Adrenal Stress

8/13/2014
Adrenal Stress Index
Functional testing and

applications
Presented by
Carrie McMillin, ND
AUGUST 2014 WEBINAR.

2014 Diagnos-Techs, Inc. All rights reserved.
Objectives
Review adrenal stress hormone physiology
Examine conditions that can affect the
cortisol rhythm
Highlight how to get the most from lab
testing
Review relevant case studies
Provide tips for incorporating adrenal stress
testing into your practice
Stress and the Adrenal Glands
8/13/2014
Steroid Hormone
Synthesis
Circadian Rhythm of Cortisol
Cortisol
Produced by the
zona fasciculata of
the adrenal cortex
Regulated by ACTH
and released in
response to:
Stress (real or
perceived)
Decreased level of
glucocorticoids in
serum
Hypoglycemia
Inflammation
Circadian rhythm
CIRCADIAN RHYTHM
Cortisol
Sleep Pattern
Light-dark Exposure
Meal Times
ACTH
HYPOGLYCEMIC
STATES
SYMPATHETIC
RESPONSE
TISSUE DAMAGE
Inflammation
Illness
Infection
MENTAL AND
EMOTIONAL STRESS
Anxiety
Depression
8/13/2014
Cortisol- Physiologic effects

Stimulates gluconeogenesis
Decreases the translocation of glucose
transporters (GLUT4) to cell membrane
May contribute to insulin resistance
Helps to activate glycogen phosphorylase

Essential for ability of epinephrine to stimulate
glycogenolysis
Inhibits collagen formation

Decreases uptake of amino acids in muscle
Inhibits protein synthesis
Stimulates secretion of gastric acid
Inhibits TNF-, IL-12 and IFN- production

Increases production of IL-4, IL-10 and IL-13
Can lead to TH2 dominance1
Anti-inflammatory
8/13/2014
Dehydroepiandrosterone (DHEA)
Produced in zona fasciculata and zona
reticularis of the adrenal gland
Precursor hormone to sex hormones
Neurosteroid
Anti-glucocorticoid effects2
Other?
Steroid Hormone
Synthesis
General Adaptation Syndrome (GAS)

General theory for animal and human stress
response (Hans Selye)
Provides a means to:
Recognize the environmental triggers and modify
them if possible
Determine the extent of general adaptation
Intervene if necessary by various means (hygienic,
endocrine, nutritional, etc.) to assist the patients
adaptation3
8/13/2014
General Adaptation Syndrome
Maladaptive Stress Syndrome4

More recently proposed model of adrenal
stress response based on Selyes work
MSS-0
MSS-1
MSS-2
MSS-3
MSS-0
Healthy, well-adapted stress response
Varies between hypovigilance and
hypervigilance
Level of vigilance properly regulated by
amount of epinephrine and cortisol produced4
MSS-1
Correlates with the alarm phase
Acute excess release of cortisol and
epinephrine
Considered maladaptive when the fight or
flight response is not appropriate4
8/13/2014
MSS-2
Suppression phase
Chronically elevated cortisol
Results in increased levels of epinephrine
Immune and inflammatory responses are
suppressed
Adrenal androgens often elevated4
Conditions Associated with MSS-2

Increased
susceptibility to
mycotic infections
Depression
OCD
Anorexia nervosa
Panic disorder
Gastritis
Hyperlipidemia
Atherosclerosis
Insulin Resistance
Metabolic syndrome
Type II diabetes
Osteoporosis
Neoplasia
Dementia
Hirsutism and
alopecia in women4
MSS-3
Exhaustion phase
Deficient glucocorticoid production
Decreased production of adrenal androgens
Decreased production of mineralocorticoids
Episodic increases in epinephrine4
8/13/2014
Conditions Associated with MSS-3

Hypotension
Functional
hypoglycemia
Chronic fatigue
syndrome
Fibromyalgia4
Environmental
sensitivities
Atypical depression
Poor stress resistance
Altered cortisol curve
Depression
PTSD
Fibromyalgia
Chronic fatigue
Attention deficit hyperactivity disorder (ADHD)
Autism spectrum disorders (ASD)
Anorexia nervosa5
Hypo- and hyperthyroidism6
Depression
May present with chaotic cortisol rhythm7
Adolescent boys
Elevated morning cortisol and high depressive sx
14x more likely to develop major depressive disorder
(MDD) than those with normal cortisol and absence of
depressive sx8
2-4x more likely to develop MDD than those with only one
of the two factors8
8/13/2014
PTSD
Hypothalamic-pituitary-adrenal (HPA) axis may be
hyporesponsive in a number of stress-related states9
Cortisol rhythm may be blunted 10
Childhood physical abuse correlated with:
Flattened diurnal cortisol rhythms

Increased cortisol responses to awakening
Markedly low levels of cortisol at the time of first awakening
Note: Severe traumatic experiences in childhood may be a factor of
adult neuroendocrine dysregulation among fibromyalgia sufferers 11
Fibromyalgia
Delay in the rate of decline from cortisol acrophase to
nadir
Elevation of cortisol in the late evening12
Loss of diurnal variation in plasma cortisol
Possible alteration in HPA axis with respect
to cortisol secretion in fibromyalgia syndrome
May be consequence of chronic pain.12,13
Chronic Fatigue Syndrome (CFS)

May see lower salivary cortisol concentrations in the
morning and higher salivary cortisol concentrations in
the evening
Attenuated decline of salivary cortisol concentrations
across the day associated with fatigue symptoms in
CFS14
Possible altered diurnal cortisol rhythm in CFS
cases14
8/13/2014
Attention Deficit Hyperactivity Disorder (ADHD)

Abnormal diurnal saliva cortisol rhythm usually seen
in ADHD children
Dexamethasone suppression test (DST)
One study showed suppression in only 46.7% of children
w/ADHD
Abnormal diurnal rhythm and nonsuppression to the DST
were more frequent in the children with severe hyperactivity
Possible abnormalities in HPA axis function in some

children with ADHD, especially those exhibiting
severe hyperactivity.15
Autism Spectrum Disorders (ASD)

Dysregulation of the circadian rhythm in autism
Gradual decrease in the morning
Elevated in evening
Increased susceptibility to external factors such as zeitgeibers16
Significantly lower serum concentrations of cortisol

and significantly higher concentrations of ACTH17
Higher peak cortisol levels
Prolonged duration and recovery of cortisol elevation
following stressor18
Autism Spectrum Disorders (ASD)

Abnormal DST response for saliva cortisol19
Negative feedback mechanism of the HPA-axis may
be disturbed owing to a disorder in the regulation by
serotonin metabolism19
Enhanced responsivity to stress20
Adolescence may be a time of increased risk for
enhanced physiological arousal and social stress20
8/13/2014
Salivary cortisol
Screening test for Cushings
The Endocrine Society includes late night
salivary cortisol (2 measurements) as a
recommendation for initial screening of
patients for Cushings syndrome21
Diagnos-Techs
Adrenal Stress Index Panel
29
Adrenal Stress Index (ASI)

4 saliva collection vials
Cotton in each vial
10
8/13/2014
Adrenal Stress Index (ASI)

Tests:
4 Cortisol measurements
6-8AM, 11AM-1PM, 4-5PM, 10PM-12AM
DHEA/DHEA-S (pooled value)

17-OH Progesterone
Insulin
Fasting, Non-Fasting
Total sIgA
Gliadin sIgA
17-OH Progesterone
Produced in zona fasciculata and zona
reticularis of adrenal gland
Important precursor to cortisol
Steroid Hormone
Synthesis
11
8/13/2014
Insulin
Preliminary screen for insulin resistance
Cortisol increases blood sugar levels
Cortisol excess may result in:
Impaired glucose tolerance
Hyperglycemia
Hyperinsulinemia
Total sIgA
Predominant antibody found on mucosal
membranes
Dimer of two IgA molecules with a secretory
component
Helps protect from enzymatic degradation
Immune exclusion
Binds to antigens and prevents their adherence
and admittance into the body
Moderates the mucosal inflammatory response
Total sIgA- Clinical implications

Elevated sIgA may be
associated with:
Some autoimmune
conditions
Diabetes
Gingivitis
Aphthous ulcers
Inflammatory
conditions
Acute physical or
emotional stress
(transient)
Depressed sIgA may

be associated with:
Chronic stress
Allergies
Upper respiratory tract
infections
Celiac disease
Selective IgA
deficiency
12
8/13/2014
Gliadin sIgA
Monitoring gluten free diet
Prioritizing foods for elimination trial
Interpreting Laboratory Findings:

Case Studies
38
Case 1
22y/o female
CC: Irregular menses
HR: 78bpm BP: 114/76mmHg T: 98.2F BMI: 31
PMHx: Chronic sinusitis
S: Fatigue w/difficulty waking, HA
O: Acne, oily skin, hirsutism, overweight
13
8/13/2014
22 y/o Female
Irregular menses
Nonclassical Congenital
Adrenal Hyperplasia (CAH)
Genetic deficiency of either 21-hydroxylase or 11hydroxylase
21-hydroxylase
17OH-progesterone
11-deoxycortisol
11-hydroxylase
11-deoxycortisol
Cortisol
Low cortisol
Low tolerance to illness, trauma, and other stressors
Precursor accumulation (converted to androgens)
Hirsutism, acne, oligomenorrhea
May have low aldosterone
Syncope, low Na/K ratio, hypotension
Extremely difficult to differentiate from PCOS with clinical

signs alone
Case 1- 22 y/o Female

CAH- Lab Findings
Low cortisol
High 17OH-progesterone (and 11-deoxycortisol in
11-hydroxylase deficiency)
Exaggerated with ACTH stimulation test
High DHEA
Low aldosterone
Low Na/K ratio
14
8/13/2014
Case 2
34y/o male
CC: Depression
PMHx: Tonsillectomy (age 12); chronic otitis
media
S: Difficulty concentrating, fatigue w/difficulty
waking, insomnia, alternating diarrhea and
constipation
O: Eczema, acne
Case 2- 34 y/o Male
Case 2- 34 y/o Male
15
8/13/2014
Case 2- 34 y/o Male
ADHD workup
DSM criteria- Consider adult manifestations
Hyperactivity symptoms:
Impulsivity symptoms:
Inattention symptoms:
Restlessness, verbosity, tendency toward very active jobs

Ending relationships, quitting jobs, more driving violations
Procrastination, difficulty making decisions, poor time
management22
Case 2- 34 y/o Male
Sample treatment protocol

Daily exercise routine
Elimination diet
Biofeedback
Withania somnifera
2mL tid 1:2 fluid extract
Withania somnifera (Ashwagandha)

Traditional use:
Treat negative effects of stress
Improve physical energy
Improve overall health23
Has been used in a combination therapy for ADHD
with some evidence of benefit23,24
Possible enhancement of immune function23
Potential
Antidepressant effects (rodent studies)25
Enhance stress response (rodent studies)26
16
8/13/2014
Withania somnifera (Ashwagandha)

Dosing:
According to secondary sources, 1-6g daily of the
whole herb has been used in capsule form
Tinctures or fluid extracts have been dosed at 24mL tid (may contain high concentrations of
ethanol)23
Case 3
19 y/o male
CC: Fatigue
PMHx: Insignificant
S: Difficulty concentrating, awakes unrefreshed,
loss of appetite
O: WNL
Case 3- 19 y/o Male
17
8/13/2014
Case 3- 19 y/o Male

PHQ-9 score: 14
PHQ-9 Score 10: Likely major depression.
Depression score ranges:
5 to 9: mild
10 to 14: moderate
15 to 19: moderately severe
20: severe
Case 3- 19 y/o Male

Sample treatment protocol
Counseling
Crisis hotline
Daily exercise regimen

Diet
Small, frequent meals
Adequate protein, fruits, vegetables
Rhodiola rosea (3% rosavins; 1% salidrosides)

200mg bid ac
Rhodiola rosea
Preliminary evidence regarding benefit in cases of:
Fatigue
Anxiety
Depression27
May increase resistance to physical stress by:
Modulating cortisol
Alleviating oxidative stress28,29
Note: Soviet space program conducted a study using a mixture
containing Rhodiola rosea, Schisandra chinensis,
and Eleutherococcus senticosus
When subjects were tired, showed benefits on:
Mental-work capacity
Problem-solving
Short-term memory
18
8/13/2014
Rhodiola rosea
Adults:
100-600mg generally considered to be clinically effective
100-300mg three times daily may be used for adaptogenic
effects
170mg twice daily for 10 weeks improved symptoms of
generalized anxiety disorder 31
General recommendation is to take on empty stomach
Caution: Inhibits MAO, therefore increases risk of serotonin

syndrome when used in conjunction with MAOIs or SSRIs4.
May decrease blood glucose levels, affect heart rate, increase
BP.
Case 4
42 y/o female
CC: Anxiety
HR: 96bpm BP: 128/84mmHgT: 98.1F BMI: 28
PMHx: Cholecystectomy (age 38)
S: Occasional dizziness, tachycardia
O: WNL
19
8/13/2014

GAD-7 Score: 13
[Score: 5 to 9 = mild anxiety; 10 to 14 = moderate anxiety;
15 to 21 = severe anxiety]
Fasting glucose: 112mg/dL

HbA1C: 6.0

Sample tx protocol
Withania somnifera
350mg bid
Rhodiola rosea
120mg bid
Dietary interventions to regulate blood sugar
Breathing techniques
Daily exercise routine
Follow-up blood glucose testing
20
8/13/2014
How to Incorporate Adrenal Stress Testing

Into Your Practice
61
Adrenal Stress Index (ASI) Panel

Screening test
Cushings, Addisons, CAH
Sleep disturbances
Fatigue
Blood sugar dysregulation
Depression, ADHD, other conditions
Allows for customized treatment plan
Evaluate treatment efficacy
Increase patient compliance
Information
Our Medical Support staff is available 8:00am
5:00pm PST, Monday through Friday, to answer
your questions about test recommendations,
results interpretation, and treatment strategies.
We have a team of multidisciplinary doctors who
are proficient in both conventional and alternative
medicine available for consultation.
Please call 1-800-878-3787 to speak with a member
of our Medical Support team.
63
21
8/13/2014
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8/13/2014

Adrenal Stress Index

Functional testing and

AUGUST 2014 WEBINAR.

2014 Diagnos-Techs, Inc. All rights reserved.

Stress and the Adrenal Glands

2014 Diagnos-Techs, Inc. All rights reserved.

Circadian Rhythm of Cortisol

2014 Diagnos-Techs, Inc. All rights reserved.

2014 Diagnos-Techs, Inc. All rights reserved.

Cortisol- Physiologic effects

Helps to activate glycogen phosphorylase

2014 Diagnos-Techs, Inc. All rights reserved.

Cortisol- Physiologic effects

Inhibits collagen formation

2014 Diagnos-Techs, Inc. All rights reserved.

Cortisol- Physiologic effects

Inhibits TNF-, IL-12 and IFN- production

2014 Diagnos-Techs, Inc. All rights reserved.

2014 Diagnos-Techs, Inc. All rights reserved.

General Adaptation Syndrome (GAS)

2014 Diagnos-Techs, Inc. All rights reserved.

General Adaptation Syndrome

Maladaptive Stress Syndrome4

2014 Diagnos-Techs, Inc. All rights reserved.

General Adaptation Syndrome

2014 Diagnos-Techs, Inc. All rights reserved.

General Adaptation Syndrome

2014 Diagnos-Techs, Inc. All rights reserved.

General Adaptation Syndrome

2014 Diagnos-Techs, Inc. All rights reserved.

General Adaptation Syndrome

Conditions Associated with MSS-2

2014 Diagnos-Techs, Inc. All rights reserved.

General Adaptation Syndrome

2014 Diagnos-Techs, Inc. All rights reserved.

General Adaptation Syndrome

Conditions Associated with MSS-3

2014 Diagnos-Techs, Inc. All rights reserved.

Altered cortisol curve

2014 Diagnos-Techs, Inc. All rights reserved.

2014 Diagnos-Techs, Inc. All rights reserved.

Flattened diurnal cortisol rhythms

2014 Diagnos-Techs, Inc. All rights reserved.

2014 Diagnos-Techs, Inc. All rights reserved.

Chronic Fatigue Syndrome (CFS)

2014 Diagnos-Techs, Inc. All rights reserved.

Attention Deficit Hyperactivity Disorder (ADHD)

Possible abnormalities in HPA axis function in some

2014 Diagnos-Techs, Inc. All rights reserved.

Autism Spectrum Disorders (ASD)

Significantly lower serum concentrations of cortisol

2014 Diagnos-Techs, Inc. All rights reserved.

Autism Spectrum Disorders (ASD)

2014 Diagnos-Techs, Inc. All rights reserved.

2014 Diagnos-Techs, Inc. All rights reserved.

2014 Diagnos-Techs, Inc. All rights reserved.

Adrenal Stress Index (ASI)

2014 Diagnos-Techs, Inc. All rights reserved.

Adrenal Stress Index (ASI)

DHEA/DHEA-S (pooled value)

2014 Diagnos-Techs, Inc. All rights reserved.

2014 Diagnos-Techs, Inc. All rights reserved.

2014 Diagnos-Techs, Inc. All rights reserved.