A Faster Way to Diagnose Cushing’s Syndrome

Diagnosing Cushing’s syndrome can take 24 hours of complicated and repeated analysis of blood and urine, brain imaging, and tissue samples from sinuses. But that may soon be in the past: National Institutes of Health (NIH) researchers have found that measuring cortisol levels in hair samples can do the same job faster.

Patients with Cushing’s syndrome have a high level of cortisol, perhaps from a tumor of the pituitary or adrenal glands, or as a side effect from medications. In the study, 36 participants—30 with Cushing’s syndrome, six without—provided hair samples divided into three equal segments. The researchers found that the segments closest to the scalp had the most cortisol (96.6 ± 267.7 pg/mg for Cushing’s syndrome patients versus 14.1 ± 9.2 pg/mg in control patients). Those segments’ cortisol content correlated most closely with the majority of the initial biochemical tests, including in blood taken at night (when cortisol levels normally drop).

The study was small; Cushing’s syndrome is rare, and it’s hard to recruit large numbers of patients. Still, the researchers believe it is the largest of its kind to compare hair cortisol levels to diagnostic tests in Cushing’s patients. “Our results are encouraging,” said Mihail Zilbermint, MD, the study’s senior author and an endocrinologist at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. “We are hopeful that hair analysis may ultimately prove useful as a less-invasive screening test for Cushing’s syndrome or in helping to confirm the diagnosis.” The authors suggest the test is also a convenient alternative with the “unique ability” for retrospective evaluation of hypercortisolemia over months.

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From https://www.ptcommunity.com/journal/article/full/2017/4/271/research-briefs-april-2017

Endocrine Society experts call for expanded screening for primary aldosteronism

Washington, DC–The Endocrine Society today issued a Clinical Practice Guideline calling on physicians to ramp up screening for primary aldosteronism, a common cause of high blood pressure.

People with primary aldosteronism face a higher risk of developing cardiovascular disease and dying from it than other people with high blood pressure. As many as one in ten people with high blood pressure may have primary aldosteronism. Uncontrolled high blood pressure can put these individuals at risk for stroke, heart attack, heart failure or kidney failure.

The guideline, entitled “The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline,” was published online and will appear in the May 2016 print issue of The Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of the Endocrine Society. The guideline updates recommendations from the Society’s 2008 guideline on primary aldosteronism.

“In the past eight years, we have come to recognize that primary aldosteronism, despite being quite common, frequently goes undiagnosed and untreated,” said John W. Funder, MD, PhD, of the Hudson Institute of Medical Research in Clayton, Australia, and chair of the task force that authored the guideline. “This is a major public health issue. Many people with primary aldosteronism are never screened due to the associated costs. Better screening processes are needed to ensure no person suffering from primary aldosteronism and the resulting risks of uncontrolled high blood pressure goes untreated.”

Primary aldosteronism occurs when the adrenal glands — the small glands located on the top of each kidney – produce too much of the hormone aldosterone. This causes aldosterone, which helps balance levels of sodium and potassium, to build up in the body. The resulting excess sodium can lead to a rise in blood pressure.

The Endocrine Society recommends primary aldosterone screening for people who meet one of the following criteria:

  • Those who have sustained blood pressure above 150/100 in three separate measurements taken on different days;
  • People who have hypertension resistant to three conventional antihypertensive drugs;
  • People whose hypertension is controlled with four or more medications;
  • People with hypertension and low levels of potassium in the blood;
  • Those who have hypertension and a mass on the adrenal gland called an adrenal incidentaloma;
  • People with both hypertension and sleep apnea;
  • People with hypertension and a family history of early-onset hypertension or stroke before age 40; and
  • All hypertensive first-degree relatives of patients with primary aldosteronism.

Other recommendations from the guideline include:

  • The plasma aldosterone-to-renin ratio (ARR) test should be used to screen for primary aldosteronism.
  • All patients diagnosed with primary aldosteronism should undergo a CT scan of the adrenal glands to screen for a rare cancer called adrenocortical carcinoma.
  • When patients choose to treat the condition by having one adrenal gland surgically removed, an experienced radiologist should take blood samples from each adrenal vein and have them analyzed. This procedure, called adrenal vein sampling, is the gold standard for determining whether one or both adrenal glands is producing excess aldosterone.
  • For people with primary aldosteronism caused by overactivity in one adrenal gland, the recommended course of treatment is minimally invasive surgery to remove that adrenal gland.
  • For patients who are unable or unwilling to have surgery, medical treatment including a mineralocorticoid receptor (MR) agonist is the preferred treatment option.

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The Hormone Health Network offers resources on primary aldosteronism athttp://www.hormone.org/questions-and-answers/2012/primary-aldosteronism.

Other members of the Endocrine Society task force that developed this guideline include: Robert M. Carey, of the University of Virginia Health System in Charlottesville, VA; Franco Mantero of the University of Padova in Padua, Italy; M. Hassan Murad of the Mayo Clinic in Rochester, MN; Martin Reincke of the Klinikum of the Ludwig-Maximilians-University of Munich in München, Bavaria, Germany; Hirotaka Shibata of Oita University in Oita, Japan; Michael Stowasser of the University of Queensland in Brisbane, Australia; and William F. Young, Jr. of the Mayo Clinic in Rochester, MN.

The Society established the Clinical Practice Guideline Program to provide endocrinologists and other clinicians with evidence-based recommendations in the diagnosis and treatment of endocrine-related conditions. Each guideline is created by a task force of topic-related experts in the field. Task forces rely on evidence-based reviews of the literature in the development of guideline recommendations. The Endocrine Society does not solicit or accept corporate support for its guidelines. All Clinical Practice Guidelines are supported entirely by Society funds.

The Clinical Practice Guideline was co-sponsored by the American Heart Association, the American Association of Endocrine Surgeons, the European Society of Endocrinology, the European Society of Hypertension, the International Association of Endocrine Surgeons, the International Society of Hypertension, the Japan Endocrine Society and The Japanese Society of Hypertension.

The guideline was published online at http://press.endocrine.org/doi/10.1210/jc.2015-4061, ahead of print.

Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

The Society, which is celebrating its centennial in 2016, has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at http://www.endocrine.org. Follow us on Twitter at @TheEndoSociety and @EndoMedia.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

From http://www.eurekalert.org/pub_releases/2016-04/tes-ese042616.php

Blood Lipid Levels Linked to High Blood Pressure in Cushing’s Disease Patients

High lipid levels in the blood may lead to elevated blood pressure in patients with Cushing’s disease, a Chinese study shows.

The study, “Evaluation of Lipid Profile and Its Relationship with Blood Pressure in Patients with Cushing’s Disease,” appeared in the journal Endocrine Connections.

Patients with Cushing’s disease often have chronic hypertension, or high blood pressure, a condition that puts them at risk for cardiovascular disease. While the mechanisms of Cushing’s-related high blood pressure are not fully understood, researchers believe that high levels of cortisol lead to chronic hypertension through increased cardiac output, vascular resistance, and reactivity to blood vessel constrictors.

In children and adults with Cushing’s syndrome, the relationship between increased cortisol levels and higher blood pressure has also been reported. Patients with Cushing’s syndrome may remain hypertensive even after surgery to lower their cortisol levels, suggesting their hypertension is caused by changes in blood vessels.

Studies have shown that Cushing’s patients have certain changes, such as increased wall thickness, in small arteries. The renin-angiotensin system, which can be activated by glucocorticoids like cortisol, is a possible factor contributing to vascular changes by increasing the uptake of LDL-cholesterol (LDL-C) — the “bad” cholesterol — in vascular cells.

Prior research showed that lowering cholesterol levels could benefit patients with hypertension and normal lipid levels by decreasing the stiffness of large arteries. However, the link between blood lipids and hypertension in Cushing’s disease patients is largely unexplored.

The study included 84 patients (70 women) referred to a hospital in China for evaluation and diagnosis of Cushing’s disease. For each patient, researchers measured body mass index, blood pressure, lipid profile, and several other biomarkers of disease.

Patients with high LDL-cholesterol had higher body mass index, blood pressure, cholesterol, triglycerides, and apolipoproteinB (apoB), a potential indicator of atherosclerosis and cardiovascular disease.

Data further revealed an association between blood pressure and lipid profile, including cholesterol, triglycerides, apoB and LDL-c. “The results strongly suggested that CHO (cholesterol), LDL-c and apoB might predict hypertension more precisely in [Cushing’s disease],” the scientists wrote.

They further add that high cholesterol, LDL-cholesterol, and apoB might be contributing to high blood pressure by increasing vessel stiffness.

Additional analysis showed that patients with higher levels of “bad” cholesterol — 3.37 mmol/L or higher — had higher blood pressure. This finding remained true, even when patients were receiving statins to lower their cholesterol levels.

No association was found between blood pressure and plasma cortisol, UFC, adrenocorticotropic hormone, or glucose levels in Cushing’s disease patients.

These findings raise some questions on whether lipid-lowering treatment for high blood pressure and cardiovascular disease would be beneficial for Cushing’s disease patients. Further studies addressing this question are warranted.

Adapted from https://cushingsdiseasenews.com/2018/04/24/blood-pressure-linked-lipid-levels-cushings-disease-study/

Cortisol Pumps May Be Viable Option to Reduce Adrenal Crisis in Severe Adrenal Insufficiency

The use of an insulin pump to deliver continuous pulsatile cortisol may be a viable treatment option in patients with severe adrenal insufficiency who are unresponsive to oral corticosteroids, according to study results presented at the 28th Annual Congress of the American Association of Clinical Endocrinologists, held April 24 to 28, 2019, in Los Angeles, California.

According to the investigators, increasing oral steroid doses may be required to prevent adrenal crisis in patients with adrenal insufficiency. However, in light of the associated side effects of long-term use of steroids, an alternative treatment method is needed. Insulin pumps, typically used to treat patients with diabetes, can be used to deliver steroids and may provide symptom control, prevent adrenal crisis, and lower required corticosteroid dose.

The current study enrolled patients with adrenal insufficiency who could not absorb oral corticosteroid treatment or were not responding to treatment. Of 118 patients with adrenal insufficiency, 6 patients were switched to pump treatment.

The results indicated that the use of cortisol pumps was associated with a 78.5% risk reduction for adrenal crisis compared with oral corticosteroids. As hydrocortisone dose was gradually tapered using the cortisol pump, there was a mean dose reduction of 62.77 mg compared with oral corticosteroid therapy.

The researchers noted that in addition to reducing the number of adrenal crises, use of a cortisol pump was found to be associated with better symptom control and quality of life.

“Continuous pulsatile cortisol replacement via pump is an option for management of severe adrenal insufficiency in patients unresponsive to oral therapy,” concluded the researchers.

Reference

Khalil A, Ahmed F, Alzohaili O. Insulin pump for adrenal insufficiency, a novel approach to the use of insulin pumps to deliver corticosteroids in patients with poor cortisol absorption. Presented at: American Association of Clinical Endocrinologists 28th Annual Scientific & Clinical Congress; April 24-28, 2019; Los Angeles, CA.

From https://www.endocrinologyadvisor.com/home/conference-highlights/aace-2019/cortisol-pumps-may-be-viable-option-to-reduce-adrenal-crisis-in-severe-adrenal-insufficiency/

Reasons You Have Flab Around Your Abdomen

Some diseases and conditions could be responsible for your abdominal fat.
Mita Majumdar | Updated: April 24, 2017 6:15 pm

Visceral fat or unhealthy belly fat that surrounds the liver and other organs in the abdomen puts you at risk for serious health problems, such as, metabolic syndrome, heart disease, and type 2 diabetes. But, what causes your pot belly or beer fat in the first place? The most obvious answers you will get is – ‘You are not exercising enough’, or, ‘you are eating too much of fatty foods or sugary foods’, or ‘you are not eating the right foods’, or ultimately, ‘It’s genetics! You got it from your parents’. All of these reasons are true, of course. However, some diseases/ disorders and conditions, too, could be responsible for your abdominal fat and these have nothing to do with not exercising or not eating right. Following are some of these disorders.

Cushing’s Syndrome

Cushing’s syndrome, also called hypercortisolism, is an endocrine disorder that occurs when your body is exposed to high cortisol levels over a long period of time. It is a treatable disorder, however, if it is chronic, the symptoms can last lifelong.

Symptoms: Symptoms vary according to the severity of the disorder. The characteristic symptoms include –

  • Fatty tissue deposits in the midsection
  • Fatty deposits in the upper back, especially between the shoulders, so that it resembles a hump
  • Puffy face
  • Violaceous stretch marks (pink or purple) on the arms, breast, stomach, and thighs that are more than 1 cm wide. [1]
  • Easy bruising
  • Fatigue
  • Hirsutism and irregularity in menstruation in women
  • Loss of libido and erectile dysfunction in men
  • Cognitive dysfunction, depression, unpredictable emotional outbursts, irritability is present in 70-85 percent of people with Cushing’s syndrome.[1]

Causes:

  • Overuse of corticosteroids
  • Overproduction of cortisol by the adrenal glands

Management:

  • Surgery is the first line of treatment for Cushing’s syndrome.
  • Medication include: [2]

a.Pituitary gland directed therapy

b.Adrenal-blocking drugs

c.Glucocorticoid receptor-antagonizing drugs

  • Pituitary radiotherapy

Addison’s disease

Addison’s disease, also called adrenal insufficiency, is a disorder where your adrenal glands produce insufficient hormones, especially, glucocorticoids including cortisol and aldosterone. It is a life-threatening disease that can affect anyone irrespective of their gender or age.

How do glucocorticoids influence abdominal fats? Glucocorticoids including cortisol convert the fats into energy in the liver. They also help your body respond to stress. When sufficient amount of glucocorticoids are not produced by the adrenal glands, the fats accumulate in the abdominal area, and you see it as flab around your middle.

Symptoms:

  • Hyperpigmentation
  • Extreme fatigue
  • Low blood sugar and low blood pressure
  • Salt craving as one of the functions of adrenal glands is to maintain the sodium-potassium balance in the body
  • Nausea, vomiting, abdominal pain
  • Weight loss but gain in abdominal fat

Causes:

  • Insufficient production of adrenal cortex hormones
  • Stopping of prescribed corticosteroids
  • Tuberculosis and other infections of adrenal glands
  • Spread of cancer to the adrenal glands

Management:

  • Oral corticosteroids or corticosteroid injections
  • Intravenous injections of hydrocortisone, saline solution, and dextrose in case of Addisonian crisis

Stress

Chronic stress is a very big cause of belly fat. When you are exposed to stress, a chain reaction starts in the body because of the dysregulation of HPA axis of the neuroendocrine system. HPA axis is a complex interaction between the hypothalamus, pituitary gland, and adrenal glands. The hypothalamus produces a corticotropin releasing hormone (CRH) and vasopressin. These together stimulate the secretion of adrenocorticotropic hormone (ACTH). ACTH is transported by the blood to the adrenal glands, which then produces corticosteroids, mainly, cortisol from cholesterol. One of the functions of cortisol is to signal the body to store fat, and specifically, the fat storage occurs in the abdominal area, where the cortisol receptors are greater. Researchers have found that stress causes hyperactivation of HPA axis, leading to accumulation of fat tissue, especially in the abdomen region.

So, the more and longer you are stressed (or if you are chronically stressed), chances are that you will be carrying more belly fat!

Ascites

Ascites is the buildup of fluid in the abdominal space. Ascites usually occurs in people with cancer, and it is then called malignant ascites. Onset of ascites is generally the terminal phase in cancer. Ascites also occurs in patients with liver cirrhosis, kidney failure, or heart disease.

Symptoms:

The first sign of ascites is an increase in abdominal girth accompanied by weight gain. [4] Although it looks like it is belly fat, it is actually the fluid that causes the bulging.

Other symptoms include:

  • Shortness of breath
  • Nausea and vomiting
  • Swelling in the feet and ankle
  • Decreased appetite, sense of fullness, bloating
  • Fatigue
  • Haemorrhoids

Management:

If the ascites is not causing any discomfort, it may not require any treatment. Treatment of ascites can have many side effects. Talk to your doctor before you go in for management/ treatment.

Abdominal hernia

Abdominal hernia is a swelling or a bulge in the abdominal area where an organ or fatty tissue pushes through a weak spot in the abdominal wall. The abdominal wall is made up of tough connective tissue and tendons that stretch from the ribs to the groin. Depending on the position of the weakness in your abdominal wall, the hernia can be inguinal (groin), femoral (upper thigh), umbilical (belly button), hiatal (upper stomach), or even incisional. Incisional hernia can occur when the intestine pushes through a weak spot at the site of abdominal surgery.

Symptoms:

  • Visible bulge that may or may not cause discomfort
  • Feeling of heaviness in the abdomen
  • Sharp pain when you strain or lift objects

Causes:

  • Constipation and diarrhoea
  • Persistent coughing and sneezing
  • Straining or suddenly lifting a heavy object

Management:

  • Umbilical hernia, common in young children, mostly resolves by itself as the abdominal muscles get stronger.
  • Other abdominal hernia normally do not resolve by themselves. Doctors suggest waiting and watching.
  • If treatment is required, surgery is the only option. Surgery involves pushing the hernia back into the abdomen and repairing the abdominal wall.

Menopause

Menopause is certainly not a disease or a disorder. It is the time in a woman’s life when she stops menstruating and cannot become pregnant because her ovaries stop producing the required amounts of hormones oestrogen and progesterone. A woman reaches menopause when she has not had her periods for 12 months.

Symptoms:

  • Hot flashes and/ or night sweats
  • Vaginal dryness
  • Mood swings
  • Sleep disturbances

It is very common to gain belly fat during menopause. This is because of the low oestrogen levels. Oestrogen seems to influence the distribution of fat in the body, in a way that the fat is redistributed from the hips, buttocks, and thighs to the belly. However, a study published in the journal Metabolism reported that though women did significantly gain belly fat, especially deep inside the belly, relative fat distribution is not significantly different after menopause. [5] But the fact remains that women do gain flab in the abdomen after menopause.

Belly fat can be seriously harmful. If your belly fat is not because of the above-mentioned conditions, you can lose it by adopting a healthy lifestyle that includes sleeping enough, exercising regularly, eating right, and reducing stress.

Reference

  1. Sharma ST, Nieman LK, Feelders RA. Cushing’s syndrome: epidemiology and developments in disease management. Clinical Epidemiology. 2015;7:281-293. doi:10.2147/CLEP.S44336.
  1. Feelders RA, Hofland LJ. Medical treatment of Cushing’s disease. J Clin Endocrinol Metab. 2013;98:425–438.
  1. Kyrou I, Chrousos GP, Tsigos C. Stress, visceral obesity, and metabolic complications. Ann N Y Acad Sci. 2006 Nov;1083:77-110.
  1. Sinicrope FA. Ascites. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003.
  2. Franklin RM, Ploutz-Snyder L, Kanaley JA. Longitudinal changes in abdominal fat distribution with menopause. Metabolism. 2009 Mar;58(3):311-5. doi: 10.1016/j.metabol.2008.09.030.

Adapted from http://www.thehealthsite.com/diseases-conditions/reasons-you-have-flab-around-your-abdomen-f0417/