Mild Cases of Cushing’s Syndrome Present Diagnostic Challenges

By Tori Rodriguez, MA, LPC

 

In the early 20th century, the term “pluriglandular syndrome” was coined by Harvey Cushing to describe the disorder that results from chronic tissue exposure to excessive levels of glucocorticoids.1 Now called Cushing’s syndrome, the condition affects an estimated 10-15 million people annually, most often women and individuals between the ages of 20 and 50 years.2 Risk factors and common comorbidities include hypertension, obesity, osteoporosis, uncontrolled diabetes, depression, and anxiety.3

Presentation

The clinical presentation of the disorder is heterogenous and varies by sex, age, and disease severity. Common signs and symptoms include central adiposity, roundness of the face or extra fat around the neck, thin skin, impaired short-term memory and concentration, irritability, hirsutism in women, fatigue, and menstrual irregularity.4 Because each of these features may be observed in a wide range of other conditions, it may be difficult to diagnose cases that are not severe.

“It can be challenging to differentiate the milder forms from pseudo-Cushing’s states,” which are characterized by altered cortisol production and many of the same clinical features as Cushing’s syndrome, according to Roberto Salvatori, MD, the medical director of the Johns Hopkins Pituitary Center, Baltimore, Maryland. These may include alcoholism, obesity, eating disorders, and depression. “Because Cushing’s can cause depression, for example, it is sometimes difficult to determine which came first,” he says. In these states, however, hypercortisolism is believed to be driven by increased secretion of hypothalamic corticotropin-releasing hormone, which is suppressed in Cushing’s syndrome.5

Causes and Diagnosis

If Cushing’s syndrome is suspected on the basis of the patient’s physical appearance, the diagnostic workup should include a thorough medical history, physical exam, and 1 or more of the following tests to establish hypercortisolism: the 24-hour urinary cortisol test, the low-dose dexamethasone suppression test, or the late-night salivary cortisol test. “We sometimes use 2 or 3 of these tests since 1 may not accurately reflect cortisol production in a particular patient,” Dr Salvatori notes. The next step is to determine the source of the hypercortisolism, which may involve the high-dose dexamethasone suppression test, magnetic resonance imaging, or petrosal sinus sampling.2

Medication is the most common cause of Cushing’s syndrome. These iatrogenic or exogenous cases typically result from corticosteroids administered for conditions such as asthma, allergies, and autoimmune disorders.6 More rarely, the disorder can be caused by the use of medroxyprogesterone. In these cases, corticosteroids should be reduced or discontinued under medical care, if possible.

Endogenous Cushing’s syndrome results from the presence of benign or malignant tumors on the adrenal or pituitary glands or elsewhere in the body. These tumors can interfere with the adrenal glands’ production of cortisol that is usually prompted by the adrenocorticotropic hormone (ACTH) released by the pituitary gland.6 There are 3 different mechanisms by which the process can occur.

  • Pituitary adenomas, which account for approximately 70% of endogenous cases of Cushing’s syndrome, secrete ACTH and stimulate additional cortisol production. Because of the large proportion of cases this condition represents, it is specifically referred to as Cushing’s disease. It is more common in women than men (with a ratio of 3 to 4:1), although in pediatric patients, it occurs more frequently in boys vs girls.5
  • Adrenal tumors (adenomas, malignant tumors, or micronodular hyperplasia) produce cortisol in their own tissue in addition to the amount produced by the adrenal glands. These tumors, which cause approximately 15% of endogenous Cushing’s syndrome cases, are more common in children vs adults and in women vs men.
  • Benign or malignant tumors elsewhere in the body, most often the lungs, thyroid, thymus, and pancreas, secrete ACTH and trigger the excessive release of cortisol. An estimated 15% of endogenous cases are attributed to these types of tumors.

Treatment

Surgery is the first-line treatment for Cushing’s syndrome. “We first want to try to figure out the cause of the disorder,” Dr Salvatori says. “Ideally, treatment involves surgery to remove the tumor that is causing it.”

When surgery is unsuccessful, contraindicated, or delayed, other treatment options include radiation or medications that inhibit cortisol, modulate the release of ACTH, or inhibit steroidogenesis.5 Bilateral adrenalectomy may be indicated for patients who do not respond to medication or other surgery.

If surgical resection of the tumor is successful, then “all of the comorbidities reverse, but if it is unsuccessful or must be delayed, you would treat each comorbidity” with the appropriate medication; for example, antihypertensives for high blood pressure and antidiabetic medications for diabetes, Dr Salvatori advises. In severe cases, prophylactic antibiotics may be indicated for the prevention of severe infections such as pneumonia.

It is also important to inquire about and address psychiatric symptoms related to Cushing’s syndrome, even in patients who are in remission. It has been proposed that the chronic hypercortisolism and dysfunction of the HPA axis may “lead to structural and functional changes in the central nervous system, developing brain atrophy, particularly in the hippocampus, which may determine the high prevalence of psychiatric disorders, such as affective and anxiety disorders or cognitive dysfunctions,” according to a recently published paper on the topic.7 Patients should be screened with self-report questionnaires such as the Beck Depression Inventory and the Hospital Anxiety and Depression Scale, and management of psychiatric symptoms may include patient education, psychotropic medications, and referral to a mental health professional.

Future Directions

Several trials are currently planned or underway, including a phase 2 randomized, double-blind, placebo-controlled study of an oral medication called ATR-101 by Millendo Therapeutics, Inc. (ClinicalTrials.gov identifier: NCT03053271). In addition to the need for novel medical therapies, refined imaging techniques could improve surgical success rates in patients with Cushing’s disease in particular, according to Dr Salvatori. “A significant portion of these patients have tumors too small to be detected by MRI, and the development of more sensitive MRI could improve detection and provide a surgical target” for neurosurgeons treating the patients, he says.

Summary

Milder cases of Cushing’s syndrome present diagnostic challenges are a result overlapping features with various other conditions. Diagnosis may require careful observation as well as biochemical and imaging tests.

References

  1. Loriaux DL. Diagnosis and differential diagnosis of Cushing’s syndromeN Engl J Med. 2017;376:1451-1459. doi:10.1056/NEJMra1505550
  2. American Association of Neurological Surgeons. Cushing’s syndrome/disease. http://www.aans.org/Patients/Neurosurgical-Conditions-and-Treatments/Cushings-Disease. Accessed August 1, 2017.
  3. León-Justel A, Madrazo-Atutxa A, Alvarez-Rios AI, et al. A probabilistic model for cushing’s syndrome screening in at-risk populations: a prospective multicenter studyJ Clin Endocrinol Metab. 2016;101:3747-3754. doi:10.1210/jc.2016-1673
  4. The Pituitary Society. Cushing’s syndrome and disease–symptoms. https://pituitarysociety.org/patient-education/pituitary-disorders/cushings/symptoms-of-cushings-disease-and-cushings-syndrome. Accessed August 1, 2017.
  5. Sharma ST, Nieman LK, Feelders RA. Cushing’s syndrome: epidemiology and developments in disease managementClin Epidemiol. 2015;7:281-293. doi:10.2147/CLEP.S44336
  6. National Institutes of Health: Eunice Kennedy Shriver National Institute of Child Health and Human Development. What causes Cushing’s syndrome?https://www.nichd.nih.gov/health/topics/cushing/conditioninfo/pages/causes.aspx. Accessed August 1, 2017.
  7. Santos A, Resmini E, Pascual JC, Crespo I, Webb SM. Psychiatric symptoms in patients with Cushing’s syndrome: prevalence, diagnosis and management. Drugs. 2017;77:829-842. doi:10.1007/s40265-017-0735-z

From http://www.endocrinologyadvisor.com/adrenal/cushings-syndrome-diagnosis-treatment/article/682302/

Adrenal myelolipoma(s) as presenting manifestation of subclinical Cushing’s disease (eutopic ACTH-dependent Cushing’s syndrome)

  1. Partha Pratim Chakraborty1,
  2. Shinjan Patra1,
  3. Sugata Narayan Biswas1,
  4. Rana Bhattacharjee2

+Author Affiliations


  1. 1Department of MedicineMidnapore Medical College and HospitalMidnaporeWest Bengal, India

  2. 2Department of Endocrinology and MetabolismIPGME&R/SSKM HospitalKolkataWest Bengal, India
  1. Correspondence to Dr Partha Pratim Chakraborty, docparthapc@yahoo.co.in
  • Accepted 5 August 2017
  • Published 16 August 2017

Summary

Primary adrenal myelolipomas, relatively rare benign tumours of the adrenal cortex are typically unilateral, hormonally inactive and asymptomatic, hence often diagnosed as ‘adrenal incidentaloma’. Bilateral adrenal myelolipomas, in particular, may be associated with underlying endocrinopathies associated with elevated circulating adrenocorticotropic hormone (ACTH) concentration.

Subclinical cortisol hypersecretion, irrespective of its ACTH dependency, does not manifest typical clinical phenotype of hypercortisolemia, and thus termed subclinical Cushing’s syndrome.

In this article, hormonal evaluation in a middle-aged woman with diabetes, hypertension and incidentally discovered unilateral adrenal myelolipoma revealed underlying subclinical Cushing’s disease. Abdominal CT revealed another tiny focus in the contralateral adrenal gland, probably representing incipient myelolipoma.

From (you may buy the whole article at this link) http://casereports.bmj.com/content/2017/bcr-2017-221674.short?rss=1

Cushing’s Syndrome: A Tale of Frequent Misdiagnosis


What is it?

Cushing’s syndrome is a condition you probably have never heard of, but for those who have it, the symptoms can be quite scary.  Worse still, getting it diagnosed can take a while.  Cushing’s syndrome occurs when the tissues of the body are exposed to high levels of cortisol for an extended amount of time. Cortisol is the hormone the body produces to help you in times of stress. It is good to have cortisol at normal levels, but when those levels get too high it causes health problems.  Although cortisol is related to stress, there is no evidence that Cushing’s syndrome is directly or indirectly caused by stress.

Cushing’s syndrome is considered rare, but that may be because it is under-reported. As a result, we don’t have good estimates for how many people have it, which is why the estimates for the actual number of cases vary so much–from 5 to 28 million people.[1] The most common age group that Cushing’s affects are those 20 to 50 years old.  It is thought that obesity, type 2 diabetes, and high blood pressure may increase your risk of developing this syndrome.[2]

What causes Cushing’s Syndrome?

Cushing’s syndrome is caused by high cortisol levels. Cushing’s disease is a specific form of Cushing’s syndrome. People with Cushing’s disease have high levels of cortisol because they have a non-cancerous (benign) tumor in the pituitary gland.  The tumor releases adrenocorticotropin hormone (ACTH), which causes the adrenal glands to produce excessive cortisol.

Cushing’s syndrome that is not Cushing’s disease can be also caused by high cortisol levels that result from tumors in other parts of the body.  One of the causes is “ectopic ACTH syndrome.” This means that the hormone-releasing tumor is growing in an abnormal place, such as the lungs or elsewhere.  The tumors can be benign, but most frequently they are cancerous. Other causes of Cushing’s syndrome are benign tumors on the adrenal gland (adrenal adenomas) and less commonly, cancerous adrenal tumors (adrenocortical carcinomas). Both secrete cortisol, causing cortisol levels to get too high.

In some cases, a person can develop Cushing’s syndrome from taking steroid medications, such as prednisone. These drugs, known as corticosteroids, mimic the cortisol produced by the body. People who have Cushing’s syndrome from steroid medications do not develop a tumor.[3]

What are the signs and symptoms of Cushing’s Syndrome?

The appearance of people with Cushing’s syndrome starts to change as cortisol levels build up. Regardless of what kind of tumor they have or where the tumor is located, people tend to put on weight in the upper body and abdomen, with their arms and legs remaining thin; their face grows rounder (“moon face”); they develop fat around the neck; and purple or pink stretch marks appear on the abdomen, thighs, buttocks or arms. Individuals with the syndrome usually experience one or more of the following symptoms: fatigue, muscle weakness, high glucose levels, anxiety, depression, and high blood pressure. Women are more likely than men to develop Cushing’s syndrome, and when they do they may have excess hair growth, irregular or absent periods, and decreased fertility.[4]

Why is Cushing’s Syndrome so frequently misdiagnosed?

These symptoms seem distinctive, yet it is often difficult for those with Cushing’s syndrome to get an accurate diagnosis.  Why?  While Cushing’s is relatively rare, the signs and symptoms are common to many other diseases. For instance, females with excess hair growth, irregular or absent periods, decreased fertility, and high glucose levels could have polycystic ovarian syndrome, a disease that affects many more women than Cushing’s.   Also, people with metabolism problems (metabolic syndrome), who are at higher than average risk for diabetes and heart disease, also tend to have abdominal fat, high glucose levels and high blood pressure.[5]

Problems in testing for Cushing’s

When Cushing’s syndrome is suspected, a test is given to measure cortisol in the urine. This test measures the amount of free or unbound cortisol filtered by the kidneys and then released over a 24 hour period through the urine. Since the amount of urinary free cortisol (UFC) can vary a lot from one test to another—even in people who don’t have Cushing’s—experts recommend that the test be repeated 3 times. A diagnosis of Cushing’s is given when a person’s UFC level is 4 times the upper limit of normal.  One study found this test to be highly accurate, with a sensitivity of 95% (meaning that 95% of people who have the disease will be correctly diagnosed by this test) and a specificity of 98% (meaning that 98% of  people who do not have the disease will have a test score confirming that).[6] However, a more recent study estimated the sensitivity as only between 45%-71%, but with 100% specificity.[7]  This means that the test is very accurate at telling people who don’t have Cushing’s that they don’t have it, but not so good at identifying the people who really do have Cushing’s.  The authors that have analyzed these studies advise that patients use the UFC test together with other tests to confirm the diagnosis, but not as the initial screening test.[8]  

Other common tests that may be used to diagnose Cushing’s syndrome are: 1) the midnight plasma cortisol and late-night salivary cortisol measurements, and 2) the low-dose dexamethasone suppression test (LDDST).  The first test measures the amount of cortisol levels in the blood and saliva at night.  For most people, their cortisol levels drop at night, but people with Cushing’s syndrome have cortisol levels that remain high all night. In the LDDST, dexamethasone is given to stop the production of ACTH.  Since ACTH produces cortisol, people who don’t have Cushing’s syndrome will get lower cortisol levels in the blood and urine. If after giving dexamethasone, the person’s cortisol levels remain high, then they are diagnosed with Cushing’s.[9]

Even when these tests, alone or in combination, are used to diagnose Cushing’s, they don’t explain the cause. They also don’t distinguish between Cushing’s syndrome, and something called pseudo-Cushing state.

Pseudo-Cushing state

Some people have an abnormal amount of cortisol that is caused by something unrelated to Cushing’s syndrome such as polycystic ovarian syndrome, depression, pregnancy, and obesity. This is called pseudo-Cushing state.  Their high levels of cortisol and resulting Cushing-like symptoms can be reversed by treating whatever disease is causing the abnormal cortisol levels. In their study, Dr. Giacomo Tirabassi and colleagues recommend using the desmopressin (DDAVP) test to differentiate between pseudo-Cushing state and Cushing’s.  The DDAVP test is especially helpful in people who, after being given dexamethasone to stop cortisol production, continue to have moderate levels of urinary free cortisol (UFC) and midnight serum cortisol.[10]

An additional test that is often used to determine if one has pseudo-Cushing state or Cushing’s syndrome is the dexamethasone-corticotropin-releasing hormone (CRH) test. Patients are injected with a hormone that causes cortisol to be produced while also being given another hormone to stop cortisol from being produced. This combination of hormones should make the patient have low cortisol levels, and this is what happens in people with pseudo-Cushing state.  People with Cushing’s syndrome, however, will still have high levels of cortisol after being given this combination of hormones.[11]

How can Cushing’s be treated?

Perhaps because Cushing’s is rare or under-diagnosed, few treatments are available. There are several medications that are typically the first line of treatment.  None of the medications can cure  Cushing’s, so they are usually taken until other treatments are given to cure Cushing’s, and only after that if the other treatment fails.

The most common treatment for Cushing’s disease is transsphenoidal surgery, which requires the surgeon to reach the pituitary gland through the nostril or upper lip and remove the tumor.  Radiation may also be used instead of surgery to shrink the tumor.  In patients whose Cushing’s is caused by ectopic ACTH syndrome, all cancerous cells need to be wiped out through surgery, chemotherapy, radiation or a variety of other methods, depending on the location of the tumor. Surgery is also recommended for adrenal tumors.  If Cushing’s syndrome is being caused by corticosteroid (steroid medications) usage, the treatment is to stop or lower your dosage.[12]

Medications to control Cushing’s (before treatment or if treatment fails)

According to a 2014 study in the Journal of Clinical Endocrinology and Metabolism, almost no new treatment options have been introduced in the last decade. Researchers and doctors have focused most of their efforts on improving existing treatments aimed at curing Cushing’s. Unfortunately, medications used to control Cushing’s prior to treatment and when treatment fails are not very effective.

Many of the medications approved by the FDA for Cushing’s syndrome and Cushing’s disease, such as pasireotide, metyrapone, and mitotane, have not been extensively studied.  The research presented to the FDA by the makers of these three drugs did not even make clear what an optimal dose was.[13] In another 2014 study, published in Clinical Epidemiology, researchers examined these three same drugs, along with ten others, and found that only pasireotide had moderate evidence to support its approval.  The other drugs, many of which are not FDA approved for Cushing’s patients, had little or no available evidence to show that they work.[14] They can be sold, however, because the FDA has approved them for other diseases.  Unfortunately, that means that neither the FDA nor anyone else has proven the drugs are safe or effective for Cushing patients.

Pasireotide, the one medication with moderate evidence supporting its approval, caused hyperglycemia (high blood sugar) in 75% of patients who participated in the main study for the medication’s approval for Cushing’s.  As a result of developing hyperglycemia, almost half (46%) of the participants had to go on blood-sugar lowering medications. The drug was approved by the FDA for Cushing’s anyway because of the lack of other effective treatments.

Other treatments used for Cushing’s have other risks.  Ketoconazole, believed to be the most commonly prescribed medications for Cushing’s syndrome, has a black box warning due to its effect on the liver that can lead to a liver transplant or death.  Other side effects include: headache, nausea, irregular periods, impotence, and decreased libido. Metyrapone can cause acne, hirsutism, and hypertension. Mitotane can cause neurological and gastrointestinal symptoms such as dizziness, nausea, and diarrhea and can cause an abortion in pregnant women.[15]

So, what should you do if you suspect you have Cushing’s Syndrome?

Cushing’s syndrome is a serious disease that needs to be treated, but there are treatment options available for you if you are diagnosed with the disease. If the symptoms in this article sound familiar, it’s time for you to go see your doctor. Make an appointment with your general practitioner, and explain your symptoms to him or her.  You will most likely be referred to an endocrinologist, who will be able to better understand your symptoms and recommend an appropriate course of action.

 

All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.

  1. Nieman, Lynette K. Epidemiology and clinical manifestations of Cushing’s syndrome, 2014. UpToDate: Wolters Kluwer Health
  2. Cushing’s syndrome/ disease, 2013. American Association of Neurological Surgeons. http://www.aans.org/Patient%20Information/Conditions%20and%20Treatments/Cushings%20Disease.aspx
  3. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  4. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  5. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  6. Newell-Price, John, Peter Trainer, Michael Besser and Ashley Grossman. The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states, 1998. Endocrine Reviews: Endocrine Society
  7. Carroll, TB and JW Findling. The diagnosis of Cushing’s syndrome, 2010. Reviews in Endocrinology and Metabolic Disorders: Springer
  8. Ifedayo, AO and AF Olufemi. Urinary free cortisol in the diagnosis of Cushing’s syndrome: How useful?, 2013. Nigerian Journal of Clinical Practice: Medknow.
  9. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  10. Tirabassi, Giacomo, Emanuela Faloia, Roberta Papa, Giorgio Furlani, Marco Boscaro, and Giorgio Arnaldi. Use of the Desmopressin test in the differential diagnosis of pseudo-Cushing state from Cushing’s disease, 2013. The Journal of Clinical Endocrinology & Metabolism: Endocrine Society.
  11. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  12. Cushing’s syndrome, 2012. National Endocrine and Metabolic Diseases: National Institutes of Health. http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx#treatment
  13. Tirabassi, Giacomo, Emanuela Faloia, Roberta Papa, Giorgio Furlani, Marco Boscaro, and Giorgio Arnaldi. Use of the Desmopressin test in the differential diagnosis of pseudo-Cushing state from Cushing’s disease, 2013. The Journal of Clinical Endocrinology & Metabolism: Endocrine Society.
  14. Galdelha, Monica R. and Leonardo Vieira Neto. Efficacy of medical treatment in Cushing’s disease: a systematic review, 2014. Clinical Endocrinology: John Wiley & Sons.
  15. Adler, Gail. Cushing syndrome treatment & management, 2014. MedScape: WebMD.

Adapted from https://www.center4research.org/cushings-syndrome-frequent-misdiagnosis/

Severe Trauma May Damage The Brain as Well as the Psyche

NOTE: This is only a portion of the article.  Read the entire post at http://www.nytimes.com/1995/08/01/science/severe-trauma-may-damage-the-brain-as-well-as-the-psyche.html?pagewanted=all

Cortisol is a major means the body uses, with adrenaline, to arouse itself so quickly; its action, for example, triggers an increase in blood pressure and mobilizes energy from fat tissue and the liver.

“The dark side of this picture is the neurological effects,” said Dr. Sapolsky. “It’s necessary for survival, but it can be disastrous if you secrete cortisol for months or years on end. We’ve known it could lead to stress-exacerbated diseases like hypertension or adult onset diabetes. But now we’re finding the hippocampus is also damaged by these secretions.”

Studies in animals show that when glucocorticoids are secreted at high levels for several hours or days, there is a detectable effect on memory, though no neuronal death. But with sustained release from repeated stress, “it eventually kills neurons in the hippocampus,” said Dr. Sapolsky. “This has been shown solidly in rats, with the cell biology well understood.”

A parallel effect has long been known among patients with Cushing’s disease, a hormonal condition in which tumors in the adrenal or pituitary glands or corticosteroid drugs used for a prolonged time cause the adrenal glands to secrete high levels of a hormone called ACTHm and of cortisol. Such patients are prone to a range of diseases “in any organ with stress sensitivity,” including diabetes, hypertension and suppression of the immune system, said Dr. Sapolsky.

Cushing’s patients also have pronounced memory problems, especially for facts like where a car was parked. “The hippocampus is essential for transferring such facts from short-term to long-term memory,” said Dr. Sapolsky.

In 1993, researchers at the University of Michigan reported that magnetic resonance imaging had shown an atrophy and shrinkage of the hippocampus in patients with Cushing’s disease; the higher their levels of cortisol, the more shrinkage.

In an apparent paradox, low levels of cortisol in post-trauma victims were found in a separate research report, also in the July issue of The American Journal of Psychiatry. Dr. Rachel Yehuda, a psychologist at Mount Sinai Medical School in New York City, found the lower levels of cortisol in Holocaust survivors who had been in concentration camps 50 years ago and who still had post-traumatic symptoms.

“There are mixed findings on cortisol levels in trauma victims, with some researchers finding very high levels and others finding very low levels,” said Dr. Sapolsky. “Biologically speaking, there may be different kinds of post-traumatic stress.”

In a series of studies, Dr. Yehuda has found that those post-trauma patients who have low cortisol levels also seem to have “a hypersensitivity in cell receptors for cortisol,” she said. To protect itself, the body seems to reset its cortisol levels at a lower point.

The low cortisol levels “seem paradoxical, but both too much and too little can be bad,” said Dr. Yehuda. “There are different kinds of cells in various regions of the hippocampus that react to cortisol. Some atrophy or die if there is too little cortisol, some if there is too much.”

Dr. Yehuda added, “In a brain scan, there’s no way to know exactly which cells have died.”

To be sure that the shrinkage found in the hippocampus of trauma victims is indeed because of the events they suffered through, researchers are now turning to prospective studies, where before-and-after brain images can be made of people who have not yet undergone trauma, but are at high risk, or who have undergone it so recently that cell death has not had time to occur.

Dr. Charney, for example, is planning to take M.R.I. scans of the brains of emergency workers like police officers and firefighters and hopes to do the same with young inner-city children, who are at very high risk of being traumatized over the course of childhood and adolescence. Dr. Pitman, with Dr. Yehuda, plans a similar study of trauma victims in Israel as they are being treated in emergency rooms.

Dr. Yehuda held out some hope for people who have suffered through traumatic events. “It’s not necessarily the case that if you’ve been traumatized your hippocampus is smaller,” she said. She cited research with rats by Dr. Bruce McEwen, a neuroscientist at Rockefeller University, showing that atrophied dendritic extensions to other cells in the hippocampus grew back when the rats were given drugs that blocked stress hormones.

Dr. Sapolsky cited similar results in patients with Cushing’s disease whose cortisol levels returned to normal after tumors were removed. “If the loss of hippocampal volume in trauma victims is due to the atrophy of dendrites rather than to cell death, then it is potentially reversible, or may be so one day,” he said.

NOTE: This is only a portion of the article.  Read the entire post at http://www.nytimes.com/1995/08/01/science/severe-trauma-may-damage-the-brain-as-well-as-the-psyche.html?pagewanted=all

Cushing’s disease best treated by endocrinologist

Dear Dr. Roach: I was told that I have Cushing’s disease, which has caused diabetes, high blood pressure, hunger, weight gain and muscle loss. I was never sick before this, and I did not have any of those things. I am told I have a tumor on my right adrenal gland. I have been to numerous doctors, but most have not been too helpful. They seem to try to treat the diabetes or blood pressure, but nothing else. They seem not to be familiar with Cushing’s. I tell them which medication works, but they still give me new medication. I have an endocrinologist and am scheduled to meet a urologist.

I have managed to go to physical therapy, exercise every day and lose over 50 pounds. I am not happy with the advice I’m getting. I was told that surgery to remove the tumor will fix everything, but that I would need to take steroids for either a short term or for life. My body is already making too much cortisol. I have 50 more pounds to lose. I work hard to keep the weight down. I feel like a science experiment. Within a week, I have had three different medications. I could not tell which was causing the side effects and making me dehydrated. I am not sure surgery is right for me, because they said it can be done laparoscopically, but if they can’t do it that way, they will have to cut me all the way across, which may take a long time to heal and may get infected.

Do you know what tests will confirm the diagnosis? Would surgery fix all these problems? I had the 24-hour urine test, the saliva test and blood tests. I want to know if it may be something else instead of Cushing’s. I’m not on anything for the high cortisol levels.

– A.L.

A: It sounds very much like you have Cushing’s syndrome, which is caused by excess cortisone, a hormone that has many effects. It is called Cushing’s disease when the underlying cause is a pituitary tumor that causes the adrenal gland to make excess cortisone. (Cortisone and cortisol are different names for the same chemical, also called a glucocorticoid.) Cushing’s syndrome also may be caused by an adenoma (benign tumor) of the adrenal gland, which sounds like the case in you.

The high amounts of cortisone produced by the adrenal tumor cause high blood pressure, glucose intolerance or frank diabetes, increased hunger, obesity (especially of the abdomen – large bellies and skinny limbs are classic), dark-colored striae (stretch marks), easy bruising, a reddish face and often weakness of arm and leg muscles. When full-blown, the syndrome is easy to spot, but many people don’t have all the characteristics, especially early in the course of the disease.

Your endocrinologist is the expert in diagnosis and management, and has done most of the tests. I am somewhat surprised that you haven’t yet seen a surgeon to have the tumor removed. Once it is removed, the body quickly starts to return to normal, although losing the weight can be a problem for many.

I have seen cases in my training where, despite many tests, the diagnosis was still uncertain. The endocrinologist orders a test where the blood is sampled from both adrenal veins (which contain the blood that leaves the adrenal glands on top of the kidneys). If the adrenal vein on the side of the tumor has much more cortisone than the opposite side, the diagnosis is certain.

By DR. KEITH ROACH For the Herald & Review at http://herald-review.com/news/opinion/editorial/columnists/roach/dr-roach-cushing-s-disease-best-treated-by-endocrinologist/article_38e71835-464d-5946-aa9c-4cb1366bcee3.html

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