Adrenal Stress

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Endocrine Stress

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  • 8/13/2014

    1

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    Adrenal Stress Index

    Functional testing and

    applications

    Presented by

    Carrie McMillin, ND

    AUGUST 2014 WEBINAR.

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    Objectives

    2

    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

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    Stress and the Adrenal Glands

    3

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    Steroid Hormone

    Synthesis

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    Circadian Rhythm of Cortisol

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    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

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    Cortisol- Physiologic effects

    Inhibits collagen formation

    Decreases uptake of amino acids in muscle

    Inhibits protein synthesis

    Stimulates secretion of gastric acid

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    Cortisol- Physiologic effects

    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?

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    Steroid Hormone

    Synthesis

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    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

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    General Adaptation Syndrome

    Healthy, well-adapted stress response

    Varies between hypovigilance and hypervigilance

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

    MSS-0

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    General Adaptation Syndrome

    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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    General Adaptation Syndrome

    Suppression phase

    Chronically elevated cortisol

    Results in increased levels of epinephrine

    Immune and inflammatory responses are suppressed

    Adrenal androgens often elevated4

    MSS-2

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    General Adaptation Syndrome

    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

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    General Adaptation Syndrome

    Exhaustion phase

    Deficient glucocorticoid production

    Decreased production of adrenal androgens

    Decreased production of mineralocorticoids

    Episodic increases in epinephrine4

    MSS-3

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    General Adaptation Syndrome

    Hypotension

    Functional hypoglycemia

    Chronic fatigue syndrome

    Fibromyalgia4

    Conditions Associated with MSS-3 Environmental

    sensitivities

    Atypical depression

    Poor stress resistance

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    Altered cortisol curve

    Depression

    PTSD

    Fibromyalgia

    Chronic fatigue

    Attention deficit hyperactivity disorder (ADHD)

    Autism spectrum disorders (ASD)

    Anorexia nervosa5

    Hypo- and hyperthyroidism6

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    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

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    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

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    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

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    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

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    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

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    Diagnos-Techs Adrenal Stress Index Panel

    29

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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

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    17-OH Progesterone

    Produced in zona fasciculata and zona reticularis of adrenal gland

    Important precursor to cortisol

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    Steroid Hormone

    Synthesis

  • 8/13/2014

    12

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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

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    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

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    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

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    Interpreting Laboratory Findings: Case Studies

    38

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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

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    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

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    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

    HR: 72bpm BP: 120/74mmHg T: 98.8F BMI: 30

    PMHx: Tonsillectomy (age 12); chronic otitis

    media

    S: Difficulty concentrating, fatigue w/difficulty

    waking, insomnia, alternating diarrhea and

    constipation

    O: Eczema, acne

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    Case 2- 34 y/o Male

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    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

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    Case 2- 34 y/o Male

    Sample treatment protocol

    Daily exercise routine

    Elimination diet

    Biofeedback

    Withania somnifera

    2mL tid 1:2 fluid extract

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    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

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    Case 3

    19 y/o male

    CC: Fatigue

    HR: 68bpm BP: 116/64mmHg T: 98.2F BMI: 24

    PMHx: Insignificant

    S: Difficulty concentrating, awakes unrefreshed,

    loss of appetite

    O: WNL

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    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

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    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

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    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.

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    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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    Case 4- 42 y/o Female

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    Case 4- 42 y/o Female

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    Case 4- 42 y/o Female

    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

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    Case 4- 42 y/o Female

    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

    61

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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

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    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

    Diagnos-Techs Sample Collection:

    Tips for Success

    Dr. Brandy Webb

    Upcoming Webinars

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