV infusion, so it is not practical.” All of these medications have severe adverse effect profiles, according to Carmichael. No replacement for surgery … yet Although mifepristone and pasireotide show some promise as treatments for Cushing’s syndrome, it is not time to put the scalpels in storage, the experts said. “Neither of these drugs, at least for the foreseeable future, will replace surgical treatment of Cushing’s syndrome,” Findling said. “Like most disorders, if you have a surgical procedure that will resolve the endocrinopathy and restore normal hormonal function, it is usually the treatment of choice.” However, these medications are a welcome addition to the armamentarium, Carmichael said. “It remains to be seen exactly what their place will be and how they will be best used. But, certainly, in cases where surgery is not an option or where you need to control the disease in someone who has very severe disease, they would have a role,” he said. Currently, Carmichael sees medical therapy as an adjuvant treatment, which would follow surgery if it was not curative. Also, endocrinologists may use them in place of surgery if surgery was not an option. “There is a lot more room for work,” Carmichael said. “The ideal paradigm of having a medication that is safe and controls the disease and in a sense would replace surgery would be an ideal goal, but we are certainly not there yet.”– by Colleen Owens For more information: Colao A. OR09-6. Presented at: The Endocrine Society 93rd Annual Meeting & Expo; June 4-7, 2011; Boston. Fleseriu M. [OR09-5] Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with refractory Cushing syndrome: results from the Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing Syndrome (SEISMIC). Presented at: The Endocrine Society 93rd Annual Meeting & Expo; June 4-7, 2011; Boston. Gross BA. Neurosurg Focus. 2007;23:E10. National Institute of Neurological Disorders and Stroke. NINDS Cushing’s syndrome information page. Available at:www.ninds.nih.gov/disorders/cushings/cushings.htm. National Endocrine and Metabolic Diseases Information Service. Cushing’s syndrome. Available at:www.endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#causes. Disclosures: Dr. Fleseriu is principal investigator in multiple Cushing’s trials and past consultant for Novartis; she is also the principal investigator on Corcept Cushing’s trials. Dr. Findling is a paid consultant for Corcept Therapeutics. The other doctors in this article did not report any relevant financial disclosures. Which is the most reliable screening method for Cushing’s syndrome? Tests are equally accurate, but have limitations The diagnosis of Cushing’s syndrome is problematic. It is one of the most difficult endocrine diseases to diagnose. Diagnosis includes assessing the symptoms and signs of Cushing’s syndrome because the symptoms and signs overlap with common disorders, including obesity, depression and polycystic ovary syndrome. Many patients consult websites in an attempt to find an explanation for their weight gain, fatigue, depression and other symptoms. They ask frequently after a Web search if their symptoms could be Cushing’s syndrome. Screening tests for Cushing’s syndrome include three different tests: an 11 p.m. or midnight salivary cortisol level; a 24-hour urine free cortisol level; and an 8 a.m. cortisol level after ingestion of 1 mg of dexamethasone at midnight the previous night. How reliable are these tests? They are equally accurate — approximately 90% to 92% reliable, which is actually good for screening tests. However, all three tests have limitations. Results of the nighttime salivary cortisol test are affected by laboratory accuracy (not all laboratories are equally reliable) and sleep patterns. In severe depression cases, the results may be falsely elevated. The 24-hour urine free cortisol test is an indicator of overall cortisol production. The most accurate method of measurement — tandem mass spectrometry with concomitant measurement of urine volume and urine creatinine — provides a good measure. It may take several 24-hour urine collections to confirm hypercortisolism. The 1-mg overnight dexamethasone suppression test is reliable, but with several caveats. The test is standardized according to administering dexamethasone at midnight and measurement of serum cortisol promptly at 8 a.m. the following day. However, while the patient may have gone to the lab at 8 a.m., the blood sample may have been obtained later, which invalidates the test. Additionally, if the patient is taking medications that alter dexamethasone metabolism, the results may not be valid. The endocrinologist must measure a serum dexamethasone level to confirm the validity of the test. The diagnosis of Cushing’s syndrome is dependent upon confirming consistent overproduction of cortisol. The diagnosis may require repeated testing and this should be done in any patient in which there is a suspicion of Cushing’s syndrome. Mary Lee Vance, MD, is professor of medicine and neurosurgery at University of Virginia Health System, Charlottesville, Va. Disclosure: Dr. Vance reports no relevant financial disclosures. Late-night salivary cortisol is best initial test Ty Carroll No test is perfect for all patients. In addition, it is important to remember that some patients will require multiple, different tests to confirm or exclude Cushing’s syndrome. However, that being said, late-night salivary cortisol is the best initial screening for most patients with suspected Cushing’s syndrome. Late-night salivary cortisol is the most specific test for Cushing’s syndrome. The sensitivity and specificity are very good. Multiple studies have examined late night salivary cortisol testing, and the majority of those studies show sensitivity of more than 95% and a specificity in the range of 90% to 100%. That is comparable to — or better than — other methods to diagnose Cushing’s syndrome. Also important to note: It is easy for patients to perform late-night salivary testing. Patients are able to do the collection at home and mail in the completed samples to a reference lab, whereas urinary free cortisol and dexamethasone suppression testing can be difficult for some patients to complete. In addition, for the most part, late-night salivary cortisol is not affected by other medications that patients take, unlike dexamethasone suppression testing, which can be affected by several medications that patients often take to treat other conditions. Ty Carroll, MD, is assistant professor of medicine at Endocrinology Center and Clinics, Menomonee Falls, Wisc. Disclosure: Dr. Carroll is an investigator in Corcept’s clinical trials of mifepristone.

Fatal Infections Linked to Neti Pots

CAUTION CUSHIES.

Many Cushie patients use Neti pots after pituitary surgery to clear the sinuses. They swear by them. But be careful.

http://abcnews.go.com/m/story?id=15170230

"If you are irrigating, flushing or rinsing your sinuses, for example, by using a Neti pot, use distilled, sterile or previously boiled water to make up the irrigation solution," Louisiana State epidemiologist Dr. Raoult Ratard said in a statement. "Tap water is safe for drinking but not for irrigating your nose."

My Friends with Adrenal Insufficiency

     Patients with Cushing's disease and those with Addison's disease face the same bully every day.

     Cortisol is an omnipresent force, always lurking and lingering, so ready to remind you that you do not control your body. The cortisol does.

     Cortisol runs through the bodies of healthy people and continues about its job without notice. Its predictable, daily function is required to sustain life. 

     For those enslaved by the adrenals' whims, it is a constant thorn in your side. You see, Cushie bodies make too much cortisol, while Addisonians make no or insufficient cortisol. While each disease respond differently to the cortisol malfunction, both patient sets deal with the life-threatening risks of adrenal crises.

     Cushies walk in the shoes of their Addi cousins after pituitary surgery (to stop excess cortisol production by renegade ACTH tumors) or adrenal surgery (to remove the cortisol-making once and for all by removing adrenals. Just look what happens when adrenal glands do not respond to signals from the pituitary gland properly.

     Both Cushies and Addis can suffer symptoms of low cortisol and the devastating consequences if these symptoms are not treated in time. 

     What starts as mild adrenal insufficiency can turn into acute adrenal crisis very quickly, putting the patient at risk for shock and sudden death.  Think you can go to a paramedic or hospital for help. Think again. As you may have caught on by now, there is nothing easy... or even FAIR... about Cushing's disease.

• Imagine if the medics in the ambulance didn't know what could save your life.
• Imagine if the medics knew, but the state has laws in place that prevent them from keeping a supply of it in the ambulances.
• Imagine if the medics refuse to administer the Solu-Cortef injectible medication you have with you, along with an adrenal crisis letter from your physician, but too disoriented to give yourself, because of state regulations limiting its availability
• Imagine getting to the hospital only to find emergency room staff ignore both your CRISIS letter from your physician and medical alert bracelets, necklaces, and even tattoos-- all intended to save your life and speak for you when you can not.
• Imagine waiting for hours and hours for your medical team to run enough tests to *believe* you are sick, and then to follow the still squabble over following the protocol outlined in your crisis letter.
• Imagine if the hospital, like the ambulance, does not carry the Solu-Cortef injectable at all, or, insist on giving you a lesser grade of cortisol shot that acts much more slowly and will not bring you out of the near coma you are in or about to fall into, despite clear instructions in the crisis letter
• Imagine your friend or family member getting hauled away by security and thrown out of the hospital for advocating emphatically on your behalf.

THIS JUST CAN NOT CONTINUE TO HAPPEN ** ANY MORE. ** 

     Do you think I may be overdramatizing things?!  Well, I can add a name to every *Imagine* line above, a name of a person who nearly died because solu-cortef and its life-saving formula was kept from them from ambulances and hospitals who are supposed to protect and save them. If you are the prove-it-to-me-one-more-time type, you can read plenty of personal testimonials for yourself.

     Access to Solu-cortef should be as standard in ambulances and ERs as glucagon shots for diabetics. Deaths due to adrenal insufficiency heartbreaking and so preventable. 

     I want to thank the Adrenal Insufficiency United organization for creating the wonderful video below. On behalf of Cushing's patients everywhere, we thank you for their efforts to increase access to Solu-Cortef for all patients with unpredictable or absent cortisol production.

     In addition, a shout out to the CARES Foundation which supports patients with congenital adrenal hyperplasia.  Like the Adrenal Insufficiency United organization, CARES advocates for the widespread availability of Solu Cortef in ambulances and hospitals -- without question -- for any patients who may face low cortisol levels.  

     In light of the dangers presented in this post, it is always best to administer Solu-cortef before you even go for medical help.  The patient or the caregiver must be ready to administer the injection on his/her own.  Here are some instructions to download, so you are prepared to save your life no matter what.

My Friends with Adrenal Insufficiency

     Patients with Cushing's disease and those with Addison's disease face the same bully every day.

     Cortisol is an omnipresent force, always lurking and lingering, so ready to remind you that you do not control your body. The cortisol does.

     Cortisol runs through the bodies of healthy people and continues about its job without notice. Its predictable, daily function is required to sustain life. 

     For those enslaved by the adrenals' whims, it is a constant thorn in your side. You see, Cushie bodies make too much cortisol, while Addisonians make no or insufficient cortisol. While each disease respond differently to the cortisol malfunction, both patient sets deal with the life-threatening risks of adrenal crises.

     Cushies walk in the shoes of their Addi cousins after pituitary surgery (to stop excess cortisol production by renegade ACTH tumors) or adrenal surgery (to remove the cortisol-making once and for all by removing adrenals. Just look what happens when adrenal glands do not respond to signals from the pituitary gland properly.

     Both Cushies and Addis can suffer symptoms of low cortisol and the devastating consequences if these symptoms are not treated in time. 

     What starts as mild adrenal insufficiency can turn into acute adrenal crisis very quickly, putting the patient at risk for shock and sudden death.  Think you can go to a paramedic or hospital for help. Think again. As you may have caught on by now, there is nothing easy... or even FAIR... about Cushing's disease.

• Imagine if the medics in the ambulance didn't know what could save your life.
• Imagine if the medics knew, but the state has laws in place that prevent them from keeping a supply of it in the ambulances.
• Imagine if the medics refuse to administer the Solu-Cortef injectible medication you have with you, along with an adrenal crisis letter from your physician, but too disoriented to give yourself, because of state regulations limiting its availability
• Imagine getting to the hospital only to find emergency room staff ignore both your CRISIS letter from your physician and medical alert bracelets, necklaces, and even tattoos-- all intended to save your life and speak for you when you can not.
• Imagine waiting for hours and hours for your medical team to run enough tests to *believe* you are sick, and then to follow the still squabble over following the protocol outlined in your crisis letter.
• Imagine if the hospital, like the ambulance, does not carry the Solu-Cortef injectable at all, or, insist on giving you a lesser grade of cortisol shot that acts much more slowly and will not bring you out of the near coma you are in or about to fall into, despite clear instructions in the crisis letter
• Imagine your friend or family member getting hauled away by security and thrown out of the hospital for advocating emphatically on your behalf.

THIS JUST CAN NOT CONTINUE TO HAPPEN ** ANY MORE. ** 

     Do you think I may be overdramatizing things?!  Well, I can add a name to every *Imagine* line above, a name of a person who nearly died because solu-cortef and its life-saving formula was kept from them from ambulances and hospitals who are supposed to protect and save them. If you are the prove-it-to-me-one-more-time type, you can read plenty of personal testimonials for yourself.

     Access to Solu-cortef should be as standard in ambulances and ERs as glucagon shots for diabetics. Deaths due to adrenal insufficiency heartbreaking and so preventable. 

     I want to thank the Adrenal Insufficiency United organization for creating the wonderful video below. On behalf of Cushing's patients everywhere, we thank you for their efforts to increase access to Solu-Cortef for all patients with unpredictable or absent cortisol production.

     In addition, a shout out to the CARES Foundation which supports patients with congenital adrenal hyperplasia.  Like the Adrenal Insufficiency United organization, CARES advocates for the widespread availability of Solu Cortef in ambulances and hospitals -- without question -- for any patients who may face low cortisol levels.  

     In light of the dangers presented in this post, it is always best to administer Solu-cortef before you even go for medical help.  The patient or the caregiver must be ready to administer the injection on his/her own.  Here are some instructions to download, so you are prepared to save your life no matter what.

Hope & Stem Cells

Lab-grown hormone factory put to work

http://www.newscientist.com/mobile/article/mg21228384.700-labgrown-hormone-fa...

Pituitary Glands Made from Stem Cells

This is the best news I have heard in a long time.

"Pituitary glands grown from mouse embryonic stem cells

If the same trick can be repeated for human pituitary glands it could transform the treatment of debilitating hormone disorders"

09.11.11 Updated 20.36

Mouse pituitary tissue grown from embryonic stem cells. Fully grown glands produced hormones when transplanted into mice. Photograph: Yoshiki Sasai/RIKEN

David Derbyshire

The Guardian, Wed 9 Nov 2011 18.26 GMT

Scientists have grown working pituitary glands in the lab that could potentially transform the treatment of people with a range of debilitating hormone disorders.

The team of Japanese researchers grew the tiny hormone-secreting organs using stem cells taken from a mouse embryo. When the tissue was transplanted into mice with pituitary gland defects, it raised levels of the missing hormones in their bodies.

Dr Yoshiki Sasai, who led the study at the RIKEN Centre for Developmental Biology in Kobe, Japan, said: "It is difficult to guess how long it will take, but we hope that we can produce human pituitary tissue in the next three years." It would take longer to develop techniques to transplant the cells, he added.

The creation of spare body parts for transplant is one of the goals of stem cell science. Stem cells are the body's "master cells" and can turn into a range of different types of tissue, such as brain, muscle or pancreatic cells.

Any tissue or organs grown from patients' own stem cells would not be rejected by the body, doing away with the need for immunosuppressant drugs.

Pituitary glands – the oval, pea-sized organs at the base of the brain – are a particular challenge for stem cell researchers because they are so complex. They have two distinct parts and secrete at least eight hormones regulating growth, fertility, breast milk production, blood pressure, contractions during childbirth, temperature and water balance.

Using mouse stem cells arranged in a three dimensional culture, Dr Sasai's team mimicked the way pituitary glands develop in the embryo. The resulting tissue contained all five types of cell found in a normal gland and took around three weeks to grow, the scientists report in the journal Nature.

"We have made hundreds of pituitary glands from embryonic stem cells," said Dr Sasai. When the tissue was transplanted into mice with pituitary defects, levels of missing hormones in their bodies rose to normal.

Although the researchers used embryonic stem cells in their experiment, they believe the technique could work with stem cells derived from adult tissue – so-called induced pluripotent stem cells. That would avoid the ethical concerns some people have about using human embryos in research and therapies.

Even if the scientists can grow a human pituitary, they still face major obstacles in creating a safe and efficient way to transplant it, Dr Sasai said. However, he believes lab-grown glands could lead to treatments for growth hormone deficiencies and damage to the pituitary glands caused by surgery and Sheehan's syndrome.

Women with Sheehan's syndrome, which results from blood loss during childbirth, have problems breastfeeding, suffer tiredness, weight gain, constipation, low blood pressure and slowed thinking.

Prof Robin Lovell-Badge, one of Britain's leading stem cell experts at the Medical Research Council's National Institute for Medical Research in London, said: "It is unlikely that these in vitro-derived pituitaries are fully developed and make hormones in precisely the same way as normal.

"However, the fact that they got as far as they did is impressive. It suggests that there is a fair amount of self-organisation, which means that it might be easier than we thought to build not just pituitaries, but also other organs from embryonic stem cells and induced pluripotent stem cells – as long as they are not too complex.

"It also opens up new possible ways for treating patients with defective or missing pituitary glands."

I'm Back, Giving Testing a Final Go

Hi to everyone.  I thank all of you for reading along and for all the letters.  I will write back soon. If I don't reply, please feel free to resend.

I accept friendly reminders.

I wanted to share this image. It made me laugh but then quickly made me upset.  Not even the coveted 'I told you so' is worth it.  Join me in Cushing's awareness.  Let's prove them all wrong.

Please promise me AND yourself that you will fight until you feel better. 

I'll be around more this fall. I'll be testing for high cortisol (already have several high ACTH values even after two pituitary surgeries) and sharing all my Cushie goodies I've rounded up over the summer.

~Melissa

PARTICIPATE: Quality of Life Survey

I encourage every Cushing's patient to complete this National Institutes for Health survey* regarding quality of life. We must seize these opportunities to educate the medical community. The Cushing's we experience is drastically more complicated than the Cushing's they study.  Please make your voice heard. ~m

Click here to go to NIH Cushing's survey.

Information about this survey and your consent to participate

Patients with Cushing's syndrome report decreased quality of life before and after surgical treatment. We are investigators at the U.S. National Institutes of Health who care for patients with Cushing's syndrome. We want to learn more about the patients' experience during the post-surgical recovery phase with particular reference to quality of life. We are inviting patients like you who have had surgical treatment to complete the survey. Your responses will be gathered anonymously and will be treated confidentially; we hope to use them in a publication so that other physicians can learn about these issues.

Please kindly complete the following online questionnaire which is comprised of approximately 27 questions and should take around 15 minutes.

Click here to go to NIH Cushing's survey.

** Thanks to MaryO for sharing this with us.

Glimmer of Hope: Delayed Remission

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

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

Elena Valassi, Beverly M. K. Biller, Brooke Swearingen, Francesca Pecori Giraldi, Marco Losa, Pietro Mortini, Douglas Hayden, Francesco Cavagnini and Anne Klibanski

Published online before print January 15, 2010, doi: 10.1210/jc.2009-1672 The Journal of Clinical Endocrinology & Metabolism February 1, 2010 vol. 95 no. 2 601-610

Full text available for free in pdf here.

Abstract

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

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

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

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

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

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

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

- Author Affiliations

1. Neuroendocrine Unit (E.V., B.M.K.B., A.K.) and Department of Neurosurgery (B.S.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Chair of Endocrinology (E.V., F.P.G., F.C.), Universita’ di Milano, Ospedale San Luca, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico, 20149 Milan, Italy; Department of Neurosurgery (M.L., P.M.), Universita’ Vita-Salute, Istituto Scientifico San Raffaele, 20132 Milan, Italy; and Biostatistics Center (D.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

1. Address all correspondence and requests for reprints to: Anne Klibanski, M.D., Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, Bulfinch 457B, Boston, Massachusetts 02114. E-mail: aklibanski@partners.org.

Why Obesity Is A Disease

Preach it. I totally agree. 

		SCOTT KAHAN, M.D.: Why Obesity Is A Disease
	Obesity is a chronic medical condition -- from a technical perspective, obesity fits any reasonable definition of disease.

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

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

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

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

Journal of Clinical Endocrinology & Metabolism. June 2010.|Tiemensma et al. 95 (6): 2699
http://jcem.endojournals.org/content/95/6/2699.abstract

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

Abstract

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

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

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

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

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

- Author Affiliations

1. Departments of Endocrinology and Metabolism (J.T., N.E.K., N.R.B., B.-J.S.A.K., M.J.E.W., A.M.P., J.A.R.) and Neurology (H.A.M.M.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands

1. Address all correspondence and requests for reprints to: J. Tiemensma, MSc., Department of Endocrinology and Metabolic Diseases C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: J.Tiemensma@lumc.nl.

CUSHING’S: Relentless and Nefarious

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

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

05/06/2011 post op day 16 @ 8 am (withheld pm dose on previous day)
cortisol 17.1 (4-22)
acth 59 (5-27)
glucose 102 (65-99)
sodium 142 (135-146)

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

 ** ** ** ** ** ** ** **

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

Obesity Research: Consequences vs. Causes

Obesity is bad, we get that
The Guardian

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

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

http://m.guardian.co.uk/commentisfree/2011/may/04/obesity-causes-dementia-research?cat=commentisfree&type=article

This is your Life.

Cushing’s Syndrome during Pregnancy

EXTENSIVE CLINICAL EXPERIENCE

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

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

Check out this original article.

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

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

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

Addison's Disease Poses Risks To Patients

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

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

Main Category: Endocrinology
Also Included In: Infectious Diseases / Bacteria / Viruses
Article Date: 03 May 2011 - 0:00 PDT
http://www.medicalnewstoday.com/articles/223926.php

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

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

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

Researcher Dr Stefanie Hahner said:

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

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

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

Researcher Dr Lisanne Smans commented:

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

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

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

Sources: European Society of Endocrinology, AlphaGalileo Foundation.

Hair Samples: Better Testing

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

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

Main Category: Endocrinology
Also Included In: Anxiety / Stress;  Heart Disease;  Preventive Medicine
Article Date: 03 May 2011 - 0:00 PDT
http://www.medicalnewstoday.com/articles/223924.php

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

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

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

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

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

Researcher Dr Laura Manenschijn from Erasmus MC said:

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

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

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

Sources: European Society of Endocrinology, AlphaGalileo Foundation.
 

Cushing's Disease: Unraveling a Medical Mystery

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

Cushing's Disease: Unraveling a Medical Mystery

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

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

~mm

Recovery: Post Op Day 14

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


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

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

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

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

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

• Mild burning/itching in sinus
• Headache
• Pressure in head, upside down
• Overall body aches
• Stiff neck and shoulders
• Sore back
• Preference for dark rooms, no noise
• No drainage in throat so probably not a cerebrospinal fluid leak (CSF leak) 

Doc said feeling bad was a great sign. He is concerned because I am showing signs of hypoatremia, or low sodium levels.  This is common after pituitary surgery, especially for those of us who experienced diabetes insipidus which leads to hyperatremia, or high blood sodium levels. He said he often sees these symptoms happen right around this time (days 7-14 post op). At 8 am on Friday, I will have blood drawn for an electrolyte panel (includes sodium) with cortisol and ACTH after withholding 1 pm dose on Thursday. He suggests that when I drink fluids, I drink Gatorade only, no water, for the next two days. This will help rebalance my electrolytes.

University of California at San Francisco's Pituitary Center mention this in their post surgical instructions:

Some patients develop disorders of salt and water metabolism following pituitary surgery. Headache, nausea, vomiting, confusion, impaired concentration, and muscle aches might be due to hyponatremia (low blood sodium levels). This disorder typically occurs 7 to 10 days after surgery and is more common in patients who have had surgery for Cushing's disease. If you develop these symptoms, contact us immediately. Excessive urination, thirst, and the need to ingest large quantities of fluids might be related to the onset of diabetes insipidus or diabetes mellitus. These disorders put you at risk for dehydration. These symptoms require urgent evaluation and determination of the underlying cause so that appropriate treatment may be given.

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

Dose schedule – can I reduce my hydrocortisone dose now, 14 days post op or wait a few days until the weekend?  What are the next dose levels?

• Do not drop more than 2.5 mg of cortef at a time.
• Currently on 20 / 5
• Stay at 20 / 5 -- next few days, get through the next 8 am blood draw this Friday
• 17.5 / 5  -- stay at this dose for 10-14 days
• 15 / 5  -- stay at this dose for 10-14 days
• Appointment with Doc before dropping dose any lower

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

When do I test?  Do I need to test 17-OHS or 8 am cortisol or 24hr UFC when dropping dose of Cortef?
No

~Moxie Melissa

93 Years Old and Still Dancing

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

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

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

Cushing's in the News

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

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

~Moxie Melissa