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

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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.

Symptoms?
Excessive tiredness, reduced fertility, irregular periods, weight gain, poor libido, dry skin and headaches.
Treatment?
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/

Interview with a Doctor on Trans-Sphenoidal surgery

Dr. Julius July: Neurosurgeon at the Neuroscience Center of Siloam Hospitals Lippo Village Karawaci 

A SIMPLE AND QUICK WAY TO REMOVE TUMORS VIA SURGERY THROUGH THE NOSTRIL

The mention of the word “surgery” evokes images of lengthy and elaborate procedures that involve delicate acts of cutting, abrading or suturing different parts of the body to treat an injury or disease.

This widely-held perception has led some to develop an irrational fear of surgery–especially if an operation involves a critical organ, such as the heart, or in the case of trans-sphenoidal surgery, a procedure used to remove tumors from the hormone-regulating pituitary gland located at the base of the brain.

Though the procedure has been around in different forms for the past three decades, individuals who may be in dire need of it might fear or avoid it.

To demystify this specific method of surgery, J+ spoke with Julius July, a neurosurgeon at the Neuroscience Center of Siloam Hospitals Lippo Village Karawaci. He has performed hundreds of trans-sphenoidal operations on patients throughout the country since 2008. Below is our interview, edited for length and clarity.

Tell us more about trans-sphenoidal surgery.

The goal is to extract benign tumors of the pituitary gland that are called pituitary adenoma. The pituitary gland controls different secretions of hormones. If there is a tumor and it grows large, one of the consequences could be that a patient goes blind. It can also lead to symptoms manifesting in other parts of the body due to excess hormone production, depending on the type of hormone affected by the tumor.

What does a neurosurgeon do during the procedure?

As neurosurgeons we use an endoscope with a camera attached to it and insert the instrument through the nostril. We go through the right nostril and through the sinus to reach the tumor and remove it. Once that is done, we add a coagulant to prevent bleeding. The operation takes only an hour to 90 minutes to perform and is minimally invasive. People come in and expect the surgery to last five or six hours. They hear “surgery” and fearfully assume that. But modern trans-sphenoidal surgery is simple, only lasting one to two hours.

What’s the prognosis after surgery?

In 80 percent of cases, all it takes is one surgery to remove a tumor. However, some need repeated intervention, while others require radiation. Some tumors want to invade their surroundings. In these cases, the surrounding area is a blood vessel. We can’t totally remove that type of tumor. But such cases are rare. If a patient needs more than two operations, we usually recommend radiation, because who wants to have a lot of operations?

What are the symptoms of pituitary adenoma?

Symptoms depend on whether a tumor affects hormone production or the optic nerve. The principal complaints are related to a patient’s field of vision becoming narrower. If there is a tumor in the pituitary gland area, the eye can’t see too widely. The tumors would press on the optic nerve, which leads to the periphery of your vision getting blurry.

If the tumor affects hormone production, the symptoms depend on the specific type of hormone that the tumor has affected. Different hormones have different roles. Excess prolactin hormones can lead to women–or even men–producing breast milk. If a woman who isn’t pregnant is producing breast milk, they need to be checked. The basic ingredient of milk is calcium. Without treatment, the woman will have porous bone problems. It also leads to reduced libido. If men have an excess of these prolactin hormones, they cannot get erections and will become impotent.

How does these problem develop in the first place?

Mutations lead to the creation of these benign tumors. Some things make mutations easier, such as smoking or exposure to radiation or specific chemicals. It could be anything. You could have eaten tofu and it had formalin or some meatballs with borax. Preventing it obviously requires a healthy lifestyle, but that’s easier said than done.

It’s not just one thing that causes these tumors.

Who does this pituitary tumor affect?

It affects both genders equally, more or less. The risk of pituitary adenoma compared to all other types of brain tumors is 15 percent. Children are also affected, though the condition is statistically much more likely to afflict adults. Of my patients, two in 70 would be children.

How is it diagnosed?

The doctor will check your hormones after a blood test and identify the problem. For example, if the condition affects growth hormones, a person can grow to two meters or more in height, which leads to gigantism. Alternatively, a condition could lead to horizontal growth–a bigger tongue, bigger fingers and changing shoes each month. The tongue can become so big that it causes breathing problems. Growth hormone overproduction is like a factory with the machine working overtime. As a result, a person’s life span can get cut in half. The heart works overtime, they keep growing and they die prematurely.

How many operations do you perform a year?

I’ve been doing these operations since 2008. I handle 60 to 70 such surgeries a year.

Any notable success stories to share?

One patient from Central Java came in blind. I examined him and said that there was no way we could save his vision by removing his tumor. He was crying. He had been blind for a week. But if no action was taken, the tumor would keep growing and would lead him to becoming crippled. At the end, he decided that he still wanted the operation. Surprisingly though, after the operation, he was able to see. Three months later, he was driving and reading newspapers. It was a fascinating case.

From http://www.thejakartapost.com/news/2016/07/30/well-being-trans-sphenoidal-surgery.html

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