Note: Secretin is not approved by the FDA for the treatment
of Autism. True, a physician may use this "off label"
at his or her own discretion. However without proper antibody
testing first this "wonder drug" might become more than
just a little problem for many. There are "theoretical"
concerns re that even if one screens for antibodies appropriately,
repeated infusions could trigger a child's immune system to "attack"
their own Secretin (or its receptors) creating major medical problems.
Also, many are concerned re "other" hormone effects
/ interactions over time on a child's young body. Researchers
remain very concerned re allergic reactions (possibly fatal when
given IV), and the unknown transmission of virus, retro-viruses,
or other unknown "vectors" (i.e. priom organism, "mad-cow"
type organisms, etc.) in the IV preparation for sure, ?? the oral
(still trying to obtain further information).
as some time is passing, while the "jury is still out,"
just as with IVGG, after a few "wonder" stories, I am
not hearing of any significant long term changes / success (beyond
some GI help). Of 10 or 11 patients of mine who have tried Secretin
(back East), only 1 has any success, 1 has had a complete disaster
for about 2 months, and the others see no significant changes
good or bad. Unless this agent had a significantly higher "cognitive"
success rate, it is very likely the risks currently appear to
be outweighing the gains by a long margin. Please review the precautions
outlined from the PDR. Remember these are your children. Appropriate
FDA trials are necessary to assure safety and determine any real
hit the US mass media , you may retrieve the stories here:
Morning America carried a story 6 October 1998 NBC's Dateline
ran a story 7 October 1998 The Abstracts that started
and language skills after secretin administration in patients
with autistic spectrum disorders. Horvath K; Stefanatos G; Sokolski
KN; Wachtel R; Nabors L; Tildon JT Department of Pediatrics, University
of Maryland School of Medicine, Maryland, USA. J Assoc Acad Minor
Phys, 1998, 9:1, 9-15
Abstract: We report three children with autistic
spectrum disorders (ed. this does not mean Autism DSMIV 299) who
underwent upper gastrointestinal endoscopy and intravenous administration
of Secretin to stimulate pancreaticobiliary secretion. All three
had an increased pancreaticobiliary secretory response when compared
with non autistic patients (7.5 to 10 mL/min versus 1 to 2 mL/min).
Within 5 weeks of the Secretin infusion, a significant amelioration
of the children's gastrointestinal symptoms was observed, as was
a dramatic improvement in their behavior, manifested by improved
eye contact, alertness, and expansion of expressive language.
These clinical observations suggest an association between gastrointestinal
and brain function in patients with autistic behavior. (ed. known
in research circles for many years is the gut-brain-immune system
a potential treatment for children with autism. Linday LA
College of Physicians and Surgeons, St Luke's-Roosevelt Hospital
Center, New York, NY 10019, USA. Med Hypotheses, 1997 May, 48:5,
Abstract: Famotidine (Pepcid, a histamine-2 receptor
blocker, is marketed for the treatment of peptic ulcer disease,
gastroesophageal reflux, and the treatment of pathological hypersecretory
conditions, including the Zollinger-Ellison syndrome. Recent reports
indicate that it is also effective in relieving the deficit (or
withdrawal) symptoms of adults with schizophrenia. Autism, a neuropsychiatric
disorder which presents within the first few years of life, is
defined by deficient social interaction, communication, language,
play, and a markedly restricted repertoire of activities and interests.
Similarities between the deficit symptoms of schizophrenia and
the social deficit symptoms of autism suggest the hypothesis that
famotidine may be useful in treating children with autism. Histamine
serves as a neurotransmitter and neuromodulator in the brain.
H2-receptors in the brain predominantly transmit inhibitory signals;
when these receptors are stimulated in animals, spontaneous activity
and exploratory behavior decrease; blockade of H2-receptors would
therefore be expected to reverse this inhibition.
From the PDR
(FERRING LABORATORIES, INC.)
USE IN PANCREATIC DYSFUNCTION
a gastrointestinal peptide hormone that was first extracted from
porcine duodenum by Jorpes & Mutt (1961). The heptacosa-peptide
was subsequently sequenced and synthesized by Mutt, Bodansky and
their coworkers at the Karolinska Institute. Secretin-Ferring
is a highly purified naturally occurring porcine hormone with
a potency of not less than 3000 clinical units (CU) per mg peptide.
Secretin is chemically defined as follows:
contains 75 CU of lyophilized, sterile purified Secretin, 1 mg
of L-cysteine hydrochloride, and 20 mg of mannitol per vial. When
reconstituted in 7.5 mL of Sodium Chloride Injection USP, each
mL of solution contains 10 CU secretin for intravenous use. The
pH of the reconstituted solution has a range of 2.5-5.0.
action of Secretin is to increase the volume and bicarbonate content
of secreted pancreatic juices. The standard unit of activity used
for Secretin- Ferring is the clinical unit defined by Jorpes &
Mutt in 1966. In a study of 6 healthy subjects the t(1/2) for
Secretin approximated 4 minutes with a clearance rate of 540 mL/min
(Kolts and McGuigan, 1977). Normal ranges for pancreatic secretory
response to intravenous Secretin in patients with defined pancreatic
diseases have been shown to vary. The variation is related to
the Secretin product used as well as inter-investigator differences
in operative technique. However, it has been demonstrated that
properly performed tests with Secretin will identify pancreatic
disease (Gutierrez and Baron, 1972, Lagerlof et al., 1967).
secretory responses to Secretin in normal subjects and patients
with well-documented pancreatitis are shown in Table 1 (Gutierrez
and Baron, 1972).
subjects (10)(a) Chronic
The values obtained for Table 1 are derived from a single study
by investigators skilled in performing the Secretin test and are
to be taken only as guidelines. These results should not be generalized
to results of Secretin testing conducted in other laboratories.
However, a volume response of less than 2.0 mL/kg/hr, bicarbonate
concentration of less than 90 mEq/liter and bicarbonate output
of less than 0.2 mEq/kg/hr are consistent with impaired pancreatic
function. A physician or institution planning to perform Secretin
testing for diagnosis of pancreatic disease should begin by assessing
enough normal subjects (>/=5) to develop proficiency in proper
technique and to generate normal response ranges for the three
commonly assessed parameters of pancreatic exocrine response to
for carrying out the Secretin test of pancreatic function is described
in DOSAGE AND ADMINISTRATION.
administered intravenously stimulates gastrin release in patients
with gastrinoma (Zollinger-Ellison syndrome), whereas no or only
small changes in serum gastrin concentrations occur in normal
subjects. Secretin- Ferring may produce a small decrease in serum
gastrin levels in patients with duodenal ulcer disease. This gastrin
response is the basis for the use of Secretin-Ferring as a provocative
test in the evaluation of patients in whom gastrinoma is a diagnostic
consideration. Accepted technique for carrying out the Secretin
provocation test is detailed in DOSAGE AND ADMINISTRATION.
(secretin) is indicated for:
of pancreatic exocrine disease.
(2) As an
adjunct in obtaining desquamated pancreatic cells for cytopathologic
of gastrinoma (Zollinger-Ellison syndrome).
from acute pancreatitis should not receive Secretin-Ferring until
the attack has subsided.
a potential allergic reaction to secretin, patients should receive
an initial intravenous test dose of 0.1-1.0 CU. If no allergic
reaction is noted after one minute the recommended dose may be
injected slowly over 1 minute. A test dose is especially important
in patients with a history of atopic allergy and/or asthma. Appropriate
measures for the treatment of acute hypersensitivity reactions
should be immediately available.
who have undergone vagotomy, or are receiving anticholinergics
at the time of Secretin testing, or who have inflammatory bowel
disease may be hyporesponsive to Secretin stimulation. This response
does not indicate pancreatic disease. A greater than normal volume
response to Secretin stimulation, which can mask coexisting pancreatic
disease, is occasionally encountered in patients with alcoholic
or other liver disease.
TEST INTERACTION: The concomitant use of anticholinergic agents
may make patients hypo responsive (false positive).
MUTAGENESIS, IMPAIRMENT OF FERTILITY: Long-term studies in animals
have not been performed to evaluate the carcinogenic, mutagenic
potential or possible impairment of fertility effects of Secretin.
(CATEGORY C): Animal reproduction studies have not been conducted
with Secretin-Ferring. It is also not known whether Secretin-Ferring
can cause fetal harm when administered to a pregnant woman or
can affect reproductive capacity. Secretin-Ferring should be given
to a pregnant woman for diagnosis of gastrinoma (Zollinger-Ellison
syndrome) only if clearly needed. Insofar as fluoroscopic guidance
is usually necessary to position the double-lumen tube used in
the pancreatic function test, this test should be postponed until
It is not known whether Secretin is excreted in human milk. Because
many drugs are excreted in human milk, caution is advised when
Secretin- Ferring is administered to a nursing woman. Further,
normal values for pancreatic secretory response to Secretin-Ferring
and for serum gastrin response have not been established for nursing
USE: Safety and effectiveness in children have not been established.
reactions to Secretin-Ferring have been reported. (Ed:
No repeat infusion studies have ever been done, as is being proposed
for the children)
should be prepared immediately prior to use. The contents of a
vial are dissolved in 7.5 mL of Sodium Chloride Injection USP,
to yield a concentration of 10 CU per mL. Avoid vigorous shaking.
Discard any unused portion after reconstitution.
drug product should be inspected visually prior to administration.
If particulate matter or discoloration are seen, the product should
FUNCTION TESTING AND PROCEDURE FOR OBTAINING DESQUAMATED PANCREATIC
CELLS FOR CYTOPATHOLOGY: 1 CU per kg body weight by slow intravenous
injection over 1 minute.
OF GASTRINOMA (Zollinger-Ellison syndrome): 2 CU per kg body weight
by slow intravenous injection over 1 minute.
FUNCTION TESTING: A Dreiling type, radiopaque, double-lumen tube
is passed through the mouth following a 12-15 hour fast. The proximal
lumen of the tube is placed in the gastric antrum and the distal
lumen just beyond the papilla of Vater with the aid of fluoroscopic
guidance. The positioning of the tube must be confirmed and the
tube secured prior to Secretin testing. A negative pressure of
25-40 mm Hg is applied to both lumens and maintained throughout
the test. Interruption of suction at 1 minute intervals improves
the reliability of fluid collections. When uncontaminated duodenal
contents are obtained--i.e., when these secretions are clear,
although possibly bile stained, and have a pH of >/=6.0--a
baseline sample of duodenal fluids is collected for 2 consecutive
10 minute periods. Subsequent to the baseline collections, Secretin-Ferring
at a dose of 1 CU/kg of body weight is injected intravenously
in approximately 1 minute. Duodenal fluid is then collected for
60 minutes after Secretin administration. The aspirate is fractioned
into four collection periods, the first two at 10 minute intervals,
and the last two at 20 minute intervals. The duodenal lumen of
the tube is cleared with an injection of air after collection
of each fraction. Wide variations in volume of the aspirate will
be indicative of incomplete aspiration or contamination. Each
fraction of duodenal fluid is to be chilled and subsequently analyzed
for volume and bicarbonate concentration.
FOR OBTAINING DESQUAMATED PANCREATIC CELLS FOR CYTOPATHOLOGY:
A duodenal aspirate obtained as under Pancreatic Function Testing
is submitted for cytopathological examination.
TESTING FOR GASTRINOMA (Zollinger-Ellison syndrome). The patient
should have fasted for at least 12 hours prior to beginning the
test. Prior to injection of Secretin-Ferring, two blood samples
are drawn for determination of fasting serum gastrin levels (baseline
values). Subsequently, 2 CU of Secretin- Ferring per kg of body
weight are administered intravenously over 1 minute; post-injection
blood samples are collected after 1,2,5,10 and 30 minutes for
determination of serum gastrin concentrations.
is strongly indicated in patients with elevated fasting serum
gastrin concentrations in the 120-500 pg/mL range (determined
by RIA using an antibody to gastrin similar to that prepared by
Rehfeld) and in patients who show an increase in serum gastrin
concentration of more than 110 pg per mL over basal level.
is supplied as a lyophilized sterile powder in 10 mL vials (NDC
55566-1075-1) containing 75 CU. The unreconstituted product should
be stored at -20° C (freezer). However, the biological activity
of Secretin-Ferring will not be significantly decreased by storage
at temperatures up to 25° C for up to 3 weeks. Expiration
date is marked on the label.
(USA) law prohibits dispensing without prescription.
Ferring Pharmaceuticals, Inc.
120 White Plains Rd., Suite 400
Tarrytown, NY 10591
DC-120: Rev. 06/88
Revision date May '92
and Mutt, V.: On the biological activity and amino acid composition
of secretin. Acta Chem Scand 15 (1961) 1790-1791.
and Mutt V.: On the biological assay of secretin. The reference
standard. Acta Physiol Scand 66 (1966) 316-325.
and Mc Guigan, J.E.: Radioimmunoassay Measurement of Secretin
Half-Life in Man. Gastroenterol. 72 (1977) 55-60.
H.O., et al.: A secretin test with high doses of secretin and
correction for incomplete recovery of duodenal juice.
52 (1967) 67-77.
L.V., and Baron, J.H.: A comparison of Boots and GIH secretin
as stimuli of pancreatic secretion in human subjects with or without
Gut 13 (1972)
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