107) Experiment continues with possible receptor desensitization and drug holiday

The case report on Sasha has been published in the print version of the JCEM for over a month and so far, a few people have been successful in getting their endos to prescribe it.  I have had three physicians/researchers from Europe (England, Italy and France) contact me and know of families in Canada, Finland, and New Zealand obtain OT since the paper has come out.  I am hopeful that more people will have the opportunity to try it for hypothalamic obesity and that future dosing studies will enlighten us on the best treatment protocols.  Until then, all of us are our own guinea pigs, navigating through unchartered waters.

Sasha is doing well overall. We have now had 6.5 years post tumor resection with our "new normal" and we've had about 18 months of using OT. We feel grateful that the he is medically stable (with high maintenance). His food drive is calm and mellow, he is doing well in school, has started a couple of new hobbies (electric guitar in a band and computer coding), and is rather content (maybe even happier than the average 15 year old boy?) in his life despite his many chronic medical conditions. Sure, there are still challenges (this goes without saying for those of us who are now "surviving surviving") but I feel the need to remind myself that Life is precarious and messy and that non-eventful/ordinary days are to be appreciated.  In the past, my husband would text me on a daily basis, "any disasters today?" and we would  celebrate these "non-disaster" days if we didn't get the dreaded phone call from school personnel on a given day... we'd rejoice if we didn't get any reports of his stealing food or getting into a power struggle at school over food. We continue with our unlocked kitchen and our relaxed attitude about food (no more policing) and it is indeed a relief since now he makes the entire family's lunches and helps with making breakfast and dinner while we stay out of the kitchen and let him do his thing.

After the completion of the case report, I relaxed a bit with my careful data collection of his weight and height.  We still keep track of his weight for the purposes of estimating his water needs for his adipisic (thirstless) diabetes insipidus and I noticed that he has been creeping up in his BMI.  It is not terribly noticeable on his appearance since he takes after his father's tall and muscular frame and since he is likely going through puberty changes into a man's body (he now weighs 183 pounds/83 kg and is 6 feet/183 cm tall). Of course, there are always other mitigating factors- we have also lowered his GH to an adult maintenance dose (from 2.0 mg/day down to 0.8 mg/day) so this will probably also increase his BMI. 

 I have been privy to read an accepted (to be published in the next couple of months) manuscript of a review article on OT's effects on feeding behaviors and it raised the question of OT's efficacy with chronic administration. With chronic administration of OT and the possibility of tolerance, I was advised that it might be a good idea to give Sasha a "drug holiday" from OT for 1-2 weeks, every 4-6 months.  Apparently, doing so may allow the OT to resume effectiveness and possibly even at a lower dose. Sasha has been on OT at 6 iu/day for the past 18 months so perhaps this was a needed step to let his oxytocin receptors "rest."

 Last week, we paused his OT and plan to restart it tomorrow (totaling a 10-day break).  Interestingly, we did not notice any changes to his moderate appetite or food drive and even trusted him to attend his first high school dance on his own last weekend (and we even knew there would be desserts served!)- call it crazy, parental letting go, or trust- we did it and he came home reporting that it was a success- he said he had a lot of fun dancing and ate only one cookie!

Although we detect no change after taking this drug holiday, we will take it slowly and restart the OT and the tracking of his weight again.  Our hope is that after the 10-day respite, the OT will keep his BMI stable.

Here's a picture of him taken today (serving the breakfast he made):

106) Updates and summary on dosing experiences

The online publication of the case report has been out for a little over a month and I've been receiving a trickling of queries from a few people who have inquired into our dosing, side effects, etc.  The medical community continues to be cautious about prescribing oxytocin; however, from the comments from some individuals, there have been a few physicians so far who have shown some interest. The report stands on its own but for the sake of answering some of the common questions, I will summarize my answers here. Before I do that, please note my disclaimer:

I am NOT a physician and I am NOT an oxytocin expert and I am NOT intending to prescribe an oxytocin dose for any patient.  I am intending to simply describe what we have done and what we have learned from our experiences with oxytocin. For peer-reviewed research on oxytocin (though there is a dearth of info on dosing), please see post #8.

1.  What OT dose was effective, how soon was it effective after you started OT, and how do you know it was effective?
We were advised to start with a low dose based on anecdotal data derived from some European PWS kids who saw anxiety and hunger-reducing effects on low doses of OT given on an intermittent basis.  We gave 6 iu every three days and it appeared to lower his food drive.  I have to say it "appeared" to lower his food drive because I don't know for a fact if he was sneaking extra food on the side and not being truthful when he exhibited reduction in his appetite.  There was, in fact, a brief period of time in July, 2016 (before trying the daily OT dose) during which we discovered he was sneaking out of the house at 4 AM and stealing/buying large amounts of chocolate from the 24-hour grocery store.  At this time, he was getting the every-three day dose.  In my case report, I ascertained OT effectiveness by his weight loss since it is a measurable observation.  If we use weight loss as the evidence of therapeutic effect,  his steady weight loss was noticed immediately after we started the daily 6 iu dose. Because we were experimenting, it took a total of 3.5 months after starting OT (at various doses) before we found the "just right" dose of 6 iu/day.

For the reduction in his hyperphagia, it was a more gradual process which involved an exposure hierarchy- we gave him food freedom in a baby-step way (partial snack cabinet increased to full kitchen access over a period of weeks).  I believe that people with HO hyperphagia are in survival mode and learn to use whatever means they can muster to survive (not starve).  This includes lying, sneaking, stealing, and hoarding food.  The end of homeostatic hunger does not suddenly end the survival behaviors and anxiety about not having enough to eat.  Hence, we did not truly let go of our intense food monitoring and locking until seven months after we started to notice the weight loss effects and the beginning of Sasha's ability to appear more relaxed around having enough to eat.

3. Did he have any side effects to OT?
OT, like vasopressin, has antidiuretic effects, and has the potential to cause fluid retention.  We actually welcomed this because my son has adipsia and is required to take a very large dose of desmopressin (0.2 mg x 18-20 pills per day) for his diabetes insipidus.  My son's desmopressin dose, however, was NOT decreased as a result of starting OT. We did experience some increased irritability and food seeking when we increased his OT dose to 9 iu.  Although it isn't possible to conclude that the higher dose caused these adverse effects, we lowered the dose and felt that it reduced these symptoms.

4.  Why did you add naltrexone? How effective was it?
We added naltrexone after Sasha found and ate all of his sister's Halloween candy.  I read up on the opiate antagonist's effects to deter cravings in alcoholics and opiate addicts and in some "food addicts" (binge eaters). Post #8 lists some research papers on naltrexone and Contrave, the weight loss medicine that is a combo of buproprion and naltrexone.  In sum, I don't believe naltrexone did what I hoped it would do- to deter his cravings for sweets- alas, if it could do that, wouldn't we have already cured obesity??  The biological theory for naltrexone's failure to decrease sweet cravings in Sasha is described in the discussion section of the case report as being due to his broken HPA- axis/panhypopituitarism (this is an explanation in a nutshell- please read the paper if you want more nitty-gritty neuroendocrine details).  However, I did learn that opiate antagonists like naltrexone DO act to potentiate OT's effects so perhaps naltrexone is helping boost OT's effects on his homeostatic hunger and energy balance??  All in all, I believe that naltrexone is an adjuctive treatment to OT which is why we put him back on it (100 mg/day) after taking him off it for several weeks.

5.  Were there other positive effects besides the ones affecting his weight and appetite?
Yes, I believe that Sasha improved in increasing his social motivation.  Before OT, he had absolutely no interest in having peer-friends.  He liked talking with adults but really didn't have any friends his age and didn't seem upset about his lack of friends either.  Since taking OT, he has made a friend on his own and expresses more interest in having friends his age.

By the way, Sasha continues to be doing well. He is now 183 cm (6 feet) tall and weighs 77 kg (170 pounds).  He just turned 15 on January 1st!

Please don't hesitate to contact me if I haven't answered your questions and if you or your physician have other questions about our experience.

105) Coming full circle: Hope for HO case report has posted to JCEM

For the last couple of years, I've been finding and posting research papers to this blog and to the various FB groups to learn and to share information that I hoped would be helpful to my son and others with his condition...

Now I am delighted to share the fruits of my labor! This online article is in its entirety.

https://academic.oup.com/jcem/article/103/2/370/4693940

The final version has been printed in the Journal of Clinical Endocrinology & Metabolism in the February, 2018 edition.

You are welcome to share the article with whomever you please. If you think you might have a comment or question that would interest others, please write it under the comments section of Hope for HO. Otherwise, I am the corresponding author and my email is listed if there are questions.

104) Actualizing more hope for HO!

Woo hoo!

After two years of slogging through endocrinology journals on oxytocin, metabolism, neurophysiology of the endocrine system, obesity, (etc.), almost a year and a half of writing in this blog on our experimental treatment of my son's hypothalamic obesity, and another four months writing and re-writing the manuscript... I'm thrilled to report that the Journal of Clinical Endocrinology and Metabolism has accepted "Oxytocin and Naltrexone successfully treat hypothalamic obesity in a boy post-craniopharyngioma resection."

The decision to conduct the experiment with oxytocin was motivated by pure desperation to escape the hellish life my son was living and would live, indefinitely, if we could not find a solution.  However, the blog and desire to publish a report in a reputable medical journal has been a labor of love and one that has been propelled by the great relief we have felt after suffering for five years with HO and hyperphagia.  To those of you who have followed the blog or who also live through the daily horrors of HO, you know the indignities that are associated with living with this disorder; the day we experienced the "HEFY" (half-eaten frozen yogurt, post #4) will always live in my mind as the moment I first felt hope for HO.

The experiment and case report would have not been possible had it not been for several key people who deserve special shout outs:

From the craniopharyngioma FB group- Martin H. opened my eyes to the fact that not all pituitary hormones are readily replaced in patients with PHP and Naomi C's pioneering work with oxytocin gave me the idea to try it in the first place. Dr. Theodore Friedman prescribed this difficult-to-obtain neurohormone and Dr. Jennifer Miller kindly provided her oxytocin expertise as a consultant to the experiment. While I pored through relevant PubMed papers, I contacted some of the scientists who authored the papers on oxytocin and hypothalamic obesity; some of them kindly returned my emails with helpful articles, answers to my questions, and moral support for my project. One of them was Dr. Christian Roth who took notice of our success with Sasha's weight loss and offered to have his MRI scans evaluated for hypothalamic damage and risk for hypothalamic obesity. He joined the project to help get the manuscript ready to submit for publication and asked Dr. Francisco Perez of U of Washington (neuro-radiologist) to assist with the MRI scan analysis. With the support from my co-authors (Drs. Miller, Perez, and Roth), I somehow wrote this case report and now it will be published...

I will let you all know when the advance article becomes available (posted to the JCEM website in about a week) and when the final paper is published.

Have hope for HO!

103) Biomarkers of Social Impairments in Individuals with Hypothalamic-Pituitary Disorders: participate in a study at Stanford

When Dr. Sue Carter discovered the social bonding properties of oxytocin in her seminal research on prairie voles, it opened up a world of research regarding oxytocin's role in autism, social anxiety, relationships, and other arenas.

Long, long overdue (in my opinion) is the need to study social impairment among survivors of pituitary and hypothalamic tumors.  Anecdotally from my own observations of Sasha as well as from hearing reports from many others with craniopharyngioma, there are some commonalities that affect social motivation and social impairment.  A while ago, I sent out a survey on the mental health of cranios and found that issues with socializing were rated among the most common and problematic areas affecting quality of life (guess what was number one...? Yep, HO!)

Now, there is a study at Stanford University recruiting 6-30 year old subjects to study this very phenomenon.  Dr. Karen Parker is the principal investigator. Please see this study flier for more info: http://med.stanford.edu/parkerlab/research/Biomarkers-of-Social-Impairments-in-Individuals-with-Hypothalamic-Pituitary-Disorders.html

From our observations before oxytocin, Sasha had an odd combination of being very warm and friendly yet lacked friends.  He also had a strong tendency to want to chat up adults but really didn't show any interest in kids his age.  He was quite content to stay by himself and didn't complain of feeling lonely.  He appeared to feel comfortable hanging out with his adult aides at school. Most adults who met him found him very charming and mature, an "old soul."  Interestingly, I have heard very similar reports from other parents of cranio kids.

What's up with these symptoms?  Could it be that something is amiss in their oxytocinergic systems since many of these brain tumor survivors have had brain damage and NOT had their oxytocin replaced by hormone replacement therapies?  Since Sasha has been getting oxytocin replacement, he has shown more social motivation.  He made a friend a year ago and continues to see him on the weekends.  He would also like to make more friends and has been making some attempts through the lunch time clubs in high school.  Because he's missed 5 years of socializing, he is behind and it will be hard for him to catch up with his peers in the social realm, but this is a noticeably different way of being for him... before OT, he was totally indifferent to wanting to hang out with kids his age.

It is my hope that more can be learned about the socialization issues of these brain tumor survivors.  Depending on what Dr. Parker learns, perhaps there will be more impetus to offer treatment (got oxytocin?) for the social needs of survivors of pituitary and hypothalamic tumors. Please consider participating in this very important study. Thank you!

102) Manuscript is still in the running (!); before OT and after OT photos

I've been away from the blog lately due to my work on the manuscript that I'm trying to publish in a highly reputable medical journal.  The first rendition of the manuscript was peer-reviewed with only minor concerns but was rejected due to its "low priority" ratings (due to its orphan disease status?). However, at the urging of my scientist husband, I made a strong case for reconsideration and the editors are now allowing us to resubmit a revised version in response to the reviewers' concerns . Apparently, it is not typical for the editors to reverse their decisions so I am cautiously optimistic about our ability to rewrite the paper so as to impress the reviewers/editors enough to reconsider publishing the paper.

I'm done revising the paper and am now waiting for my co-authors to look over my revisions.  In the meantime, we are continuing to cruise along.  Sasha continues to take a 6 iu/day OT spray and has been off naltrexone now for 14 weeks. His weight has stayed more or less the same (weight has increased slightly from the end of July- BMI was at its all time low then in the 79th percentile- now it is in the 81st percentile). Here are some photos (sorry for the photo-edited decapitation) of before and after OT:

Sasha before OT (July, 2016) with 
5 years of tight food supervision and locked kitchen

170 cm tall, 77 kg, BMI=96%

Sasha today after 62 weeks of OT with 24 weeks 
of loose supervision and unlocked kitchen access
180.3 cm tall, 73.1 kg, BMI=81%

His eating habits have remained moderate and he is able to exercise control over himself with our greatly reduced supervision and unlocked kitchen (now unlocked a total of 24 weeks)!  We have had very good reports from school regarding his food seeking behaviors- in fact, we weren't getting any reports (no news is good news) so we inquired and they reassured us that they were keeping close tabs on him and that they would report incidents if they had any to report.

When I re-read and think back to our lives before OT, I shudder with horror at the hell we had to live through for 5 long years.  The constant, unblinking vigilance, rapid weight gain, food obsession, kitchen locking, tearful episodes over food, food stealing, etc.  It was truly the bane of our existence. I know that many of you who read the blog are currently living through this hell.  It is my hope that the eventual publication of our report will enlighten more researchers and physicians to consider oxytocin as a viable treatment option for HO and hyperphagia so others can also find the relief that we have found.

I promise to work as hard as I possible can to get this case report accepted for publication and will update the blog when I get some (good) news.  Keep your fingers crossed!

101) Experiment is over...what's next?

Hello!  It's been a long while since I've blogged here.  During this absence, I've been writing the case report and getting it ready for publication in a clinical endocrinology journal.  I submitted it last week and it is now "under review."  We are crossing our fingers and I hope to share some good news with you all if it gets selected for publication.

Now that Sasha has been on a therapeutic dose of oxytocin for over a year, I believe I can conclude that it has been a successful experiment.  My original treatment goals were to decrease his hyperphagia in order to normalize his relationship with food and to improve his socialization (increase social motivation and friendships). Our lives now are vastly improved compared to the old days of living with the stress and dread about keeping all food under lock and key, limiting access to social events, and having to keep an unblinking eye on him when he was around food. Sasha's steady and sustained improvements have allowed us to loosen up on his supervision and now he walks to and from school by himself.  So far, we have not detected any signs of food sneaking.  He still has an aide at school and they do keep a close eye on him (part of his IEP) just in case his food sneaking returns, but so far, no reports from the school about any "disasters"- we are happy and relieved about this! As for the goals regarding socialization, he has kept up with his friendship with his buddy and they continue to see each other on the weekends.  He has also begun to join some social clubs at his high school (robotics, Best Buddies, card and board games, etc.) so we are hopeful he will be able to make some new friends at school.

His dose has been steady at 6 iu/day intranasal oxytocin and we haven't missed the naltrexone (stopped before the end of July) to date.  At home, he's been observed to have the same eating habits and we still keep to a low-ish carbohydrate diet (100 grams of carbs/day, give or take). I have been even more lax about supervising his food and eating since the beginning of school.  In fact, I have not once supervised or even seen what he is packing in his school lunch.  We keep the kitchen stocked with healthy foods that Sasha enjoys and he appears to be handling his free access to the kitchen without a problem; the fridge and all cabinets remain unlocked 24 hours a day and the Kitchen Bitch hasn't been around...! I am trusting that he is making good choices about his food selection and eating in moderation. We do indulge, on occasion (3-4 times per month), in a sweet treat and so far, it has not led to any problems.  Lastly, if his physical appearance is any indication of his choices, he's doing a good job because he looks and feels great at 5'10.5" and 160 pounds (179 cm, 72.5 kg).

Regarding oxytocin's social bonding function, last Saturday I had the great privilege to meet and spend the afternoon with Dr. Sue Carter.  She is the scientist who discovered the bonding properties of oxytocin in her seminal work on socially monogamous prairie voles and is currently the director of the Kinsey Institute. Sharing a couple of articles about her work- the first is written by her and her husband, Stephen Porges (another internationally celebrated scientist, widely known for his Polyvagal Theory). The second is an article and interview written by their son, Seth Porges, journalist. The third paper explains oxytocin's role in the evolution of human behavior.
1. The biochemistry of love: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537144/
2. Seven things you didn't know about oxytocin: https://www.forbes.com/sites/sethporges/2016/02/12/7-things-you-probably-didnt-know-about-oxytocin-and-the-science-of-love/#bd37080670b3
3. Oxytocin Pathways and the Evolution of Human Behavior: http://ccare.stanford.edu/wp-content/uploads/2013/09/Oxytocin-Pathways-and-the-Evolution-of-Human-Behavior.pdf

Dr. Carter has shown interest in our experiment and has been very supportive to me over the last year so it was a great honor to finally meet her.  Talking with her has inspired me to continue to learn more about oxytocin and to understand other untreated conditions (social impairment, compulsive behaviors, anxiety, etc.) that may be connected to the impaired oxytocinergic system of people with pituitary/hypothalamic tumors.  I am very excited about a research study that is launching from Stanford University on this subject and will post more info about it after I gain permission from the principal investigator.