I am just pulling out a discussion started in a rather long thread as it seems we might be able to get a little more input in doing this.

Rick suggested that PD may indeed start out as an endocrine disorder and based on what I have been reading I am inclined to agree. Thyroid dysfunction was broached, and I immediately started reading up on parathyroidism. The paraythyroid is very interesting because it acts independently of our thyroid and its entire purpose is to modulate calcium in our systems. Vitamin D is often found to be at insufficient levels when there is a parathyroid dysfunction, but from what I have read, supplementing with more Vitamin D may not always be the answer as it can cause even higher levels of circulating calcium in our systems.

So we know that many of us show Vitamin D deficiencies. Where does calcium come into play and what does it all have to do with PD. Obviously, I don't know the answers, but there are some interesting links and hints out there.The main thing to know is that any sort of parathyroid dsyfunction results in dysregulation between calcium, Vitamin D, and phosphate in the blood stream. It often is not detected by common blood tests run by doctor. Longstanding and untreated it has shown in some rare cases to result in Parkinsonism. I am not saying that this is concomitant in us but am feeling there are very strong connections to PD.

Calcium is a neuromodulator controlling electrical signaling and it is hypothesized that calcium meets up with oxidative stress and cell system failure = what looks like idiopathic PD. <A really great interactive model here> Note that PD has shown some response to ECD (Electro-convulsive Therapy).

People with hypoparathryoidism have increased chance of getting Addison's or Parkinson's Disease- the symptom/features of Addison's (result is body's inability to produce enough steroid hormones)- these may mimic some symptoms of PD as well: the key thing is that the parathyroid impairs the nervous system and muscles so obvious to see it as a link to a movement disorder. How so? Parathyroid problems lead to calcium dysregulation- calcium is vital to us as it helps conduct electrical impulses and energy for muscular control. When the parathyroid can't produce the right levels of Parathyroid Hormones (PTH); note this often happens as an autoimmune and inflammatory response. I wonder if PD doesn't begin somewhere in the endocrine system for us? This impaired PTH production; PD aside, results in hypocalcemia and too much phosphate in our system and has manifested with both symptoms of PD, cognitive impairment, and dementia.

Calcium Disorders. Disorders of calcium metabolism may occur in association with parkinsonism. Hypoparathyroidism has been reported to cause parkinsonism both in the presence and absence of basal ganglia calcifications. It may occur as a late complication after thyroidectomy[5] and may be responsive to levodopa in some cases.[6] Pseudohypoparathyroidism, characterized by end-organ resistance to normal endogenous parathyroid hormone, may be associated with parkinsonism in up to 4 to 12% of patients, either with or without evidence of basal ganglia calcifications,[7] and may respond partly to normalization of serum calcium.[8] Hyperparathyroidism due to parathyroid adenomas can rarely cause parkinsonism, which is reversible after surgical removal of the tumor.[9] Bilateral subcortical calcification involving the basal ganglia and cerebellum, often labeled as Fahr's disease, represents a heterogeneous collection of disorders that are not associated with a known disorder of calcium metabolism. Movement disorders in Fahr's disease most commonly present as parkinsonism (55%), often in association with dementia, cerebellar signs, or other hyperkinetic movements including chorea, tremor, and dystonia.[10]

Please register at Medscape and read the full article "Movement Disorders caused by Medical Diseases: Parkinsonism"

Hypoparathyroidism hallmarks include low Vita D and the main thing is not enough calcium in the system. Here are two case studies of note; one involves the pseudo version and the other straight on thyroid disorder. I love a good puzzle, but know that there is more than simple links. Anyone else have anything to go on...where does the fight or flight and stress fit into all this. It is noted that hypoparathyroidism and Addison's Disease (absence of steroid hormones also linked to thyroid disorder) are both negatively impacted by stress.

Case studies:


Pseudohypoparathyroidism, Parkinsonian Syndrome, with No Basal Ganglia Calcification Jounal of Neurology...1988.

Idiopathic Hypoparathyroidism Presenting as Dementia. British Medical Journal...1974.


Last interesting thing, it is now considered common for parathyroid dysfunction to occur as result of pregnancy, and is often invisible as symptoms mimic hormonal changes. It looks like it can be a permanent condition or just make an appearance in times of stress? Just what Rick and some of us have been looking at...so clearly our chronic lower level stress I'm sure would also play a part.

Just how does this fit together? Why is dopamine and basal ganglia the hardest hit neuro aspect? Anyone have any insights? I feel like I am just either putting together the obvious for any doctor or scientist, so maybe there is nothing more to all this. Just feel there has got to be some sort of major connection or maybe common pathway. Would all this further indicate that the autoimmune system does have a role in PD. BTW, it is noted that pseudohypoparathryoid causes anosmia or the impaired sense of smell many PD people have.

Laura

This is excellent, thanks for sharing. I have to add, perhaps this is also why calcium channel blockers have indicated some success, they are looking at this at Northwestern and we got one of our docs to script us for Dynacirc which is the calcium channel blocker they are using in the trial (I think isradipine is another name for it). Who knows, but I'm not seeing a one pill fits all for PD, there are just too many variations on a theme as we all know all too well.

We sure have some excellent minds here. I'm so grateful.

Thanks, Lurking for adding the calcium channel blocker connection; this is a biggie! I just learned that not only is the protein CACN1S (this is key in Isradipine therapeutics for PD) linked to schizophrena...and the other team of scientists and researchers who can't get past dopamine. In other words, schizophrenia, long touted as result of excess dopamine, and its opposite manifesting as PD, are both perhaps channelopathies.

Interestingly, only the "L Type" Calcium Channel blockers may be neuroprotective (this is Isradipine). Other old school channel blockers like Verapimil actually have induced Parkinsonism! I have no idea why only the L Type seems to be our friend.

Rick, I just ran across this morsel when researching L type calcium dealies. Apparently, a certain receptor protein is essential for proper function of L type. It is known impacted by the gene CLCNL1A3

From Wikipedia:
This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility.[1]

Rick- if you have haven't run across the Thyrotoxic Periodic Paralysis info, please connect to a brief NYT article- it sounds alarmingly familiar! Even lists salty foods as a possible trigger.

Next up:

Moreover, rom the ER that consistently induced mitochondrial Ca2+ uptake, with a rise of mitochondrial matrix free Ca2+. In other words...too many free radical Ca2+ cells resulting in toxicity.

I sure wish we could put all these pieces together into actually beginning to make sense of how the substantia nigra ends up taking the biggest hit for us. I also wonder if this model of how PD might originate allows for potential autoimmune role and my hope for a vaccine.

From: http://www.answers.com/topic/channelopathy

"Cells of the body, including nerve and muscle cells, are surrounded by thin coverings called membranes. Embedded in these membranes are a large and varied set of proteins that control the movement of materials across the membrane, in and out of the cell. One major type of material that crosses through such proteins are called ions, and the proteins that transport them are called ion channels.

Ions perform many different functions in cells. In neurons (nerve cells), they help transmit the electrical messages that allow neurons to communicate with each other, and with muscle cells. In muscle cells, they allow the muscle to contract. When the ion channels are defective, these activities may be disrupted."

<Think of ion channels as the port holes in a great ocean liner and pretend they are the only way to pass stuff onto or off of the ship. Suppose you are going to load a shipment of beach balls 18"in diameter through ports that the ship specs say are 19" in diam. No problem. But you find that due to a mutation that the ports are actually 17" in diam. That is a channelopathy. You may still be able to squeeze the beach balls through the port, but it will be slower, some will be damaged, etc. Things won't work right.>

From http://www.kcnq.org/health/channelopathies.php

"When an ion channel goes wrong or does not function as it should, it may produce a disease in an individual. Certain forms of skeletal and cardiac muscle and brain diseases such as the myotonias, epilepsies, migraine or arrhythmias are due to pathological alterations in channel proteins and thus, can be considered as "Channelopathies".

" Another important cause of channelopathies is auto-immune attack. However, mutations in associated proteins, alterations in the expression of ion channels, and changes in the activity of
non-mutated channel genes or associated proteins can also produce what are known as acquired channelopathies. Such acquired channelopathies may occur as a result of nerve-injury or after drug treatments that perturb cellular function.
This huge variety in the causes of channelopathies, as varied as the diseases themselves, not only makes it difficult to study these diseases but it often makes the clinical diagnosis of these diseases problematic. "

"As stated, Channelopathies may also be due to the body producing antibodies that destroy specific ion channel proteins. These types of disease are known as autoimmune channelopathies of which myasthenia gravis and neuromyotonia are good examples. In these diseases, the antibodies mainly affect the function of the nicotinic acetylcholine receptors at the endplate and dendrotoxin-sensitive potassium channels, respectively. "

From http://www.associatedcontent.com/art...sm.html?cat=70

"The activation of these proteins leads to altered cell behaviour. Increased calcium within cells results in increased damaging oxygen free radical production by mitochondria. Abnormal mitochondrial function is associated with autism. Palmieri et al confirmed the importance of these associations in a study of several patients with autism.

L-type calcium channels (LTCC) are voltage-gated calcium channels that are found in

1. The central nervous system - LTCC are important in the regulation of nerve cell development.

2. The immune system - LTCC are important in the function of white cells including regulatory T-cells TREGS which control immune system activity

3. Gastro-intestinal tract - LTCC are related to activity and inflammation of the stomach, intestines and pancreas."

No, Laura, you are not putting together the obvious. This is a tangled knot that we are tugging on. What do we know? In particular, what do we know as patients that researchers may not? Or it is known but dismissed or simply not explained?

One is the knowledge of just how involved emotion is in PD. Emotion generates stress, both good and bad. It is said that we don't seek out novelty, or take risks, or show emotion like normal folk. Is it true? In my case it is, sort of. I enjoy novelty but not for novelty's sake. I take risks but I do my homework to minimize them. I don't show my emotions I must admit. Why? I don't know, but I have a suspicion.

I suspect that we, for whatever reason, cling to stability at all levels. It is a way to minimize stress.

I have an appointment with my neuro tomorrow to discuss some of this. One of the things I expect is an agreement that I should see an endocrinologist just to figure out what is real. So I started looking at the local endos to see if any stood out. There aren't many in my little town and I didn't have any hopes of anything special. I settled on one that got two favorable ratings. He was the only rated one in town. He had a short bio on his website. Seemed normal enough and it mentioned that had one journal publication to his credit, but no link, no title. I went to Medline and found it from five years ago. Checkit out...


1. Endocr Pract. 2005 Jan-Feb;11(1):37-42.

Urinary calcium excretion in primary hyperparathyroidism: relationship to
25-hydroxyvitamin d status.

Bussey AD, Bruder JM.

Division of Endocrinology, University of Texas Health Science Center, San
Antonio, TX 78284-7877, USA.

OBJECTIVE: To determine the prevalence of vitamin D deficiency in patients with
primary hyperparathyroidism (PHPT) and evaluate the relationship between urinary
calcium excretion and serum 25-hydroxyvitamin D (25-OH-D) levels in patients with
PHPT. METHODS: We present a case report and a review of the medical records of
patients with PHPT. Of 75 patients with PHPT substantiated by hypercalcemia and
increased levels of intact parathyroid hormone (iPTH), 35 were identified with
laboratory evaluation of vitamin D levels and 24-hour urinary calcium excretion.
These study subjects were stratified as 25-OH-D deficient, insufficient, or
replete (on the basis of serum values of <15, 15 to 25, or >25 ng/mL,
respectively). Total 24-hour urinary calcium excretion and the fractional
excretion of calcium (FECa) were analyzed as a function of 25-OH-D status.
RESULTS: Of the 35 study subjects, 14 (40%) and 13 (37%) had 25-OH-D deficiency
or insufficiency, respectively. Those patients with a 25-OH-D level <15 ng/mL had
higher serum iPTH concentrations as well as lower urinary calcium excretion and
FECa. No significant correlations were found, however, between 25-OH-D status and
iPTH concentrations (r = -0.21; P = 0.23), total 24-hour urinary calcium
excretion (r = 0.07; P = 0.7), or FECa (r = 0.04; P = 0.8). CONCLUSION: Vitamin D
deficiency (25-OH-D levels <15 ng/mL) was common in our population of patients
with PHPT. Urinary calcium excretion was not significantly altered by 25-OH-D
deficiency in patients with newly recognized PHPT. Measurements of total urinary
calcium excretion and FECa can be reliably used to rule out familial benign
hypocalciuric hypercalcemia in the initial evaluation of PHPT, regardless of
25-OH-D status. Determining 25-OH-D concentrations best assesses the vitamin D
status.

PMID: 16033734 [PubMed - indexed for MEDLINE]

We've come to a more rocky place now, full of polyps, things broken down, unidentified pain, at the same time as arthritis,weak bones, plus our lengthy and narrow exit pipery. There are many ways to get a stomach ache.

Getting things to pass would logically need a moist and large enough pathway and uncluttered circuitry. Where is the clean up commttee?

I 'm in over my head not quite sure how it happened. lol i am really learning from this thread tho and am researching toward another contribution.

Wow, Rick that is what I call serendipity! I'll be curious to see if he mentions any relation between PD and thyroiditis. I too plan on seeing an endocrinologist just as a follow up to our discussion and the fact that I largely started feeling like crap a few months post partum and it has worsened if anything. The symptoms point toward hypothyroidism like weight gain, fatigue, depression...yet I am having attacks very similar to what you experience which is result of hyperthyroidism. Talk about confusing!

My pregnancy and that of many other YO moms hold secrets to all this too. In fact, in researching how most women I know who have had babies while having PD and permanently worsened (me included)as a result, I ran right into all this thyroid info and when I hit parathyroid it gelled even more with PD.

One or two scarce articles even dare broach the effect of pregnancy on PD. The lone researcher in this area has suggested our PD is worsened by rapidly fluctuating hormones. Maybe this is so, but estrogen is supposed to be neuroprotective, so I could see a symptom exacerbation as our estrogen drops rather quickly after delivery, but I would then think we might return to baseline, but this is not the case. I'd say estrogen might still be a factor but something else is working against us, and I started thinking "thyroid".

About thyroid and pregnancy:

Many women develop thyroiditis post partum. It begins as hyperthyroidism and the thyroid never recovers from the inflammatory autoimmune attack (our immune system is stunted in favor of fetal develop) and we then become hypothyroid. It can disappear within a year or remain a permanent state for some women and clinically this autoimmune form is indistinguishable from Hoshimoto's Disease. Even more interesting...look at these case reports- longstanding, untreated Hashimoto's hypothyroidism can turn into neurodegenerative disease like cerebellar degeneration that looks like Ataxia, Parkinsonism, and MSA. In other words there is clear evidence that what begins as an autoimmune attack on the thyroid ends as an autoimmune attack in the person's brain. I can say that in seeing four different neurologists, not one ever asked if my thyroid had been checked.

I am not at all saying that my PD is not what it is, but I do wonder now if I developed a thyroid problem from pregnancy and untreated it has impacted the PD. I will be suggesting this to my PD mama friends; clearly it can do this. I am most definitely having all things thyroid checked very soon.

Oh, one last anecdote of interest...patients with untreated or under
treated hypothyroid report experiencing "brain fog".

Please report back after your neurology visit.

Laura