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Cortisol Rythm
Concept
Definition
The Temporal Adrenal Profile (TAP) refers to the assessment of free, biologically
active circulating cortisol over a complete circadian cycle (one day).
Four salivary specimens are collected at specified times during a 24 hour
circadian cycle. The patient values are plotted and the graph is compared
to the expected normal profile (Figure 1- to be added). Replacing a single
serum measurement with a trend related analysis substantially increases
sensitivity and specificity for diagnosis of abnormalities in the highly
responsive HPA axis.
Advantages of Salivary Testing-Scientific Advantages
· Stress avoidance - naturalistic approach: Stress and apprehension associated
with blood drawing can induce an artificial cortisol elevation. Repeated
venipunctures (usually used) can alter or mask the results. In contrast,
the stress-free multiple saliva collections are highly suited in studies
of the hypothalmic-pituitary-adrenal axis (HPA). · Salivary levels reflect
the bioactive plasma fraction with a 97% correlation: Free Cortisol is
bioactive at the cell level. Salivary cortisol accurately reflects this
non-protein bound bioactive fraction (Figure 3- to be added) (2-5). In
contrast, total serum cortisol does not differentiate the bioactive from
the bound fractions. Many factors alter the level of serum binding proteins.
Pregnancy and contraceptives (6,7), hyperthyroid function (8) and various
pharmacological agents (9) can lead to "artifactual" serum cortisol levels.
· Sample stability: Free cortisol in saliva is extremely stable with minimum
temperature dependence thus allowing specimens to be collected and shipped
with no special handling requirements.
Cortisol Rhythm
Basis of Test
The validity and superiority of multiple salivary sampling is based on
several facts: Saliva reflects the free bioactive circulating cortisol
fraction (2-5). The correlation coefficient is 0.97. Shifts are reflected
within 60 Salivary flow rate does not affect cortisol levels (11,12).
Multiple salivary sampling is an accurate and easy approach in he assessment
of circadian and ultradian rhythms of adrenal steroids. Temporal Stability:
Salivary circadin rhythms are stable over time as long as the same prevailing
conditions are in effect.
Clinical Applications
Temporal Adrenal Profiling is usually beneficial in investigating and
evaluating hyper and hypo adrenocortisol states, and dysregulation of
the HPA axis. Some clinical applications · Stress-induced dysregulation
of HPA axis, Adrenal fatigue · Hypoglycemia and blood sugar dysregulation
· Food intolerance · Depression and Psychosomatic illness · Hypocortisol
following chronic glucocorticoid use · Chronic fatigue · Immune function
disturbances · Adrenal hyperplasia and adenomas · Hypothalmic-pituitary
lesions · Multiple Endocrinopathies · Asymptomatic hypercortisol and Procatabolic
state · Stress Management Programs
Functional Tests
· ACTH stimulation test · Carbohydrate Challenge test
· CRH stimulation test · Exercise Challenge test
· Dexamethasone suppression test
Stress and Adrenal Dysfunction
Individuals subjected to chronic and severe stress usually undergo the
"General Adaptation Syndrome," (Figure 4- to be added) as Dr. Selye indicated
in his early research(13). These people may eventually develop hypoadreno-corticism,
or adrenal insufficiency. Subsequent to over stimulation of the adrenal
glands, there is an alarm response followed by a phase of adaptation,
and finally a stage of adrenal exhaustion. Temporal Adrenal Profiling
(TAP) is an excellent tool for investigating all stages of the "General
Adaptation Syndrome."
Symptomatology The presenting complaints and associated signs and symptoms
were closely examined and documented in 200 individual cases (14) and
are summarized in Tables 1 to 4, on the following page. Because the symptoms
associated with adrenal dysfunction overlap with those found in other
Table 1: Chief Complaints in Adrenal Insufficiency N=200 cases
| Complaint | % incidence |
| Excessive Fatigue | 94 |
| Nervousness / Irritability | 86 |
| Mental Depression | 79 |
| Inability to Concentrate | 77 |
| Apprehensions | 71 |
| Confused intervals | 61 |
| Weakness | 65 |
| Feelings of frustration | 56 |
| Light headedness | 47 |
| Insomnia | 40 |
Table 2: Systemic Symptoms in Adrenal Insufficiency N=200 cases
| Symptoms | % Incidence |
| Premenstrual Tension | 85 |
| Tachycardia | 15 |
| Craving for sweets | 75 |
| Headaches | 68 |
| Alcohol Intolerance | 66 |
| Sternomastoid / Trapezius muscle pain | 65 |
| Epigastric Discomfort | 51 |
| Alternate Diarrhea & Constipation | 45 |
| Dyspepsia-Indigestion | 40 |
| Chronic colitis | 4 |
| Vertigo | 20 |
| Poor Memory | 59 |
| Palpitation | 57 |
Table 3: Associated Conditions in Adrenal Insufficiency N=200 cases
| Condition | % Incidence |
| Food & other allergies | 73 |
| Hay fever | 23 |
| Urticaria | 20 |
| Asthma | 12 |
| Skin Dermatitis | 39 |
| Rheumatoid Arthritis | 21 |
Table 4: Other Findings in Adrenal Insufficiency N=200 cases
| Physical Findings | % Incidence |
| Postural hypotension (sympathetic hypofunction) | 93 |
| Dry and thin skin | 91 |
| Scanty perspiration | 91 |
| Positive Rogoff sign1 | 71 |
| Low Basal Metabolic Rate (Low Body Temperature) | 85 |
| Increased Eosinophils2 | 58 |
Findings & Correlations: Low Basal Metabolism Low basal metabolism (often gauged by morning body temperature) is not necessarily a sign of a hypothyroid state. By no means is this reduced metabolism a sufficient indication for supplemental thyroid hormone (14). This is an antiquated paradigm and treatment must be based on appropriate laboratory evaluation of adrenal and thyroid function. In addition to thyroid and cortisol, melatonin also regulates metabolism. Elevated morning melatonin keeps temperature low. Zinc Intake & Adrenal Function Recent research (15) indicates that oral zinc doses as small as 25 mg can suppress adrenal cortisol output in healthy individuals by 40-60% for durations of at least 4 hours. The exact site(s) of action and the mechanisms involved have yet to be elucidated. Sympathetic Activity, Adrenal Function and Extra Pituitary Control Recently a study conducted in healthy humans (16) suggested the existence of a circadian alpha- adrenergic regulation of the hypo-thalmic-pituitary-adrenal axis (HPA). Alpha-adrenergic stimulation at 8:00 AM caused a pronounced increase in cortisol output. However, the same stimulus at 6:00 PM caused no observable increase in cortisol output. Furthermore, the accompanying ACTH increments could not fully account for the pronounced cortisol increase. This finding lends credence to the hypothesis that postulates the existence of a peripheral adrenergic regulatory component for the adrenals (l7). This indicates the existence of an additional modulation mechanism to the well established HPA regulatory axis. (continued on following page)
Findings & Correlations (continued): Depression & Adrenal Function A common finding in biologically-based depression is disruption of the circadian rhythm as exemplified by an elevated salivary cortisol at 11:00 PM (1). Frequently, the hypothalmic-pituitary axis is insensitive to elevated glucocorticoid induced suppression. This is best demonstrated by the absence of adrenal suppression, or premature escape following a 1mg injection of dexamethasone (18) at 11:00 PM, with subsequent measurements of serum or salivary cortisol at 4:00 PM and 11:00 PM of the following day. The serum cortisol values should be less than 140 nM (19) and Salivary Cortisol < InM. Hypercortisol, Gonadal Function & Osteoporosis A clinical study conducted in amenorrheic women athletes (20) showed a 300% increase in mean serum cortisol levels versus the control group. Their estradiol and progesterone levels were expectedly low. The study noted that the bone density of these young athletes was about 21% less than the control group. The researchers indicate that their study and several other observations (21,22) show that increased glucocorticoids may be a marker of an altered HP-gonadal axis, and a contributor to reduction in bone density. Therapeutic Aspects Traditionally, the wholistic treatment of non-life threatening adrenal dysfunction has taken several complimentary routes. Tables 5 & 6 (shown on the following page) are a brief summary of the most common therapeutic approaches used.
Table 5: Therapeutic Aspects (Please scroll to see entire chart)
| Type of Dysfunction | Therapeutic Approach or Modality | Remarks |
| Adrenal Hyperfunction. | Stress
reduction, regular excercise, sufficient sleep & glycemic control. Botanical adaptogens are used in oriental medicine practice. |
Side
effects include: Immunosuppression, Osteoporosis, Muscle Atrophy, Arteriosclerosis, Hyperlipidemia and Insomnia. Further investigation of hypothalamic-pituitary locus is recommended. |
| Reduced Cortisol output (single abnormal finding) |
Stress reduction, avoidance of blood sugar fluctuations (hypoglycemic diet) Ref. 24 Botanicals: Panax Ginseng, Licorice extracts, and flavanoids. Physciological dose of Cortisol (20-40 mg/day) not large enough to suprress ACTH output. |
Full spectrum light or sun light exposure is encouraged. Pantothenic acid intake is especially increased. Some practitioners use Adrenal Cortex extracts in oral or injectable forms. |
| Elevated Cortisol with low DHEA and DHEA-Sulfate (DHEA-S) levels. | These individuals are given supplemental amounts of DHEA coupled with stress reduction if applicable. | Refer to the Adrenal Stress Index test information sheet. |
| Hypothalamic-pituitary axis disturbance, loss of sensitivity to suppression. | The use of 3x100mg daily of phosphatidylserine (PS) is beneficial in correcting premature escape in the Dexamethasone suppression test. | Phosphatidylserine is believed to act at the neurotransmitter level in the brain (Ref.23) and reduces ACTH Pulse height. |
Table
6: Commonly Used Treatments (Please scroll
to see entire chart)
| AM | Noon | Afternoon | Night | Mean: Noon Afternoon | Hormones | Other | Botanicals | Other | |
| Typical of Endogenous Depression | N | N | N | up | N | PS | Light Therapy | ||
| Immunosuppression Osteoporosis Sleep pattern disturbance Fatigue |
up | up | up | up | up | DHEA | SRI ASC PS PA | Adaptogens | Acupuncture
Exercise Glycemic control Stress Management |
| Sleep pattern disturbance Early chronic stress pattern | up | up | up | up | up | Acupuncture Stress Management Exercise |
|||
| Immunosuppression Osteoporosis Estrogen Effect Fatigue |
up | up | up | up | down | DHEA | ASC SMR PA SRI | Wild Yam | Stress Management Light Therapy |
| May represent pre-fatigue phase | N | N | N | N | down | DHEA | |||
| Typical of adrenal fatigue | down | down | down | N | N | Cortisol | SMR PA | Adaptogens | Light Therapy Glycemic control |
| Adrenal Exhausation | down | down | down | N | down | Cortisol DHEA | Light Therapy Glycemic control | ||
| Marginal Adrenal performance | down | N | N | N | N or down | Cortisol DHEA | Adaptogens | Light Therapy Stress Management |
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