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Supporting the Adrenals

©2016. All Rights Reserved. 1

DisclosureBaylor Rice, RPh, FIACP, is the pharmacist and owner of South River Compounding Pharmacy & Wellness Center. Conflict of interest was resolved through peer review of slide content.

Professional Education Services Group staff have no financial interest or relationships to disclose.


DisclosureThis continuing education activity is managed and accredited by Professional Education Services Group. Neither PESG nor any accrediting organization supports or endorses any product or service mentioned in this activity.


Educational Grant SupportThis continuing education activity is supported by an educational grant from PCCA.


Learning Objectives• At the conclusion of this activity, the

participant will be able to:• Describe the underlying physiology of Adrenal

Fatigue.• Discuss techniques for relieving stress. • Explain various compounding treatment options

and nutritional supplements for the person suffering from Adrenal Fatigue.


Educational objectives• Review adrenal anatomy, physiology and HPA axis

regulation• Understand assessment of adrenal

function• Learn to identify the phases of

adrenal dysfunction • Obtain treatment protocols for

adrenal vitality and health optimization

• Review the definition and role of neurotransmitters• Discuss strategies for treating the symptoms of

neurotransmitter imbalances without prescription medications


Stress and stressors are essential ingredients of an effective, efficient, productive and satisfying life

We need stress (but too much or too little is counter-productive)

R.M. Yerkes and J.D. Dodson 1908


Over-exposure to stress hormonesaccounts for 75%-90% of all primary care visits in the U.S.

Almost all illness is stress-related• Caused by stress• Aggravated by stress• Causes stressLinked to the 6 leading causes of death: heart disease, cancer, lung ailments, accidents, cirrhosis, and suicide#1 reason why people… • Eat poorly • Quit healthy lifestyle programs• Practice substance abuse

(National Institute for Occupational Safety and Health)American Institute of Stress, “America’s #1 health problem.” 12‐16‐01. http://www.stress.org/problem.htm


Stress proneness• “The main stress to the majority of us - most

of the time - is not due to external stimuli but to the pressure of our own suppressed emotions…

• …these suppressed emotions become the primary stressor so that even in a calm external environment we are still subject to chronic internal stress”David Hawkins MD Ph.D Letting Go p 197


It’s not what we have to deal with, it’s how we deal with it that makes all the difference…let’s differentiate between stress and stressor

VERY empowering to distinguish between being a victim to all that is happening outside us, versus being in charge and deciding how to manage one’s internal state regardless of stressors.


1 Sympathetic ALARMResponse (SNS*)

(norepinephrine “noradrenalin”)

AdrenalGlands

Kidneys

Hypothalamus

A healthy stress response is short lived

PituitaryGland

ACTH♦

Perceived Stressor

2. ♦Adrenocorticotrophin hormone

3. †Corticotrophin releasing hormone

1.*Sympathetic Nervous System

Resolution

2

3

Resolution turns off stress response

Facilitates Negative Feedback Loop

Cortisol3


Kyrou I Ann N Y Acad Sci 2006

Continual exposure to stressors is a biochemical event that excites the sympathetic nervous system, putting the entire body on the alert.

An individual’s stressor-tolerance varies based on:• genetics• diet• toxic burden• health status• occupation• lifestyle • social skills• community network• family and friends• human experience


When we exceed our personal threshold of stressor-tolerance we break down.

Everyone’s breakdown is unique…• Digestive upset

• Breathing difficulties

• Cardiovascular

• Physical problems

• Emotional & social challenges

• Mental impairment

• Sleep disorders


Americans are over “working”"Workers in the United States are putting in more hours than anyone else in the industrialized world.“

~ Lawrence Jeff Johnson – the chief labor market economist

CNN. Study: U.S. employees put in most hours. Available at: http://archives.cnn.com/2001/CAREER/trends/08/30/ilo.study/ . Accessibility verified October 3, 2012.


Japan, Belgium and France rank well ahead of us for productivity and working less hours

And yet… we are less efficient and less productive than many industrialized nations


HPA Over-responsiveness

• Excess SNS • Hyper-aroused, hyper-vigilant

– anxious, worried• Elevated cortisol• Belly fat or weight loss• Decreased appetite• Decreased libido• Insomnia• Hypertension, tachycardia• Pain and inflammation

HPA Under-responsiveness

• Excess PSN• Lethargy and fatigue• Apathy, low motivation• Low cortisol• Weight gain• Increased appetite• Hypersomnia – excessive

sleep• Depressed immune activity• Autoimmune disorders• Chronic pain

Pathological symptoms of binary brain imbalance


Over-production (excitatory)• Cushing’s syndrome• Depression & OCD• Diabetes• Anorexia nervosa• Myocardial ischemia,

arrhythmia• Hypertension• Lipid disorders• Childhood abuse• Hyperthyroidism• Depression

Under-production (inhibitory))• Addison’s disease• Seasonal depression• CFIDS and Fibromyalgia• Myocardial infarction• Allergies/Asthma• Rheumatoid arthritis• Post traumatic Stress

Syndrome• Hypothyroidism• Atypical depression• Chronic pain

Conditions linked with over- & under-production of cortisol

B. McEwen. The End of Stress as We Know It. 2002, p.64


Common Adrenal Symptoms

• Fatigue/lack of energy• Energy crashes mid-afternoon• Craving salty food• Craving sugars• Exhausting easily• Decreased sex drive• Sensitive to changes in weather• Dark circles under eyes• Wounds healing slowly• Body tender/sensitive to touch• Feel puffy/swollen all over• Mind racing at bedtime


Role of Cortisol• Cortisol has two modes of operation:

• “Proactive" mode - It promotes coordination of circadian events, such as the sleep/wake cycle and food intake and is involved in processes underlying selective attention, integration of sensory information, and response selection.

• “Re-active" mode - It facilitates our ability to cope with, adapt to, and recover from stress; cortisol promotes learning and memory processes.

Lopen-Duran NL, et al. Hypothalamic pituitary adrenal axis functioning in reactive and proactive aggression in children. J Abnorm Child Psychol. 2009; 37: 169-182. Koolhaas JM, et al. Coping styles in animals: current status in behavior and stress physiology. Neurosci Biobehav Rev. 1999; 23: 925-35.


• With all the negative side-effects, doctors became wary of cortisol use.

• But cortisol is essential for life. It is a normal hormone secreted by the body.

• In physiological doses, when cortisol levels are low, it can greatly improve quality of life.

• “It gave me a life again” 48 yo CFS patient

Cortisol is needed for life


The obvious candidates for hydrocortisone therapy

The “Flat Liners” (hypoadrenia, ICD-10: E27.40) on salivary adrenal testing


Role of DHEA• Throughout our

reproductive years DHEA serves as a “prohormone” for androgens and estrogens

• All the enzymes required to transform DHEA into androgens and estrogens are expressed in a cell specific manner in a large series of peripheral target tissues like the breast, prostate and skin

• This permits the local tissue to make decisions and control the level of sex steroids according to their local needs


Role of DHEA• DHEA has a clear role in

sexual development• For many years scientists thought that DHEA

production in adults functioned only as a precursor reservoir for testosterone and estrogens.

• However, it is now well understood that in adulthood, DHEA can be secreted in response to ACTH stimulation just as cortisol is. Therefore, it also plays a role in the stress response.


Role of DHEA:stress management

• DHEA has been shown to elevate mood, calm emotions and increase alertness. All very important qualities to have during stress.

• It appears that the actions of DHEA during stress may in fact be more on mood than on physical preparedness.

• DHEA helps our mind cope more evenly with stress and helps improve memory.

Xie, L et al. 2006


Roth et al. showed that the lifespan of a person and the serum concentrations of DHEA are positively related. There are also reports suggesting DHEA has…

• Anti-atherosclerotic• Anti-diabetic• Anti-inflammatory • Anti-osteoporotic• Anti-senility functions

DHEA and health


Testing adrenal hormones• Before beginning any treatment protocol on

the adrenal glands a complete history should be taken and testing should be done.

• There are 3 fluids which can be tested:• Saliva• Serum• Urine


Adrenal function testing• Diurnal cortisol = 4 cortisols (AM, noon,

evening, PM)• DHEA… (NOT DHEA-S)


Phases of adrenal gland fatigue


Adrenal Treatment GuidelinesPhase 0 Multivitamin/Multi mineral

Omega 3 EFA’s Consider Vitamin D3, iodine, and probiotics

Phase 1 Phosphorylated serine 100mg TID or when cortisol is elevated Vitamins B5 (500mg), Vit. C (1000mg) TID, B 6 (100mg) BID, E (800iu) QD Melatonin 3-5mg HS if cortisol levels elevated HS Lifestyle modifications: deep breathing, stress management, exercise, optimal

diet, etc.Phase 2 Vitamins B5 (500mg), Vit. C (1000mg) TID, B 6 (100mg) BID, E (800iu) QD

Adrenal glandular and/or herbal adaptogens in AM and Noon Lifestyle modifications: deep breathing, stress management, exercise, optimal

diet, etc.Phase 3 Vitamins B5 (500mg), Vit. C (1000mg) TID, B 6 (100mg) BID, E (800iu) QD

Adrenal glandular and/or herbal adaptogens in AM and noon Hydrocortisone supplementation 5-10mg in AM and 5-10mg at noon Lifestyle modifications: deep breathing, stress management, exercise, optimal

diet, etc.


TreatmentMind-Body-Spirit

• List top ten stressors• Identify and recognize the significant sources of

internalized stress in one’s life.• Unravel underlying fatalistic attitudes and internalized

beliefs which may be unconsciously promoting helplessness and faulty self-talk like ‘there’s nothing I can do about it”

• Cultivates positive healing potential• Opens the door to planning a coping plan which is pro

active


Balanced Cortisol Secretion (Phase 0)

• A balanced adrenal panel has the following properties…• Samples earlier in the day are always higher than samples later in the

day. • Most people’s samples peak at 8am (30 min after waking) and decline

rapidly over the next few hours and then decline more slowly across the day to reach the lowest point around midnight.

• 8am – 18.9nmol/L (14-32)• 12noon – 6.7nmol/L (4-13)• 5pm – 5.5nmol/L (3-7)• 9pm – 3.3nmol/L (1-4)

Hour of Sample Collection

Sal

ivar

y C

ortis

ol

0


• Newborns do not have a diurnal cortisol pattern (any parent could tell you that)

• It develops during the first 12-20 weeks after birth. They also don’t make DHEA.

Newborns

Iwata O, et al. Diurnal cortisol changes in newborn infants suggesting entrainment of peripheral circadian clock in utero and at birth. J Clin Endocrinol Metab. 2012; Nov 12: Epub. Hui XG, et al. Development of the human adrenal zona reticularis: morphometric and immunohistochemical studies from birth to adolescence. Endocrinol. 2009; 203: 241-52.


Teenagers

Matchock RL, et al. Dirunal and seasonal cortisol, testosterone and DHEA rhythms in boys and girls during puberty. Chronobiol Int. 2007; 24: 969-90.Oskis A, et al. Differences between diurnal patterns of salivary cortisol and dehydroepiandrosterone in healthy female adolescents. Stress. 2012; 15: 110-14.

• A teenagers diurnal rhythm shifts by 1-2 hours, with a cortisol awakening response (CAR) at between 9 and 10 am. This may be why it is so hard to get them up in the morning.


HPA axis dysregulation: cortisol elevations or zig zag pattern

• In this situation the cells that secrete CRH become less sensitive to cortisol later in the day rather than early in the morning.

• It is seen more often in depressed individuals. Depressed individuals exhibit increased cortisol secretion in the afternoon.

• Elevated evening cortisol levels are often seen in people with financial difficulties and unemployed individuals.

• It can lead to a change in the sleep wake cycle. People will have difficulty settling down and falling asleep at night and then have trouble waking up in the morning.


“Flatliner” cortisol slopes (AKA: hypoadrenia)

• This is referred to as “A Little bit of Addison’s”.• These slopes have comparatively the least variation in morning to night

cortisol levels.

• Flatter slopes are also associated with exposure to stressful social experiences, chronic fatigue, fibromyalgia, and rheumatoid arthritis.

• (Adam et al. 2001)

• Very low circulating cortisol is associated with debilitating fatigue.

• (Cleare et al. 2003)


Prescription• Tablets are available for oral administration

in three strengths; each tablet contains either 5 mg, 10 mg, or 20 mg of cortisol.

• Inactive ingredients: calcium stearate, corn starch, lactose, mineral oil, sorbic acid, sucrose.


Compounding Options

• HydrocortisoneIRSRTapering

• DHEA• Nutritionals


Potency comparisons• 0.5 mg of dexamethasone = 15 mg cortisol (40x stronger)• In a dexamethasone suppression test usually 1 mg of dex is

given orally (about 30 mg cortisol).• 5 mg prednisone = 20 mg cortisol (4x stronger)• A normal starting dose of prednisone is between 5-60

mg/day.• Multiple sclerosis treatment starts at 200 mg/day and tapers

to 80 mg/day.Cortisol

(hydrocortisone)Prednisone Dexamethasone

20mg 5mg 0.75mg


Metabolism of cortisolShort half-life: 8 to 12 hours

1. Cortisone 2. Cortisol

• Cortisol is metabolized in most tissues, but primarily in the liver to biologically inactive compounds. The half-life of cortisol may be prolonged in patients with hypothyroidism.

• Inactive metabolites are excreted by the kidneys. Negligible amounts are excreted in bile.


Monitoring levels• Monitor patients on cortisol via four salivary

cortisol levels collected throughout the day one month after starting.

• Patients can be instructed to dose as usual the day of testing.

• Discontinue supplementation for 4-5 days prior to testing to assess endogenous levels.

Hour of Sample CollectionS

aliv

ary

Cor

tisol

0


DHEA supplementation does NOT increase cortisol levels!

• DHEA will not increase cortisol levels, it will not strengthen the area of the adrenal glands that makes cortisol (zona fasciculata) and it will not exert a negative feedback on the HP axis.


Dosing of DHEA• The amount of DHEA needed to bring a male with

Addison’s disease into normal physiological range is 50-70 mg (Hunt et al. 2000).

• If you are following physiological (not replacement) doses you would most likely not exceed:• Males – 15-50 mg/day• Females – 5-15 mg/day

• Starting place: 10 mg for males and 5 mg for females.

Hunt PJ, et al . Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial. J Clin Endocrinol Metab. 2000; 85: 4650-6.


Dosing of DHEA

25 mg of DHEA per day given to a man over the age of 41 brings DHEA, androstenedione and estrogen levels into a range seen in 20 year olds.

(Yamada et al. 2006)


DHEA dosing• It can be dosed:

• Orally• Sublingually• Topically• All work well

• Pearl: When DHEA is put into a cream with other hormones such as progesterone and BiEst, DHEA will “out compete” the receptors and and interfere with absorption of other hormones.


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