Parkinson's, Parlodel, Pituitary
I'm posting this long message for two reasons: (1) I'd like to hear
from medical professionals any explanation of the apparent riddles
or contradictions. (2) Other listmembers might be interested in
followup with their own physicians.
During the introduction to my new primary care doctor, he casually
offered to start me on Parlodel (bromocriptine). Like a smart aleck,
I quickly replied no thanks, I know the reputation for bad side
effects and would just as soon continue with Sinemet and Eldepryl
only. But to my astonishment he was talking NOT about Parkinson's
Disease but hyperprolactinemia, for which bromocriptine is also the
established therapy (and to which I'll refer hence as HPRL). Huh?
Driven by twin demons of ignorance and insatiable curiosity, I
consulted my little personal library and soon was beset with
questions. The answers may be important to others with Parkinson's
as well as to me, so I'd like to hear specially from doctors or
other authorities who are Parkinsn listmembers.
To avoid the clutter of individual footnotes to every statement,
I'll just list my references here:
1. Physician's Desk Reference, 1995:2178-2180
2. The Merck Manual, XVI ed: 1059,1066,1067,1799
3. L. Rolak MD, Neurology Secrets: 249

Pituitary
All the cells and organs of the body must communicate with one
another, commonly by means of hormones or by nerve connections.
Each organ responds with its various outputs to specific input
signals, often in chains of several links, of which we perceive
only the external origin or the end effect. For example, when it's
hot we sweat; but a lot happens in between that simple cause and
effect. The pituitary, sometimes called the hypophysis, is a bean-
size endocrine (ductless) gland just below the center of the brain,
attached to the base of the thalamus by a short bundle of dopamin-
ergic neurons called the "tubero-infundibular process" (doctorese
for "stalk"). It resides in a depression, called the sella turcica
for its fancied resemblance to a Turkish saddle, in the bone that
forms the base of the cranial cavity. The pituitary secretes
several important hormones, for example one whose malfunction
produces dwarfism or gigantism. Another is prolactin, which enables
newly delivered mothers to nurse. Sometimes the secretion of
prolactin is excessive, usually in women but occasionally in men.
The condition is called hyperprolactinemia (HPRL), and of itself
has no serious effect, but since tumors of the pituitary also
secrete prolactin, it always calls for a scan (CAT or MRI) to check
for possible tumor. Some tumors are big enough to see and treat by
surgery, but some occur as multiple small bodies that don't show
in the scan. HPRL also may result indirectly from, say, tumor in
the hypothalamus or, I suppose, failure of the dopaminergic
neurons in the pituitary connecting stalk. Interestingly,
prolactin secretion is inhibited by dopamine or a dopamine
receptor agonist. Women with HPRL, or the level normal after a
stillbirth or abortion, or who just don't wish to nurse a baby,
can be relieved by dopamine agonist therapy. Although others
such as cabergoline have been shown effective, bromocriptine is
the standard dopamine agonist prescribed in such cases. Even more
interesting, dopaminergic therapy is claimed to shrink pituitary
tumors! It's also claimed that bromocriptine in dosage adequate to
relieve HPRL doesn't affect the output of other pituitary hormones.



Parlodel
The ergot derivative Parlodel (bromocriptine mesylate) is a potent
dopamine agonist that works by stimulating post-synaptic dopamine
receptors, rather than by actually replacing dopamine. As PD users
of the drug well know, its most common adverse effects are nausea,
hallucinations, and mental confusion. Some reported effects such
as dyskinesia, I surmise, may result indirectly from failure to
balance the agonist action by reducing levodopa dosage. Pituitary
secretion of prolactin, as mentioned above, is thought to be
inhibited by dopamine which comes, not from the substantia nigra as
in PD, but from the stalk connecting the pituitary with the brain.
Hence the action of bromocriptine or another dopamine receptor
agonist against HPRL should be analogous to the action in PD.

Parkinson's Disease
It's well established that PD features a lack of dopamine, due to
degeneration of the substantia nigra. HPRL may not always be due to
lack of dopamine, but at least responds to dopaminergic therapy in
the same way. The two sites where PD and HPRL originate are rather
close together, suggesting the notion of a link between the two
conditions. In my own case, doctors found a deficiency in one
pituitary hormone and an excess in another (prolactin) at the same
time, nearly 10 years before diagnosis of PD. The CAT and MRI scans
of the pituitary showed no tumor, but the organ was atrophied as in
the "empty sella syndrome" that ordinarily affects growth in
childhood. Therapy was (is) continued replacement of the deficient
hormone, and nothing for the prolactin. Since diagnosis of PD about
3 years ago, I've been getting dopamine replacement via Sinemet.

Questions
1. How many other Parkinsn listmembers have had the blood test to
   check for HPRL? Of those, how many tested positive?
2. Is it possible there could be a link between HPRL and PD?
3. If HPRL responds as claimed to a dopamine agonist such as
   bromocriptine, which only mimics dopamine, why has it not
   responded, in my case, to the real thing (dopamine replacement)?
4. Is there something special about bromocriptine in its ability
   to shrink pituitary tumors, as compared to other dopamine
   agonists which do inhibit prolactin?

I hope some of you will find these questions of interest. Cheers,
Joe

J. R. Bruman   (818) 789-3694
3527 Cody Road
Sherman Oaks, CA 91403-5013