Beruflich Dokumente
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Review article
Irwin D. Mandel
Columbia University, School of Dental and
Oral Surgery, New York, USA
Mandel ID: The diagnostic uses of saliva. J Oral Pathol Med 1990; 19: 119-25.
It is becoming increasingly apparent to investigators and clinicians in a variety
of disciplines that saliva has many diagnostic uses and is especially valuable in
the young, the old and infirm and in large scale screening and epidemiologic
studies. The highly sensitive test procedures that are now commonplace makes
it practical to quantitate, despite very low concentrations, a large number of
hormones and drugs in saliva. Indeed, all steroids of diagnostic significance in
routine clinical endocrinology can now be readily measured in saliva. Drug
monitoring can include abusive as well as therapeutic agents. The concordance
between anti HIV antibodies in saliva and serum has stimulated application to
various other antiviral antibodies as well as to viral antigens per se. Saliva has
found use as a diagnostic aid in an increasing number of clinical situations and
in systemic diseases that can affect salivary gland function and composition
such as Sjogren's syndrome, cystic fibrosis and diseases of the adrenal cortex.
The list keeps growing.
This negative image of saliva, however, was not uniform. In the cosmologies of ancient Egypt, Thoth the wise is
said to have spat into the empty eye
socket of Horus, the sun god, to restore
his vision (4). The new testament (Mark
8: 23-25) tells us that Jesus took the
blind man by the hand and led him out
of town; and when he had spit on his
eyes, and put his hands upon him, he
asked him if he saw ought; and he was
restored and saw every man clearly.
The people who really appreciate the
"miracle" of saliva, however, are not
the blind, but those who suffer from
xerostomia (dry mouth) from a variety
of causes (5). They recognize belatedly
that saliva is a natural resource with
many functional capabilities that include food preparation, digestion, lubrication and protection of the teeth and
mucous membranes (6).
One function not bestowed by nature
is the use of saliva for diagnostic
purposes. Historically this diagnostic
value may have been recognized first
by the ancient judicial community who
employed salivary flow (or its absence)
as the basis for a primitive lie detector
test. The accused was given a handful
of dry rice. If anxiety (and presumably
guilt) so inhibited salivation that he or
she could not form an adequate bolus
to chew and swallow, than off with their
head. In more recent times, where the
vagaries of the secretory-motor system
have been replaced by those of the court
120
MANDEL
(7).
Disposable and individualized collectors have also been introduced (8, 9).
Submandibular-sublingual saliva can be
collected by customization of a basic
plastic collector (10, 11) or by aspiration
from the duct openings with a micropipette (5).
Oral diseases
Hromonal dysfunction
Diabetes
Pancreatitis
Adrenal-cortical diseases
Thyroiditis
Acromegaly
Neurological diseases
Parkinsonism
Bell's palsy
Cerebral palsy
of the lymphocytic infiltration characteristic of this disease (20). Siaiochemistry provides a helpful screening
procedure to determine whether the biopsy is indicated. A number of studies
have shown that if the disease is developing in the salivary glands the periductal infiltrate and its products (cytokines)
can have a profound effect on the resorptive, transport and synthetic function of the striated duct cells which results in: a) elevated sodium and chloride
concentration and a decreased phosphate concentration despite reduced
fiow rate (1, 21); b) elevation in lactoferrin (21-24); c) elevation in beta 2-microglobulin (25, 26) and in d) kaUikrein
(27). Parotid lysozyme was found to be
elevated in patients with primary Sjogren's syndrome (dry eyes, dry mouth
but no rheumatoid disease) but not in
secondary Sjogren's syndrome (with an
accompanying rheumatoid disease)
(28). The alteration in glandular structure produced by the disease resulted in
a marked impact on the lipid content of
saliva with a 20 fold elevation in the
concentration of phospholipids (29). If
confirmed in a larger group of subjects
this could be the basis of a valuable
diagnostic test. Salivary gland chemistry
in Sjogren's syndrome is not only potentially useful for diagnostic purposes but
for following disease development and
monitoring therapy (1, 26).
Cystic fibrosis affects all of the exocrine glands to varying degrees. The impact on salivary gland function at a clinical level is minimal, but there are very
definite effects on the composition of
saliva (1, 30, 31). The most dramatic
changes reported have been an elevation
in calcium and proteins, especially apparent in the submandibular-sublingual
glands and minor salivary glands. In the
former these elevations result in a very
apparent turbidity in the fluid secreted
due to formation of a calcium-protein
complex (32) and possibly of hydroxyapatite as well (33). In the minor salivary glands the precipitate physically
obstructs the narrow excretory duct and
markedly reduces the rate of secretion
to virtually zero. This phenomenon can
be used as a diagnostic test by measuring the fiow from the readily accessible
labial glands on the lower lip with a
capillary tube (34).
Although many hormones influence
the composition of saliva, the most dramatic changes have been noted in diseases of the adrenal cortex. The sodium
and potassium concentration is markedly affected by corticosteroids, especially
Since the pioneering studies of SHANNON et al. (60) it has generally been
recognized that the lipid-soluble unconjugated steroids pass readily into saliva
and that their concentrations in saliva
are proportional to the concentrations
of free, unbound steroids in plasma (2).
The conjugated steroids diffuse with
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MANDEL
Progesterone
I7p-Estradiol
Estriol
Estrone
Insulin
Melatonin
great difficulty because of their low lipid-solubility and high molecular weight
(62). An exception has recently been
noted for corticosteroid binding globulin (CBG) and some modification of the
assay may be required (63). A workshop
on the immunoassay of steroids in saliva
concluded that, "All steroids of diagnostic significance in routine clinical endocrinology can now be measured in
saliva" (67). The list of steroid hormones currently being assayed in saliva
includes cortisol, aldosterone, dehydroepiandrosterone, testosterone, 5adihydrotestosterone, 17P-hydroxy-progesterone, progesterone, 17P-estradial,
estriol and estrone (2, 65) (Table 3).
The literature on the clinical utilization of salivary monitoring of steroid
hormones is rapidly expanding. According to RIAD-FAHMY et al. (66) salivary
progesterone is being used for: 1) assessing the functional capacity of the corpus
luteum in both normal women and
those with defects in the hypothalamicpituitary-ovarian axis; 2) studies of
subfertile women; 3) studies of pregnant
women; 4) examining the effect of contraceptive steroids on ovarian activity
and 5) assessing hormonal changes during adolescence. Salivary estriol measurement during pregnancy has been
shown to be an excellent means of detecting fetal growth retardation (67) and
the estriol to progesterone ratio shows
promise as a predictor of preterm labor
(68).
Some investigators have found that
salivary cortisol is a better measure of
adrenal cortical function than serum
cortisol (69) and is particularly useful in
studies with children (70-72). In many
instances the children have been taught
to collect their own saliva (71). Measurement of salivary cortisol at 11 P.M.
Lithium
Methadone
Cyclosporine
Marijuana
Cocaine
Alcohol
ing on this basis can overcome this difficulty. Monitoring for salivary lithium in
manic depressive patients is also subject
to the problem of individual variation
in the ratio and can be dealt with in the
same way (88).
Salivary monitoring is being used for
patients on methadone, (84) for assay
of cyclosporine in kidney-transplant patients (85) and for detection of marijuana smoking (86, 87) and cocaine use (88,
89). It also is a very practical way for
determining alcohol concentration (90).
Salivary caffeine levels can be accurately
measured and overnight caffeine clearance appears to be a simple, safe test
for measuring liver function (91). There
are numerous other examples.
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