Oral Test for Adult Growth Hormone Deficiency Approved in US

The US Food and Drug Administration (FDA) has approved an orally available ghrelin agonistmacimorelin (Macrilen, Aeterna Zentaris), to be used in the diagnosis of patients with adult growth-hormone deficiency (AGHD).

Macimorelin stimulates the secretion of growth hormone from the pituitary gland into the circulatory system. Stimulated growth-hormone levels are measured in four blood samples over 90 minutes after oral administration of the agent for the assessment of growth-hormone deficiency.

Prior to the approval of macimorelin, the historical gold standard for evaluation of adult growth-hormone deficiency was the insulin tolerance test (ITT), an intravenous test requiring many blood draws over several hours.

The ITT procedure is inconvenient for patients and medical practitioners and is contraindicated in some patients, such as those with coronary heart disease or seizure disorder, because it requires the patient to experience hypoglycemia to obtain an accurate result.

Adult growth-hormone deficiency is a rare disorder characterized by the inadequate secretion of growth hormone from the pituitary gland. It can be hereditary; acquired as a result of trauma, infection, radiation therapy, or brain tumor growth; or can even emerge without a diagnosable cause. Currently, it is treated with once-daily injections of subcutaneous growth hormone.

“Clinical studies have demonstrated that growth-hormone stimulation testing for adult growth-hormone deficiency with oral…macimorelin is reliable, well-tolerated, reproducible, and safe and a much simpler test to conduct than currently available options,” said Kevin Yuen, MD, clinical investigator and neuroendocrinologist, Barrow Neurological Institute, and medical director of the Barrow Neuroendocrinology Clinic, Phoenix, Arizona, in a press release issued by Aeterna Zentaris.

“The availability of…macimorelin will greatly relieve the burden of endocrinologists in reliably and accurately diagnosing adult growth-hormone deficiency,” he added.

Aeterna Zentaris estimates that approximately 60,000 tests for suspected adult growth-hormone deficiency are conducted each year across the United States, Canada, and Europe.

“In the absence of an FDA-approved diagnostic test for adult growth-hormone deficiency, Macrilen fills an important gap and addresses a medical need for a convenient test that will better serve patients and health providers,” said Michael V Ward, chief executive officer, Aeterna Zentaris.

Macrilen is expected to be launched in the United States during the first quarter of 2018.

It is also awaiting approval in the European Union.

Follow Lisa Nainggolan on Twitter: @lisanainggolan1. For more diabetes and endocrinology news, follow us on Twitter and on Facebook.

From https://www.medscape.com/viewarticle/890457

Increase in Glucose Uptake by Cushing’s Disease-associated Tumors Could Improve Early Detection

An increase in glucose uptake by Cushing’s disease-associated pituitary tumors could improve their detection, new research shows.

The study, “Corticotropin releasing hormone can selectively stimulate glucose uptake in corticotropinoma via glucose transporter 1,” appeared in the journal Molecular and Cellular Endocrinology.

The study’s senior author was Dr. Prashant Chittiboina, MD, from the Department of Neurosurgery, Wexner Medical Center, The Ohio State University, in Columbus, Ohio.

Microadenomas – tumors in the pituitary gland measuring less than 10 mm in diameter – that release corticotropin, or corticotropinomas, can lead to Cushing’s disease. The presurgical detection of these microadenomas could improve surgical outcomes in patients with Cushing’s.

But current tumor visualization methodologies – magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) – failed to detect a significant percentage of pituitary microadenomas.

Stimulation with corticotropin-releasing hormone (CRH), which increases glucose uptake, has been suggested as a method of increasing the detection of adenomas with 18F-FDG PET, by augmenting the uptake of 18F-FDG – a glucose analog.

However, previous studies aiming to validate this idea have failed, leading the research team to hypothesize that it may be due to a delayed elevation in glucose uptake in corticotropinomas.

The scientists used clinical data to determine the effectiveness of CRH in improving the detection of corticotropinomas with 18F-FDG PET in Cushing’s disease.

They found that CRH increased glucose uptake in human and mouse tumor cells, but not in healthy mouse or human pituitary cells that produce the adrenocorticotropic hormone (ACTH). Exposure to CRH increased glucose uptake in mouse tumor cells, with a maximal effect at four hours after stimulation.

Similarly, the glucose transporter GLUT1, which is located at the cell membrane, was increased two hours after stimulation, as was GLUT1-mediated glucose transport.

These findings indicate a potential mechanism linking CRH exposure to augmented glucose uptake through GLUT1. Expectedly, the inhibition of glucose transport with fasentin suppressed glucose uptake.

The researchers consistently observed exaggerated evidence of GLUT1 in human corticotropinomas. In addition, human corticotroph tumor cells showed an increased breakdown of glucose, which indicates that, unlike healthy cells, pituitary adenomas use glucose as their primary source of energy.

Overall, the study shows that corticotropin-releasing hormone (CRH) leads to a specific and delayed increase in glucose uptake in tumor corticotrophs.

“Taken together, these novel findings support the potential use of delayed 18F-FDG PET imaging following CRH stimulation to improve microadenoma detection in [Cushing’s disease],” researchers wrote. The scientists are now conducting a clinical trial to further explore this promising finding.

From https://cushingsdiseasenews.com/2017/10/12/glucose-uptake-in-cushings-disease-could-improve-presurgical-tumor-detection/

An Amusing Look At Hormones And The Pituitary Gland

A moment in the scheming mind of Professor Pituitary and his sidekick, Dr. Hypothalamus!! And… their minions, the Hormonal Kitties!

Low Oxytocin Levels Linked to Reduced Empathy

People suffering from low levels of oxytocin perform worse on empathy tasks, according to new research presented at the 2016 Society for Endocrinology annual conference.

The research suggests that hormone replacement could improve the psychological well-being of those living with low levels, according to researchers at the University of Cardiff.

Oxytocin is often referred to as the “love hormone” due to its role in human behavior, including sexual arousal, recognition, trust, anxiety, and mother-infant bonding. It is produced by the hypothalamus — an area of the brain that controls mood and appetite — and stored in the pituitary gland.

For the study, researchers investigated empathic behavior in people who they suspected of having reduced oxytocin levels due to one of two medical conditions caused in response to pituitary surgery.

The study assessed 20 people with cranial diabetes insipidus (CDI). In CDI, the body has reduced levels of ADH, a chemical also produced in the hypothalamus and structurally very similar to oxytocin.

The researchers also assessed 15 people with hypopituitarism (HP), a condition in which the pituitary gland does not release enough hormones.

These two patient groups were compared to a group of 20 healthy people.

The researchers gave all participants two tasks designed to test empathy, both relating to the recognition of emotional expression. They also measured each group’s oxytocin levels and found that the 35 CDI and HP participants had slightly lower oxytocin compared to the healthy people. The researchers noted that a larger sample is required to establish statistical significance.

The researchers also discovered that the CDI and HP groups performed significantly worse on empathy tasks, compared to the healthy control group. In particular, CDI participants’ ability to identify expressions was predicted by their oxytocin levels — those with the lowest levels of oxytocin produced the worst performances, according to the study’s findings.

“This is the first study which looks at low oxytocin as a result of medical, as opposed to psychological, disorders,” said Katie Daughters, lead researcher. “If replicated, the results from our patient groups suggest it is also important to consider medical conditions carrying a risk of low oxytocin levels.”

“Patients who have undergone pituitary surgery, and in particular those who have acquired CDI as a consequence, may present with lower oxytocin levels,” she continued. “This could impact on their emotional behavior, and in turn affect their psychological well-being. Perhaps we should be considering the introduction of oxytocin level checks in these cases.”

The researchers said they hope to expand their study to further replicate and confirm their findings. They added that the study presents only preliminary results, and has not been peer reviewed.

Source: Society for Endocrinology

From http://psychcentral.com/news/2016/11/06/low-oxytocin-levels-linked-to-reduced-empathy/112110.html

All About the Pituitary Gland



The pituitary gland stimulates all the other endocrine glands to produce their own hormones. It produces a number of hormones including Human Growth Hormone (hGH) responsible for bone and muscle growth and Follicle Stimulating Hormone (FSH) which stimulates the production of the female egg or male sperm.  It is found at the base of the brain.
What can happen when it goes wrong?

When the pituitary gland doesn’t produce enough ‘trigger’ hormones, hypopituitarism occurs. Most often, it is caused by a benign tumor of the pituitary gland although it can also be caused by infections, head injury or even stroke.

Excessive tiredness, reduced fertility, irregular periods, weight gain, poor libido, dry skin and headaches.
If caused by a tumor, surgery will be required to remove it. Regardless of whether this is successful, daily hormones will then be required to replace those no longer produced.

Adapted from http://www.hippocraticpost.com/palliative/whole-story-hormones/

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