Enzyme linked to obesity

Posted on September 11, 2013 by MaryO

Researchers find that increased levels of an enzyme in fat cells lead to dangerous levels of abdominal obesity.

Previous studies have shown that the stress hormone cortisol can lead to an accumulation of fat round the abdomen. For instance, people with Cushing’s disease – where there’s excess cortisol in the blood – have too much abdominal fat. It’s bad for health to have fat in this area – it’s linked to diabetes and heart disease. That’s why it’s healthier to be a ‘pear shape’ rather than an ‘apple shape’. The distribution of fat in your body really does matter.

Researchers in Scotland and the US have now focussed upon an enzyme that produces cortisol to see what effect it has on abdominal fat. Working on mice genetically-modified to produce the enzyme – and therefore cortisol – in fat cells, they find that even a small increase in levels produces dramatic effects. The mice, compared with normal animals, gained fat in the abdominal area even on a low fat diet. They developed diabetes, high blood pressure, and also tended to eat more. It opens up the possibility of further studies on human obesity, and also perhaps could lead to therapies that block this enzyme and so reduce fat accumulation.

From http://www.tele-management.ca/2013/09/enzyme-linked-to-obesity/

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Differences Between Cushing’s Syndrome and Cushing’s Disease

Posted on August 28, 2013 by MaryO

What’s the difference between Cushing’s Disease and Cushing’s Syndrome?

disease-syndrome

Cushing’s syndrome is a hormonal disorder

Cortisol is a normal hormone produced in the outer portion of the adrenal glands. When functioning normally, cortisol helps the body respond to stress and change. It mobilizes nutrients, modifies the body’s response to inflammation, stimulates the liver to raise blood sugar, and helps control the amount of water in the body. Cortisol production is regulated by the adrenocorticotrophic hormone (ACTH), produced in the pituitary gland. Spontaneous overproduction of cortisol in the adrenals is divided into two groups – those attributed to an excess of ACTH and those that are independent of ACTH.

Cushing’s syndrome is the term used to describe a group of symptoms that occur when a persons’ cortisol levels are too high (known as hypercortisolism) for too long. The majority of people have Cushing’s syndrome because they are regularly taking certain medicine(s) that continually add too much cortisol to the body. Doctors call this an “exogenous” (outside the body) cause of Cushing’s syndrome. Other people have Cushing’s syndrome because something is causing the adrenal gland(s) to overproduce cortisol. Doctors call this an “endogenous” (inside the body) cause of Cushing’s syndrome.

Cushings-causes.png

Cushing’s disease is a form of Cushing’s syndrome

Cushing’s disease is the most common form of endogenous Cushing’s syndrome. It is caused by a tumor in the pituitary gland that secretes excessive amounts of a hormone called Adrenocorticotropic hormone, or ACTH. Fortunately, this type of tumor is typically benign. Unlike a cancerous (malignant) tumor, a benign tumor stays in its original location and will not spread. After you are diagnosed with Cushing’s syndrome, it is important that your doctor continues the diagnostic process to determine the cause of hypercortisolism.

From the message boards It is not only a tumor that causes Cushings Disease—many of us have the rarer form of this rare disease which is Pituitary Hyperplasia. It also causes CD and may be nodular (shown on MRI s a tumor) or dispersed (meaning spread throughout the gland).

How a pituitary tumor causes Cushing’s disease

Pituitary.jpg

ACTH is a hormone produced in your pituitary gland. ACTH travels to your adrenal glands and signals them to produce cortisol.

Pituitary adenomas are benign tumors of the pituitary gland which secrete increased amounts of ACTH, causing excessive cortisol production. Most patients have a single adenoma. First described in 1912 by neurosurgeon Harvey Cushing in his book The Pituitary Body and its Disorders, Cushing’s disease is the most common cause of spontaneous Cushing’s syndrome, accounting for 60 to 70 percent of cases.

If a person has Cushing’s disease, it means that a group of abnormal cells has built up in the pituitary gland to form an ACTH-producing pituitary tumor. These abnormal cells produce ACTH, just as normal pituitary gland cells do—only far too much. The excess ACTH travels to adrenal glands. The adrenal glands are then bombarded with signals to produce more and more cortisol. As a result, the adrenal glands continuously secrete too much cortisol.

Ectopic ACTH Syndrome

Some benign or malignant (cancerous) tumors that arise outside the pituitary can produce ACTH. This condition is known as ectopic ACTH syndrome. Lung tumors cause more than 50 percent of these cases. Other less common types of tumors that can produce ACTH are thymomas, pancreatic islet cell tumors, and medullary carcinomas of the thyroid.

Adrenal Tumors

Adrenal glands.jpg

An abnormality of the adrenal glands such as an adrenal tumor may cause Cushing’s syndrome. Most of these cases involve non-cancerous tumors called adrenal adenomas, which release excess cortisol into the blood.

Adrenocortical carcinomas, or adrenal cancers, are the least common cause of Cushing’s syndrome. Cancer cells secrete excess levels of several adrenal cortical hormones, including cortisol and adrenal androgens. Adrenocortical carcinomas often cause very high hormone levels and rapid onset of symptoms.

Familial Cushing’s syndrome

Most cases of Cushing’s syndrome are not genetic. However, some individuals may develop Cushing’s syndrome due to an inherited tendency to develop tumors of one or more endocrine glands. In Primary Pigmented Micronodular Adrenal Disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. In Multiple Endocrine Neoplasia Type I (MEN I), hormone secreting tumors of the parathyroid glands, pancreas and pituitary occur. Cushing’s syndrome in MEN I may be due to pituitary, ectopic or adrenal tumors.

Risk factors

Obesity, type 2 diabetes, poorly controlled blood glucose (blood sugar levels), and high blood pressure may increase the risk of developing this disorder.

Adapted from http://www.cushiewiki.com/index.php?title=Cushing%27s_Disease_or_Syndrome

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Cyclic Cushing’s syndrome: a clinical challenge

Posted on August 11, 2013 by MaryO
  1. J R Meinardi1,2,
  2. B H R Wolffenbuttel2 and
  3. R P F Dullaart2

+Author Affiliations


  1. 1Department of Internal Medicine, Canisius Wilhelmina Ziekenhuis, PO Box 9015, 6500 GS Nijmegen, The Netherlands and 2Department of Endocrinology, University Medical Centre Groningen, University of Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands
  1. (Correspondence should be addressed to: R P F Dullaart; Email:r.p.f.dullaart@int.umcg.nl)

Abstract

Cyclic Cushing’s syndrome (CS) is a rare disorder, characterized by repeated episodes of cortisol excess interspersed by periods of normal cortisol secretion. The so-called cycles of hypercortisolism can occur regularly or irregularly with intercyclic phases ranging from days to years.

To formally diagnose cyclic CS, three peaks and two troughs of cortisol production should be demonstrated. Our review of 65 reported cases demonstrates that cyclic CS originates in 54% of cases from a pituitary corticotroph adenoma, in 26% from an ectopic ACTH-producing tumour and in about 11% from an adrenal tumour, the remainder being unclassified. The pathophysiology of cyclic CS is largely unknown.

The majority of patients with cyclic CS have clinical signs of CS, which can be either fluctuating or permanent. In a minority of patients, clinical signs of CS are absent. The fluctuating clinical picture and discrepant biochemical findings make cyclic CS extremely hard to diagnose. Clinicians should therefore be aware of this clinical entity and actively search for it in all patients with suspected CS but normal biochemistry or vice versa.

Frequent measurements of urinary cortisol or salivary cortisol levels are a reliable and convenient screening tool for suspected cyclic CS. Cortisol stimulation or suppression tests may give spurious results owing to spontaneous falls or rises in serum cortisol at the time of testing. When cyclic CS is biochemically confirmed, further imaging and laboratory studies are guided by the presence or absence of ACTH dependency. In cases of suspected ectopic ACTH production, specific biochemical testing for carcinoids or neuroendocrine tumours is required, including measurements of serotonin in platelets and/or urine, chromogranin A and calcitonin.

Read the entire article here:  http://www.scribd.com/doc/159503297/Cyclic-Cushing%E2%80%99s-syndrome-a-clinical-challenge

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Cushing’s Disease – Rare Disease Quick Facts

Posted on July 13, 2013 by MaryO

cushings-diagnosis

 

 

Cushing’s disease is a rare condition due to excess cortisol levels that result from a pituitary tumor secreting adrenocorticotropic hormone (ACTH), which stimulates cortisol secretion.  Cushing’s disease should not be confused with Cushing’s syndrome which is increased cortisol levels but that increase can be due to any number of factors. However, Cushing’s disease is the most common form of Cushing’s syndrome.

Symptoms

The symptoms related to Cushing’s disease and Cushing’s syndrome are the same, since both are related to an excess of cortisol. Also, symptoms vary extensively among patients and that, with the inherent fluctuation in hormone levels make it difficult to diagnosis both conditions.

Changes in physical characteristics of the body

  • Fullness and rounding of the face
  • Added fat on back of neck (so-called “buffalo hump”)
  • Easy bruising
  • Purplish stretch marks on the abdomen (abdominal striae)
  • Excessive weight gain, especially in abdominal region
  • Red cheeks
  • Excess hair growth on the face, neck, chest, abdomen and thighs

Changes in physiology/psychology

  • Generalized weakness and fatigue
  • Menstrual disorder
  • Decreased fertility and/or sex drive
  • High blood pressure that is often difficult to treat
  • Diabetes mellitus
  • Mood and behavior disorders

Diagnosis

The early stages of Cushing’s disease may be difficult to recognize. However, if it is suspected, diagnosis is generally a 2 stage process. First to determine if cortisol levels are high, and if so, why they are high.

Tests to confirm high cortisol levels:

  • 24-hour urine cortisol
  • Dexamethasone suppression test (low dose)

Tests to determine cause:

  • Blood ACTH level
  • Brain MRI
  • Corticotropin-releasing hormone test
  • Dexamethasone suppression test (high dose)
  • Petrosal sinus sampling

Treatment

Surgery

  • Most patients with Cushing’s disease undergo surgery to remove the pituitary adenoma offers.
  • If the tumor is isolated to the pituitary, cure rates of 80-85% are common.
  • If the tumor has spread to nearby organs, cure rates of 50-55% are common.

Medicine (approved orphan drugs)

Signifor (pasireotide)

  • Approved for patients with Cushing’s disease for whom pituitary is not an option or surgery has been ineffective.
  • Signifor is a somatostatin receptor agonist that leads to inhibition of ACTY secretion (and subsequently decreased cortisol levels).

Korlym (mifepristone)

  • Approved for patients with Cushing’s syndrome who have type 2 diabetes or glucose intolerance and have failed surgery (or not candidates for surgery).
  • Korlym is a glucocorticoid receptor antagonist which in turn blocks the effects of the high levels of cortisol in the body. Korlym is used to treat high glucose levels due to elevated cortisol.

Medicines used but not indicated for Cushing’s disease include

Mitoden

ketoconazole

Metyrapone

Etomidate

Radiation

  • Radiation therapy may be used in some patients and can be very effective in controlling the growth of these tumors.

Prognosis

In most cases, treatment can cure Cushing’s disease. If not treated properly, the chronic hypercortisolism can lead to excess morbidity and mortality due to increased cardiovascular and other risk factors.

For more information

National Library of Medicine, National Institute of Health

Cushing’s Disease Information (provided by Novartis Pharmaceuticals)

 

Images courtesy of the open access journal Orhanet Journal for Rare Diseases.  Castinetti et al. Orphanet J Rare Dis. 2012 7:41   doi:10.1186/1750-1172-7-41

– See more at: http://www.raredr.com/front-page-medicine/articles/cushings-disease-rare-disease-quick-facts-0

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Pituitary tumor size not definitive for Cushing’s

Posted on July 12, 2013 by MaryO

By: SHERRY BOSCHERT, Family Practice News Digital Network

SAN FRANCISCO – The size of a pituitary tumor on magnetic resonance imaging in a patient with ACTH-dependent Cushing’s syndrome can’t differentiate between etiologies, but combining that information with biochemical test results could help avoid costly and difficult inferior petrosal sinus sampling in some patients, a study of 131 cases suggests.

If MRI shows a pituitary tumor larger than 6 mm in size, the finding is 40% sensitive and 96% specific for a diagnosis of Cushing’s disease as the cause of adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, and additional information from biochemical testing may help further differentiate this from ectopic ACTH secretion, Dr. Divya Yogi-Morren and her associates reported at the Endocrine Society’s Annual Meeting.

Pituitary tumors were seen on MRI in 6 of 26 patients with ectopic ACTH secretion (23%) and 73 of 105 patients with Cushing’s disease (69%), with mean measurements of 4.5 mm in the ectopic ACTH secretion group and 8 mm in the Cushing’s disease group. All but one tumor in the ectopic ACTH secretion group were 6 mm or smaller in diameter, but one was 14 mm.

Because pituitary “incidentalomas” as large as 14 mm can be seen in patients with ectopic ACTH secretion, the presence of a pituitary tumor can’t definitively discriminate between ectopic ACTH secretion and Cushing’s disease, said Dr. Yogi-Morren, a fellow at the Cleveland Clinic.

That finding contradicts part of a 2003 consensus statement that said the presence of a focal pituitary lesion larger than 6 mm on MRI could provide a definitive diagnosis of Cushing’s disease, with no further evaluation needed in patients who have a classic clinical presentation and dynamic biochemical testing results that are compatible with a pituitary etiology (J. Clin. Endocrinol. Metab. 2003;88:5593-602). The 6-mm cutoff, said Dr. Yogi-Morren, came from an earlier study reporting that 10% of 100 normal, healthy adults had focal pituitary abnormalities on MRI ranging from 3 to 6 mm in diameter that were consistent with a diagnosis of asymptomatic pituitary adenomas (Ann. Intern. Med. 1994;120:817-20).

A traditional workup of a patient with ACTH-dependent Cushing’s syndrome might include a clinical history, biochemical testing, neuroimaging, and an inferior petrosal sinus sampling (IPSS). Biochemical testing typically includes tests for hypokalemia, measurement of cortisol and ACTH levels, a high-dose dexamethasone suppression test, and a corticotropin-releasing hormone (CRH) stimulation test. Although IPSS is the gold standard for differentiating between the two etiologies, it is expensive and technically difficult, especially in institutions that don’t regularly do the procedure, so it would be desirable to avoid IPSS if it’s not needed in a subset of patients, Dr. Yogi-Morren said.

The investigators reviewed charts from two centers (the Cleveland Clinic and the M.D. Anderson Cancer Center, Houston) for patients with ACTH-dependent Cushing’s syndrome seen during 2000-2012.

ACTH levels were significantly different between groups, averaging 162 pg/mL (range, 58-671 pg/mL) in patients with ectopic ACTH secretion, compared with a mean 71 pg/mL in patients with Cushing’s disease (range, 16-209 pg/mL), she reported. Although there was some overlap between groups in the range of ACTH levels, all patients with an ACTH level higher than 210 pg/mL had ectopic ACTH secretion.

Median serum potassium levels at baseline were 2.9 mmol/L in the ectopic ACTH secretion group and 3.8 mmol/L in the Cushing’s disease group, a significant difference. Again, there was some overlap between groups in the range of potassium levels, but all patients with a baseline potassium level lower than 2.7 mmol/L had ectopic ACTH secretion, she said.

Among patients who underwent a high-dose dexamethasone suppression test, cortisol levels decreased by less than 50% in 88% of patients with ectopic ACTH secretion and in 26% of patients with Cushing’s disease.

Most patients did not undergo a standardized, formal CRH stimulation test, so investigators extracted the ACTH response to CRH in peripheral plasma during the IPSS test. As expected, they found a significantly higher percent increase in ACTH in response to CRH during IPSS in the Cushing’s disease group, ranging up to more than a 1,000% increase. In the ectopic ACTH secretion group, 40% of patients did have an ACTH increase greater than 50%, ranging as high as a 200%-300% increase in ACTH in a couple of patients.

“Although there was some overlap in the biochemical testing, it is possible that it provides some additional proof to differentiate between ectopic ACTH secretion and Cushing’s disease,” Dr. Yogi-Morren said.

In the ectopic ACTH secretion group, the source of the secretion remained occult in seven patients. The most common identifiable cause was a bronchial carcinoid tumor, in six patients. Three patients each had small cell lung cancer, a thymic carcinoid tumor, or a pancreatic neuroendocrine tumor. One patient each had a bladder neuroendocrine tumor, ovarian endometrioid cancer, medullary thyroid cancer, or a metastatic neuroendocrine tumor from an unknown primary cancer.

The ectopic ACTH secretion group had a median age of 41 years and was 63% female. The Cushing’s disease group had a median age of 46 years and was 76% female.

Dr. Yogi-Morren reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

From Famiiy Practice News

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