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        New Message Board Archives >> Medications, Treatments, Therapies 2004 >> fresh research - octreotide & pituitary CH
        
(Message started by: floridian on Nov 2^nd, 2004, 2:16pm)

Title: fresh research - octreotide & pituitary CH
Post by floridian on Nov 2^nd, 2004, 2:16pm

This is the second recent study on octreotide - this one seems limited as it was on the relief of cluster headaches caused by a pituitary tumor, which doesn't apply to most of us. But other studies have shown that octreotide injections help some with cluster headache, and this suggests that the pituitary plays an important role in clusters. The pituitary and hypothalamus have a big influence on each other.

Octreotide is an endorphin-like polypeptide (mini-protein) that has both pain relieving properties and mimics some of the activity of the hormone somatostatin. The two main uses of octreotide (brand name: Sandostatin) is for acromegaly (overactive pituitary) and gastro-entero-pancreatic cancers.

side note: while a big majority of us have not been diagnosed with pituitary problems, could a subtle change in the pituitary account for the variation in "midface height" that has been reported for clusterheads? Acromegaly and other pituitary problems are often first diagnosed by changes in the shape of the face.

Quote:

Endocr J. 2004 Oct;51(5):449-52.

Long-term Effects of Octreotide on Pituitary Gigantism: Its Analgesic Action on Cluster Headache.

Otsuka F, Mizobuchi S, Ogura T, Sato K, Yokoyama M, Makino H.
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine and Dentistry.

We report the case of 19-year-old man with pituitary gigantism due to growth hormone-producing pituitary macroadenoma. The patient complained of recurrent headache and excessive growth spurt since age 15. Octreotide administration was initiated following transsphenoidal pituitary adenomectomy. Octreotide injection for 4 years efficaciously reduced the size of remnant adenoma as well as serum growth hormone levels. Notably, octreotide exhibited a potent analgesic effect on his intractable cluster headache that has continued even after reduction of the adenoma volume. The analgesic effect lasted 2 to 6 hours after each injection and no tachyphylaxis to octreotide appeared during 4-year treatment. To characterize the headache and the pain intensity, analgesic drugs including octreotide, lidocaine, morphine and thiopental were tested using a visual analogue scale (VAS) evaluation, with the result that octreotide exhibited a prompt and complete disappearance of the headache. Headache relief was in part reproduced by morphine injection (56% reduction) but not by lidocaine or thiopental. The present case suggests that the intractable headache associated with pituitary gigantism is possibly related to the endogenous opioid system. Thus, the headache control by octreotide is clinically helpful for continuation of the self-injection regimen.

Title: Re: fresh research - octreotide & pituitary CH
Post by JJA on Nov 2^nd, 2004, 4:38pm

It's also interesting that octreotide and somatostatin inhibit VIP (vasoactive intestinal peptide) which is a potent vasodilator that is known to be locally elevated during a CH attack. I forget the source...any memory of this Floridian?

Jesse

Title: VIP and Clusters
Post by floridian on Nov 2^nd, 2004, 11:00pm

Here is VIP, CGRP and cluster headaches. Edvinsson seems to think that the VIP is more related to the facial symptoms than the pain, I think.

Quote:

ScientificWorldJournal. 2002 May 30;2:1484-90. Print 2002 May 30.

Calcitonin gene-related peptide (CGRP) in cerebrovascular disease.

Edvinsson L. Department of Internal Medicine, Lund University Hospital, S-221 85 Lund, Sweden. lars.edvinsson@med.lu.se

Cerebral blood vessels are innervated by sensory nerves that store several neurotransmitters among which calcitonin gene-related peptide (CGRP) is the most abundant. In primary headaches, there is a clear association between the head pain and the release of CGRP. In cluster headache there is an additional release of vasoactive intestinal peptide (VIP). In connection with administration of triptans, the headache subsides and the neuropeptide release normalises, in part via a presynaptic effect. In subarachnoid hemorrhage (SAH), CGRP is released to counterbalance the blood-induced vasospasm. In severe cases, the stored CGRP may be exhausted while infusion of CGRP may limit cerebral vasospasm. Thus, interactions with the trigeminovascular system at CGRP receptors may be a useful target for understanding of cerebrovascular disease and to design novel treatments.

Quote:

Lakartidningen. 2001 Sep 26;98(39):4176-83. Related Articles, Links

[Both neurogenic and vascular causes of primary headache]

[Article in Swedish]

Edvinsson L. Verksamhetsomrade akutmedicin, Universitetssjukhuset i Lund. lars.edvinsson@med.lu.se

The cerebral circulation is innervated by sympathetic, parasympathetic and sensory nerves which store a number of neurotransmitters. The significance of these for primary headache has been evaluated. A clear association between head pain and the release of calcitonin gene-related peptide (CGRP) was demonstrated. In cluster headache and in chronic paroxysmal hemicrania, there was additionally a release of vasoactive intestinal peptide (VIP) in association with facial symptoms (nasal congestion, rhinorrhea). Upon treatment with sumatriptan, head pain subsided and neuropeptide release normalized. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headache.

Title: Somatostatin and Parasites
Post by floridian on Nov 2^nd, 2004, 11:25pm

Interesting thread that may or not be relevant - many parasites seem to mess with somatostatin production as part of their mechanism of infection, including Schistosomas, Cryptosporidium, Malaria, and Leishmania. Somatostatin can be used to block the diarrhea that some parasites induce.

The cluster headache research has demonstrated possible links to viruses (herpes and epstein-bar) and maybe bacteria (sinusitis), but I couldn't find anything where they even looked for parasites. Given the nature of clusters, my hunch is that if there is anything to this, it is less likely to be an active infection than a change in the body - maybe immune.

On the other hand, somatostatin (and octreotide) won't cross the blood-brain barrier, so a somatostatin deficiency from the pancreas or gut wouldn't directly affect anything in the brain. Most brain somatostatin is from the hypothalamus, which isn't working right, we know we know. On the other hand, the trigeminal nerve is not shielded by the blood - brain barrier, and an octreotide injection can be effective in blocking CH pain.

Title: VIP and Somatostatin/Octreotide
Post by floridian on Nov 2^nd, 2004, 11:36pm

Here's a citation on somatostatin/octreotide inhibiting VIP, among other things:

Quote:

The pharmacologic effects of octreotide are similar to those of somatostatin, a hypothalamic peptide. Although the exact mechanism of action is not known, octreotide is believed to act at somatostatin receptors. Octreotide inhibits the secretion of both pituitary and gastrointestinal hormones including serotonin, gastrin, vasoactive intestinal peptide (VIP), insulin, glucagon, secretin, motilin, pancreatic polypeptide, growth hormone, and thyrotropin.

http://www.rockford.uic.edu/jc/octreotide.htm

Title: Re: fresh research - octreotide & pituitary CH
Post by sandie99 on Nov 3^rd, 2004, 1:07am

Hmm... interesting.

Title: Re: fresh research - octreotide & pituitary CH
Post by JJA on Nov 3^rd, 2004, 6:37am

Thanks Floridian, I owe you.

I also saw some stuff on the diarrhea when I researched octreotide after you posted on it. The list of medications used was familiar: Corticosterone, calcium channel blockers, octreotide.

Your infection/immune comment intrigues me. I recall a lot of posts about Candida and CH in the archives. I don't want to abuse your knowledge base, but any chance you could give some sources of the research involving CH and viruses/bacteria? Don't trouble yourself though.

Jesse

Title: Re: fresh research - octreotide & pituitary CH
Post by floridian on Nov 3^rd, 2004, 8:53am

Quote:

Ann Ital Med Int. 1990 Jul-Sep;5(3 Pt 3):303-11.

New findings in cluster headache.

Giacovazzo M.
Cattedra di Patologia Speciale Medica e Metodologia Clinica VI, Universita degli Studi, Roma La Sapienza, Italy.

The clinical profile of cluster headache, in Italy better known as "Horton's histaminic headache" is described. The Author makes an inventory of all pathogenetic theories about this excruciating pain syndrome that strikes men more than women. On the basis of findings of the Author and his School over a ten-year period, there is a "periodic lack of immunitary oversee". The salient points of various stages of this study are: low frequency of HLA-B14 antigen with, in contrast, high frequency of the HLA-DR5 antigen of the major histocompatibility system. The HLA B18 antigen of the same major histocompatibility system has been found in patients who respond to lithium therapy. A lack of the HLA-B18 antigen has been found in cluster headache patients who are "non-responders" to lithium therapy. Low titers of antibody response in the pain free periods of these subjects, and high titers in the painful periods has also been found in the serum of cluster headache patients; the lack of alpha 1-antitrypsin in basal conditions; increase of IgE (PRIST) values in painful periods; high titers of C1qSp and KgBt circulating immuno-complexes. The cellular immunity studies of the patients showed an increase of the leukocyte subpopulations Leu7+ and Leu M3+. Besides, the natural killer function that contributes to the defense-mechanism against viral disease, was very low. High titers of anti-herpes simplex 1 and 2 viruses and anti-Epstein-Barr virus have been found in cluster headache patients and in a few observations of Burkitt's lymphoma with associated cluster headache, studied in Sahel area too.

This one is pretty weak (1 case):

Quote:

Headache. 1998 Feb;38(2):132-4.
Cluster headache associated with parainfluenza virus, preceded and succeeded by migraine.

Blanchard BM.
Hartford Hospital, Hartford, Conn., USA.

A serologically proven case of parainfluenza viral infection was associated with the onset and disappearance of cluster headache. The patient had long-standing migraine that ceased during the cluster headache period and recurred when the latter stopped. Possibly, the virus was neurally transmitted to the trigeminal-autonomic system, creating an inflammatory response that transiently precipitated cluster headache and obliterated migraine.

(Burkitt's lymphoma is associated with Epstein-Barr virus)

Quote:

Riv Eur Sci Med Farmacol. 1989 Jun;11(3):207-10.

[Cluster headache, Epstein-Barr and Burkitt's lymphoma virus infections]

[Article in Italian]
Giacovazzo M, Di Sabato F, Bernoni RM, Martelletti P.

Thirteen patients affected by Burkitt's lymphoma were studied. Six out of them had cluster headache associated with Burkitt's lymphoma, and in this group we observed the absence of HLA-B14 antigen. The presence of HLA-B14 antigen in the remaining seven patients, confirm the hypothesis of a protective role of this antigen against cluster headache.

Title: Re: fresh research - octreotide & pituitary CH
Post by JJA on Nov 3^rd, 2004, 11:40am

Thanks again, Floridian.

Jesse

Title: Re: fresh research - octreotide & pituitary CH
Post by aggiegran on Nov 9^th, 2004, 2:45pm

I don't know if this is relevant but I started having CH when my hands were shaking like a leaf and finally the doctor ran a Thyroid function test, and mine was sky high, I have had 2 (really 3 but threw one up) 131, which as you know is the radio active Iodine.....my thyroid is still high, I will not take the 131 anymore cause they tell me I would have a higher risk of Leukemia.....so I take PTU.....its high again and I have been having the CH for the last 4 months....I just got back on the PTU...he did say however that my thyroid was so high it had cancelled two of my numbers...what ever that means.....All I want is help have been dealing with this crap for 16 yrs.....and I really am in the mood to blow up insurance co's, they have decided I can only have headaches 6 times a month.....Talk about people controlling your life and I don't even know them.....Sorry just frustrated!!!!!

Title: Re: fresh research - octreotide & pituitary CH
Post by floridian on Nov 9^th, 2004, 3:18pm

Know what you mean when you say frustrated.

The hypothalamus and thyroid affect each other - not sure if a crazy hypothalamus is making your thyroid overactive, or if an overactive thyroid is giving you clusters.

Quote:

The secretion of T3 and T4 by the thyroid is controlled by an endocrine feedback system involving the pituitary gland and the hypothalamus in the brain. Calcitonin is regulated by the amount of calcium in the blood and acts in conjunction with the parathyroid gland to control calcium levels. Since the thyroid gland is regulated by the pituitary gland and the hypothalamus, thyroid disorders may result not only from defects in the gland itself, but also from disruption of the control system.

Do you take any preventive medicines? That is something to talk to your doctor about - for some people, a preventive could control both the headaches and the overactive thyroid.