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Conceptual
Framework of Adrenal Stress Index
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Abstracts
Abstracts
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1.An
Ideal HPA Axis Assessment
W.
Mck, Jefferies, Cortisol & Immunity. Med. Hypot. 34: 198-208
(1991)
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An
Ideal HPA Axis Assessment
Autoimmune disorders, chronic fatigue syndrome, depression and allergies
seem to share a common denominator, best described as "A defective
Hypothalmic-Pituitary- Adrenal (HPA) axis response to stress (or
ACTH) not usually detected by routine testing." *
*
Routine testing refers to random blood sampling or 24 hour urine
for steroid evaluation
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2.Chronic
Fatigue
Mark
A. Diametric, et al. J. Clin. Endocrinol. & Metabl. 1991. 73:1224.
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Chronic
Fatigue
Evidence of impaired activation of the HPA axis in patients with Chronic
Fatigue Syndrome. Patients with chronic fatigue show exaggerated responses
to low ACTH stimulus (or to stress-induced ACTH). They show significant
increase in integrated (or temporal) cortisol responses to ACTH, i.e.
exaggerated cortisol response relative to the amount of ACTH (or stress)
they are subjected. These patients also show a blunted ACTH response
to Corticotropin Release Factor (CRF). |
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3.Depression
among patients with Chronic Fatigue
Manu,
P.J. Affective Disorders 1989. 17:165.
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Depression
among patients
with Chronic Fatigue
"By making a positive diagnosis of depression in patients with
an elusive complaint of chronic fatigue, the practitioner has identified
a disorder with significant morbidity which can nonetheless be treated
successfully." |
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4.Cortisol
hypersecretion in depressed individual
Croes,
S., et al. Psychoneuroendocrinology. 1993. 18(1):23.
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Cortisol
hypersecretion in depressed individuals
The temporal cortisol in 40-50% of depressed individuals is elevated
over the entire day with special reference to the midnight elevation.
Hypersecretion is a common finding. |
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5.Allergy
and Chronic Fatigue Syndrome
Straus,
S., et al.
J. Allergy & Clin. Immunol. 1988. 81:79.
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Allergy
and Chronic Fatigue Syndrome
Among the features of this syndrome is a high prevalence of allergy.
Atopic conditions coexist with chronic fatigue syndrome in over 50%
of patients studied. |
Abstracts (continued)
(please scroll down to view entire chart)
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6.Reduced
Cortisol in Patients with Iron Deficiency
Ann.
Nutr. Metab. 1991. 35:311.
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Reduced
Cortisol in Patients
with Iron Deficiency
Among the features of this syndrome is a high prevalence of allergy.
Atopic
conditions coexist with chronic fatigue syndrome in over 50% of patient
studied. |
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7.AIDS
and Adrenal Dysfunction
Cortisol
& Immunity Jefferies. W.McK. Med Hypoth. 34:198-208 (1991).
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AIDS
and Adrenal Dysfunction
The abnormalities in the Hypothalmic- Pituitary-Adrenal axis (HPA)
function found in some patients with AIDS, suggest that HPA dysfunction
might be a factor in the development of progression of disease. Administration
of replacement doses of glucocorticoids tailored to the patients need
resulted in significant clinical improvements. |
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8.Influenza
& Cortisol
Jefferies,
W.McK. Safe Uses of Cortisone. Thomas, Springfield. P.124-42 (1981).
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Influenza
& Cortisol
Administration of low doses of cortisol, 5 mg four times per day,
in patients with low cortisol during influenza infections resulted
in impressive clinical improvement. No complicating bacterial infections
occurred.
Note: Prolonged use of 5 mg gid of Cortisol will cause disruption
of cortisol Circadian Rhythm and several dependent rhythms such as
bone, skin regeneration, and immune traffic. |
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9.Mononucleosis
& Cortisol
Chappel,
M.R. Soulhes. Med. 43:253 (1962).
Manji, R.J., et al.
NEJM 291:1149 (1984).
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Mononucleosis
& Cortisol
Several reports have demonstrated the beneficial effects of short
duration use of cortisol (and other glucocorticoids) in controlling
the symptoms of infectious mononucleosis. This viral infection (in
some patients) is believed to affect the HPA axis and these patients
may benefit from testing HPA axis function to determine optimal cortisol
dosing. |
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10.Hepatitis
& Cortisol
See
Reference in Abstract 8.
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Hepatitis
& Cortisol
The continuation of use of low dose cortisol or glucocorticoids can
maintain remission in patients with chronic autoimmune hepatitis.
Chronic illness is believed to increase the need for cortisol but
an inadequate production may lead to the chronicity. HPA axis evaluation
in hepatitis patients allows objective evaluation and determination
of optimal cortisol dosing.
See Note in Abstract 8. |
Abstracts(continued) (please scroll down to view entire chart)
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11.The
Safe Use of Cortisol and Glucocortonids
Tapper.
M.L., et al.
Ann. Intern. Med. 101:497 (1984)
Glasgow, B.J., et al
Am. J. Clin. Path. 84:495 (1985)
Hilton, C.W., et al.
South Med. J. 81:1493 (1988)
Membreno, L., et al.
Clin. Endocranial. Metab. 65:482 (1987)
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The
Safe Use of Cortisol and Glucocorticoids
A. Clinical Prerequisite
In order to prescribe a safe and effective regimen of glucocorticoids
for a patient, a baseline evaluation of the Hypothalmic-Pituitary-Adrenal
(HPA) axis function is required. The Adrenal Stress Index profile
evaluates both the cortisol levels and rhythm, and DHEA(S). It has
several advantages:
·Salivary
steroids reflect the free bioactive hormone concentration, while
serum values reflect total concentrations and urinary steroids have
limited diagnostic value.
·Non-invasive
salivary sampling reduces the biohazard to clinic staff that usually
perform venipunctures.
·The
nature of these tests allows real life HPA function assessment.
In contrast, clinic based ACTH stimulation tests and serum cortisol
response are rather artificial and do not reflect true physiology
under real life conditions. If ACTH injection must be used, serial
salivary collections after the injection can replace the multiple
venipuncture samplings required. Expected salivary cortisol values
are well defined. On the other hand urinary steroids evaluation
is devoid of the rhythm component and its interpretation is fraught
with pitfalls.
B.
The Adrenals in Clinical Practice:
A Second Look
Traditionally, base line hormone assessments are performed before
administering most hormones. However, it is not the case for the
use of glucocorticoids that are often empirically prescribed. To
the clinicians, adrenal function has traditionally been portrayed
in the light of two extremes: insufficiency (Addison's disease)
on one hand and over production (Cushings' disease) on the other
with much to be desired in between.
C.
Implementing the Safe Use Of Cortisol
Clinically, the safe use of cortisol involves the administration
of sufficient amounts to maintain the regulatory/counter regulatory
cortisol influence that is commensurate to the degree, duration
and type of stress. The physiologic doses of cortisol that are needed
vary and are patient specific. Some do not need any cortisol, others
need amounts tailored to their HPA axis status. Glucocorticoid doses
that are harmful under normal conditions may be well tolerated during
disease or stress periods. Stress induced endogenous hypercortisol
is believed to prevent autoimmunity to self-antigens exposed by
trauma, disease, toxicity and other stressors.
Example
1:
Non-Stressed Conditions: clinical studies show that 2.5 mg cortisone
acetate four times a day suppress endogenous cortisol by 30%, while
5 mg qid suppress it by 60%. A total of 35-40 mg cortisol in patient
specific doses is proper replacement for adrenal exhaustion under
non-stressed conditions.
Example
2:
Stressed Conditions: with increased stress, the dose requirement
increases. 20 mg of cortisol qid produces relief in influenza and
infectious mononucleosis if a person is producing insufficient amounts
in response to the stress. The Temporal Adrenal Profile results
allow the clinician to intelligently tailor the dose in tandem with
the observed circadian profile. For example, 15 mg AM, 10 mg noon,
10 mg afternoon and 5 mg night may be ideal for one patient but
can disrupt the rhythm of another.
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Abstracts
(continued) i(please scroll down to view entire chart)
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12.Salivary
Cortisol Rhythm-the
Neurobiology Connection
References
1. Partridge, W.M., et el. J. Clin. Endocrinol. & Meta. 57:160-163
(1983).
2. Laudat, M.H., et al. Ibid. 66:343-346 (1988).
3. Halbriech, U., et al Arch. Gen. Psych. 42:909-914 (1885).
4. Healy, D., et al. Psychol. Bull. 103:l-15 (1988).
5. Kathol, G., et aI. Am. J. Psych. 146:311-317 (1989).
6. Goodyer, I., et al. Psych. Res. 37:237-244 (1991).
7. Bom, J., et al. Am J. Physiol. 280 pt 2:3: 183-188 (1991).
8. Kobayashi, T., et al. Exp. Brain. Res. Suppl. 1:260-268 (1985).
9. Bom, et al. Biol. Psychiatry. 2:1415 (1986).
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Salivary
Cortisol Rhythm - The Neurobiology Connection
More Applications of Salivary Cortisol
Cortisol uptake by the brain is limited to the free (unbound) bioactive
fraction (1) which constitutes a small fraction of total circulating
cortisol. Therefore, salivary cortisol assessments which measure
the free fraction (2), are ideal for neurobio- logical investigations.
Research indicates that pattern disruption as well as magnitude
changes in cortisol secretion may indicate abnormal conditions (3-5).
The temporal salivary cortisol assessment (ASI) gives both pattern
and magnitude. Salivary cortisol evaluation can also be performed
following dexamethasone suppression.
Depression:
Our laboratory findings and several published reports (4-6) indicate
that depressed individuals often show disrupted circadian rhythms
coupled with hypersecretion of cortisol states.
Following
treatment and recovery, the cortisol secretion profile is dramatically
altered (Figure 1- to be added) (6). Clinical recovery was assessed
by a reduction in the Modified Hamilton Index of Depression (MHID)
scores.
Cortisol
Rhythm & Sleep (7)
Free cortisol entering the hippocampal neurons can modulate the
activity of the Limbic System. Two brain receptors interact with
glucocorticoids. A high affinity (HA) type that can also bind aldosterone
and a low affinity type (LA). The HA receptors maintain limbic neuron
excitability while the LA receptors are restorative, and suppress
excitability due to over stimulation. The interplay of LA and HA
receptors controls the behavioral outcome of the individuals. When
the cortisol levels are high, the Rapid Eye Movement (REM) sleep
is curtailed and non-REM sleep is stimulated. Simply stated, sleep
patterns and processes, are susceptible to central corticosteroid
influences (9). Nocturnal hypercortisol states can alter REM and
non-REM sleep cycles that are considered the basic units of sleep
(8). Under such conditions the restorative and regenerative effects
of night sleep may be compromised.
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Abstracts
(continued) (please scroll down to view entire chart)
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13.Glucocorticoid
Therapy: How?
Rubens,
R. Bull. Soc. Belge.
Opthalmol. 236;45-55 (1990).
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Glucocorticoid
Therapy: How?
Corticosteroids are very potent medications. The use of a high dose
of glucocorticoids will suppress the pituitary adrenal axis. In the
use of the medication a knowledge of the equivalence of the different
preparations is necessary (hydrocortisone 1,
prednisolone 4, dexamethasone 25). The ultimate dose will be differentiated
and adapted to the basal disease. In the cutting down of a long therapy
with corticoids (greater than 6 weeks with a dose more than 7.5 mg
prednisolone a day or equivalent) a long and careful running down
period is necessary. At first a switch over to a normal substitutive
treatment (20 and 10 mg hydrocortisone a day) is necessary. At regular
intervals the recovery of the adrenal glands will be tested. If a
sufficient basal level of cortisol is obtained a dynamic exploration
using ACTH and insulin will be performed. The evidence of a fully
recovered gland is a normal insulin response. |
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14.Attentuated
Cortisol Response to Psychological Stress, but not to CRH or Ergometry
in young habitual smokers.
Kirschbaum
C., Strasburger C.J., Langkrar J., Pharmacol Biochem Behav. 1993
Mar 44(3). 527-531.
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Attenuated
Cortisol Response to Psychological Stress
Salivary Cortisol and heart rate responses to a) psychological stress
(public speaking and mental arithmetic), b) human corticotropin-releasing
hormone (hCRH), and c) bicycle ergometry until exhaustion were investigated
in 10 smokers and 10 nonsmokers. Compared to d), an injection of physiological
saline, psychological stress as well as hCRH resulted in significant
elevations of salivary cortisol levels in the control group. Ergometry
workload induced only moderately enhanced cortisol concentrations.
Profound changes in heart rates were observed following bicycle ergometry
[+83 beats per minute (bpm)] and after the psychological stress (+29
bpm). hCRH injection increased heart rate by 5 bpm while heart rates
dropped after saline administration (-2 bpm). Smokers showed an attenuated
cortisol response to the psychological stressor. Mean cortisol increases
reached only one third in smokers compared to nonsmokers. Similarly,
cortisol levels in smokers tended to be lower after hCRH injection;
however, this difference was not statistically significant. Cortisol
responses to ergometry did not differ between the two groups. Likewise,
heart rates did not reveal different profiles in any of the three
stimulations in smokers compared to nonsmokers. |
Abstracts
(continued) (please scroll down to view entire chart)
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15.Psychological
and Physiological Assessments on American Hostages freed from captivity
in Iran.
Rahe,
R.H., Karson S., Howards N.S. Jr., Rubin R.T., Poland R.E., Psychosom
Med. 1990 Jan-Feb. 52(1). 1-16.
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Psychological
and Physiological Assessments on American Hostages
Medical evaluations of 52 Americans held hostage in Iran for 444 days
included psychological testing and physiological measurements. Psychological
testing utilized the Minnesota Multiphasic Personality Inventory (MMPI)
and the 16 Personality Factor Questionnaire (16-PF) and focused on
the stress management capabilities of the group upon their arrival
at Wiesbaden, West Germany. Physiological testing utilized plasma
and urinary cortisol along with plasma and urinary catecholamine levels
to help document former hostages' stress responses following their
release from captivity. Saliva cortisol and testosterone were measured
over the first three hospital days to assess the group's psychophysiological
recovery. Psychological
testing indicated that the former hostages, as a group, were generally
well defended, appearing to have endured their ordeal well. In contrast,
plasma and saliva cortisol, urinary catecholamines, and saliva testosterone
were seen to be highly elevated. These physiological measures appeared
to reflect three strong affects: distress, anxiety, and elation. Saliva
cortisol was the only physiological measurement that demonstrated
a significant correlation with psychiatrists' ratings of the released
hostages' psychological disturbance. Psychiatrists' disturbance ratings
appeared to be a valid psychometric estimate, as adduced from their
correlations with MMPI and 16-PF scales. |
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16.Usefulness
of the determination of Saliva Cortisol in the study of Adrenal
Gland Glucocorticoid Function.
Montanes
R., Rodriguez J., Perez A., Cortes M., Ordonez J., Gonzalez F.,
Med Clin Barc. 1989 Oct 14. 93(11). 406-410
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Usefulness
of the Determination of Saliva Cortisol
To validate the adequacy of saliva as a biological specimen for the
study of glucocorticoid adrenal function, the concentrations of salivary
cortisol (SC) and serum total cortisol (TC) were measured by radioimmunoassay
(RIA) in several groups of individuals in baseline state and during
stimulation tests. The study of diurnal variations of SC in the reference
population (n = 29) showed a noctohemeral rhythm similar to that of
TC, with maximal concentrations at 08:00-09:00 hr (18 +/- 9 nmol/L)
and 61% and 80% decreases at 15:30 and 23:00 h, respectively. After
the administration of 1 mg of dexamethasone, SC was reduced by 95%
of its baseline value (n = 11), while TC was normal in 4. The SC response
to stimulation with intravenous synthetic adrenocorticotropin (Nuvacthen)
(with and without previous suppression with 1 mg dexamethasone), insulin
hypoglycemia and glucagon were qualitatively similar to those of TC,
although more marked in proportion. These results, together with the
practical advantages of saliva as a biological sample (easy specimen
collection, absence of stress during its collection, and stability
of measurement) over TC, demonstrate that SC is a useful clinical
test to detect glucocorticoid dysfunction. |
Abstracts
(continued) (please scroll down to view entire chart)
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17.Behavioral
Stress Responses in Premenopausal and Postmenopausal women and the
effects of Estrogen.
Am.
J Obstet Gynecol. 1992 Dec. 167(6). 1831-1836.
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Behavioral
Stress Responses in Premenopausal and Postmenopausal Women
Objective: Our purpose was to determine the pattern of reactivity
to stress in premenopausal and postmenopausal women and to assess
the effects of estrogen. Study Design: A behavioral stress test was
given to premenopausal (n = 13) and
postmenopausal women (n = 36). Biophysical and neuroendocrine responses
were measured during and on completion of the stress test. The postmenopausal
women were then randomized to placebo or transdermal estradiol treatment
for 6 weeks, at which time another behavioral stress test was given.
Results: Stress reactivity to math and speech tasks elicited significantly
greater systolic blood pressure responses in postmenopausal women
compared with premenopausal women (p < 0.05). On retesting, significant
biophysical responses that were present during the initial stress
testing were still present (p < 0.05) in the placebo group but
were blunted with estrogen treatment. Plasma corticotropin, cortisol,
androstenedione, and norepinephrine increased during testing to a
similar degree in premenopausal and postmenopausal women; this response
was maintained after placebo treatment. Postmenopausal women treated
with estrogen had blunted responses. Conclusion: Significant differences
in responses to psychologic stress exist in premenopausal and postmenopausal
women. The lack of adaptation may account
in part for the increased risk of cardiovascular disease in postmenopausal
women. Estrogen appears to blunt the stress-induced response. |
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18.Efficacy
of Tai Chi, Brisk Walking, Meditation, and Reading in reducing Mental
& Emotional Stress.
Ji
n P. J Psychosom Res. 1992 May. 36(4). 361-370.
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Efficacy
of Tai Chi, Brisk Walking, Meditation, and Reading
Tai Chi, a moving meditation, is examined for its efficacy in post-stressor
recovery. Forty-eight male and 48 female Tai Chi practitioners were
randomly assigned to four treatment groups: Tai Chi, brisk walking,
meditation and neutral reading. Mental arithmetic and other difficult
tests were chosen as mental challenges, and a stressful film was used
to produce emotional disturbance. Tai Chi and the other treatments
were applied after these stressors. After all treatments, the salivary
cortisol level dropped significantly, and the mood states were also
improved. In general the stress-reduction effect of Tai Chi were similar
to moderate physical exercise. Heart rate, blood pressure, and urinary
catecholamine changes for Tai Chi were found to be similar to those
for walking at a speed of 6 km/hr. Although Tai Chi appeared to be
superior to neutral reading in the reduction of state anxiety and
the enhancement of vigour, this effect could be partially accounted
for by the subjects' high expectations about gains from Tai Chi. Approaches
controlling for expectancy level are recommended for further assessment. |
Abstracts
(continued) (please scroll down to view entire chart)
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19.Salivary
and Serum Antibodies to Gliadin in the diagnosis of Celiac Disease
Al-Bayaty
HF, Aldred MJ, Walker DM, Newcombe RG, Swift G, Smith PM, Ciclitira
PJ. J Oral Pathol Med 1989, 18:578-581.
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Salivary
and Serum Antibodies to Gliadin
Salivary IgA and serum IgA and IgG antibodies to crude gliadin and
alpha gliadin were measured in adult patients with untreated celiac
disease, ulcerative colitis, Crohn's disease and normal controls.
Antibody levels in saliva and serum in untreated celiac disease were
significantly higher than in other groups. The assay of salivary IgA
antibodies to gliadin offers a non-invasive test which would be particularly
useful in the investigation of celiac disease and for monitoring compliance
with a gluten-free diet. |
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20.Salivary
IgA Antigliadin Antibody as a marker for Coeliac Disease
Hakeem
V, Fifield R, Al-Bayaty HF, Aldred MJ, Walker DM, Williams J, Jenkins
HR. Arch of Disease in Child 1992, 67: 724-727.
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Salivary
IgA Antigliadin Antibody as a Marker for Coeliac Disease
In recent years, serum antibodies to gliadin (AGA) have been reported
to be useful markers of coeliac disease. IgA-AGA have also been found
in intestinal secretions and saliva in coeliac disease and may offer
a convenient, non-invasive screening test. In order to test this hypothesis,
salivary and serum AGA were measured in children with coeliac disease
proved by biopsy and compared with several control groups. Measurement
of salivary IgA-AGA provided excellent discrimination between those
children with coeliac disease and the control groups, and our study
suggests that it may provide a rapid, non-invasive method of screening
for this disease before an intestinal biopsy is performed. |
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