Experts recommend tumor removal as first-line treatment for Cushing’s syndrome

Posted on July 30, 2015 by MaryO

The Endocrine Society today issued a Clinical Practice Guideline (CPG) on strategies for treating Cushing’s syndrome, a condition caused by overexposure to the hormone cortisol.

The CPG, entitled “Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline,” was published online and will appear in the August 2015 print issue of the Journal of Clinical Endocrinology and Metabolism (JCEM), a publication of the Endocrine Society.

Cushing’s syndrome occurs when a person has excess cortisol in the blood for an extended period, according to the Hormone Health Network. When it is present in normal amounts, cortisol is involved in the body’s response to stress, maintains blood pressure and cardiovascular function, keeps the immune system in check, and converts fat, carbohydrates and proteins into energy. Chronic overexposure to the hormone can contribute to the development of cardiovascular disease, infections and blood clots in veins.

People who take cortisol-like medications such as prednisone to treat inflammatory conditions, including asthma and rheumatoid arthritis, can develop Cushing’s syndrome. The high cortisol levels return to normal when they stop taking the medication. This is called exogenous Cushing’s syndrome.

In other cases, tumors found on the adrenal or pituitary glands or elsewhere in the body cause the overproduction of cortisol and lead to the development of Cushing’s syndrome. The Clinical Practice Guidelines focus on this form of the condition, known as endogenous Cushing’s syndrome.

“People who have active Cushing’s syndrome face a greater risk of death – anywhere from nearly twice as high to nearly five times higher – than the general population,” said Lynnette K. Nieman, MD, of the National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, MD, and chair of the task force that authored the guideline. “To reduce the risk of fatal cardiovascular disease, infections or blood clots, it is critical to identify the cause of the Cushing’s syndrome and restore cortisol levels to the normal range.”

In the CPG, the Endocrine Society recommends that the first-line treatment for endogenous Cushing’s syndrome be the removal of the tumor unless surgery is not possible or unlikely to address the excess cortisol. Surgical removal of the tumor is optimal because it leaves intact the hypothalamic-pituitary-adrenal axis, which is integral to the body’s central stress response.

Other recommendations from the CPG include:

  • Tumors should be removed by experienced surgeons in the following situations:— A tumor has formed on one or both of the two adrenal glands.— A tumor that secretes adrenocorticotropic hormone (ACTH) – the hormone that signals the adrenal glands to produce cortisol – has formed somewhere in the body other than the adrenal or pituitary gland.

    — A tumor has formed on the pituitary gland itself.

  • Patients who continue to have high levels of cortisol in the blood after surgery should undergo additional treatment.
  • People who had an ACTH-producing tumor should be screened regularly for the rest of their lives for high cortisol levels to spot recurrences.
  • If patients’ cortisol levels are too low following surgery, they should receive glucocorticoid replacement medications and be educated about adrenal insufficiency, a condition where the adrenal glands produce too little cortisol. This condition often resolves in 1-2 years.
  • Morning cortisol and/or ACTH stimulation tests, or insulin-induced hypoglycemia, can be used to test for the recovery of the hypothalamic-pituitary-adrenal axis in people who have low cortisol levels after surgery. Once the tests results return to normal, glucocorticoid replacement can be stopped.
  • People who have undergone pituitary surgery should be re-evaluated for other pituitary hormone deficiencies during the post-operative period.
  • Patients who have a pituitary tumor and have undergone surgery to remove both adrenal glands should be regularly evaluated for tumor progression using pituitary MRIs and tests for ACTH levels.
  • Radiation therapy may be used to treat a pituitary tumor, especially if it is growing. While awaiting the effect of radiation, which may take months to years, treatment with medication is advised.
  • To assess the effect of radiation therapy, the patient’s cortisol levels should be measured at 6- to 12-month intervals.
  • Medications may be used to control cortisol levels as a second-line treatment after surgery for a pituitary gland tumor, as a primary treatment for ACTH-secreting tumors that have spread to other parts of the body or suspected ACTH-secreting tumors that cannot be detected on scans. Medications also can be used as adjunctive treatment to reduce cortisol levels in people with adrenal cortical carcinoma, a rare condition where a cancerous growth develops in the adrenal gland.
  • People with Cushing’s syndrome should be treated for conditions associated with the disease, such as cardiovascular disease risk factors, osteoporosis and psychiatric symptoms.
  • Patients should be tested for recurrence throughout their lives except in cases where the person had a benign adrenal tumor removed.
  • Patients should undergo urgent treatment within 24 to 72 hours of detecting excess cortisol if life-threatening complications such as serious infection, pulmonary thromboembolism, cardiovascular complications and acute psychosis are present.

More information: The Hormone Health Network offers resources on Cushing’s syndrome at www.hormone.org/questions-and-answers/2012/cushing-syndrome

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What Genes are Related to Cushing’s Disease?

Posted on July 29, 2015 by MaryO

genetic

 

The genetic cause of Cushing disease is often unknown. In only a few instances, mutations in certain genes have been found to lead to Cushing disease. These genetic changes are called somatic mutations. They are acquired during a person’s lifetime and are present only in certain cells. The genes involved often play a role in regulating the activity of hormones.

Cushing disease is caused by an increase in the hormone cortisol, which helps maintain blood sugar levels, protects the body from stress, and stops (suppresses) inflammation. Cortisol is produced by the adrenal glands, which are small glands located at the top of each kidney. The production of cortisol is triggered by the release of a hormone called adrenocorticotropic hormone (ACTH) from the pituitary gland, located at the base of the brain. The adrenal and pituitary glands are part of the hormone-producing (endocrine) system in the body that regulates development, metabolism, mood, and many other processes.

Cushing disease occurs when a noncancerous (benign) tumor called an adenoma forms in the pituitary gland, causing excessive release of ACTH and, subsequently, elevated production of cortisol. Prolonged exposure to increased cortisol levels results in the signs and symptoms of Cushing disease: changes to the amount and distribution of body fat, decreased muscle mass leading to weakness and reduced stamina, thinning skin causing stretch marks and easy bruising, thinning of the bones resulting in osteoporosis, increased blood pressure, impaired regulation of blood sugar leading to diabetes, a weakened immune system, neurological problems, irregular menstruation in women, and slow growth in children. The overactive adrenal glands that produce cortisol may also produce increased amounts of male sex hormones (androgens), leading to hirsutism in females. The effect of the excess androgens on males is unclear.

Most often, Cushing disease occurs alone, but rarely, it appears as a symptom of genetic syndromes that have pituitary adenomas as a feature, such as multiple endocrine neoplasia type 1 (MEN1) or familial isolated pituitary adenoma (FIPA).

Cushing disease is a subset of a larger condition called Cushing syndrome, which results when cortisol levels are increased by one of a number of possible causes. Sometimes adenomas that occur in organs or tissues other than the pituitary gland, such as adrenal gland adenomas, can also increase cortisol production, causing Cushing syndrome. Certain prescription drugs can result in an increase in cortisol production and lead to Cushing syndrome. Sometimes prolonged periods of stress or depression can cause an increase in cortisol levels; when this occurs, the condition is known as pseudo-Cushing syndrome. Not accounting for increases in cortisol due to prescription drugs, pituitary adenomas cause the vast majority of Cushing syndrome in adults and children.

Read more about familial isolated pituitary adenoma.

 

How do people inherit Cushing disease?

Most cases of Cushing disease are sporadic, which means they occur in people with no history of the disorder in their family. Rarely, the condition has been reported to run in families; however, it does not have a clear pattern of inheritance.

The various syndromes that have Cushing disease as a feature can have different inheritance patterns. Most of these disorders are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

From http://ghr.nlm.nih.gov/condition/cushing-disease

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Hydrocortisone Replacement Patient Information

Posted on July 26, 2015 by MaryO

steroids
Patient Information

What is Hydrocortisone?
Hydrocortisone is a steriod hormone produced by the adrenal gland.  It regulates many of the bodies functions and is essential for life.
Hydrocortisone is taken as a replacement for the natural hormone where this is deficient, either because of pituitary deficieny of ACTH (the hormone that stimulates the production of hydrocortisone by the adrenal gland) or failure of hydrocortisone production by the adrenal gland.

How do I take it?
A common dose is 15-20mg orally split over two or three times daily, and depending on your individual Endocrinologist’s recommendations, e.g., 10mg before rising, 5mg at mid-day and 5mg at 4 p.m.

When would I need to take more hydrocortisone?

If you become ill then the body would naturally increase the output of steroid from your adrenals.  Therefore if you are taking replacement steroid (hydrocortisone) it is essential to mimic the natural response by increasing your dose appropriately.

How can I let others know I take replacement hydrocortisone?
When you are prescribed your medication you will be given a ‘blue steroid card’ from the hospital to carry.  You should also purchase and wear a medical necklace or bracelet, such as MedicAlert, to show your Cortisol replacement therapy.

Emergency Injections – should I have these at home?
It is advisable for all patients on hydrocortisone replacement to have a 100mg injection pack at home and for them or their partners to be taught how to administer it.  If you don’t have one of these already, you can ask your GP or endocrinologist if they will prescribe this for you.  Please check regularly that these preparations are not expired.  Some endocrine clinics will help to show you how to inject in an emergency.

When do I know that I would need an emergency injection?

If you cannot absorb your tablets, or your usual replacement wasn’t sufficient for an acute shock or illness, then gradually or perhaps quite quickly you would feel weak, sickly and light-headed.

Recommendations for changes in oral dose ‘The Sick Rules’
If you become unwell you should take additional hydrocortisone. The amount depends on how unwell you are and the type of illness. The pituitary foundation provides some sensible examples:

If a patient is unwell they should take additional hydrocortisone. The amount depends on how unwell they are and the type of illness. Some examples:

Situtation  Increase in dose Duration  Emergency?
Cold without fever   none
Fever, flu, infection         double dose duration of illness see GP after 48 hours
Vomiting > once, diarrhoea and severe illness Emergency 100mg injection if extra dose of 10-20mg cannot be kept down restart usual dose once stable Phone GP or go to A&E. Administer injection prior to this if emergency pack available (but still seek help)
Minor surgical procedure e.g. tooth extraction     20mg hydrocortisone before procedure resume on usual dose immediately afterward
Minor operation e.g. hernia repair  100mg im every 6 hours for 24 hours  resume on usual dose immediately afterward
Major operation e.g. abdomen or chest 100mg im injection every 6 hours for 24 -72 hours and eating and drinking reduce rapidly to usual dose tell the surgeon and anaesthetist before the operation
Endoscopy Double the dose the day before during bowel prep. For colonoscopy 100mg im before procedure take usual dose on the morning of the procedure drink lots of water to prevent dehydration. Inform your doctor.
Cystoscopy Double dose on the day of procedure. resume as normal inform your doctor.
Severe shock e.g. bereavment or road traffic accident 20mg as tablet or 100mg intramuscular injection See GP or hospital for further advice Sudden and severe shock may be classed as an emergency – seek advice
Long haul flight > 12 hours double dose on the day of the flight extra dose every 6-8 hours when the day is legnthened. Usual regimen in timing with sleep / wake cycle when day is shortened. Speak to your consultant before travel.
General stress, exams etc  not usually required ask GP if concerned

How do I cope if I’m travelling away from home?

You should travel with a 100mg injection kit  in case of emergency.  This injection should be placed in a small cool bag, labelled with your name and kept with you at all times during your journey. You should ask your GP or endocrinologist for a letter about your injection kit, medication and your doses prescribed.  This letter is essential to travel through security checks and will be helpful should you become unwell and have to see a doctor. It is wise to take an extra two weeks supply of hydrocortisone tablets with you in case you need to increase your usual dose whilst away.  All medication should be kept in your hand luggage.

Printable patient information

From http://www.imperialendo.com/for-doctors/hydrocortisone-replacement/hydrocortisone-replacement-patient-information

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Food-dependent Cushing syndrome: a new entity of organic hypercorticism

Posted on July 9, 2015 by MaryO
Matejka G, et al. Rev Med Interne. 1996.

Abstract

Diagnosis of Cushing’s syndrome is quite difficult in endocrinology. Spontaneous Cushing’s syndrome is usually divided into two subgroups, one which is dependent on corticotropin (ACTH) and another one which is not.

In the first class are Cushing’s disease, the ectopic corticotropin syndrome and the rare ectopic corticotropin-releasing hormone (CRH) syndrome; these ACTH-dependent Cushing’s syndrome have usually diffusely enlarged adrenal glands.

In the second class are cortisol producing unilateral adrenocortical adenomas or carcinomas, and the recent Cushing’s syndrome with food dependent periodic hormonogenesis.

This food dependent Cushing’s syndrome is an ACTH-independent Cushing’s syndrome with multinodular enlargement of both adrenal glands. Pathogenesis is an aberrant adrenal sensitivity to physiologic secretion of gastric inhibitory peptide (GIP). Ectopic expression of GIP receptors on adrenal cells involve pathologic food induced cortisol secretion.

Food dependent Cushing’s syndrome is a new cause of Cushing’s syndrome. Food induced cortisol secretion may have to be explored in the ACTH-independent Cushing’s syndrome.

PMID

8758532 [PubMed – indexed for MEDLINE]

Full text

Full text from provider (Elsevier Science) Article in French.

From http://www.ncbi.nlm.nih.gov/m/pubmed/8758532/

Biography of a Food-Dependent Cushing’s patient

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Moderately impaired renal function increases morning cortisol and cortisol levels at dexamethasone suppression test in patients with incidentally detected adrenal adenomas

Posted on June 26, 2015 by MaryO
Clin Endocrinol (Oxf). 2015 May 23. doi: 10.1111/cen.12823. [Epub ahead of print]
Olsen H1, Mjöman M2.

Author information

Abstract

OBJECTIVE:

Patients with incidentally detected adrenal adenomas may have subclinical hypercortisolism. We hypothesized that impaired renal function could lead to increased cortisol levels in these patients.

DESIGN:

Descriptive retrospective study of consecutive patients.

PATIENTS:

A total of 166 patients with incidentally detected unilateral adrenal adenomas were examined during 2008-2013.

MEASUREMENTS:

Levels of cortisol, ACTH and cortisol at 1 mg overnight dexamethasone suppression test (DST) were measured. The estimated glomerular filtration rate (eGFR) was calculated using the MDRD equation.

RESULTS:

Renal function was normal, mildly impaired, moderately impaired or severely impaired (eGFR >90, 60-90, 30-60 and 15-30 ml/min/1·73 m2 ) in 34, 54, 10 and 1% of the patients, respectively. Patients with normal and mildly impaired renal function had similar cortisol levels. Patients with moderately impaired renal function, compared to all the patients with eGFR >60 ml/min/1·73 m2 , exhibited increased cortisol (541 vs 456 nmol/l, P = 0·02), increased cortisol at DST (62 vs 37 nmol/l, P = 0·001), but similar ACTH levels (4·1 vs 2·9 pmol/l, P = 0·21). Patients with moderately impaired renal function thus exhibited cortisol at DST ≥50 nmol/l, more often than patients with eGFR >60 ml/min/1·73 m2 (76% vs 30%, P = 0·000), while the prevalence of ACTH below 2 pmol/l was similar (24% vs 31%, P = 0·51).

CONCLUSIONS:

Moderately impaired renal function increases cortisol and cortisol at DST in patients with adrenal adenomas, while mildly impaired renal function has no such effect. Cortisol level at DST ≥50 nmol/l therefore seems to have low specificity in diagnosing subclinical adrenal hypercortisolism, and an additional criterion, for example low ACTH, is required.

© 2015 John Wiley & Sons Ltd.

PMID:
26010731
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/26010731

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