October 24, 2000 - Jean E. Miller

"Finally, there are some rare causes of hypothyroidism related to brain  diseases, also called secondary hypothyroidism. Disorders of the pituitary gland or hypothalamus  portions of the brain may cause thyroid hormone deficiency in addition to other hormonal imbalances.  This type of rare hypothyroidism can also be treated with thyroid hormone medication."

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This is rather long, but follow me here for a few minutes.  Reading the above really perked an interest since I knew that unexplained high fevers in HD have also been attributed to HD damaging the hypothalamus based on:

Dr. Herwig W. Lange, a noted HD specialist in Germany, posted the following message to the MGH HD forum:
   

 "If viral and bacterial causes of fever are excluded, the fever probably is caused by a malfunction of the hypothalamus, an area in the brain which shrinks during the course of HD.  It loses about 15% in volume.  This hypothalamic atrophy makes the brain vulnerable to the effects of dopamine, as seen in cases of malignant neuroleptic hyperthermia in patients with HD, a very serious complication of neuroleptic drugs."
~Herwig W. Lange, MD. NTC  Dusseldorf/Cologne  4.7.97 04:25pm

Now, when you read all the below information on this tiny little power house (I like the UN-scientific version the best) tell me if you reach the same conclusion/therory that I have:

THEORY:  If the hypothalamus is atrophied as a result of degeneration due to Huntington's, then couldn't that be the cause of a whole multitude of HD-related symptoms experienced by some pHD's like Anger/Sexual Promiscuity/Appetite/Hot-Cold Flashes/Thirst/Insomina, Weight Gain-Loss/etc. etc. etc.?  Wouldn't an MRI or like scan show whether or not the hypothalamus has or is atrophying from HD?

If the answer to any of these questions is YES then IS medication for any or all of these symptoms really necessary IF the symptom is not harmful to the person with HD or is causing an emotional problem in their home?   Are we over medicating our loved ones due to a malfunction in the hypothalamus caused by HD which can not be cured?

Am I missing something here?
Love
Jean
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Huntington's:
Pathologically, there is atrophy of certain forebrain structures including the entire cerebral cortex and even more notably of the caudate nucleus and putamen  The head of the caudate is reduced to a narrow brownish band of tissue that is flattened or concave.  In normal brain the ratio of small neurons to large neurons in the corpus striatum is approximately 160:1 in Huntingtons patients the ratio is reduced to 40:1 with a marked decrease in the number of astrocytes.

Parts of the hypothalamus are visible in basal and mid-sagittal views of the gross brain

HYPOTHALAMUS -  [hI"puthal'umus] (hype' oh thal uh mus)
For a detailed description go to: http://lifesci.rutgers.edu/~auerbach/BMlec15/sld008.htm

Less scientific :   The hypothalamus is one of the most important parts of the brain, involved in many kinds of motivation, among other functions.  It controls the "Four F's":   1. fighting; 2. fleeing; 3. feeding; and 4.  mating.

Scientific:   The hypothalamus is a very small region of the brain, making up only around 0.3% of the total brain weight and is about the size of an almond.  Located in the middle of the brain, it lies beneath the thalamus and secretes substances which control metabolism by exerting an influence on pituitary gland function.  It encapsulates the
ventral portion of the third ventricle.  It is a limbic system that runs from forebrain to cerebral cortex.

• The hypothalamus is involved in the regulation of body temperature, water balance, blood sugar, and fat metabolism.
• It also regulates other glands such as the ovaries, parathyroids, and thyroid.   
• It known to be involved in the expression of emotions, almost all aspects of behaviour, including feeding, thirst, sleeping, metabolism,  preservation of individual, pleasant/unpleasant sensations and movement. 
• It is thought to be involved in the expression of emotions,
  such as fear and rage, and in sexual behaviors. 
• It also controls appetite and regulates sleep.
• The pituitary gland may be king, but the power behind the throne is clearly  the hypothalamus.
• All information that enters the brain must pass through the hypothalamus.

PITUARY - The pituitary gland, also known as the hypophysis, is a roundish organ that lies immediately beneath the hypothalamus, resting in a depression of the base of the skull called the sella turcica ("Turkish saddle"). In an adult human or sheep, the pituitary is roughly the size and shape of a large garbonzo bean. The pituitary gland is often portrayed as the "master gland" of the body. Such praise is justified in the sense that the anterior and posterior pituitary secrete a battery of hormones that collectively influence all cells and affect virtually all physiologic processes.

A key to understanding the endocrine relationship between hypothalamus and anterior pituitary is to appreciate the vascular connections between these organs. Secretion of hormones from the anterior pituitary is under strict control by hypothalamic hormones.

HYPOTHALAMUS AND AUTONOMIC NERVOUS SYSTEM http://thalamus.wustl.edu/course/hypoANS.html
From the The Washington University School of Medicine Neuroscience Tutorial

A. Hypothalamus = Homeostasis
The main function of the hypothalamus is homeostasis, or maintaining the body's status quo. Factors such as

• blood pressure
• body temperature
• fluid and electrolyte balance, and
• body weight

are held to a precise value called the set-point. Although this set-point can migrate over time, from day to day it is remarkably fixed.

To achieve this task, the hypothalamus must receive inputs about the state of the body, and must be able to initiate compensatory changes if anything drifts out of whack. The inputs include:

• nucleus of the solitary tract - this nucleus collects all of the visceral sensory information from the vagus and relays it to the hypothalamus and other targets. Information includes blood pressure and gut distension.
• reticular formation - this catchall nucleus in the brainstem receives a variety of inputs from the spinal cord. Among
  them is information about skin temperature, which is relayed to the hypothalamus.
• retina - some fibers from the optic nerve go directly to a small nucleus within the hypothalamus called the suprachiasmatic
  nucleus. This nucleus regulates circadian rhythms, and couples the rhythms to the light/dark cycles.
• circumventricular organs - these nuclei are located along the ventricles, and are unique in the brain in that they lack a blood-brain barrier. This allows them to monitor substances in the blood that would normally be shielded from neural tissue. Examples are the OVLT, which is sensitive to changes in osmolarity, and the area postrema, which is sensitive to toxins in the blood and can induce vomiting. Both of these project to the hypothalamus.
• limbic and olfactory systems - structures such as the amygdala, the hippocampus, and the olfactory cortex project to the hypothalamus, and probably help to regulate behaviors such as eating and reproduction.

The hypothalamus also has some intrinsic receptors, including thermoreceptors and osmoreceptors to monitor temperature and ionic balance, respectively.

Once the hypothalamus is aware of a problem, how does it fix it? Essentially, there are two main outputs:

• neural signals to the autonomic system - the (lateral) hypothalamus projects to the (lateral) medulla, where the cells that drive the autonomic systems are located. These include the parasympathetic vagal nuclei and a group of cells that descend to the sympathetic system in the spinal cord. With access to these systems, the hypothalamus can control heart rate, vasoconstriction, digestion, sweating, etc.
• endocrine signals to/through the pituitary - recall that an endocrine signal is a chemical signal sent via the bloodstream. Large hypothalamic cells around the third ventricle send their axons directly to the posterior pituitary, where the axon terminals release oxytocin and vasopressin into the bloodstream. Smaller cells in the same area send their axons only as far as the base of the pituitary, where they empty releasing factors into the capillary system of the anterior pituitary. These releasing factors induce the anterior pituitary to secrete any one of at least six hormones, including ACTH and thyroid-stimulating hormone (TSH).

Ultimately the hypothalamus can control every endocrine gland in the body, and alter blood pressure (through vasopressin
and vasoconstriction), body temperature, metabolism (through TSH), and adrenaline levels (through ACTH).

In the news lately:

The hypothalamus controls body weight and appetite, but it is not entirely clear how. Sensory inputs, including taste, smell, and gut distension, all tell the hypothalamus if we are hungry, full, or smelling a steak. Yet it is mysterious how we are able to vary our eating habits day to day and yet maintain about the same weight (sometimes despite all efforts to the contrary!) . The "set-point" theory is an old one in diet science, but until recently the mechanics of maintaining that set point were unknown. It appears that there is an endocrine component to the appetite system.

Recent studies in mice have shown that the fat cells of normal overfed mice will release a protein called leptin (or OB, after the gene name), which reduces appetite and perks up metabolism. Leptin is presumably acting on the hypothalamus.

Underfed mice, on the other hand, produce little or no leptin, and they experience an increase in appetite and a decrease in metabolism. In both of these mice, the result is a return to normal weight.

But what would happen if a mouse (or human) had a defective OB gene?

Weight gain would never trigger fat cells to release leptin, the hypothalamus would never slow the appetite or increase metabolism, and the mouse would slowly but surely become obese (how the gene got its name).

Sure enough, shortly after these experiments hit the news, the human OB gene was discovered and a few obese patients were found to have the mutation. Many more obese patients had normal OB genes, however, indicating that there is much more to the story yet to be discovered.

~~

Sorry, I forgot to add one thing.   Based on this part of the Wash. U article, could it also be causing vomiting?  Is the HD damaged hypothalamus causing the body's natural protection against toxins in
the blood?  Just another thought since several people have talked about vomiting or projectile vomiting. I wonder if a blood test to check for a higher toxin concentration would answer any questions??


"circumventricular organs - these nuclei are located along the ventricles, and are unique in the brain in that they lack a blood-brain barrier. This allows them to monitor substances in the blood that would normally be shielded from neural tissue. Examples are the OVLT, which is sensitive to changes in osmolarity, and the area postrema,
which is sensitive to toxins in the blood and can induce vomiting. Both of these project to the hypothalamus.
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Sites where information was taken from:
http://www.ets.uidaho.edu/med532/Huntington.htm
http://www.lalaland.cl.msu.edu/~vanhoose/humor/0326.html
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/hypopit/anatomy.html
http://www.stmarys.medford.or.us/curriculum/bio/hbsm/glands/hypo.htm
http://www.sci.sdsu.edu/Faculty/Paul.Paolini/ppp/lecture14/tsld010.htm
http://live.looksmart.com/cgi-bin/view_a_question.cgi?qptr=qa_2000-05-31.dat:000161665
http://www.encyclopedia.com/articles/06219.html
http://infoplease.lycos.com/ce6/sci/A0824782.html
http://www.dazbert.freeserve.co.uk/brain/hypo.htm
http://my.webmd.com/content/dmk/dmk_article_1458040
http://www.ascd.org/pdi/brain/hypothalamus.html
http://thalamus.wustl.edu/course/hypoANS.html

COMMENTS

Marsha M  October 24, 2000:

HD symptoms are caused by dysfunctional cells and the loss of cells in
the affected areas of the brain which include the frontal lobes, the
basal ganglia, and the hypothalamus.  As we know, there is no treatment yet that has been proven to affect the underlying disease (although they are coming, I am sure of that).  All the treatments currently prescribed are to improve symptoms.  It's a quality of life issue.

Over medication can certainly be a problem though. From the Saturday HD conference: 

• Dr. Amy Colcher, a neurologist with the University of  Pennsylvania, stated that chorea does not need to be treated unless it is bothering the person or causing them to hurt themselves. 
• Dr. Allan Rubin said that when treating HD, doctors need to
  be careful to look at which symptoms will get better with a particular treatment AND which will get worse. 
• As an example, he then showed a list of HD symptoms with the symptoms that would get better with Haldol highlighted.  He showed the list again with the symptoms of HD which would worsen with Haldol - there were several times the number
  highlighted (Once again, it is incomprehensible to me why any doctor would give an HD patient Haldol).

Dr. Rubin also said that every psychiatric symptom of HD could be
treated except for apathy. Because HD isn't curable at this time certainly shouldn't mean that doctors don't treat the symptoms, as long as the side effects of doing so aren't problematic.  I know my husband much prefers to be on medication than not.  It was not pleasant for him to feel irritable and angry over every little thing all day long and he has the wrong wife not to ask the doctor to treat inflexibility! <g>

You mentioned sexual promiscuity.  Dr. Colcher says that this kind of
symptom results from disinhibition caused by front lobe damage.

Jean

Marsha - Gosh, I wasn't trying to imply symptoms not be treated with medications, just care needs to be taken with over medications for, like the doctor's seemed to indicate ie where it wasn't bothering the patient and the symptom couldn't be cured. 

There are some pHD's on medications to treat every symptom (insomnia, depression, stomach, nerves etc) where I would question if the total of all the medications aren't  causing some of the symptoms being experienced.  For example, some medications cause insomnia, confusion, movements, etc.

Dr.  Colcher is saying what Dr. Choi has been saying for years!   It would be interesting to see Dr. Rubin's listing of which symptoms they feel Haldol does help.   The majority of people have had bad experiences with this drug but some families have found it successful.   Having a listing of the symptoms it has been most successful for might "temper" a lot of our personal feelings against this drug (might)!
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"They arise from part of the hypothalamus, a region prominently involved in regulation of the autonomic nervous system, endocrine activity, and mood and motivational states. Recently, these proteins
have been implicated in the regulation of behaviors associated with arousal such as feeding and sleep."

Public release date: 10-Jan-2002
Contact: Leslie Lang
919-843-9687
University of North Carolina School of Medicine

Brain protein tied to sleep and feeding also involved in bodily sensations

CHAPEL HILL - A brain protein linked to narcolepsy, the sudden, uncontrollable and inexplicable onset of sleep, helps regulate bodily sensations .

Exactly how that protein, hypocretin-2, is involved in narcolepsy remains unclear. Indications are that people and animals exhibiting narcoleptic symptoms are deficient in this protein or the molecular receptor to which it attaches.

But the new findings by neuroscientists at the University of North Carolina at Chapel Hill and Yale University may open a door to the answer. Their report is the cover story for the January 15 issue of
the Journal of Physiology.

According to Dr. Edward R. Perl, professor of cell and molecular physiology at UNC-Chapel Hill School of Medicine and the report's corresponding author, hypocretin peptides are distributed widely throughout the brain. They arise from part of the hypothalamus, a region prominently involved in regulation of the autonomic nervous system, endocrine activity, and mood and motivational states.

Recently, these proteins have been implicated in the regulation of behaviors associated with arousal such as feeding and sleep.
Perl and his colleagues were intrigued by the observation that hypocretin nerve fibers terminate in a spinal cord region involved in sensations about pain-causing events.

"We wanted to learn the effects of hypocretin peptide on neurones of the dorsal portion of the spinal cord that processes information from pain and temperature sense organs. The protein the researchers
tested was hypocrtin-2, which specifically target the cell receptor associated with narcolepsy.

The effects they found were complex. Hypocretin-2 excited a subset of nerve cells in the outermost cell layers in the spinal dorsal horn, and apparently these neurons, in turn, inhibited activity of other neurons, "as if a complex re-setting of the apparatus that was receiving sensory input from the body is modulated by hypocretin," Perl said.

"Our presumption from these observations is that when neurons distributing hypocretin-2 become active, this produces a suppression of activity in certain neurons associated with pain and temperature sensation," he said.

Perl is no stranger to pain research. He was first to document the existence of nociceptors, sensory fibers specially activated by tissue damage and their relation to the pain sensation. "This is the first report on the effects of hypocretin on the spinal cord neurones," Perl stated.

It may be that a decrease of the protein "helps people sleep and minimizes attention to minor inputs. Conversely, an increase helps a person to continue to do an essential function like eating even when there are minor inputs from the peripheral nervous system, such as occurs when one sits on a rough edge," the neurophysiologist explained.

The implications for narcolepsy remain hypothetical, he added. "The link at this stage is circumstantial. But it does suggest there's a mechanism connecting what keeps us behaviorally awake to modulation of sensory input from the body. We've uncovered a piece of that mechanism."

Perl thinks "a much more general role" for hypocretin-2 exists than narcolepsy alone would suggest. "These proteins are obviously important and significant parts of the brain processes regulating essential behaviors."
###

Co-authors with Perl were Drs. Timothy J. Grudt of UNC and Anthony N. van den Pol of Yale University School of Medicine. Study funding came from the National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Media note: Contact Dr. Perl at 919-966-3560; erp@med.unc.edu  

School of Medicine contact: Les Lang, 919-843-9687, llang@med.unc.edu