Adrenal Stress

8/13/2014

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2014 Diagnos-Techs, Inc. All rights reserved.

Adrenal Stress Index

Functional testing and

applications

Presented by

Carrie McMillin, ND

AUGUST 2014 WEBINAR.


Objectives

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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

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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

HYPOGLYCEMICSTATES

SYMPATHETIC RESPONSE

TISSUE DAMAGE Inflammation Illness Infection

MENTAL AND EMOTIONAL STRESS Anxiety Depression

CIRCADIAN RHYTHM Sleep Pattern Light-dark Exposure Meal Times

ACTH

Cortisol

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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

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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

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General Adaptation Syndrome

More recently proposed model of adrenal stress response based on Selyes work

MSS-0

MSS-1

MSS-2

MSS-3

Maladaptive Stress Syndrome4



Healthy, well-adapted stress response

Varies between hypovigilance and hypervigilance

Level of vigilance properly regulated by amount of epinephrine and cortisol produced4

MSS-0



Correlates with the alarm phase

Acute excess release of cortisol and epinephrine

Considered maladaptive when the fight or flight response is not appropriate4

MSS-1

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Suppression phase

Chronically elevated cortisol

Results in increased levels of epinephrine

Immune and inflammatory responses are suppressed

Adrenal androgens often elevated4

MSS-2



Increased susceptibility to mycotic infections

Depression

OCD

Anorexia nervosa

Panic disorder

Gastritis

Hyperlipidemia

Conditions Associated with MSS-2 Atherosclerosis

Insulin Resistance

Metabolic syndrome

Type II diabetes

Osteoporosis

Neoplasia

Dementia

Hirsutism and alopecia in women4



Exhaustion phase

Deficient glucocorticoid production

Decreased production of adrenal androgens

Decreased production of mineralocorticoids

Episodic increases in epinephrine4

MSS-3

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Hypotension

Functional hypoglycemia

Chronic fatigue syndrome

Fibromyalgia4

Conditions Associated with MSS-3 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

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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

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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

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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

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Adrenal Stress Index (ASI)

4 saliva collection vials

Cotton in each vial

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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

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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

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Gliadin sIgA

Monitoring gluten free diet

Prioritizing foods for elimination trial


Interpreting Laboratory Findings: Case Studies

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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

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22 y/o Female

Irregular menses


Nonclassical Congenital

Adrenal Hyperplasia (CAH)

Genetic deficiency of either 21-hydroxylase or 11-hydroxylase

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

17OH-progesterone

11-deoxycortisol

21-hydroxylase

11-hydroxylase 11-deoxycortisol

Cortisol


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

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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

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Case 2- 34 y/o Male

ADHD workup

DSM criteria- Consider adult manifestations Hyperactivity symptoms:

Restlessness, verbosity, tendency toward very active jobs

Impulsivity symptoms:

Ending relationships, quitting jobs, more driving violations

Inattention symptoms:

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

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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 2-4mL 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

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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

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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



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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

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How to Incorporate Adrenal Stress Testing Into Your Practice

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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 8:00am5:00pm 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.

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September 11, 2014

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Dr. Brandy Webb

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Adrenal Stress