Ed Friedlander, M.D., Pathologist
scalpel_blade@yahoo.com
Cyberfriends: The help you're looking for is probably here.
Welcome to Ed's Pathology Notes, placed here originally for the convenience of medical students at my school. You need to check the accuracy of any information, from any source, against other credible sources. I cannot diagnose or treat over the web, I cannot comment on the health care you have already received, and these notes cannot substitute for your own doctor's care. I am good at helping people find resources and answers. If you need me, send me an E-mail at scalpel_blade@yahoo.com Your confidentiality is completely respected.
DoctorGeorge.com is a larger, full-time service.
There is also a fee site at myphysicians.com,
and another at www.afraidtoask.com.
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I'm still doing my best to answer
everybody.
Sometimes I get backlogged,
sometimes my E-mail crashes, and sometimes my
literature search software crashes. If you've not heard
from me in a week, post me again. I send my most
challenging questions to the medical student pathology
interest group, minus the name, but with your E-mail
where you can receive a reply.
Numbers in {curly braces} are from the magnificent Slice of Life videodisk. No medical student should be without access to this wonderful resource. Someday you may be able to access these pictures directly from this page.
Also:
Medmark Pathology -- massive listing of pathology sites
Freely have you received, freely give. -- Matthew 10:8. My
site receives an enormous amount of traffic, and I'm
handling about 200 requests for information weekly, all
as a public service.
Pathology's modern founder,
Rudolf
Virchow M.D., left a legacy
of realism and social conscience for the discipline. I am
a mainstream Christian, a man of science, and a proponent of
common sense and common kindness. I am an outspoken enemy
of all the make-believe and bunk that interfere with
peoples' health, reasonable freedom, and happiness. I
talk and write straight, and without apology.
Throughout these notes, I am speaking only
for myself, and not for any employer, organization,
or associate.
Special thanks to my friend and colleague,
Charles Wheeler M.D.,
pathologist and former Kansas City mayor. Thanks also
to the real Patch
Adams M.D., who wrote me encouragement when we were both
beginning our unusual medical careers.
If you're a private individual who's
enjoyed this site, and want to say, "Thank you, Ed!", then
what I'd like best is a contribution to the Episcopalian home for
abandoned, neglected, and abused kids in Nevada:
My home page
Especially if you're looking for
information on a disease with a name
that you know, here are a couple of
great places for you to go right now
and use Medline, which will
allow you to find every relevant
current scientific publication.
You owe it to yourself to learn to
use this invaluable internet resource.
Not only will you find some information
immediately, but you'll have references
to journal articles that you can obtain
by interlibrary loan, plus the names of
the world's foremost experts and their
institutions.
Alternative (complementary) medicine has made real progress since my
generally-unfavorable 1983 review linked below. If you are
interested in complementary medicine, then I would urge you
to visit my new
Alternative Medicine page.
If you are looking for something on complementary
medicine, please go first to
the American
Association of Naturopathic Physicians.
And for your enjoyment... here are some of my old pathology
exams
for medical school undergraduates.
I cannot examine every claim that my correspondents
share with me. Sometimes the independent thinkers
prove to be correct, and paradigms shift as a result.
You also know that extraordinary claims require
extraordinary evidence. When a discovery proves to
square with the observable world, scientists make
reputations by confirming it, and corporations
are soon making profits from it. When a
decades-old claim by a "persecuted genius"
finds no acceptance from mainstream science,
it probably failed some basic experimental tests designed
to eliminate self-deception. If you ask me about
something like this, I will simply invite you to
do some tests yourself, perhaps as a high-school
science project. Who knows? Perhaps
it'll be you who makes the next great discovery!
Our world is full of people who have found peace, fulfillment, and friendship
by suspending their own reasoning and
simply accepting a single authority that seems wise and good.
I've learned that they leave the movements when, and only when, they
discover they have been maliciously deceived.
In the meantime, nothing that I can say or do will
convince such people that I am a decent human being. I no longer
answer my crank mail.
This site is my hobby, and I presently have no sponsor.
This page was last updated February 6, 2006.
During the ten years my site has been online, it's proved to be
one of the most popular of all internet sites for undergraduate
physician and allied-health education. It is so well-known
that I'm not worried about borrowers.
I never refuse requests from colleagues for permission to
adapt or duplicate it for their own courses... and many do.
So, fellow-teachers,
help yourselves. Don't sell it for a profit, don't use it for a bad purpose,
and at some time in your course, mention me as author and KCUMB as my institution. Drop me a note about
your successes. And special
thanks to everyone who's helped and encouraged me, and especially the
people at KCUMB
for making it possible, and my teaching assistants over the years.
Whatever you're looking for on the web, I hope you find it,
here or elsewhere. Health and friendship!
{14945} anterior (A) and posterior (B) pituitary
QUIZBANK Endocrine (It's impossible to separate pituitary, adrenal, thyroid, parathyroid, etc. Look at it all
now.)
Recognize grossly and/or microscopically as appropriate:
Vocabulary:
Do a basic lab workup for the diagnosis of each disease listed above.
INTRODUCTION
Pituitary disease, like other endocrine disease, is fairly common, and is generally treatable if (and
only if!) you discover it.
The adenohypophysis ("anterior pituitary"), derived embryologically from the mouth via Rathke's
pouch, produces ACTH, TSH, FSH, LH, GH, and prolactin. No need to review these (or even what
they stand for), beyond mentioning that if the input from the hypothalamus is interrupted, the
adenohypophysis makes more prolactin and less of everything else.
Hyperpituitarism is defined to mean too much of one (or maybe two) of the hormones from the
adenohypophysis. This may be due either to autonomous over-production (i.e., from a primary
adenoma here, cancer of the adenohypophysis very rare: Cancer
79: 804, 1997, J. Neurosurg. 96: 352, 2002), from excess production of
hypophyseal stimulating factors or underproduction of inhibiting factors, or loss of inhibition following
destruction of other endocrine glands.
Hypopituitarism ("Simmonds's disease") is defined to mean loss of one or more (often all) of the
hormones from the adenohypophysis. You need to lose about 75% of the mass of the
adenohypophysis before any clinical changes occur. Panhypopituitarism indicates loss of most or all
of the hormones of the adenohypophysis.
The neurohypophysis ("posterior pituitary") is composed of the axons of hypothalamic neurons. The
"pituicytes" are modified glial elements. You may notice "Herring bodies" here, composed of ADH
awaiting release. (The other hormone secreted here is, of course, oxytocin).
* The pars intermedia, which seems to be vestigial in humans, consists of a few colloidal cysts that look
like thyroid gland. They contain some odd breakdown products of the endorphin-and-ACTH
precursor molecule. It's long been known that the pars intermedia
enables
frogs and chameleons change skin color; now we know this is done by
chromogranin (Endocrinology 140:
4104, 1999).
You also know that the pituitary itself lies in the "sella turcica" (Turkish
saddle) of the skull, with an extension of
dura (the "diaphragma sellae") serving as the roof. The pituitary stalk passes through a hole in the
middle of the sella. The pituitary gets its blood via a portal system from the hypothalamus, which
carries the various brain hormones that control its function.
LABS TO LOOK FOR PITUITARY INSUFFICIENCY
To confirm endocrine insufficiency, you'll usually perform a stimulation test.
In other words, you'll do something that should make the patient produce the hormone in
question. If enough of the hormone does not appear in the blood, you have
confirmed that disease is present.
I suggest you leave the arcane tests to the endocrinology consultant. Here's
a what's-worth-knowing account for each pituitary hormone.
Not enough ACTH... Careful!
"CRH test": Give corticotropin releasing hormone by vein. Look for an appropriate increase
in ACTH and cortisol.
"Insulin tolerance test": Give insulin to drop the blood glucose below 40 mg%. Look
for an appropriate increase in serum cortisol.
"Metyrapone test": Give metyrapone, which blocks conversion of 11-deoxycortisol
into cortisol, at midnight. This renders the patient unable to make cortisol
and
if the pituitary kicks in as it should and there's a good adrenal,
there should be a great deal of 11-deoxycortisol
in the blood in the morning.
Also measure plasma cortisol to see if the patient took the
medicine and has good adrenals. I cannot recommend this test to screen for pituitary insufficiency.
"ACTH stimulation test": Give ACTH and see if you get a cortisol
and aldosterone response.
Of course this is really testing the adrenal gland's ability to respond, but if
the pituitary hasn't been making ACTH, the adrenal will be atrophic. You can repeat
the test over the next few days, and if the response is better each time,
the problem is in the pituitary (why?); if not, the problem is in the adrenal (why?)
Catheter artists sampling petrosal sinus blood for ACTH levels ("Where's that
tumor?") may give CRH beforehand.
Not enough Anti-diuretic hormone Restrict water for a while, perhaps overnight and/or until the patient
is uncomfortable. If the urine does not rise above 1.010 SG / 300 mOSM/L,
you have diabetes insipidus. To see whether ADH deficiency is the cause
(rather than a kidney tubule problem), give an injection of ADH (as desmopressin).
Hardcore physicians may administer hypertonic saline to get the test over with,
and/or assay plasma ADH before and during the procedure.
Not enough FSH, LH
"GnRH test": If you must do a stimulation test, this is the way to see whether FSH
and LH can be raised.
"Arginine test": A large amount of arginine is infused slowly by vein.
"GHRH test": Growth hormone releasing hormone is given by vein.
"Insulin tolerance test": Give insulin to drop the blood glucose below 40 mg%.
"L-DOPA test": A big dose of L-Dopa is given orally.
"TRH test": A dose is given by vein. This should greatly increase TSH levels.
Same warning as before.
Too much ACTH
"High dose dexamethasone suppression test": 8 gm of dexamethasone is usually
enough to suppress an ACTH-producing pituitary adenoma and the cortisol
production that results from it. Other protocols exist.
Of course, this has
no effect on an oat cell carcinoma, thymoma, or carcinoid that is pumping out
ACTH and/or CRF, or on an adrenal cortical adenoma that is putting out cortisol autonomously.
* Midnight salivary cortisol to screen for cushingism: J. Clin. Endo. Metab. 89: 3345, 2004.
Please don't order a plasma ADH if you're looking for SIADH.
ANTERIOR LOBE ADENOMAS (NEJM 324: 822, 1991; curious five-tier
WHO classification Cancer 78: 502, 1996; tumorigenesis J. Clin. Inv. 112:
1603, 2003)
{15683} pituitary adenoma, gross
Pituitary adenomas constitute 10% of all diagnosed primary intracranial tumors. They can occur at
any age, with no great sex predominance. They are more
common in patients with autosomal dominant multiple endocrine neoplasia (MEN) I syndrome
(gene MENIN).
While the etiology of these tumors is almost entirely unknown (apart from MEN I, there are no
obvious risk factors), current work
confirms clonality, at least for prolactinomas (Cancer 95:
258, 2002), i.e., regardless of what hormonal factors at work,
they are true tumors.
Most of these tumors are not completely autonomous, and remain to a limited extent under feedback
control of the usual non-pituitary hormones.
* An oncogene PTTG is known (J. Clin. Endo. Metab. 84: 761, 1999).
However, unlike other common tumors, there's little uniformity in the
known genetics of pituitary adenomas from patient to patient: J. Clin. Path. 56: 561, 2003.
Around 40% of pituitary tumors from acromegalics have activation,
by mutation, of gene for the alpha-chain of Gs, (oncogene gsp), the stimulatory regulator of adenyl
cyclase (J. Clin. End. Met. 71: 1416, 1990;
J. Clin. End. Metab. 83: 1604, 1998;
Cancer 72: 1386, 1993; J. Clin. Invest. 91: 2815,
1993).
Pituitary adenomas typically present as one or more of the following:
(1) endocrine problems, both from hormones produced by the tumor itself and from damage to the
rest of the adenohypophysis and/or the neurohypophysis;
(2) visual problems, from an expanding mass impinging on the optic chiasm (i.e., bitemporal
hemianopsia; "Big Robbins" contains an error here) or optic nerves (blindness in one eye);
(3) enlarged sella turcica on skull x-rays, again due to expanding masses;
(4) least often, signs of increased intracranial pressure (i.e., headache, nausea and vomiting).
Large pituitary adenomas eventually erode the sella, clinoid processes, diaphragma sellae, optic
nerves and chiasm, and even the cavernous sinuses, nasal sinuses, or brain.
Despite this local destruction, cancers (i.e., metastasizing tumors) of the adenohypophysis are very
rare, and the presence of metastases is the only criterion for malignancy.
Hemorrhage into a large pituitary adenoma can produce pituitary apoplexy, which can simulate a
berry aneurysm rupture. Large tumors may also infarct themselves, leading to remission or
destruction of the remaining normal gland as well.
Microscopically, pituitary adenomas are typical endocrine adenomas, i.e. they are composed of
cuboidal cells, with round nuclei and a good blood supply.
Acidophilic adenomas (eosinophilic adenomas) typically make growth hormone and/or prolactin.
Basophilic adenomas typically make ACTH; less often, they make TSH or the gonadotropins.
Chromophobe adenomas typically make prolactin or "nothing" ("null cell adenoma", * stains as a
apudoma).
However, there are many exceptions. We recommend immunostaining over reliance on either H&E,
other histochemical stains, or electron microscopy.
We would like you to know the approximate frequencies of production of various hormones by
pituitary tumors:
Prolactin... 30%...Men: impotence, loss of libido;
Women: amenorrhea, galactorrhea, infertility;
Both: Obesity (Acta Endo. 125: 392, 1991)
Growth hormone...20%... Children: gigantism;
Adults: acromegaly (* may be silent: Am. J. Path. 134: 345, 1989);
* (Actually, all hGH-producers also produce some: Hum. Path. 24: 10, 1993)
GH + prolactin...10%... As above; growth hormone effects dominate
ACTH... 15%... Cushing's disease
LH, FSH... 25%?...
Most are silent until mass effect or autopsy makes the tumor known. NOTE: FSH and LH
production by pituitary adenomas was, until recently, considered "rare". Now it is clear, thanks to
improved staining (Am. J. Clin. Path. 106: 16, 1996) and clinicians' studies, that many (if not most)
"non-functioning" pituitary adenomas will produce FSH and/or LH (or some subunit thereof), at
least if TRH is given for stimulation (NEJM 324: 589, 1991). Review Mayo Clin. Proc. 71: 649,
1996.
TSH... rare...
Hyperthyroidism (Ann. Int. Med. 111: 827, 1989; South. Med. J. 96: 933, 2003)
None... ??
* Pancreastatin... An obscure hormone still in search of a disease, found in most or all non-prolactin-producing
pituitary adenomas; derived from chromogranin, it inhibits insulin and PTH production (Am. J.
Path. 148: 2057, 1996).
Real functioning prolactinomas in women generally declare themselves while quite small. But
remember that there are many other causes of hyperprolactinemia, including hypothalamic tumors
(* i.e., craniopharyngiomas, gliomas, hypothalamic germinomas) and anti-dopamine drugs
(phenothiazines, reserpine, alpha-methyldopa -- common). Try to demonstrate a mass before
operating.
The treatment of choice for prolactinomas is the dopamine agonist bromocriptine with or without
surgery (Am. J. Dis. Child. 144: 20, 1990) or gamma knife; bromocriptine almost invariably causes some significant
tumor regression. Newer agents are available including cabergoline (now widely
used: J. Clin. Endo. Metab. 86: 5256, 2001; J. Clin. Endo. Metab. 89: 1704, 2004).
After a few years on treatment, these tumors may regress and the bromocriptine
is no longer necessary: J. Clin. Endo. Metab. 87: 3578, 2002.
* Very large, invasive prolactinomas are tough to treat: Q. J. Med. 74: 227, 1990.
* Note that the treatment of choice for all other kinds of anterior pituitary adenomas is probably still
surgery. Gamma knife radiosurgery is also coming into use.
Gigantism and acromegaly (NEJM 322: 966, 1990):
{49419} giant and her sisters
Excess growth hormone before puberty produces excessively tall stature. In the past, these people
typically were crippled by nerve, muscle, and joint problems, acquired acromegalic features as they
got older, and died young of complications of their diabetes.
A giant is defined to be a human over seven feet tall (you may hear 200 cm instead).
Excess growth hormone after puberty produces acromegaly.
The typical acromegalic has a huge jaw ("prognathism"), huge brows, huge tongue, and huge hands
(with "spade fingers"), develops a deep guttural voice, gets an oily skin (extra sebaceous glands),
gets joint deformities (if not frank arthritis), and suffers from secondary diabetes and often
sleep apnea.
The popular wisdom is that
acromegalics are around 2.5 x more likely to develop tumors (benign,
malignant) than their counterparts (Arch. Int. Med. 151: 1629, 1991).
Lately this hasn't held up (J. Clin. Endo. Metab. 85: 3417, 2000).
Acromegaly kills its victims, taking an average of 10 years off life. Effective treatment of the adenomas
brings overall mortality back to levels similar to the unaffected
(J. Clin. End. Metab. 83: 3409, 1998).
* The lab workup of acromegaly is straightforward. Your screening
test is a spot
blood insulin-like growth factor I (IGF-I). If this is normal, you have ruled
out acromegaly. Next, attempt suppression of the hGH levels to <1 microgram/L
by administering 75 mg of glucose orally (yuck). If this fails, your patient probably
has acromegaly.
Most pituitary giants and acromegalic patients
have a pituitary macro-adenoma (i.e., >10 mm). The
best treatment is still surgical removal of this adenoma,
though some patients get fair results with octreotide
(J. Clin. End. Metab. 87: 4554, 2002).
The big news in pituitary disease during the last few years has been the application of the long-acting somatostatin
analogue
octreotide ("Sandostatin") to the treatment of acromegaly. This often
shrinks the tumor, and seems to make these tumors physically softer, making it easier to remove
them surgically (J. Clin. End. Metab. 86: 2779 & 5194, 2001,
J. Clin. Endo. Metab. 90: 440 & 1588, 2005; lots more). A long-acting depot
form is available.
Not surprisingly, the new transgenic mice that overproduce human growth-hormone releasing factor
get hyperplasia and adenomas of growth hormone and prolactin producing cells (Endocrinology
131: 2083, 1992), and morphologic changes elsewhere resembling those in acromegaly (Am. J. Path.
141: 895, 1992).
* There are a couple of poorly-understood "acromegaloid" syndromes, with the acromegaly look and
the insulin resistance, but normal growth hormone levels. Some of these folks have elevated levels
of other growth factors. There is also a familial tumor syndrome, 11q13, the gene
not yet cloned, which produces only GH-omas (J. Clin. Endo. Metab. 86: 542, 2001).
Cushing's disease:
{09367} Cushingism
You are already acquainted with the signs of Cushingism. "Cushing's disease" implies production of
ACTH by a pituitary tumor, usually a small microadenomas. There is usually not enough ACTH
production to darken the skin.
While the role of CRF in producing these adenomas may be important, they do appear to be
monoclonal overgrowths (J. Clin. End. Met. 75: 472, 1992)
that have lost some, but not all, of the ability of high levels of
cortisol to inhibit their growth (Endo. Rev. 20: 136, 1999).
* Transgenic mice (two kinds) with Cushing's disease: Am. J. Path. 140: 1071, 1992.
As you know, most cases of "idiopathic adrenal hyperplasia" are really due to ACTH-omas. In the
old days when we'd remove both hyperplastic adrenals, the ACTH-oma, which was under some
feedback inhibition, would grow to a tremendous size, turn the patient's skin brown, and blind and
kill the patient ("Nelson's syndrome"). Establish your diagnosis and take the pituitary out instead.
Back in the Bad Old Days, if you got an ACTH-producing pituitary adenoma, you
would probably be really sick for a while and then die of it. Today you will probably
get a cure (Ann. Int. Med. 130: 821, 1999); however persistence / recurrence
is disturbingly common (J. Clin. Endo. Metab. 89: 6348, 2004).
* Future catheter artists: Even today, it's often hard to find the adenoma
on imaging studies, especially in younger folks (J. Clin. Endo. Metab. 90:
5134, 2005). It's long been a practice to find and lateralize non-visualized adenomas by
comparing simultaneous ACTH measurements in the petrosal sinuses (see, for example, Am. J. Ob.
Gyn. 171: 563, 1994). This is being applied to more diseases (Am. J. Med. 87: 679, 1989; NEJM
324: 822, 1991).
Secondary hyperthyroidism
Mysteriously (and fortunately), TSH-producing adenomas of the pituitary gland are ultra-rare.
"Pituitary hyperplasia due to resistance to thyroid hormone" (J. Clin. End. Met. 75: 1071, 1992) isn't well-understood.
Patients have excess hTSH and become hyperthyroid.
* Future pathologists:
Incidentalomas: It's been
known for decades that in maybe 30% autopsies on grown-ups, if you look really hard, you'll find a "pituitary
microadenoma", generally "prolactin-producing". (One recent series of old autopsy pituitaries,
without a diligent search of each, found 10% with 1 "adenoma", 1% with 2 or more: J. Neurosurg. 74:
243, 1991; we're now using our high-resolution MRI's to find that around 10% of live folks have
them, too: Ann. Int. Med. 120: 817, 1994; Cancer 101: 613, 2004). Just how "autonomous" these "tumors" are, and their
real status as "neoplasms", is very dubious; the one's I've seen look like typical endocrine-gland
hyperplastic nodules ("gland bumps"). Nowadays they're routinely called
"incidentalomas"; if there are no hormonal abnormalities, leave them
alone, even if the pituitary seems a bit large (J. Clin. Endo. Metab. 86:
3009, 2001).
Clinicians are now picking these up on NMR scans and learning to ignore them, except for the rare
ones over 10 mm (Ann. Int. Med. 122: 925, 1990; Arch. Int. Med. 155: 181, 1995).
Sometimes telling microadenoma from normal gland is tricky. Microadenomas
will lack the normal reticulin pattern of pituitary gland, and have homogeneous cells
(morphology, immunostaining).
Occasionally, secondary prolactin production is caused by the tumor blocking the portal system,
keeping dopamine from reaching the non-neoplastic gland.
Most of the pituitary hormones can be secreted by carcinoids and oat-cell carcinomas elsewhere in
the body.
Some pituitary adenomas are eosinophilic not because they derive from GH- or prolactin-producing cells, but because
they are
packed with mitochondria. You've seen these "oncocytomas"
or "Hürthle cell adenomas" elsewhere.
PANHYPOPITUITARISM (NEJM 330: 1651, 1994)
The symptoms of panhypopituitarism are highly variable.
Growth hormone doesn't have spectacular effects on adults, and for years, we taught that its impact
is negligible. Now we know this isn't true. It slows the body wasting that occurs in old age (NEJM
323: 1, 1990). Adults lacking growth hormone have more fat and less muscle per pound of body
weight (Am. J. Clin. Nutr. 55: 918, 1992); the heart may also actually be weaker (Br. Heart. J. 67:
92, 1992), and growth hormone also helps maintain the skeletal muscles. See below.
Loss of gonadotropins produce loss of libido and body hair.
* There's an idiopathic, adult-onset loss of gonadotropin that produces treatable male infertility
NEJM 336: 410, 1997.
Loss of prolactin prevents lactation, which would only be noticed after childbirth.
Loss of thyrotropin produces secondary hypothyroidism (i.e., cretinism in children, problems
culminating in myxedema in adults).
Loss of ACTH produces secondary adrenal insufficiency, which is just as deadly as primary adrenal
insufficiency. (Fortunately, this happens only very late in the progression
of the disease.)
If the posterior pituitary gland is involved, loss of ADH produces pituitary diabetes insipidus.
Patients with hypopituitarism from a variety of causes are unusually prone to precocious
atherosclerosis. No one knows why (Lancet 340: 1188, 1992.) It appears to translate into
premature cardiovascular disease mortality (Lancet 336: 285, 1990).
Most of the time, hypopituitarism is due to (1) destruction of the pituitary by a pituitary adenoma, surgery, radiation (Q. J. Med. 70: 145,
1989), or trauma;
(2) Sheehan's pituitary necrosis, or
(3) the "empty sella syndrome".
* Also worth considering are vascular problems (i.e., cavernous sinus thrombosis, obvious) and
sarcoidosis (not at all obvious).
* Lymphocytic hypophysitis is a rare cause of pituitary insufficiency and a mass lesion; the
traditional teaching is that most patients
are postpartum women but more recently sex ratios have been about equal
(J. Neurosurg. 101: 262, 2004).
Granulomatous hypophysitis produces a mass and sometimes
pituitary insufficiency: J. Neurosurg. 71: 681, 1999; I've seen a case. Both will be operated as
"adenomas" and the correct diagnosis established later by the pathologist; one must be
extremely alert to suspect the diagnosis before the (? unnecessary) surgery
(J. Clin. Endo. Metab. 86: 1048, 2001)
* A genetic syndrome lacks a transcription factor needed for making growth-hormone, prolactin, and
TSH
(Science 257: 1118, 1992.)
* Yet another mutation, lack of PROP1, prevents production of all the hormones
of the adenohypophysis except for (sometimes) ACTH (Nat. Genet. 18: 147, 1998;
J. Clin. Endo. Metab. 85: 4566, 2000; J. Clin. Endo. Metab. 89: 5256, 2004).
POU1F prevents productions of GH, prolactin, and TSH (J. Clin. Endo. Metab. 90:
4762, 2005).
Hypopituitarism after TB meningitis in childhood is a problem in the poor nations (Ann. Int. Med.
118: 701, 1993). In this series, around 1/5 of childhood survivors of TB meningitis were left with
hypopituitarism.
Sheehan's pituitary necrosis ("postpartum pituitary necrosis") occurs when shock complicates a
problem delivery. The drop in blood pressure results in inadequate blood supply to the gland, which
is already hyperplastic and has its vessels squeezed half-shut.
Less often, pituitary necrosis results from sickle cell disease, temporal arteritis, or trauma.
* For some reason, diabetics are prone to hemorrhages and necrosis in the pituitary. This may even
help the diabetic state.
Usually the gonadotropins and prolactin are the most decreased. The typical Sheehan's patient fails
to lactate or resume menstruating after delivery. When necrosis is less complete, the disease tends to
progress "as the remaining cells are entrapped in scar tissue" (more likely, the scar diverts blood
from the good gland).
The empty sella syndrome classically results from slow crushing of the gland by CSF pressure when
the hole in the diaphragma sellae is wide enough (or there is another defect) to allow arachnoid to
herniate into the sella (most common).
Some of these patients develop pituitary insufficiency.
Future radiologists: Other reasons to have an empty sella include old Sheehan's, or total necrosis of
an old adenoma, or previous surgery. Again, many of these patients have hypopituitarism of one
kind or another.
The older medical literature is full of descriptions of extreme weight loss in
end-stage hypopituitarism ("Simmonds's cachexia"). These must
be the patients who finally lose
ACTH (often the last to go). Failure to produce normal amounts of growth hormone in childhood results in miniature, well-proportioned people.
Causes
range from "idiopathic" to various genetic syndromes to other causes
of hypopituitarism.
Around 50% of "idiopathic dwarves" are breech or transverse deliveries, and the damage to the
hypothalamic-pituitary axis may occur when their little skulls get crunched: Lancet 338: 480, 1991
After traumatic brain injury, there is often considerable loss of
growth hormone (Arch. Phys. Med. 86: 463, 2005).
Laron dwarves (short, frontal bossing;
the defect is in the
growth hormone receptors;
update J. Clin. Endo. 83: 4481, 1998).
Quite a few adults who are "just short" turn out to have marginal
ability to make growth hormone, and they seem to benefit
from replacement (J. Clin. Endo. Metab. 89: 1586, 2004).
Pygmies also have tissues that do not respond well to growth hormone;
apparently in Africa and the Philippines there is a relative deficiency
of the growth hormone receptor ("pituitary dwarfism type II";
J. Ped. Endo. 15: 269, 2002; Clin. Endo. 51: 741, 1999).
"Get Shorty!" Now it turns out that a lot of just-plain-short people have minor defects in their
growth hormone receptors: NEJM 333: 1093, 1995.
If thyrotropin is normal or thyroid hormone is replaced, the children will be of normal intelligence.
If gonadotropin production is normal or sex steroids are administered, puberty should occur
normally. And please don't miss adrenal insufficiency in these kids; they continue to die of sudden
adrenal crisis in disturbingly large numbers.... (J. Clin. End. Metab. 81: 1693, 1996).
And of course, we used to donate autopsy pituitaries to make growth hormone to help these kids
attain normal height. (* Regrettably, a significant amount of this precious substance ended up at the
gym instead, as part of quack "muscle building" schemes.) Now we have recombinant hGH.
NOTE: Before you diagnose an endocrine problem, remember that mysterious "failure to grow" can
and does result from lack of parental warmth and emotional nurturing. This is more common
than
endocrine dwarfism.
Adult growth hormone deficiency, unheard-of a few years ago,
is now being diagnosed both in patients who've had previous pituitary
surgery or tumors, and in people who seem to waste their lean tissues and
simply do not feel or perform well. The screening test is IGF-I, which
should be low for age-and-sex-matched controls. I believe AGHD is real,
since the patients report a spectacular improvement in sense of well-being upon
hormone replacement (Clin. Endo. 54: 709, 2001).
Especially, suspect it when the voice starts getting
higher and raspier (J. Clin. Endo. Metab. 90: 4128, 2005).
CRANIOPHARYNGIOMA ("adamantinoma", "ameloblastoma", both named for tooth enamel)
{15685} craniopharyngioma, gross
This is a benign tumor of Rathke's pouch remnants that generally occurs just above the pituitary
and sella turcica. It is locally aggressive but does not metastasize (* like the closely-related
ameloblastoma of the jaw). The optic nerves and chiasm, and then the hypothalamus, are damaged.
Most patients are under twenty, but no age is immune. Little is known
of the etiology or genetics (J. Neurosurg. 98: 162, 2003).
Grossly, the tumor is usually filled with little
cysts that contain an unsavory, cholesterol-rich fluid ("machine oil").
Microscopically, the tumor generally recalls developing tooth enamel, with areas of columnar cells,
stellate mesenchyme, usually calcification, sometimes stratified squamous stuff and/or bone.
* The mainstay of craniopharyngioma treatment is surgery (series with pretty
good results 97: 3, 2002), but intratumoral injection of bleomycin
is a possibility for poor-surgical risk cases: J. Neurosurg. 84: 124, 1996.
* Future pathologists: The papillary variant mostly occurs in adults, and is less aggressive (J.
Neurosurg. 83: 206, 1995). Rathke's cleft cysts, a common
tiny incidental autopsy finding, may sometimes be large enough
to be seen in life; must be distinguished from craniopharyngiomas.
These cysts can compromise eyesight, too (Am. J. Ophth. 119: 86, 1995'
J. Neurosurg. 102: 189, 2005).
Very rarely, a squamous cell carcinoma arises in a craniopharyngioma (Arch. Path.
Lab. Med. 124: 1356, 2000).
DIABETES INSIPIDUS (Am. Fam. Phys. 55: 2146, 1997;
Arch. Int. Med. 157: 1293, 1997).
Because the posterior pituitary gland is really processes of hypothalamic neurons, a variety of
processes can damage it. Remember:
Causes within the sella
Causes above the sella
Also remember nephrogenic diabetes insipidus, the inability of the kidney to respond to ADH (mutant
ADH receptor: Nature 359: 235, 1992; also other medullary diseases and lithium therapy).
* There are two posterior pituitary gland tumors.
Pituitcytomas are astrocytomas arising from the pituitcytes. I've never seen one.
The granular cell tumor resembles similar tumors of Schwann cell origin seen elsewhere (but see
Virch. Arch. B., 60: 413, 1991). Think of McCune-Albright.
SYNDROME OF INAPPROPRIATE ADH PRODUCTION
Patients have continual ADH production no matter what the current plasma osmolality. Water leaks back freely
from the collecting ducts, the blood becomes hypotonic, and the patient loses the ability to produce
dilute urine.
Low blood tonicity leads to seizures and then to death. Correct it too fast by pushing in sodium, and
your patient develops central pontine myelinolysis. Be sure you know what you're doing.
The syndrome, when really present, is almost always due to ectopic ADH production by a tumor
(typically, oat cell carcinoma; occasionally a carcinoid, * thymoma, or * lymphoma; rarely,
widespread pulmonary TB produces excess ADH for some reason, and the last one to remember is
acute intermittent porphyria and its variants). Pituitary problems almost never produce
inappropriate ADH.
The best treatment is to make the "inappropriate ADH" appropriate by restricting water.
Before you wrongly diagnose "syndrome of inappropriate ADH" in your cachectic, hyponatremic
cancer patient, remember that generalized body protein depletion re-sets the "osmostat", and
hyponatremia is usual and normal. Don't add to your patient's discomfort by foolishly denying him
or her access to the water pitcher.
There is no known oxytocin-excess or deficiency syndrome. PITUITARY-HYPOTHALAMIC SYNDROMES
These result from abnormal function of the hypothalamus, reflected in problems with sexual
development.
Froehlich's syndrome is hypothalamic hypogonadism plus obesity. Affected boys are obese (i.e.,
have increased appetite), show a female pattern of fat distribution, and have delayed (if ever)
appearance of primary or secondary sex characteristics.
The problem in "adiposogenital dystrophy" may be in the hypothalamus (true Froehlich's -- these
kids may or may not be retarded; do you think emotions could be the cause?). It can equally well be
due to hypopituitarism from any cause in someone who like to eat. It could also be "constitutional"
without a demonstrable hypothalamic lesion (the fat boy that stays child-like; you knew him).
Good
luck sorting all these out; endocrinologists use sophisticated stimulation and suppression tests.
Current thinking focuses on a variety of etiologies, known and unknown,
that prevent the normal pulsatile secretion of GnRH.
{49423} Froehlich's man, age twenty
After surgery for craniopharyngioma, which often damages the hypothalamus, MRI can predict
who, and will not, get morbid weight gain (J. Clin. End. Metab. 81: 2734, 1996).
You already know Prader-Willi.
* Bardet-Biedl syndrome (used to be "Laurence-Moon-Biedl")
is a hereditary complex with retinitis pigmentosa, polydactyly,
and a similar picture to Froehlich's. There are at least three loci (Am. J. Hum. Genet. 72: 650, 2003).
An autosomal dominant Kallman's: Nat. Genet. 33: 463, 2003. * GPR54 mutations lead to no-puberty (NEJM 349: 114, 2003).
McCune-Albright syndrome (often just "Albright") is a syndrome with cutaneous café-au-lait
("coffee with milk") spots (with irregular borders), polyostotic fibrous dysplasia, and precocious
puberty caused (maybe sometimes) by a curious hypothalamic hamartoma that produces LH-releasing hormone. (These
hamartomas are
infamous for causing puberty before age 2. McCune-Albright kids also have other reasons for having hormonal problems.)
Much more about McCune-Albright (a genetic disease that cannot be transmitted
parent to child) when we study bone.
* Septo-optic dysplasia, homeobox gene HESX1, multiple birth defects including
several malformations of the forebrain; there are others (Nature 403: 658, 2000).
* Update on all the genes involved in pituitary development and
neoplasia: J. Clin. Inv. 112: 1603, 2003.
* I have "HPA Axis Disease!" There's considerable research interest right now in
subtle physiological alterations of the hypophyseal-pituitary axis
as a result of life experience and/or subtle genetic differences.
This supposedly explains why some
people overeat, get post-traumatic stress disorder (J. Clin. Psych. 62S17:
41, 2001), functional GI
troubles (Am. J. Med. 107(5A): 12S, 1999), fibromyalgia,
etc., etc. Cause or effect, the results are interesting;
the axis is easy to study by stimulation and suppression tests.
Respectable psychiatrists are rediscovering the dexamethasone suppression
test (if abnormal, the patient is MUCH more likely to suicide: Am. J. Psych.
158: 748, 2001; circadian and day-to-day
rhythms distinguish various types of severe depression Arch. Gen. Psych.
57: 755, 2000).
Having been badly abused as a child seems to make a person oversecrete CRF /
downregulate CRF receptors etc., etc. (Am. J. Psych. 158: 575, 2001), and this will make "nature vs. nurture"
almost impossible to sort out for now.
"HPA axis" is now becoming a "pop" diagnosis, in a class with
chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivities
(except for the last, I think there is something real but it is hard to sort out.)
* PITUITARY NON-DISEASES
Little pituitary infarcts are common in patients who die with intracranial problems.
{10747} pituitary infarct
Crooke's hyaline change, discussed in certain pathology texts as if it were important, merely refers to
absence of granules and an overly-dense cytoskeleton in pituitary cells that ordinarily make
ACTH, when they have suffered chronic suppression by exogenous glucocorticoid administration
(iatrogenic, from an autonomous adrenal adenoma.)
FINAL NOTE:
Endocrine disease is especially worthy of your serious attention because (1) it is prevalent; (2) it is
generally very treatable; (3) if you diagnose it incorrectly, you doom the patient to lifelong
medication; (4) if you miss it, you doom the patient to long-term ill health and probably "mental
illness"; (5) Many (if not most) cases of endocrine disease get missed for a long, long time.
You'll learn how to establish the presence of various endocrine syndromes and diseases while you
are on Internal Medicine. Again, remember that for most suspected non-thyroid endocrine
diseases, you'll need a stimulation test ("Can the patient produce the hormone in question at all?") or
a suppression test ("Can we suppress production of the hormone in question as we could in a healthy
patient?"). I don't want any more requests for a "random growth hormone assay" on a short kid.
{00135} thyroid, normal
I am presently adding clickable links to
images in these notes. Let me know about good online
sources in addition to these:
Pathology Education Instructional Resource -- U. of Alabama; includes a digital library
Houston Pathology -- loads of great pictures for student doctors
Pathopic -- Swiss site; great resource for the truly hard-core
Syracuse -- pathology cases
Walter Reed -- surgical cases
Alabama's Interactive Pathology Lab
"Companion to Big Robbins" -- very little here yet
Alberta
Pathology Images --hard-core!
Cornell
Image Collection -- great site
Bristol Biomedical
Image Archive
EMBBS Clinical
Photo Library
Chilean Image Bank -- General Pathology -- en Español
Chilean Image Bank -- Systemic Pathology -- en Español
Connecticut
Virtual Pathology Museum
Australian
Interactive Pathology Museum
Semmelweis U.,
Budapest -- enormous pathology photo collection
Iowa Skin
Pathology
Loyola
Dermatology
History of Medicine -- National Library of Medicine
KU
Pathology Home
Page -- friends of mine
The Medical Algorithms Project -- not so much pathology, but worth a visit
National Museum of Health & Medicine -- Armed Forces Institute of Pathology
Telmeds -- brilliant site by the medical students of Panama (Spanish language)
U of
Iowa Dermatology Images
U Wash
Cytogenetics Image Gallery
Urbana
Atlas of Pathology -- great site
Visible
Human Project at NLM
WebPath:
Internet Pathology
Laboratory -- great site
My team:Ed Lulo's Pathology Gallery
Bryan Lee's Pathology Museum
Dino Laporte: Pathology Museum
Tom Demark: Pathology Museum
Dan Hammoudi's Site
Claude Roofian's Site
Pathology Handout -- Korean student-generated site; I am pleased to permit their use of my cartoons
Estimating the Time of Death -- computer program right on a webpage
Pathology Field Guide -- recognizing anatomic lesions, no pictures
St.
Jude's Ranch for Children
I've spent time there and they are good. Write "Thanks
Ed" on your check.
PO Box 60100
Boulder City, NV 89006--0100
More of my notes
My medical students
Clinical
Queries -- PubMed from the National Institutes of Health.
Take your questions here first.
HealthWorld
Yahoo! Medline lists other sites that may work well for you
We comply with the
HONcode standard for health trust worthy
information:
verify
here. 
Tulane Pathology Course
Great for this unit
Exact links are always changing
{02294} anterior pituitary, histology; curious stain, don't worry about the colors
{14948} posterior pituitary, histology (arrow: Herring body)
Endocrine
Introductory Pathology Course
University of Texas, Houston
OBJECTIVES;
Know when to suspect each of these clinical syndromes, and give the likely etiologies,
pathophysiology, and anatomic pathology:
Acromegaly-Gigantism
Diabetes insipidus
Hypopituitarism (describe the course of the acquired disease)
Hyperprolactinemia
Inappropriate ADH
Pituitary dwarfism
Pituitary-hypothalamic syndromes
adrenal hyperplasia
empty sella
pituitary adenoma (no need to subtype without immunostains)
pituitary carcinoma
craniopharyngioma
Cushing's disease
Cushing's syndrome
Diabetes insipidus
Empty sella syndrome
Hypopituitarism
Panhypopituitarism
Sheehan's syndrome
Simmonds's disease
Loss of the hormones follows a predictable sequence. First growth hormone
goes ("I don't feel good"), then FSH/LH ("My libido is gone"), then TSH and ACTH (danger to life).
Most hormones are secreted in spurts ("pulsatile"). For these, a random sample
of blood isn't much use in determining whether your patient is making
enough of a particular hormone.
LABS TO LOOK FOR PITUITARY HORMONE OVERPRODUCTION
This is fraught with pitfalls. First, it is hard to measure ACTH accurately,
since it sticks to the glass tubes. Second, in suspected addisonism, stressing
patients by putting them through tests like these can kill them. Think about covering
them with a bit of cortisol.
You'll suspect ADH deficiency when your patient is putting out a lot of
urine that is hypotonic (SG <1.010, concentration <300 milliosmoles/L).
Baseline levels are okay, and you can also order estrogen and testosterone levels.
Check for normals for age and sex; remember that if a post-menopausal woman's
FSH and LH levels aren't high, something may be wrong.
Not enough Growth Hormone
Nowadays you'll probably just get a spot IGF-I assay. In growth hormone deficiency,
it will be low. If you must pursue the issue...
Not enough Prolactin
"TRH test": A dose is given by vein. This should greatly increase prolactin.
The curious side effect of intravenous TRH is urinary incontinence. You have
been warned.
Not enough Thyroid stimulating hormone
"Baseline T3, T4, and TSH": These are not so pulsatile
as other hormones, and may be spot-checked.
Both the pulsatile nature of hormone production, and the stress of getting
blood drawn, make "spot" checks less helpful for most hormones. To prove
overproduction, you may need to demonstrate that you cannot suppress production
of a particular hormone. Again, here's the "need to know".
"Low dose dexamethasone suppression test": 2 mg of dexamethasone, a
synthetic glucocorticoid, given at midnight, should drop one's ACTH and cortisol to near-zero
by 8 AM. Other protocols exist.
Too much Anti-diuretic hormoneIn suspected "syndrome of inappropriate ADH secretion", the basic findings
(hyponatremia not otherwise explainable, inappropriately high urine sodium levels and concentration, no edema,
good response to water restriction)
are a lot more help than any additional labs.
Too much FSH/LH
Spot checks are okay. Remember that most people with pituitary adenomas producing
gonadotropins make alpha and beta chains rather than intact hormones.
Too much Growth hormone
Rather than do a suppression test, you should probably just get a spot IGF-I,
at least for starters. Future endocrinologists see J. Clin. Endo. Metab. 87:
3537, 2002 (giants and acromegalics can have normal spot growth hormone levels).
Too much Prolactin
Various suppression tests have been proposed, but a series of spot-checks in the morning
seems to be the usual.
Too much Thyroid-stimulating hormone
A spot check is enough. Remember that overproduction of TSH by a pituitary tumor
("secondary hyperthyroidism")
is very rare.
{15682} pituitary adenoma with hemorrhage
{49422} pituitary adenoma, gross
{49612} pituitary adenoma, gross
{09214} pituitary adenoma, histology (this was a prolactinoma; you couldn't tell)
{24821} pituitary acidophilic adenoma, Orange G stain (acromegaly)
{09215} pituitary adenoma, histology
{15679} pituitary adenoma, histology
{05026} pituitary adenoma, x-ray
{00344} pituitary adenoma, x-ray
{16101} acromegaly
{25668} acromegaly (which twin has it?)
{49421} acromegaly, hand (compared with normal)
* Andre "the Giant" Rousimoff, the famous wrestler, had acromegaly; he was 7'4" tall
and weighed 520 lb when he died at age 46.
Several movie villains have been played by acromegalics.
My favorite is Richard Kiel as "Jaws" from "Moonraker".
Acromegalic Rondo Hatton (here
or here, from the 1940's B-movies, "could have played
Frankenstein witout make-up".
Dalip Singh evidently
has gigantism-acromegaly;
he remains very physically fit.
{09368} Cushingism
{09369} Cushingism
{09370} Cushingism
{16110} Cushingism
{16111} Cushingism
{49427} Cushingism
{25669} Cushingism, before and after treatment
Pituitary adenoma
Pittsburgh Illustrated Case
PITUITARY DWARFISM
{15686} craniopharyngioma, gross
{15687} craniopharyngioma, histology
{15688} craniopharyngioma, histology
Craniopharyngioma
Notice the benign squamous pearl
KU Collection
Kallmann's syndrome
is a brain malformation with anosmia (no sense of smell) and Froehlich's.
The best-known gene is KAL1, which directs neuronal migration.
* Jazz singer/musician "Little Jimmy Scott", who's
delighted audiences for over half a century,
has Kallmann's, which gave him his disctinctive child-like appearance and voice.
* SLICE OF LIFE REVIEW: ALL GLANDS
{09213} pituitary, normal
{09362} thyroid scan radionucleotide, normal
{11204} adrenal and nerve, normal
{11207} adrenal and nerve, normal
{11210} adrenal and nerve, normal
{11754} thyroid, normal
{11755} thyroid, normal
{11803} thyroid, normal
{12866} sella turcica, normal anatomy
{12903} thyroid gland, normal
{12983} sella turcica, normal
{12986} sella turcica, normal
{12992} sella turcica, normal anatomy
{12995} sella turcica, normal
{12998} sella turcica, normal
{13004} sella turcica, normal
{13007} sella turcica, normal
{13010} sella turcica, normal
{13013} sella turcica, normal
{13016} sella turcica, normal
{13019} sella turcica, normal
{13022} sella turcica, normal
{13025} sella turcica, normal
{13028} sella turcica, norma
{13169} adenoma, pituitary
{14942} hypophysis, normal
{14942} hypophysis, normal
{14943} adenohypophysis (pars distalis), normal
{14943} adenohypophysis (pars distalis), normal
{14944} pituitary (anterior & posterior)
{14945} pituitary (anterior & posterior)
{14946} pituitary trabeculae, normal
{14947} neurohypophysis, normal
{14948} neurohypophysis, normal
{15034} adrenal, normal
{15035} adrenal gland (zones), normal
{15036} adrenal gland (zones), normal
{15037} adrenal gland (cortex), normal
{15038} adrenal gland (cortex), normal
{15039} adrenal gland (cortex), normal
{15040} adrenal gland (cortex), normal
{15041} adrenal gland (cortex, lipid stain)
{15042} adrenal gland (cortex, lipid stain)
{15043} adrenal gland (medulla), normal
{15044} adrenal gland (medulla), normal
{15045} adrenal gland (medulla, chromaffin stain)
{15046} adrenal gland (medulla, chromaffin stain)
{15048} thyroid gland, normal
{15049} thyroid gland, normal
{15050} thyroid inactive, normal
{15051} thyroid gland (follicle cells), normal
{15052} thyroid gland (active follicle cells)
{15053} thyroid gland (inactive follicle cells)
{15054} thyroid gland (parafollicular cells)
{15055} thyroid gland (parafollicular cells)
{15056} parathyroid gland fetal, normal
{15057} parathyroid gland, normal
{15058} parathyroid gland, oxyphil cells
{15059} parathyroid gland, oxyphil cells
{15060} parathyroid gland, oxyphil & chief cells
{15680} adenoma, pituitary with normal tissue
{20695} pituitary gland, both lobes
{20696} pituitary gland, both lobes
{20697} pituitary, pars distalis
{20698} pituitary, pars intermedia
{20699} pituitary, intermedia and * nervosa
{20700} pituitary, pars nervosa
{20701} adrenal gland with layers labeled, #98
{20702} adrenal gland with layers labeled, #98
{20703} adrenal gland with layers labeled, #98
{20704} adrenal gland with layers labeled, #98
{20705} adrenal gland, medulla
{20706} thyroid, normal
{20707} thyroid, normal
{20708} thyroid, normal
{20709} parathyroid, normal
{20711} pineal gland, normal
{20712} pineal gland, normal
{20795} parathyroid
{20796} parathyroid, oxyphil cell
{20797} parathyroid, oxyphil cell
{20970} hypophysis, all three regions
{20971} adenohypophysis, anterior lobe of pit.
{20972} neurohypophysis, posterior lobe pituit.
{20973} pars * intermedia, pituitary
{20974} pars * intermedia, pituitary
{20975} neurohypophysis, herring body
{20976} adrenal
{20977} adrenal, glomerulosa layer
{20978} adrenal, fasciculata layer
{20979} adrenal, reticularis layer
{20980} adrenal, medulla
{20981} adrenal, fasciculata
{24712} adrenal, normal
{24823} thyroid, normal
{25393} adrenal cortex, normal
{31090} pituitary in sella, normal
{34355} pituitary, normal
{36419} thyroid, normal
{36425} thyroid, normal
{36452} thyroid cytology, normal glandular cells
{36455} thyroid cytology, sheet of normal glandular cells
| Visitors to www.pathguy.com reset Jan. 30, 2005: |
Ed says, "This world would be a sorry place if
people like me who call ourselves Christians
didn't try to act as good as
other
good people
."
Prayer Request
Teaching Pathology
PathMax -- Shawn E. Cowper MD's
pathology education links
Ed's Autopsy Page
Notes for Good Lecturers
Small Group Teaching
Socratic
Teaching
Preventing "F"'s
Classroom Control
"I Hate Histology!"
Ed's Physiology Challenge
Pathology Identification
Keys ("Kansas City Field Guide to Pathology")
Ed's Basic Science
Trivia Quiz -- have a chuckle!
Rudolf
Virchow on Pathology Education -- humor
Curriculum Position Paper -- humor
The Pathology Blues
Ed's Pathology Review for USMLE I
 | Pathological Chess |
 |
Taser Video 83.4 MB 7:26 min |
Normal pituitary
Pituitary adenoma
Craniopharyngioma