Conceptual Framework of Adrenal Stress Index
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Abstracts

Abstracts

1.An Ideal HPA Axis Assessment

W. Mck, Jefferies, Cortisol & Immunity. Med. Hypot. 34: 198-208 (1991)

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

 2.Chronic Fatigue

 

Mark A. Diametric, et al. J. Clin. Endocrinol. & Metabl. 1991. 73:1224.

 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).

 3.Depression among patients with Chronic Fatigue

Manu, P.J. Affective Disorders 1989. 17:165.

 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."

4.Cortisol hypersecretion in depressed individual

Croes, S., et al. Psychoneuroendocrinology. 1993. 18(1):23.

 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.

5.Allergy and Chronic Fatigue Syndrome

Straus, S., et al.
J. Allergy & Clin. Immunol. 1988. 81:79.

 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)

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6.Reduced Cortisol in Patients with Iron Deficiency

Ann. Nutr. Metab. 1991. 35:311.

 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.

7.AIDS and Adrenal Dysfunction

Cortisol & Immunity Jefferies. W.McK. Med Hypoth. 34:198-208 (1991).

 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.

8.Influenza & Cortisol


Jefferies, W.McK. Safe Uses of Cortisone. Thomas, Springfield. P.124-42 (1981).

 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.

9.Mononucleosis & Cortisol

Chappel, M.R. Soulhes. Med. 43:253 (1962).
Manji, R.J., et al.
NEJM 291:1149 (1984).

 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.

10.Hepatitis & Cortisol



See Reference in Abstract 8.

 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)

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)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 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.


Abstracts (continued) i(please scroll down to view entire chart)

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).

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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.


Abstracts (continued) (please scroll down to view entire chart)

13.Glucocorticoid Therapy: How?

 

 

Rubens, R. Bull. Soc. Belge.
Opthalmol. 236;45-55 (1990).

 

 

 

 

 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.

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.

 

 

 

 

 

 

 

 

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)

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.

 

 

 

 

 

 

 

 

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.

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

 

 

 

 

 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)

17.Behavioral Stress Responses in Premenopausal and Postmenopausal women and the effects of Estrogen.

 

 

 

 

 

 

Am. J Obstet Gynecol. 1992 Dec. 167(6). 1831-1836.

 

 

 

 

 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.

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.

 

 

 

 

 

 

 

 

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)

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.

 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.

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.

 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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