Endocrine Society issues new guidelines on hypopituitarism

Posted on October 15, 2016 by MaryO

The Endocrine Society today issued a Clinical Practice Guideline that recommends treating insufficient hormone levels in individuals with hypopituitarism by replacing hormones at levels as close to the body’s natural patterns as possible.

The guideline, titled “Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline,” was published online and will appear in the November 2016 print issue of The Journal of Clinical Endocrinology & Metabolism (JCEM), a publication of the Endocrine Society.

Hypopituitarism, or pituitary insufficiency, occurs when the pituitary gland does not produce sufficient amounts of hormones–the chemical signals that regulate respiration, reproduction, growth, metabolism, sexual function and other important biological functions. The pituitary gland is often called the master gland because the hormones it produces impact many bodily functions. As a result, hypopituitarism can cause a range of symptoms, according to the Hormone Health Network.

The rare disorder can occur due to abnormal development or later in life as a result of a tumor, traumatic brain injury, hemorrhage or autoimmune condition, according to the Society’s

“Hypopituitarism can manifest as low levels of a variety of hormones, including cortisol, thyroid hormone, estrogen, testosterone and growth hormone,” said Maria Fleseriu, MD, FACE, of Oregon Health & Science University in Portland, OR. Fleseriu chaired the task force that developed the guideline. “The goal of treatment should be to restore hormone levels as close to healthy levels as possible The interactions between these hormones also are very important, and patients might require dose changes of one or more of the replacement hormones after starting or discontinuing another one.”

In recommending treatment options, the guideline task force followed the overriding principle of using hormone replacement therapy dose size and timing to mimic the body’s natural functioning as closely as possible.

Accurate and reliable measurements of hormones play a central role in diagnosing hypopituitarism and monitoring the effectiveness of treatments, Fleseriu said. Healthcare providers need to keep in mind technical considerations to ensure the testing procedure is as accurate as possible.

The guideline addresses special circumstances that may affect the treatment of patients with hypopituitarism, including pregnancy care, post-surgical care following pituitary or other operations, treatment in combination with anti-epilepsy medication, and care following pituitary apoplexy–a serious condition that occurs when there is bleeding into the gland or blood flow to it is blocked.

Recommendations from the guideline include:

  • Measurements of both free thyroxine and thyroid-stimulating hormone are needed to evaluate central hypothyroidism, a condition where the thyroid gland does not produce enough hormones because it isn’t stimulated by the pituitary gland.
  • People who have central hypothyroidism should be treated with levothyroxine in doses sufficient to raise levels of the thyroid hormone free thyroxine to the upper half of the reference range.
  • Growth hormone stimulation testing should be used to diagnose patients with suspected growth hormone deficiency.
  • People who have proven cases of growth hormone deficiency and no contraindications should be offered growth hormone replacement as a treatment option.
  • Premenopausal women who have central hypogonadism, a condition where the sex glands produce minimal amounts or no hormones, can undergo hormone treatment, provided there are no contraindications.
  • People producing abnormally large volumes of dilute urine should be tested for central diabetes insipidus–a rare condition that leads to frequent urination–by analyzing the concentration of their blood and urine.
  • For patients who have low levels of glucocorticoid hormones, hydrocortisone can be given in a daily single or divided dose.
  • All hypopituitarism patients should be instructed to obtain an emergency card, bracelet or necklace warning about the possibility of adrenal insufficiency.
  • Patients who are suspected of having an adrenal crisis due to secondary adrenal insufficiency should receive an immediate injection of 50 to 100 milligrams of hydrocortisone.
  • People who have central adrenal insufficiency should receive the lowest tolerable dose of hydrocortisone replacement on a long-term basis to reduce the risk of metabolic and cardiovascular disease.
Source:

The Endocrine Society

From http://www.news-medical.net/news/20161013/Endocrine-Society-issues-new-guidelines-on-hypopituitarism.aspx

Filed under: Cushing's, pituitary, Treatments | Tagged: , , , , , , , , , | Leave a comment »

Cushing’s disease best treated by endocrinologist

Posted on October 4, 2016 by MaryO

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

Filed under: adrenal, Cushing's, Diagnostic Testing, pituitary, symptoms, Treatments | Tagged: , , , , , , , , , | Leave a comment »

“How can you leave her like this?”

Posted on September 8, 2016 by MaryO

A mother has revealed the anguish her family suffered after her daughter (16), who is in need of brain surgery, was turned away from Beaumont Hospital.

The National Centre for Neurosurgery had no beds or theatre access for nine patients with malignant brain tumours last Friday.
One of the people who was turned away was 16-year-old Chloe Holian from Donegal.

Her mother Caitriona explained to the Anton Savage Show on TodayFM that the road to treatment has been fraught with setbacks.

“I can’t stress how happy I am with the neurosurgeon and his team are there but it seems our consultant’s hands are tied, what am I supposed to do?” she said.

Chloe was diagnosed in July with a recurrence of Cushing’s syndrome, a metabolic disorder which is caused by abnormally high levels of the hormone cortisol in the blood stream.

After being promised treatment in July and then August, the Letterkenny girl was finally admitted on Thursday and was fasting for a procedure on Friday morning when she was told it was cancelled.

“When we got down they told us that they decided to put off the surgery for a couple of days,” said Caitriona.

She was told that the doctors wanted to perform a dexamethasone suppression test first to confirm that Chloe was, in fact, suffering from Cushing’s – despite previous diagnosis revealing that she was.

However, she soon found out that the test couldn’t be performed.

“At 11am someone in scrubs came around to say it wasn’t fair but he had to tell us she won’t be doing the surgery… and she wouldn’t be getting the major test either,” said Caitriona.

She said he was very empathetic of their situation.

“I felt sorry for him having to tell us that news… I asked him ‘how can you leave her like this?’

“He promised that he was going to organise this test himself. It was quite difficult as you need four people in the surgery to do this test, you need the radiographer, neurosurgeon, endocrinologist and anesthetist.”

Unfortunately, an anesthetist was not available for the test.

Caitriona said that Chloe was quite upset at the news. One of the side-effects of her condition is excessive weight gain and the student has gained six stone since last September.

“She had psyched herself up for the surgery,” explained her mother.

“Everybody was around her encouraging her, they threw a party for her before she went because it was a big thing. Chloe has no confidence because she’s put on an extra six stone. She was looking forward to getting her old self back, she just wanted to go and do this operation and get it over and done with.

“For anybody to have a little bit of a weight gain they can be conscious of it but if you’re 16-years-old and you’ve gained six stone and you can’t explain it…”

Caitriona said the family were forced to pack their bags and return to Donegal but, as of today, they have still not received a rescheduled appointment.

The mother-of-three is struggling to juggle home life with trips to Dublin but she said the family’s life is on hold until the tumour is removed.

This is the second time that Chloe has developed Cushing’s, in 2009 she was sent to London for surgery as treatment was not yet available in Ireland.

Patients lives are being threatened by delays, according to the head of the country’s national brain surgery centre. Clinical Director Mohsen Javadpour says people are at risk of dying while they’re waiting for treatment.

From http://www.independent.ie/life/how-can-you-leave-her-like-this-mothers-anguish-as-daughter-16-in-need-of-brain-surgery-is-turned-away-from-beaumont-35029557.html

Filed under: Cushing's, pituitary, Treatments | Tagged: , , , , , | 2 Comments »

Experimental Drug Improves Cushing’s Disease

Posted on August 12, 2016 by MaryO

International phase 3 trial is largest study ever of rare endocrine disorder

A new investigational drug significantly reduced urinary cortisol levels and improved symptoms of Cushing’s disease in the largest clinical study of this endocrine disorder ever conducted.

Results of the clinical trial conducted at centers on four continents appear in the March 8 issue of the New England Journal of Medicine and show that treatment with pasireotide cut cortisol secretion an average of 50 percent and returned some patients’ levels to normal.

“Cushing’s disease is a rare disorder, with three to five cases per million people. It can affect all ages and both genders but is most common in otherwise healthy young women,” says Harvard Medical School Professor of Medicine Beverly M.K. Biller of the Massachusetts General Hospital (MGH) Neuroendocrine Unit, senior author of the study.

“Often misdiagnosed, Cushing’s is associated with a broad range of health problems – causing physical changes, metabolic abnormalities, and emotional difficulties – and if not controlled, significantly increases patients’ risk of dying much younger than expected,” Biller says.

Cushing’s disease, one of several conditions that lead to Cushing’s syndrome, is characterized by chronically elevated secretion of the hormone cortisol. The disease is caused by a benign pituitary tumor that oversecretes the hormone ACTH, which in turn induces increased cortisol secretion by the adrenal glands.

Symptoms of Cushing’s syndrome include weight gain, hypertension, mood swings, irregular or absent periods, abnormalities of glucose processing (insulin resistance, glucose intolerance, and type 2 diabetes), and cardiovascular disease. Because those symptoms are associated with many health problems, physicians may not consider the rare possibility of Cushing’s. The diagnosis can be difficult to make and usually requires the expertise of an endocrinologist. Because cortisol levels normally fluctuate during the day, a single blood test is unlikely to identify chronic elevation, and thus the most common diagnostic test measures a patient’s 24-hour urinary output.

First-line treatment for Cushing’s disease is surgical removal of the ACTH-secreting tumor, which leads to remission in 65 to 90 percent of patients. But symptoms return in 10 to 30 percent of those patients, requiring repeat surgery, radiation therapy, or treatment with drugs that interfere with part of the cortisol control system. Until last month, there was no specific FDA-approved medical treatment for Cushing’s syndrome; the newly approved drug mifepristone should benefit some patients, but it does not affect the pituitary source of the condition or reduce cortisol levels.

The current phase 3 trial of pasireotide — the first drug that blocks ACTH secretion by binding to somatostatin receptors on the pituitary tumor — was sponsored by Novartis Pharma. The trial enrolled 162 patients at 62 sites in 18 countries. Nearly 85 percent of participants had either persistent disease that had not responded to surgery or had recurrent disease; the other 15 percent were recently diagnosed but not appropriate candidates for surgery.

Participants were randomly assigned to two groups, one starting at two daily 600-microgram injections of pasireotide and the other receiving 900-microgram doses. Three months into the 12-month trial, participants whose urinary cortisol levels remained more than twice the normal range had their dosage levels increased. During the rest of the trial, dosage could be further increased, if necessary, or reduced if side effects occurred.

At the end of the study period, many patients had a significant decrease in their urinary cortisol levels, with 33 achieving levels within normal range at their original dosage by month six of the trial. Participants whose baseline levels were less than five times the upper limit of normal were more likely to achieve normal levels than those with higher baseline levels, and the average urinary cortisol decrease across all participants was approximately 50 percent. Many Cushing’s disease symptoms decreased, and it became apparent within the first two months whether or not an individual was going to respond to pasireotide.

Transient gastrointestinal discomfort, known to be associated with medications in the same family as pasireotide, was an expected side effect. Another side effect was elevated glucose levels in 73 percent of participants, something not seen to the same extent with other medications in this family. These elevated levels will require close attention, because many Cushing’s patients already have trouble metabolizing glucose. Biller explains, “Those patients who already were diabetic had the greatest increases in blood sugar, and those who were pre-diabetic were more likely to become diabetic than those who began with normal blood sugar. However, elevations were even seen in those who started at normal glucose levels, so this is real and needs to be monitored carefully.”

Additional trials of pasireotide are in the works, and a phase 3 study of a long-acting version of the drug was recently announced. Biller notes that the potential addition of pasireotide to available medical treatments for Cushing’s disease would have a number of advantages. “It’s very important to have medications that work at different parts of the cortisol control system – which is the case for the currently used medications that work at the adrenal gland level; pasireotide, which works at the pituitary gland; and mifepristone, which blocks the action of cortisol at receptors in the body. Having more options that work in different ways is valuable because not all patients respond to one medicine and some may be unable to tolerate a specific drug’s side effects.

“As we have more drugs available to treat Cushing’s,” Biller adds, “I think in the long run we may start using combinations of drugs, which is the approach we use in some patients with acromegaly, another disorder in which a pituitary tumor causes excess hormone secretion. Ultimately, we hope to be able to give lower doses leading to fewer overall side effects, but that remains to be determined by future studies.”

Annamaria Colao, University of Naples, Italy, is the lead author of the report. Additional co-authors are Stephan Petersenn, University of Duisberg-Essen, Germany; John Newell-Price, University of Sheffield, U.K.; James Findling, Medical College of Wisconsin, Milwaukee; Feng Gu, Peking Union Medical College Hospital, Beijing; Mario Maldonado, Ulrike Schoenherr, and David Mills, Novartis Pharma; and Luiz Roberto Salgado, University of São Paulo Medical School, Brazil.

From http://dailyrecords.us/experimental-drug-improves-cushings-disease/

Filed under: adrenal, Clinical trials, Cushing's, Diagnostic Testing, pituitary, Treatments | Tagged: , , , , , , , , , , | Leave a comment »

New Diagnostic Criteria for Subclinical Hypercortisolism using Postsurgical Hypocortisolism

Posted on August 12, 2016 by MaryO

Clin Endocrinol (Oxf). 2016 Jun 24. doi: 10.1111/cen.13145. [Epub ahead of print]

 

Abstract

OBJECTIVE:

There is no consensus on the biochemical diagnostic criteria for subclinical hypercortisolism (SH). Using parameters related to the hypothalamic-pituitary-adrenal axis, we aimed to develop a diagnostic model of SH for predicting postsurgical hypocortisolism and metabolic complications.

DESIGN:

Prospective and cross-sectional, observational, multicentre study in Korea.

METHODS:

After exclusion of overt Cushing’s syndrome, adrenal incidentaloma (AI) patients who underwent unilateral adrenalectomy (n = 99) and AI patients (n = 843) were included. Primary outcome was defined as the presence of postsurgical hypocortisolism; secondary outcome was the presence of ≥4 complications (components of the metabolic syndrome and low bone mass). Postsurgical hypocortisolism was determined on the fifth postsurgery day using the ACTH stimulation test.

RESULTS:

Thirty-three of the 99 patients developed postsurgical hypocortisolism. Analysis of the presurgery overnight 1-mg dexamethasone suppression test (1-mg DST) showed that all patients with cortisol levels of >138 nmol/l experienced postsurgical hypocortisolism, whereas those with levels of ≤61 nmol/l did not. The models of (i) 1-mg DST >138 nmol/l or (ii) >61 nmol/l with the presence of one among low levels of ACTH and dehydroepiandrosterone-sulphate had the highest accuracy (89·9%, P < 0·001) and odds ratio [OR 111·62, 95% confidence interval (CI) 21·98-566·74, P < 0·001] for predicting postsurgical hypocortisolism. Finally, patients with the same criteria in the 843 AI patients showed the highest risk for having ≥4 complications (OR 3·51, 95% CI 1·84-6·69, P < 0·001), regardless of gender, age, body mass index and bilaterality.

CONCLUSIONS:

Our proposed model is able to accurately predict subtle cortisol excess and its chronic manifestations in AI patients.

© 2016 John Wiley & Sons Ltd.

PMID:
27341314
DOI:
10.1111/cen.13145

From http://www.ncbi.nlm.nih.gov/pubmed/27341314

Filed under: adrenal, Cushing's, Treatments | Tagged: , , , , , , , , | Leave a comment »

« Previous Page — Next Page »