Secretory Diarrhea
Lawrence R. Schiller, MD
Address
Baylor University Medical Center, 3500 Gaston Avenue,
Dallas, TX 75246, USA.
Current Gastroenterology Reports 1999, 1:389397
Current Science Inc. ISSN 1522-8037
Copyright 1999 by Current Science Inc.
Diarrhea, defined as loose stools, occurs when the
intestine does not complete absorption of electrolytes
and water from luminal contents. This can happen
when a nonabsorbable, osmotically active substance
is ingested (osmotic diarrhea) or when electrolyte
absorption is impaired (secretory diarrhea). Most
cases of acute and chronic diarrhea are due to the
latter mechanism. Secretory diarrhea can result from
bacterial toxins, reduced absorptive surface area caused
by disease or resection, luminal secretagogues (such
as bile acids or laxatives), circulating secretagogues
(such as various hormones, drugs, and poisons),
and medical problems that compromise regulation
of intestinal function. Evaluation of patients with
secretory diarrhea must be tailored to find the likely
causes of this problem. Specific and nonspecific
treatment can be valuable.
Introduction
Each day 9 to 10 liters of fluid enter the jejunum. This fluid
consists of the food and drink ingested each day plus sali-
vary, gastric, pancreatic, and biliary secretions. In health,
the small intestine absorbs 90% of this fluid load, passing
800 to 1000 mL of fluid on to the colon each day. The
colon absorbs 90% of that amount, leaving approximately
80 to 100 mL excreted each day in feces [1].
Loosening of the stool occurs when daily fecal water
output increases by only 50 to 60 mL. An increase in fecal
water excretion of 100 mL is sufficient to increase stool
weight above 200 g/24 h, the upper limit of normal. Thus,
a decrease in overall intestinal water absorption of only 1%
to 2% is sufficient to cause diarrhea [2].
Many disorders can disrupt intestinal fluid and electro-
lyte absorption by at least this amount. This accounts for
the frequency of diarrhea as a symptom and also for the
extensive differential diagnosis that confronts the clinician
attempting to treat a patient with diarrhea. This article
reviews the causes, classification, evaluation, and manage-
ment of diarrhea in the framework of recent publications.
Causes of Diarrhea
Excess stool water can result from ingestion of poorly
absorbed substances that remain in the lumen of the intes-
tine and obligate retention of water within the lumen by vir-
tue of their osmotic effects. This is so-called osmotic
diarrhea. Examples of osmotic diarrhea include lactose mal-
absorption and diarrhea caused by ingestion of magnesium
laxatives (Table 1). Electrolyte absorption is unaffected by
these osmotically active substances, and, typically, stool
water contains very little unabsorbed sodium or potassium
[3]. This is the basis for calculation of the fecal osmotic
gap. In this calculation the difference between luminal
osmolality (equal to body fluid osmolality, approximately
290 mOsm/kg, because the colon cannot maintain an
osmotic gradient against plasma) and the osmolality of
luminal contents contributed by fecal electrolytes is esti-
mated. The contribution of fecal electrolytes is calculated as
twice the sum of sodium and potassium ions to account for
the anions that accompany these cations. Recent work indi-
cates that a fecal osmotic gap of greater than 50 mOsm/kg
suggests osmotic diarrhea [3]. For example, an individual
with diarrhea caused by ingestion of magnesium hydroxide
might have the following stool water analysis: [Na + ]=7
mmol/L, [K+]=10 mmol/L, and [Mg+2]=80 mmol/L (equiva-
lent to 194 mg/dL, almost twice the upper limit of normal,
which is 45.2 mmol/L [110 mg/dL]). The fecal osmotic gap
would be calculated as 290 - 2 (7 + 10) or 256 mOsm/kg.
Most of this osmotic space is accounted for by magnesium
and its associated anions.
When the osmotic gap is small, electrolytes account for
most of the luminal osmolality, and secretory diarrhea is said
to be present. To some extent secretory diarrhea is a misno-
mer; most patients with secretory diarrhea, defined by a
small osmotic gap, still absorb most of the 9 to 10 liters of
fluid entering the jejunum each day, but they do not absorb
almost all of it, as they would under normal circumstances
[4]. It could be argued that this condition should be called
nonosmotic diarrhea because daily stool volume rarely
exceeds 9 to 10 liters, but the term secretory diarrhea seems
fixed and is unlikely to change in the near future.
A number of conditions can lead to secretory diarrhea
(Table 1). These include many small bowel disorders such
as bacterial infections and Crohns disease of the small
intestine and mucosal diseases such as celiac disease and
Whipples disease. In addition, several diseases affecting
the colon exclusively can produce secretory diarrhea, such
as ulcerative colitis or microscopic colitis.
390 Small Intestine

Table 1. Major Causes of Diarrhea

Osmotic diarrhea Secretory diarrhea
Osmotic laxative abuse Nonosmotic laxative abuse
Mg++, SO4-2, PO4-3, lactulose, PEG Congenital chloridorrhea
Carbohydrate malabsorption Bacterial toxins
Fatty diarrhea Ileal bile acid malabsorption
Malabsorption syndromes Inflammatory bowel disease
Mucosal diseases Ileal Crohns disease
Short-bowel syndrome Lymphocytic colitis
Postresection diarrhea Collagenous colitis
Small bowel bacterial overgrowth Diverticulitis
Mesenteric ischemia Vasculitis
Maldigestion Drugs and poisons
Pancreatic insufficiency Disordered regulation
Reduced luminal bile acid Postvagotomy
Inflammatory diarrhea Postsympathectomy
Inflammatory bowel disease Diabetic neuropathy
Ulcerative colitis Hyperthyroidism
Crohns disease Addisons disease
Diverticulitis Irritable bowel syndrome
Ulcerative jejunoileitis Neuroendocrine tumors
Infections Gastrinoma
Invasive bacterial infection VIPoma
Clostridium difficile, Somatostatinoma
Escherichia coli, tuberculosis, others Mastocytosis
Ulcerating viral infection Carcinoid syndrome
Cytomegalovirus, Herpes simplex Medullary carcinoma of the thyroid
Invasive parasites Neoplasia
Amebiasis Carcinoma of colon
Ischemic colitis Lymphoma
Radiation enterocolitis Villous adenoma
Neoplasia Epidemic secretory diarrhea
Carcinoma of colon (Brainerds)
Lymphoma Idiopathic secretory diarrhea
(sporadic)

Table 2. Historic Clues to the Etiology of Diarrhea

Historic feature Aspects to record
Characteristics of onset Congenital, abrupt, or gradual
Pattern of diarrhea Continuous or intermittent
Duration of symptoms Days, weeks, months, or years
Epidemiologic factors Travel, potentially contaminated foods or water,
illness in other family members
Stool characteristics Watery, bloody, or fatty
Presence of fecal incontinence None, occasional, or always
Presence of abdominal pain Location, relation to meals and bowel movements, type
Presence of weight loss None, initial and then stable, or continuing
Aggravating factors Diet, stress
Mitigating factors Alteration of diet; prescription and over-the-counter medications
Results of previous evaluations Written records, existing radiograms, and biopsy specimens
History of medications, surgery, and radiation Relation to onset of diarrhea
Possibility of surreptitious laxative abuse History of eating disorders, secondary gain, malingering,
or psychiatric problems
Systems review Presence of diseases that might cause diarrhea: hyperthyroidism,
diabetes, collagenvascular diseases, tumor syndromes, AIDS,
or other immune problems

Infections
Bacterial and viral infections account for the vast majority of
acute diarrheas and for some chronic diarrheas. Several
mechanisms by which diarrhea is produced by microorgan-
isms have been discovered by researchers [59]. These mech-
anisms include enterotoxins that subvert mucosal transport,
invasion of the mucosa, bacterial adhesion to the entero-
cytes, and production of cytotoxins that destroy enterocytes.
All pathogenic bacteria must adhere to the apical membrane
of the enterocyte to cause disease. For example, enterotoxi-
genic Escherichia coli adhere to specific glycoprotein recep-
tors on the intact microvillous membrane by means of pili.
In contrast, enteropathogenic E. coli obliterate microvilli,
producing pedestals to which they adhere. Salmonella and
Shigella species invade the mucosa to produce disease. Shi-
gella species are internalized by endocytosis and spread later-
ally from cell to cell. Salmonella species penetrate the brush
border and tight junction to gain access not only to the
mucosa but also to the bloodstream.
Bacterial toxins have also attracted the attention of
researchers [8,9]. Reports indicate that toxins coopt the regu-
latory machinery of the intestine both at the cellular and at
the organ level. For example, cholera toxin binds to the api-
cal membrane of the enterocyte and is internalized, making
its way to adenylate cyclase located on the basolateral mem-
brane. There, it binds to and activates the catalytic unit of
this G protein, causing the unregulated production of cyclic
adenosine monophosphate (cAMP). This action, in turn,
blocks sodium absorption and stimulates chloride secretion
by the enterocyte. For many years this was thought to be the
sole mechanism of action of cholera toxin. It is now clear
that cholera toxin also interacts with enteroendocrine cells,
stimulating the release of endogenous secretagogues, and
with the enteric nervous system, altering both electrolyte
transport and motility [10]. Another example is E. coli STa
toxin, which is a ligand for a brush-border receptor for gua-
nylin, an endogenous regulatory peptide that is distributed
intraluminally to the enterocyte [11]. Binding of guanylin or
STa to this receptor results in activation of guanylate cyclase
C and production of cyclic guanylate monophosphate
(cGMP), which causes chloride secretion by the enterocyte.
Campylobacter jejuni remains a common cause of acute
community-acquired diarrhea [12]. Tissue invasion occurs
frequently, and severe colitis mimicking idiopathic ulcer-
ative colitis can occur. Results from recent studies suggest
an association between C. jejuni infection and Guillain-
Barr syndrome.
Because of the morbidity and relatively high casefatal-
ity rate, acute diarrhea from E. coli O157:H7 has received
much attention lately [13,14]. This organism produces a
hemorrhagic segmental colitis and is associated with
hemolyticuremic syndrome. Infection has been associ-
ated with eating undercooked hamburger, and outbreaks
are distressingly frequent [13,14]. Stool electrolyte analysis
suggests secretory diarrhea, but bloody diarrhea or a
strongly positive fecal occult blood test is typical.
Secretory Diarrhea Schiller 391
Clostridium difficileassociated colitis is the most com-
mon cause of infectious diarrhea in hospitalized patients
[15]. It usually occurs following broad-spectrum antibiotic
therapy and produces pseudomembranous colitis. Diagno-
sis in adults is confirmed by finding C. difficile toxin in
stool samples. Symptomatic improvement with metro-
nidazole is rapid, but relapse of diarrhea occurs in more
than 20% of patients when antibiotic therapy is discontin-
ued [15,16]. Leukocytosis with a left shift can be dra-
matic, and fecal leukocytes are easy to find in patients with
pseudomembranous colitis.
Reduction of mucosal surface area
The intestine has a reserve absorptive capacity to compensate
for variation in daily intake and minor abnormalities in
absorptive function, but this reserve has some limitations.
First, because absorptive function in different parts of the
intestine is specialized, some segments cannot compensate
for the missing functions of other segments. For example, if
the terminal ileum is resected or diseased, the colon cannot
compensate by absorbing bile acids or vitamin B12. Second,
a sufficient reserve capacity must be present more distally to
compensate for missing absorptive function. For instance, if
small bowel fluid and electrolyte absorption are reduced, the
colon can compensate, but only to a certain extent. Likewise,
there is no distal segment to compensate when colonic
absorptive function is disrupted.
These theoretical considerations are confirmed by
results of studies involving patients with ileocolonic resec-
tion [17]. Such patients not only have problems with bile
acid and vitamin B12 absorption, but they also develop a
watery diarrhea that is resistant to therapy with bile acid
sequestrants. This problem is caused by compromise of the
ability to absorb sodium against a concentration gradient
and inability of the remaining colon to absorb sufficient
sodium to fully compensate for this defect.
Absence of an ion transport mechanism
Secretory diarrhea can result from congenital absence of an
ion transport mechanism. This situation occurs in patients
with congenital chloridorrhea, an absence of the chloride
bicarbonate exchanger in the intestinal mucosa. Chloride
cannot be removed from the lumen against a concentration
gradient, and thus it accumulates, obligating retention of
cations and fluid within the lumen. Reducing chloride load
to the intestine by inhibiting gastric chloride secretion with
proton-pump inhibitors can decrease stool weight [18].
Inflammation
The immune system in the intestine modulates electrolyte
absorption by release of cytokines and by effects on the
enteric nervous system. These interactions have been stud-
ied best in animal models of infection and hypersensitivity
[19]. It is likely that similar interactions occur in humans.
Sellin [20] coined the acronym PINES to identify the
interaction of paracrine, immune, neural, and endocrine
392 Small Intestine
systems in the regulation of ion transport by the mucosa.
Efforts to modulate this system with drugs may produce
new classes of antidiarrheal agents in the future.
The importance of inflammation to the pathogenesis
of secretory diarrhea in the absence of tissue disruption is
exemplified by microscopic colitis syndrome (lymphocytic
colitis and collagenous colitis). In this condition the
colonic mucosa is grossly normal, but there is histologic
evidence of mucosal inflammation with intraepithelial
lymphocytes and an expanded lamina propria inflamma-
tory cell infiltrate. Under intestinal perfusion conditions,
fluid and electrolyte absorption is inversely proportional
to the intensity of mucosal inflammation [21].
Dysregulation
Secretory diarrhea may occur as a complication of dia-
betic autonomic neuropathy [2124]. Abnormal function
of the enteric nervous system may alter the dynamics of
intestinal fluid and electrolyte absorption or motility
[2224]. Similar difficulties may occur in patients who
develop diarrhea after vagotomy, sympathectomy, or
celiac plexus neurolysis.
Luminal secretagogues
In addition to bacterial toxins, bile acids, fatty acids, and
some laxatives can act as luminal secretagogues. Bile
acids and fatty acids that evade absorption in the small
intestine reduce absorption or promote secretion in the
colon in a dose-related fashion [1]. This can occur in a
number of scenarios. Patients with terminal ileal disease
or resection routinely malabsorb bile acid, but the bile
acid concentration in the colon may not reach the cathar-
tic threshold (35 mmol/L) if water absorption is com-
promised concurrently. Patients who have undergone
cholecystectomy keep their bile acid pool in the intestine
(because there is no gallbladder to serve as a reservoir for
bile), where it can be swept into the colon by the interdi-
gestive migrating motor complex during the night; some
patients develop a secretory diarrhea that is responsive to
bile acid sequestering agents. Patients with short-bowel
syndrome may deliver sufficient long-chain fatty acids to
the colon to impair absorption. Most nonosmotic laxa-
tives also work as intraluminal secretagogues, but some
only do so after metabolism by the colonic flora.
Circulating secretagogues
Tumors of endocrine cells in the gut, pancreas, and else-
where can produce sufficiently high circulating levels of
secretagogues in the blood to inhibit absorption or to pro-
duce secretion by the intestine. Although gastroenterolo-
gists and internists often consider the existence of these
tumors when caring for patients with secretory diarrhea,
they are actually quite rare. Estimates of prevalence range
from one per 1000 to one per 10,000 patients with chronic
diarrhea. Thus, the chance of finding any of these tumors is
very low in evaluation of a given patient [25].
Classification of Diarrheal Diseases
With so many potential causes for diarrhea, classification is
useful in order to limit the number of possibilities that the
clinician must include in his or her differential diagnosis.
Several classifications have been proposed.
Acute versus chronic diarrhea
One of the simplest schemes for classifying diarrhea is by
duration of the complaint. The moot point is where to
draw the line between acute and chronic diarrhea. Experts
vary in their recommendations from as little as 2 weeks to
as long as 8 weeks [26]. The main purpose of this divi-
sion is to separate cases that are likely to be infectious and
self-limited from cases that can have any of the many
causes of chronic diarrhea. At our institution we use 4
weeks as a dividing point.
Osmotic versus secretory diarrhea
As mentioned above, analysis of stool electrolytes allows
the clinician to categorize diarrhea as osmotic or secretory
[3]. Whereas finding an osmotic diarrhea produces a short
list of suspect conditions, finding a secretory diarrhea
leaves many possibilities. Consequently, exclusive use of
this classification scheme is not recommended.
Watery versus fatty versus inflammatory diarrhea
Another way of classifying diarrheal diseases is by the
characteristics of the stool. Watery diarrhea is character-
ized as very liquid stools without evidence of blood, pus,
or fat. The implication of watery diarrhea is that either an
osmotically active substance or unabsorbed electrolytes
cause excess water to be retained intraluminally. Fatty
diarrhea (steatorrhea) suggests the presence of a condi-
tion reducing fat absorption in the small intestine.
Inflammatory diarrhea is characterized as stools with pus
or blood, suggesting disruption of the mucosa by infec-
tion or inflammation.
Recently, an expert committee of physicians from the
American College of Gastroenterology [27] and the Prac-
tice Economics Committee of the American Gastroentero-
logical Association [28] endorsed the use of these stool
characteristics as a way to classify diarrhea in evaluation of
patients who suffer from it. Combining all of these classifi-
cation schemes should allow for more efficient diagnosis,
although this has not been proven scientifically (Table 1).
Evaluation of Patients with Diarrhea
Before assessing the cause of diarrhea or attempting
empiric therapy it is essential for the clinician to evaluate
the patients fluid and electrolyte status [26,27]. Diar-
rhea can be life threatening if volume or electrolyte deple-
tion has occurred. Orthostatic changes in pulse and blood
pressure should be measured. Patients with long-standing
or voluminous diarrhea should have serum electrolyte con-
centrations assayed. Intravenous or oral rehydration and

electrolyte repletion takes precedence over diagnosis in the
management of these patients.
Diagnostic evaluation of patients with diarrhea should
be directed at the most likely possibilities [26,27,28,
29,31]. This judgment, in turn, depends on the patients low in relation to the risk of the procedure, and others
history and on the classification of the diarrhea. Historical
features that should be elicited from the patient are out-
lined in Table 2. Physical findings are of little use in most
patients with diarrhea, but occasionally they can be valu-
able [26,27,28,29,31]. For example, flushing, that produce gross or histologic findings can be diagnosed
hepatomegaly, and a heart murmur may be clues to the
diagnosis of carcinoid syndrome.
Because most acute diarrhea resolves spontaneously
without specific therapy, the clinician must establish which
patients with acute diarrhea require a more extensive diag-
nostic evaluation. Patients with acute diarrhea who have
high fever, prostration, volume depletion, severe abdominal
pain, blood or pus in the stool, or a protracted course of
symptoms (>96 hours) should undergo the following tests:
complete blood count, serum electrolyte panel, serum creat-
inine and blood urea nitrogen assays, stool bacterial culture,
stool ova and parasite examination, and C. difficile toxin titer
(if the patient was treated with antimicrobials within 90
days or if the patient is a health care worker or resident in an
institution with a high rate of C. difficile infection) [32]. If
the diagnosis is still obscure and the diarrhea continues, rec-
tal biopsy should be considered in order to differentiate self-
limited colitis from early idiopathic inflammatory bowel
disease [33]. Symptomatic management with oral fluids and
antidiarrheal drugs should be sufficient for most other
patients. Travelers who develop diarrhea during or shortly
after a trip may not need specific testing before starting
empiric antibiotic therapy [32].
Chronic diarrhea (ie, diarrhea that lasts more than 4
weeks) is less likely to be caused by infections and has a
broader differential diagnosis. Efforts to further classify the
type of diarrhea by examining stools for the presence of
occult blood (guaiac testing), leukocytes (Wrights stain or
fecal lactoferrin assay), and fat (Sudan stain) can be useful
[26]. Stool sodium and potassium assays and stool pH
can be used to further classify watery diarrhea as osmotic
or secretory (Fig. 1) [3]. These tests can be done on spot
samples or on a quantitative stool collection. Quantitative
collection for 48 or 72 hours provides a better idea of stool
output and fat excretion, but it is not essential for classifi-
cation. Once these tests have been completed, further eval-
uation can proceed depending upon the classification of
the diarrhea (Fig. 2).
For chronic secretory diarrhea, further evaluation
should include bacterial culture and examination of stool
for other pathogens, including parasites such as cryptospo-
ridia and microsporidia. Structural disease of the intestine
should be excluded with small bowel radiography, small
bowel biopsy and aspirate for quantitative bacterial
culture, computerized tomography of the abdomen, and
colonoscopy or sigmoidoscopy with colonic biopsy. There
Secretory Diarrhea Schiller 393
is some controversy about whether biopsy can be justified
and about the choice of technique for visualizing the
colonic mucosa. Some authors believe that the yield of
biopsy in unselected patients with chronic diarrhea is too
disagree [3435]. In my opinion, patients with chronic
continuous diarrhea (as opposed to intermittent diarrhea,
which is more characteristic of irritable bowel syndrome)
ought to have biopsies obtained [26]. Most disorders
by means of sigmoidoscopy and biopsy, but some lesions
exclusively in the right colon will be missed without a full
colonoscopy, especially in patients with AIDS [37].
An e mp iri c tr ia l of a b ile a ci d seq ue ste ri ng re sin
(eg, cholestyramine) may be more germane than direct
measurement of bile acid absorption, which is often
abnormal in patients with chronic diarrhea, because such
measurements do not predict responsiveness to these
agents [38,39]. Testing for secretagogue-induced diarrhea
should be selective, based on findings of a tumor on CT
scanning or presentation with a typical tumor syndrome
because the pretest probability of tumor-associated
diarrhea is very low [25]. Measurement of plasma peptide
concentrations should be limited to those peptides with
well-described tumor syndromes, gastrin, calcitonin, vaso-
active intestinal polypeptide, and somatostatin. Urine test-
ing for 5-hydroxyindole acetic acid, metanephrines, and
histamine can be used to screen for carcinoid syndrome,
pheochromocytoma, and mastocytosis. Other assessment
measures that occasionally aid in diagnosis of patients
with chronic diarrhea include thyroid tests, tests of adrenal
sufficiency, serum protein electrophoresis, and quantita-
tion of immunoglobulins [26,27,28,29,30,31].
Nonspecific Treatment
Although the goal for a clinician evaluating a patients diar-
rhea is to find a specifically treatable disorder, this goal is
not always met, and nonspecific therapy must be used.
Nonspecific agents also can be helpful when a diagnosis is
established but specific therapy is not available or has not
been effective.
Oral rehydration solutions have saved the lives of
many patients with acute diarrhea and have allowed some
patients with chronic diarrhea to do without intravenous
fluid replacement. The principle behind their use is that
nutrients such as glucose and amino acids are transported
across the apical membrane of the enterocyte by a carrier
that cotransports sodium [40]. Unlike apical sodium
hydrogen exchange, nutrientsodium cotransport is not
impeded by elevated intracellular cyclic AMP levels, so
that efforts to stimulate sodium entry by providing nutri-
ents and salt can be very successful. Total intestinal perfu-
sion studies in humans given cholera toxin show that the
mechanism of enhanced sodium absorption involves not
only cotransport across the apical membrane but also an
394 Small Intestine

Figure 1. Flow chart or mind map for the evaluation of chronic diarrhea. Initial efforts should be directed to the classification of chronic
diarrhea, based on history, physical examination, basic laboratory tests, and stool analysis. From Fine and Schiller [26]; with permission.

element of solvent drag across tight junctions [41]. Recent
work has emphasized the usefulness of complex carbohy-
drates that allow ingestion of a hypotonic oral rehydra-
tion fluid, which can be more effective than traditional
glucose-based fluids [42]. It is important to note that oral
rehydration fluids are not designed to reduce stool vol-
ume as much as to increase net sodium chloride absorp-
tion. Consequently, the adequacy of rehydration should
be judged by increased body weight and reduction of
blood urea nitrogen and serum creatinine, not by changes
in stool output.
Traditional antidiarrheal medications depend on
increasing the rate of fluid and electrolyte absorption by
the intestinal mucosa or slowing transit through the
intestine and increasing contact time, thereby allowing
more time for absorption to occur. Opiates such as
codeine seem to work mainly by the latter mechanism
[43]. A new agent, acetorphan, inhibits enkephalinase
activity in the intestine, allowing prolonged stimulation
of d-opiate receptors by endogenous opiates and increas-
ing the net rate of absorption by the mucosa [44]. This
agent offers the prospect of reducing diarrhea without
producing rebound constipation.
Clonidine is another agent that can increase the rate of
absorption by the mucosa [45]. In addition, clonidine can
slow transit, increasing net absorption by increasing con-
tact time. This seemingly ideal combination of effects has
been difficult to employ clinically because of the central
 Secretory Diarrhea Schiller 395

Figure 2. Flow charts or mind maps for further evaluation of secretory diarrhea (upper left), osmotic diarrhea (upper right),
inflammatory diarrhea (lower left), and fatty diarrhea (lower right). Every test in a given pathway need not be done once a
diagnosis is reached. From Fine and Schiller [26]; with permission.

hypotensive effect of clonidine. Efforts to design nonhy-
potensive a2-adrenergic agonists have been stymied.
Octreotide, a somatostatin analogue, is useful in the
treatment of tumor syndromes, such as carcinoid syn-
drome or VIPoma. In these conditions, octreotide reduces
tumor secretion of the secretagogue and may have an
antitumor effect by reducing trophic factors released else-
where. Octreotide has been employed in secretory diar-
rhea of nontumor origin with mixed results [46,47].
Patients with high-volume diarrheas can have a 30% to
40% reduction of stool output with octreotide, but this
result is often insufficient to allow elimination of supple-
mental intravenous fluids.
Conclusions
Secretory diarrhea is a common condition, and yet there is
much more to learn about it. The evaluative scheme pre-
396 Small Intestine
sented in this article needs to be tested prospectively to assess
its cost effectiveness and sensitivity in identifying treatable
causes of diarrhea. Better nonspecific therapies would be
helpful for many patients with acute and chronic diarrhea.
References and Recommended Reading
Recently published papers of particular interest
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Of importance
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