We, the parents of kids with rare diseases, become default experts of their medical conditions in order to find answers where the medical profession falls short. We read the research literature, network with other parents/patients in similar situations, network with experts, and act as sleuths to solve problems that doctors cannot solve; we do it out of love and out of desperation. One such mother is CM (who prefers to remain anonymous for now). CM has been a relentless medical sleuth for her son's idiosyncratic and idiopathic conditions since his birth and I am very excited to share an interview of her on her recent discoveries that provide even more hope for HO and more!
- Please
give a brief description of your son’s medical history
Since birth my son has experienced unusual
difficulty regulating stress. But aside from situational stress regulation, he
has had no other social, intellectual or emotional issues. It’s been a baffling
and frustrating experience for him. Difficulties escalated at age 12, likely
with the onset of puberty. Serious and sudden
depression began at this age along with strong Cushings-like features. He
reported constant hunger and began intense food-seeking. Depression was
treatment-resistant to several trials of psych meds from ages 12-16.
Professionals often remarked that he was not a typical case.
At age 19, lab work revealed endocrine issues and
much of his puzzle began making sense. At age 20, a week-long visit at the National
Institute of Health confirmed that the issues were hypothalamic
in nature. Doctor’s believed that my son had something resembling Froelich syndrome, but they did not know
the cause and assumed that it might be genetic. Whole exome genetic testing was
ordered for my entire family, but nothing was identified.
[Note that my personal hypothesis is that my
son’s endocrine issues relate to his time in utero. I have an auto-immune condition
called antiphospholipid
syndrome that causes my blood to clot too well and can cause issues during
pregnancy. My son was not growing well because of my blood clotting and was
considered to be growth-restricted (IUGR). I was given three full courses of
betamethasone to increase lung growth before his premature birth at 34 weeks.
This dosing would be considered excessive today.]
2. What treatments have you tried in the past to help your son?
Unfortunately, we did not know the origins of
our son’s condition for many years. His HO behavior began at age 12.5 along
with very serious, suicidal depression and sleep issues. We began traditional antidepressants and other psych drugs. These consistently
made problems worse and also caused adverse side effects. After four years
of trying different medication combinations, we had him tested for genetic
markers that relate to psychiatric medicines and learned that he was lacking liver enzymes
to process many psych drugs. We turned to Neurofeedback (NF). Although NF didn’t bring
fast relief, over time it helped him normalize his sleeping hours and
resolved his depression. We could see by his EEG that his brain waves were
functioning much better. He felt much better too, but issues remained. His
daily life was still impaired by the constant hunger, serious fatigue (even
with better sleep patterns), and an inability to complete basic work tasks.
Additionally, he was dealing with severe Seasonal Affective Disorder (SAD),
making the winter months very tough.
When we did finally learn of his hormone
deficiencies, he was 19. I quit my job and began my research, looking for
connections. So much now made sense, but there were still questions.
Treating the hormones helped greatly with the fatigue, but problems still
remained. The HO and SAD did not resolve with the hormone treatments, and his
ability to complete basic tasks remained a curious problem that didn’t fit the
endocrine pathology. In fact, it was this inability to do the things he wanted
to do that bothered him most and confused me greatly.
His local endocrinologist was fantastic and
assisted me as we explored novel treatments based on the research I was doing.
Overtime, we tried several approaches including oxytocin, metformin, Victoza,
ADHD medication, and micro-dosing of dexamethasone. None of these treatments
helped much and we discontinued the trials. But I continued to amass research
as I tried to understand the biology and think through new options.
3. For which vexing symptoms have you found successful treatment?
Demand Avoidance
The most vexing symptom to our son was his
inability to complete things that should be easy. This problem bothered him
most and made very little sense to anyone who observed him. Tasks that were
demanded daily, like brushing his teeth or doing homework, were the hardest.
Doctors at the NIH called this an “atypical psych symptom.”
The only other population who seemed to
experience this unusual problem was the autistic population. But our son was
not autistic in any other way. He has had full psych evaluations, had seen many
therapists, and had years of schooling where no professional thought he was the
least bit autistic.
As I researched further, I learned about a
sub-classification of autism used only in the UK called Pathological Demand
Avoidance (PDA). Proposed criteria as listed on Wikipedia include:
1.
Passive early history in the first year, avoiding ordinary
demands and missing milestones
2.
Continuing to avoid demands, panic attacks if demands are
escalated
3.
Surface sociability, but apparent lack of sense of social
identity
4.
Lability of mood and impulsive
5.
Comfortable in role play and pretending
6.
Language delay, seemingly the result of
passivity, often caught up quickly
7.
Obsessive behavior
8.
Neurological signs (awkwardness, similar to autism
spectrum disorders)
Wikipedia contributors. (2019, June 21). Pathological demand
avoidance. In Wikipedia, The Free Encyclopedia. Retrieved 21:27, July 5,
2019, from https://en.wikipedia.org/w/index.php?title=Pathological_demand_avoidance&oldid=902800995
My
son ONLY fits the second of these criteria. But I kept this connection to
autism in mind as I researched.
Last
fall I was introduced to the work of Dr T.C. Theoharides , he believes that mast
cell activation in the hypothalamus is the cause of autism for a subset of the
autistic population. This was fascinating to me as I knew that my son had
hypothalamic disease of unknown origin and he had one unusual trait that was
shared with the autistic population.
I
learned that inflammation in the hypothalamus can be exasperated when mast
cells (immune cells) react to cortisol releasing hormone (CRH). CRH is released
when our body experiences stress. Dr Theoharides believes that these mast cells
degranulate, which is sort of like a mini explosion, and affect nearby neurons
that influence behavior. He treats with an antihistamine that can cross the
blood-brain barrier and a flavonoid supplement that acts as a mast cell
stabilizer.
I
began this treatment with my son on March 15th and by April 4th he was noticing
changes. I was expecting to be treating the one autistic trait that he hated,
his inability to handle demands.
Turns
out we got a big bonus!
Hypothalamic Obesity
Not
only did the demand problem show improvement, the HO with hyperphagia has shockingly resolved! His
constant hunger subsided. Of course his hypothalamic obesity has been a seriously vexing problem too and it was contributing to horrible weight gain
and the related problems that accompany metabolic syndrome and morbid
obesity.
Because
of the appetite decrease, he began to employ intermittent fasting in an attempt
to lose weight. This would have been impossible prior to treatment. My son is 5'10" (177.8 cm) and on March 28, he weighed 337 pounds (153 kg). He’s been
actively trying to lose weight this way with for the last three months and is
now 293 pounds (133 kg), down 44 pounds (20 kg). Now that his hunger is controlled, losing weight is far less
work now compared to before when he was trying not to binge every night.
Iron, WBC & Insulin Normalize
But
there was more! Labs run seven weeks after starting the treatment had some
great surprises. Iron which had been chronically low when my son wasn’t
supplementing was fully normalized even though my son hadn’t taken iron in
seven months. Additionally his chronically high white blood count and insulin
level both normalized too.
4. What medicines and at what doses is your son using?
For Growth Hormone Deficiency (diagnosed April
2017)
- Omnitrope 0.6 mg -injected daily
For Hypogonadotropic Hypogonadism (dx April
2017)
- Testosterone
cypionate 200mg/ml - 0.25ml (44mg) IM/SQ TIW -injected
- HCG
250iu SQ TIW -injected
- Anastrozole 0.30mg po EOD -oral
For Hypothyroidism (dx April 2017)
- Liothyronine 50mg ( 25mg 2x/day) -oral
For Seasonal Affective Disorder (treating since
late summer 2018)
- Bupropion
XL 300mg (added mid-Aug 2018, started 150 and went up after 3 weeks) -oral
- Desvenlafax Succ ER 12.5mg (added 9/13/2018) -oral (only a small dose is tolerated)
For Inflammation (began 3/15/2019): these are the featured medicines of this interview
- Hydroxyzine HCL 25mg- 2x/day -oral
- Neuroprotek (flavonoid supplement containing Luteolin, Quercetin, Rutin) 4-6 per day, although he started with 2/day for the first four weeks -oral
Other Supplements:
- Vit C (500mg) -oral
- Vit D3 (42,000iu/ week) -oral
- Multivitamin (no iron) -oral
- ProbioMax Lean DF probiotic (began 4/25/19)
5. How did you discover the treatment?
An internet friend who knew of my son’s diagnosis forwarded me a video by Dr T.C. Theoharides entitled Brain Allergy and ASD. There was no mention of hormone deficiencies or hypothalamic obesity but I watched intently wondering if my son’s hypothalamic dysfunction could be tied to inflammation.
My previous research had been focused on the endocrine effects of over-exposure to steroids in utero. I had learned from this work that there are immune system effects as well as endocrine effects, but I didn’t understand the immune component.
My previous research had been focused on the endocrine effects of over-exposure to steroids in utero. I had learned from this work that there are immune system effects as well as endocrine effects, but I didn’t understand the immune component.
I then gleaned more specific information about
the actual treatments that Dr. Theoharides was using by listening to podcast
interviews and taking notes. I shared the findings with his endocrinologist who
was very positive about doing a trail of treatments:
Some articles of interest:
7.
Involvement of hypothalamic histamine H1 receptor in the
regulation of feeding rhythm and obesity.***
***Note
that these articles suggest that an H1 antihistamine like hydroxyzine would be
contraindicated for obesity. Yet, the opposite is occurring in my son’s case and
he reports that his hunger is significantly decreased when he takes
Hydroxyzine. More research is needed to understand this paradox. But clearly
there exists a relationship between histamine receptors and feeding behavior.
6. What is the theory of how treatment is working?
The hypothesis goes like this:
Brain inflammation, particularly inflammation in
the hypothalamus, was an unidentified problem for my son. This inflammation was
made worse by any and all stress he experienced in life. Stress would cause his
hypothalamus to produce higher amounts of cortisol-releasing hormone (CRH) and
the CRH would trigger a reaction, like an allergy, that would in turn trigger
neurons in his hypothalamus that adversely affect behavior and increase
hunger.
Treating with anti-inflammatory agents that can
cross the blood-brain barrier would theoretically bring down the inflammation
and stop the allergic-type reaction. In my son’s case behavior and hunger are
improved, hunger drastically so!
Specifically hydroxyzine and flavonoids
(Luteolin, Quercetin and Rutin as found in Neuroprotek)
were trialled with success.
7. How might these treatments may be helpful to persons with similar conditions?
The treatments we are using were developed for a
subset of the autistic population thought to be suffering from brain and
hypothalamic mast cell (immune cell) issues.
My son’s condition was marked by one
autistic-like symptom, along with hormone deficiencies, hypothalamic obesity
and premature gray hair.
It’s interesting to note that individuals with
Prader-Willi syndrome also exhibit autistic-like symptoms, hormone
deficiencies, and hypothalamic obesity. Informal surveys on in the
craniopharyngioma Facebook groups also indicate that the cranio population
exhibits some autistic-like characteristics as well as the more commonly
experienced hormonal deficiencies and HO.
I currently know of one craniopharyngioma teen* who is trying an antihistamine based on my son’s success. This young man is
also reporting notable weight loss and positive behavioral changes based on
six-weeks of treatment.
Could others benefit too? We surely hope so!
Could others benefit too? We surely hope so!
* ADDENDUM (by Eugenie)
I have been in contact with the mother of this cranio teen boy with HO and she has also reported some remarkable findings with her son's use of an antihistamine. Interestingly, she noticed that he seemed to lose weight without reason or intention in the month of August; about 1 pound per week. He would strangely regain the weight in September. After learning about CM's discovery, she realized that it was probably because her son always took an antihistamine medication to help with his seasonal allergies only in the month of August. Since learning of CM's success, she has re-administered the antihistamine (citrazine, 10 mg, a super inexpensive OTC Costco-brand drug, lol!) to her son (not for allergies this time) and has noticed weight loss, loss of hunger, less inhibition (acting more like a carefree, playful teenager), less inflammation (less "puffy"), more motivation, and better heat tolerance. In the last six weeks since starting citrazine, her son has lost almost 9 pounds (4 kg) in only 6 weeks without really trying.
As both of these cases are only in the first several weeks of their results, I will post an update in a few months on the progress of these young men.
If, after reading this post and investigating the links, you have questions for these moms, please post them under comments on the blog. This will help economize their time and help all readers (from various FB groups) be able to see the answers. Thank you.
