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

Screening tool accurately predicts Cushing’s syndrome in most at-risk patients

León-Justel A, et al. J Clin Endocrinol Metab. 2016;doi:10.1210/jc.2016-1673.

A scoring system based on clinical signs and a late-night salivary cortisol test accurately predicted Cushing’s syndrome in at-risk patients, with only one missed case, according to recent findings.

In a prospective, multicenter study, Antonio León-Justel, PhD, of the biochemistry department at the Hospital Universitario Virgen del Rocío in Seville, Spain, and colleagues analyzed data from 353 patients treated in endocrinology units in 13 university hospitals in Spain between 2012 and July 2013. All participants had at least two of five features compatible with Cushing’s syndrome, including obesity, hypertension, poorly controlled diabetes,hirsutism with menstrual disorders and osteoporosis; none of the included patients was referred to clinic with the suspicion of Cushing’s syndrome. All patients underwent late-night salivary cortisol and serum cortisol measurements after a low-dose (1 mg) dexamethasone test; those with discordant results were followed until December 2014 (mean follow-up time, 22.2 months).

Within the cohort, 26 (7.4%) patients were diagnosed with Cushing’s syndrome (20 adrenocorticotropic hormone-dependent; six of adrenal origin). In univariate logistic regression analysis, researchers found that muscular atrophy (OR = 15.2), followed by osteoporosis (OR = 4.6), dorsocervical fat pad (OR = 3.32), absence of obesity (OR = 0.21) and absence of type 2 diabetes (OR = 0.26), were associated with Cushing’s syndrome; late-night salivary cortisol values were also related (OR = 1.26). However, after multivariable adjustment, researchers found that muscular atrophy (OR = 9.04; 95% CI, 2.36-34.65), osteoporosis (OR = 3.62; 95% CI, 1.16-11.35) and dorsocervical fat (OR = 3.3; 95% CI, 1.52-7.17) remained as independent variables with Cushing’s syndrome.

“Obesity and type 2 diabetes displayed a negative association with [Cushing’s syndrome],” the researchers wrote. “These results might seem paradoxical a priori, but we want to stress that in our analyzed cohort, the prevalence of obesity and diabetes was exceedingly high (likely reflecting the reasons for referral to endocrinology units).”

In receiver operating characteristic (ROC) analysis, researchers determined that a cutoff value of 9.17 nmol/L for late-night salivary cortisol provided the best results, with an area under the curve of 0.893 (P < .001), a sensitivity of 88.5% and specificity of 83.2%.

Researchers developed a risk-scoring system, determining cutoff values from a ROC curve. The estimated area under the ROC curve was 0.93 (P < .001), with a sensitivity of 96.2% and specificity of 82.9%.

“Selecting this cutoff value of four, 271 of 327 subjects (83%) without [Cushing’s syndrome] were correctly identified, while only 1 of 26 [Cushing’s syndrome] cases was missed,” the researchers wrote. “Our model yielded 56 false positives.

“Although all the assessments were performed by specialists (endocrinologists) in our study, this scoring system could be easily tested in independent cohorts and different settings such as primary care or hypertension clinics,” the researchers wrote. “At the very least, our diagnostic prediction model could be used as a framework for future studies and potential improvements in diagnostic performance.” – by Regina Schaffer

Disclosure: Leon-Justel and another researcher report receiving a research grant from Novartis Oncology, Spain.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B50d3d398-c8fe-41e9-b815-87626bfe8a4b%7D/screening-tool-accurately-predicts-cushings-syndrome-in-most-at-risk-patients

Cushing’s Syndrome Epidemiology

By Yolanda Smith, BPharm

Cushing’s syndrome is considered to be a rare disorder that results from prolonged exposure to glucocorticoids. However, there are few epidemiological studies to provide adequate data to describe the incidence and prevalence of the condition accurately. Most cases are diagnosed between the ages of 20 and 50, although any individual may be affected at any age.

The presentation of the symptoms of Cushing’s syndrome can vary greatly. In addition, many of the symptoms overlap with those caused by other health conditions, such as metabolic syndrome and polycystic ovary syndrome. This can make the diagnosis of the condition difficult. It is also difficult to establish epidemiological trends in Cushing’s syndrome, because not all cases of the disease are diagnosed. However, it is important that diagnosis is made as soon as possible, because early diagnosis and treatment of the condition are associated with improved morbidity and mortality rates.

Population-based Studies

There are several population-based studies that have reported the incidence and mortality rates of Cushing’s syndrome in certain populations over a discrete period of time.

A study in Denmark followed 166 patients with Cushing’s syndrome for 11 years, finding an incidence of 2 cases per million population per year. Of the 166 patients, 139 had benign disease. There was a mortality rate of 16.5% in the follow-up period of 8 years, with most deaths occurring in the year after the initial diagnosis, often before the initiation of treatment. The causes of death of patients with Cushing’s syndrome in the study included severe infections, cardiac rupture, stroke and suicide.

A study in Spain found 49 cases of Cushing’s syndrome over a period of 18 years, with an incidence of 2.4 cases per million inhabitants per year and a prevalence of 39.1 cases per million. The standard mortality ratio in this study was 3.8, in addition to an increase in morbidity rates.

Incidence

A low incidence of endogenous Cushing’s syndrome was established by the population-based studies outlined above, corresponding to approximately 2 cases per million. Some studies have an estimated incidence as low as 0.7 people per million.

However, the incidence of subclinical Cushing’s syndrome may be underestimated in certain population groups, such as those with osteoporosis, uncontrolled diabetes mellitus or hypertension. For example, of 90 obese patients with uncontrolled diabetes mellitus in one study, three had Cushing’s syndrome. This yielded a prevalence of 3.3%, which is considerably higher than the incidence reported in the population-based studies. However, these findings should be supported by larger studies.

Females are more likely to be affected by Cushing’s syndrome than males, with a risk ratio of approximately 3:1. There does not appear to be a genetic link that involves an ethnic susceptibility to the condition.

Treatment Outcomes

Surgery is the first-line treatment option for most cases of overt disease and remission is achieved in the majority of patients, approximately 65-85%. However, for up to 1 in 5 patients the condition recurs, and the risk does not appear to level off, even after 20 years of follow-up.

The risk of mortality for individuals with Cushing’s syndrome is estimated to be 2-3 times higher than that of the general population, based on epidemiological studies.

Reviewed by Dr Liji Thomas, MD.

From http://www.news-medical.net/health/Cushings-Syndrome-Epidemiology.aspx

Primary hyperaldosteronism: a case of unilateral adrenal hyperplasia with contralateral incidentaloma

BMJ Case Reports 2016; doi:10.1136/bcr-2016-216209
  • CASE REPORT
  1. Sujit Vakkalanka1,
  2. Andrew Zhao1,
  3. Mohammed Samannodi2

+Author Affiliations


  1. 1University at Buffalo, Buffalo, New York, USA

  2. 2Department of Medicine, Buffalo, New York, USA
  1. Correspondence toDr Mohammed Samannodi, samannodi@gmail.com
  • Accepted 28 June 2016
  • Published 14 July 2016

Summary

Primary hyperaldosteronism is one of the most common causes of secondary hypertension but clear differentiation between its various subtypes can be a clinical challenge.

We report the case of a 37-year-old African-American woman with refractory hypertension who was admitted to our hospital for palpitations, shortness of breath and headache. Her laboratory results showed hypokalaemia and an elevated aldosterone/renin ratio. An abdominal CT scan showed a nodule in the left adrenal gland but adrenal venous sampling showed elevated aldosterone/renin ratio from the right adrenal vein. The patient began a new medical regimen but declined any surgical options.

We recommend clinicians to maintain a high level of suspicion to consider the less common subtypes of primary hyperaldosteronism, especially given the fact that the management greatly varies.

From http://casereports.bmj.com/content/2016/bcr-2016-216209.short?rss=1

Six controversial issues on subclinical Cushing’s syndrome

Abstract

Subclinical Cushing’s syndrome is a condition of hypercortisolism in the absence of signs specific of overt cortisol excess, and it is associated with an increased risk of diabetes, hypertension, fragility fractures, cardiovascular events and mortality.

The subclinical Cushing’s syndrome is not rare, being estimated to be between 0.2–2 % in the adult population. Despite the huge number of studies that have been published in the recent years, several issues remain controversial for the subclinical Cushing’s syndrome screening, diagnosis and treatment.

The Altogether to Beat Cushing’s syndrome Group was founded in 2012 for bringing together the leading Italian experts in the hypercortisolism-related diseases. This document represents the Altogether to Beat Cushing’s syndrome viewpoint regarding the following controversial issues on Subclinical Cushing’s syndrome (SCS):

(1) Who has to be screened for subclinical Cushing’s syndrome?
(2) How to screen the populations at risk?
(3) How to diagnose subclinical Cushing’s syndrome in patients with an adrenal incidentaloma?
(4) Which consequence of subclinical Cushing’s syndrome has to be searched for?
(5) How to address the therapy of choice in AI patients with subclinical Cushing’s syndrome?
(6) How to follow-up adrenal incidentaloma patients with subclinical Cushing’s syndrome surgically or conservatively treated?

Notwithstanding the fact that most studies that faced these points may have several biases (e.g., retrospective design, small sample size, different criteria for the subclinical Cushing’s syndrome diagnosis), we believe that the literature evidence is sufficient to affirm that the subclinical Cushing’s syndrome condition is not harmless and that the currently available diagnostic tools are reliable for identifying the majority of individuals with subclinical Cushing’s syndrome.

Keywords

Subclinical hypercortisolism, Adrenal incidentalomas, Hypertension, Diabetes, Osteoporosis

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