adrenal dysfunction ii - educational review systems · review clinically relevant case studies ......

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HPA AXIS & ADRENAL DYSFUNCTIONHPA AXIS & ADRENAL DYSFUNCTIONAN EVIDENCE BASED DISCUSSION OFAN EVIDENCE BASED DISCUSSION OF

TREATMENT MODALITIESTREATMENT MODALITIES

Lena D. Edwards, MD, FAARM

Internal MedicineAnti-Aging and Regenerative Medicine

OBJECTIVES OF DISCUSSIONOBJECTIVES OF DISCUSSION

Discuss the importance of lifestyle modification and institution of stress reduction techniques as an essential component of treatment

Discuss the effects of sleep disturbances on adrenal dysfunction and review viable treatment options

Review the vitamins, minerals, and other supplements beneficial in the treatment of adrenal dysfunction

Discuss the evidence for and clinical utility of adrenal and multiglandular extracts

Define the term plant adaptogen and discuss some of the most well studied adaptogens used in treating adrenal dysfunction

Discuss the appropriate use of pharmacologic agents in the treatment of adrenal dysfunction

Review clinically relevant case studies

DEFINITION OFDEFINITION OFADRENAL DYSFUNCTIONADRENAL DYSFUNCTION

The inability of the adrenal glands to produce adequate amounts of stress hormones

in a normal diurnal pattern, whether primarily or secondarily in responsewhether primarily or secondarily, in response

to allostatic load ultimately resulting in

Proposed Progression to Adrenal Proposed Progression to Adrenal DysfunctionDysfunction

Hypercortisolism

Hypocortisolism

SUMMARY OF TREATMENT MODALITIESSUMMARY OF TREATMENT MODALITIES Stress reduction techniques Sleep hygiene Lifestyle modification Vitamins and minerals Glandular extracts Glandular extracts Plant adaptogens Pharmacologic therapy

STRESS REDUCTION TECHNIQUESSTRESS REDUCTION TECHNIQUES

Identify and eliminate stressors Adjust attitude or response to the stressor Eat regular meals; adequate mastication Gentle exercise

Tai Chi Yoga Pilates

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STRESS REDUCTION TECHNIQUESSTRESS REDUCTION TECHNIQUES

Spirituality/Religiousity Dietary modification Meditation Adequate sleep Rest & Relaxation

Frequent daily breaks

MEDITATIONMEDITATION

Reduces stress induced cortisol secretion Increases levels of brain derived neurtrophic factor

thereby conferring neuroprotection Reduces levels of Interleukin-6 Improved cortisol release patterns and immune

function improved quality of life and stress tolerance in breast and prostate cancer survivors

Annals of the New York Academy of Sciences. 1172:63-9, 2009 Aug.

Psychoneuroendocrinology. 34(1):87-98, 2009 Jan.

Brain, Behavior, & Immunity. 21(8):1038-49, 2007 Nov.

MEDITATIONMEDITATION

Reduces risk of CVD in postmenopausal women Positively impacts patients with inflammatory

bowel diseases Improves HPA axis regulation Improves HPA axis regulation

Annals of the New York Academy of Sciences. 1032:211-5, 2004 Dec.Seminars in Gastrointestinal Disease. 10(1):14-9, 1999 Jan.

Physiology & Behavior. 64(3):311-5, 1998 Jun 1.

DIETARY MODIFICATIONDIETARY MODIFICATION

Ingest good quality protein Combine unrefined carbohydrates (whole grains)

with good quality protein and oils (nuts and seeds) at most meals. U ld d il li l filb fl Use cold pressed oils - olive, walnut, filbert, flax

Emphasize vegetables (alkaline foods) Small frequent meals throughout the day

DIETARY MODIFICATIONDIETARY MODIFICATION

Avoid the following Hydrogenated fats Caffeine Chocolate

R fi d b h d Refined carbohydrates Junk foods Allergenic or sensitive foods

Digestive aids may be needed by most until recovery is more complete

Allow unrefined salt to be added

TREATMENT OF ADRENAL DYSFUNCTION

SLEEP HYGIENESLEEP HYGIENE

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SLEEPSLEEPCONSEQUENCES OF SLEEP DEPRIVATIONCONSEQUENCES OF SLEEP DEPRIVATION

J Clin Endocrinol Metab. 90(5): 3106-3114, 2004.

Am J Physiol Endocrinol Metab. 295: E380-384, 2008.

Sleep

Sleep deprivation results in: Activation of the sympathetic nervous system Dysregulation and activation of the HPA axis

Nocturnal CRH hyperreactivity

SLEEPSLEEPCONSEQUENCES OF SLEEP DEPRIVATIONCONSEQUENCES OF SLEEP DEPRIVATION

yp y Sleep fragmentation or nocturnal awakenings cause

increased nocturnal pulsatile release of cortisol Subsequent HPA axis dysregulation induces

hypercortisolism which further fragments sleep

J Clin Endocrinol Metab. 90(5): 3106-3114, 2004.Am J Physiol Endocrinol Metab. 295: E380-384, 2008.

INSOMNIAINSOMNIA


Behavioral modification Sleep hygiene

Regular sleep-wake cycle

Stress reduction techniques

TREATMENT OF INSOMNIATREATMENT OF INSOMNIA

Stress reduction techniques Avoid prescription sleep aides and alcohol Bedroom is to be used for sleep and intimacy only Avoid third shift work

5-HTP (25 to 300 mg QHS)

Melatonin (0.5 to 6 mg (SR better) 30 to 60 minutes before bedtime)

SLEEP DISTURBANCESSLEEP DISTURBANCESNONNON--PHARMACOLOGIC TREATMENT OPTIONSPHARMACOLOGIC TREATMENT OPTIONS

Seditol (365 to 730 mg QHS)

Phosphatidylserine (300 mg 60 to 90 minutes before bedtime)

L-Theanine (100 to 200 mg 30 to 60 minutes before bedtime)

Calming herbs (Valerian root, Chamomile, Hops, Passion flower)

Magnesium Glycinate (400 to 800 mg QHS)

•Suppress amygdala driven CRH activation

•Resets HPA axis upon discontinuation

GlucocorticoidReceptor Antagonists

(Mifepristone)

A g t t l hi lMineralocorticoid

PHARMACOLOGIC TREATMENTS PHARMACOLOGIC TREATMENTS FOR INSOMNIAFOR INSOMNIA

•Augments nocturnal hippocampalsuppression of CRH

Mineralocorticoidagonists

(Fludricortisone)

•Antagonizes effects of CRHCRH-R1 antagonist

(Antalarmin)


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OBSTRUCTIVE SLEEP APNEAOBSTRUCTIVE SLEEP APNEA

Affects 1 in every 22 people in this country…

approximately 12 million and rising

Intermittent

Sleepfragmentation

Recurrentb l


HPA axis activation

hypoxiacerebral arousals


NocturnalHypercortisolism

Lack of cortisolsuppression to

ACTH

Impaired cortisolrelease pattern

Therapy with CPAP Improvement in nocturnal salivary hypercortisolism Reduction in SNS induced tachycardia Improved cortisol suppression after low dose

d th


dexamethasone Decreases nadir cortisol concentrations Reversed dampening of normal nocturnal HPA axis

oscillation

Am J Physiol Endocrinol Metab. 295: E380-384, 2008.Metab Clin & Experimental. 58: 848-853, 2009


VITAMINS AND MINERALSVITAMINS AND MINERALS

VITAMINS AND MINERALSVITAMINS AND MINERALS

Magnesium (400 mg daily, Glycinate or Citrate form) Vitamin C (2 to 5 grams daily) B Vitamins (especially B5 up to 1.5 grams daily) Selenium

Zi Zinc Calcium (800 to 1000 mg daily) Copper Sodium Manganese Vitamin E with mixed tocopherols (800 IU daily)

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MAGNESIUMMAGNESIUM

Primary functions of magnesium: Calcium antagonist Membrane function Energy transfer

Critical component of over 300 enzymatic pathways

MAGNESIUMMAGNESIUM

Intense physical stress increases magnesium loss via bodily fluids

Intense physical activity, cell membranes’ permeability increases increasing magnesium requirement

Serum inadequate measure of total body magnesium since 99 7% of total body magnesium in located in the since 99.7% of total body magnesium in located in the bones and cells

Increased supplies of magnesium increase insulin sensitivity to glucose

Magnesium homeostasis exerts an anti-stress effect

Cardiovascular Drugs and Therapy. 12: 197-202, 1998

MAGNESIUMMAGNESIUM

GABA (A) agonist effects on sleep and nocturnal hormone secretion of melatonin, growth hormone, and cortisol

NMDA antagonistic effects on sleep and nocturnal hormone secretion of melatonin, growth hormone, and cortisolR d t l ACTH ti Reduces nocturnal ACTH secretion

Supplementation prevents excessive post-exercise hypercortisolism

Psychopharmacology. 137(3):247-52, 1998Cardiovascular Drugs and Therapy. 12: 197-202, 1998

.

MAGNESIUMMAGNESIUM

Psychopharmacology. 137(3):247-52, 1998Cardiovascular Drugs and Therapy. 12: 197-202, 1998

.

VITAMIN C (VITAMIN C (ASCORBATEASCORBATE))

Vitamin C required for norepinephrineproduction

Organ with highest concentration of vitamin C

VITAMIN C (VITAMIN C (ASCORBATEASCORBATE))

Both the adrenal medulla and the adrenal cortex accumulate high levels of ascorbate

ACTH stimulation results in adrenal release of ascorbate

During periods of stress, adrenal glands release vitamin C which has been found to have primarily a vitamin C which has been found to have primarily a local, rather than systemic, effect to: Increase nitric oxide production or synthesis to

promote cortisol release Modifies ACTH receptor sensitivity Local vasodilation to increase cortisol delivery

Endocrine Research. 30(4): 871-875, 2004Am J Clin Nutrition. 86: 145-149, 2007

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VITAMIN C (VITAMIN C (ASCORBATEASCORBATE)) 2001 study in ultramarathon runners

“Supplementation with vitamin C may blunt the adaptive

mobilization of this vitamin from the adrenals during

exercise-induces oxidative stress and may be associated

with an enhancement of the acute phase protein

response and attenuation of the exercise-induced

increase in serum cortisol.”

Int J Sports Med. 22(2): 120-126, 2001

OTHER NUTRIENTSOTHER NUTRIENTS

Curcumin Inhibits ACTH stimulation of cortisol release Inhibits Angiotensin II stimulation of cortisol release

Thiamine Prevents post-surgical hypercortisolemia

Pantothenol Increases urinary excretion of 17-hydroxyketo

steroids Increase glucocorticoid production

Journal of Natural Products. 72(8):1533-7, 2009Bollettino-Societa Italiana Biologia Sperimentale. 57(18): 1869-72, 1981


GLANDULAR EXTRACTSGLANDULAR EXTRACTS

GLANDULAR EXTRACTSGLANDULAR EXTRACTS

Invented and made commercially available in 1931.

Heavily researched in the 1940’s as potentially ff ti f ltit d i d d d l t i effective for altitude induced adrenal stress in

military pilots Use does not decrease endogenous hormone

production May assist in adrenal gland self repair

ADRENAL GLANDULAR EXTRACTSADRENAL GLANDULAR EXTRACTS

Contain small amounts of cortisone and other adrenal hormones

Preparations may also contain peptides which promote endogenous adrenal hormone production

Multi-glandular extracts Contain adrenal, hypothalamus, pituitary, thyroid,

and/or gonadal extracts Do not use as monotherapy or as alternative to

standard medical treatment

STUDIES ON CLINICAL EFFICACY OF STUDIES ON CLINICAL EFFICACY OF GLANDULAR EXTRACTSGLANDULAR EXTRACTS

Porcine thyroid glandular extracts may potentiate ACTH induced corticosterone production (Endocrinologia Japonica. 31(4):443-9, 1984 Aug. )

f 19 0 Administration of adrenal cortical extracts in a 1950 study showed (Blood. 5(8):732-41, 1950 Aug.) : Reduced eosinophils and lymphocytes in normal

patients Reduction in lymphocytosis in patients with infectious

mononucleosis

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STUDIES ON CLINICAL EFFICACY OF STUDIES ON CLINICAL EFFICACY OF GLANDULAR EXTRACTSGLANDULAR EXTRACTS

MANY clinical studies were conducted in the 1950’s in Russia, Germany, and Italy

Some clinical utility of adrenal cortex preparations:S Surgery

Tuberculosis Psoriasis Diabetes Various inflammatory diseases in children


PLANT ADAPTOGENSPLANT ADAPTOGENS

ADAPTOGENSADAPTOGENS: DEFINITION: DEFINITION

“Compounds that increase the ability of an organism to adapt to environmental a o ga s to adapt to e o e tafactors and to avoid damage from such

factors”

Panossian et al. Phytomedicine. 6: 147-155. 1999.

ADAPTOGENSADAPTOGENS: OVERVIEW: OVERVIEW

Promote physiological resistance of organism to stress, fatigue, trauma, and anxiety

Used for thousands of yearsin ancient Chinese & Indian medicine

Research on adaptogens began in the 1940’s

Panossian et al. Phytother Res. 2005; 19: 819-838Berdyshev V, Breckmann II (ed). Int Collection of Scientific Papers, Issue 2, Vladivostok,

Dalnauka, 105-117

ADAPTOGENSADAPTOGENS: OVERVIEW: OVERVIEW

Up-regulate hypofunctional stress responses Down-regulate hyperfunctional stress responses Maintain adaptive state of homeostasis Many contain polysaccharides which have been Many contain polysaccharides which have been

shown to enhance immune function

Panossian et al. Phytother Res. 2005; 19: 819-838Winston & Maimes. “Adaptogens: Herbs for Strength, Stamina, and Stress Relief”. Healing

Arts Press. 2007Berdyshev V, Breckmann II (ed). Int Collection of Scientific Papers, Issue 2, Vladivostok,

Dalnauka, 105-117

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ADAPTOGENSADAPTOGENS: ALL ABOUT BALANCE: ALL ABOUT BALANCE

Adrenalineswitch on hormone

Panossian et al. Phytother Res. 2005; 19: 819-838

Cortisol

Adaptogen

Nitric Oxide

•Switch off hormone•Protects against over-reaction

•Hormone biosynthesis•Modulates end organ hormoneeffects

ADAPTOGENSADAPTOGENS: MECHANISM OF ACTION: MECHANISM OF ACTION

Stress agonist effects on HPA axis regulation Stimulate the nervous system in a different

manner than traditional stimulants Regulation of elements of the stress system Modulate stimulus-response coupling

C l k di f Control key mediators of stress Hsp70* JNK1(c-Jun-N-terminal protein kinase) Forkhead Box O transcription factor DAF-16 Cortisol Nitric oxide

Panossian et al. Phytother Res. 2005; 19: 819-838Panossian et al. Curr Clin Pharm. 2009; 4(3): 198-219.


Adaptogens cause up regulation and stress mimetic effects on the stress sensor protein mimetic effects on the stress sensor protein

Panossian et al. Curr Clin Pharm. 2009; 4(3): 198-219.


Cell survival and apoptosis

Inhibits expression of nitric

Panossian et al. Curr Clin Pharm. 2009; 4(3): 198-219.

Inhibits expression of nitric oxide synthase II gene

prevents stress induced increase in NO production

Directly interacts with glucocorticoid receptors

ADAPTOGENSADAPTOGENS: MODES OF : MODES OF ADMINISTRATIONADMINISTRATION

Single dose application Important in situations that require a rapid response to

strain Effects are associated with the sympatho-adrenal-

tsystem Increases levels of

CatecholaminesNeuropeptides ATPNitric oxideEicosanoids


ADAPTOGENSADAPTOGENS: TYPES OF : TYPES OF ADMINISTRATIONADMINISTRATION

Repeated dose application Stress positive effect in a manner similar to physical

exercise leading to increased endurance and stamina Does not inhibit the stress response but rather acts as a Does not inhibit the stress response but rather acts as a

stress agonist to induce adaptive responses to stress Particularly useful in sports medicine by increasing

physical endurance and promoting enhanced recovery

Panossian et al. Phytother Res. 2005; 19: 819-838Panossian et al. Phytomedicine. 1999; 6: 147-155Lupandin. Fiziologia Cheloveka. 1990; 16: 114-119

Bucci. Am J Clin Nutr. 2000; 72: 624S-636S

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ADAPTOGENSADAPTOGENS: SUBCLASSES: SUBCLASSES

Triterpenes

Saponins

Dammarane Curcurbitacins

Phytosterols

Beta-sitosterol

Phytoecdysteroid

20-ecdysone Turkesterone


Phenylpropanes

Flavinoids

Glucopyranoside Prenylatedflavonoids

Flavanglycosides

Lignans

Schizandrin Sesamin Syringaresinol


Oxylipins

Hydroxylatedfatty acids

Licorice Glycyrrhiza

ADRENAL ADRENAL ADAPTOGENSADAPTOGENS

Ashwaganda Rhodiola PanaxGinseng Licorice

Cordyceps Relora Maca Holy Basil

Bacopa Schisandra Astragalus Siberian Ginseng

ADAPTOGENSADAPTOGENS: : ASHWAGANDAASHWAGANDA

Withania somnifera Cardioprotective Augmentation of endogenous anti-oxidant

productionR d t ll lif ti Reduces tumor cell proliferation

Dose related anti-stress activity Stimulate thyroid function Free radical scavenger Neuroprotective

ADAPTOGENSADAPTOGENS: : ASHWAGANDAASHWAGANDA

Immunomodulatory Rejuvenating Used as an adjunct in several CNS disorders

(Parkinson’s, cerebral ischemia, Alzheimer’s disease, tardive dyskinesia)

Adjunctive utility in drug addiction Completely safe…no adverse side effects

reported Typical dose is 3 to 6 grams daily

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ADAPTOGENSADAPTOGENS: HOLY BASIL: HOLY BASIL

Ocimum Sanctum Also known as Indian Ginseng Stimulates insulin secretion Protects pancreatic beta cells Antioxidant Reduces lipid peroxidation Free radical scavenger Cardioprotective during

chronic stress

ADAPTOGENSADAPTOGENS: HOLY BASIL: HOLY BASIL

Improves physical endurance Modulates adrenal corticosterone levels Lowers cholesterol ImmunomodulatorImmunomodulator Anti-bacterial activity against Neisseria gonorrhea Possible antidepressant activity Typical dose 400 – 800 mg BID (std. to 1% ursolic

acid)

ADAPTOGENSADAPTOGENS: : RHODIOLARHODIOLA

Rhodiola rosea Also known as Golden/Arctic Root Native to the Himalayas, Parts of

Europe, Artic Regulates brain function Improves mental performance Improves ability to concentrate May help patients with stress induced mental and

physical fatigue

Olsson et al. Planta Med. 2009; 75: 105-112


Improves physical endurance Radioprotective Anti-cancer

Anti oxidant Anti-oxidant Superoxide ion radical scavenger Improves attention, cognition, and mental

performance in fatigue and chronic fatigue syndrome

Arora et al. Mol Cell Biochem. 2005; 273(1-2): 209-23.


Improves visual acuity Prevents stress induced adrenal catecholamine

depletion Reduces levels of circulating C-reactive protein

I fl l l d i i f i d Influences levels and activity of monoamines and opioid peptides

250 mg QD to TID (3-5% rosavin + 1-3% salidroside)


ADAPTOGENSADAPTOGENS: : SCHIZANDRASCHIZANDRA

Generates alterations in the basal levels of nitric oxide and cortisol in blood and saliva with subsequent effects on the blood cells, vessels and CNS

Increases physical work capacity and enduranceI t l f ti t l it d Improves mental function, mental capacity, and mental accuracy

Reduces fatigue, muscle pain, shortness of breath after extreme physical activity

Pouisson et al. J Ethnopharm. 2008; 118: 183-212Pouisson et al. Phytother Res. 2005; 19: 819-838

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ADAPTOGENSADAPTOGENS: : SCHIZANDRASCHIZANDRANumerous clinical trials have demonstrated the efficacy of

Schizandra in:

Mood disorders

Asthenia Neuralgic disorders Alcoholism Alcoholism Psychiatric disorders

NeurosisPsychogenic depressionAstheno-depressive statesSchizophrenia

Pouisson et al. J Ethnopharm. 2008; 118: 183-212


hypotension and cardiotonic disorders Infectious diseases

Influenza chronic sinusitisOtitisNeuritisOtosclerosis Pneumonia


Radioprotecion of the fetoplacental system of pregnant women

Allergic dermatitis Gastrointestinal diseases

Gastric hyper- and hypo-secretion Chronic gastritis Gastric and duodenal ulcers Wound healing Trophic ulcers

Pouisson et al. J Ethnopharm. 2008; 118: 183-212

ADAPTOGENSADAPTOGENS: : MACAMACA

Lepidium perumianum Employed by the Incas and other cultures in the

A d i f it h di i d f tilit Andean region for its aphrodisiac and fertility enhancing powers

Improves sperm production and motility independent of hormones

Eliminates variations in homeostasis induced by stress

Lopez-Fando et al.Phytother Res, June 1, 2004; 18(6): 471-4.

ADAPTOGENSADAPTOGENS: : MACAMACA

Reduces stress induced adrenal hyperplasia Eliminates stress induced ulcers Reduces corticosterone levels Reduces stress induced hyperglycemia Dose: 5-10 grams BID dried powder

ADAPTOGENSADAPTOGENS: LICORICE ROOT: LICORICE ROOT

Glycyrrhiza glabra Inhibits 11 beta hydroxysteroid Dehydrogenase thereby

blocking cortisol’s transformation into cortisone Higher doses reduce testosterone levels in PCOS Improves memory (decreases Ach’ase) Antibacterial Inhibits tumor cell angiogenesis Antidepressant Adrenocorticoid-like activity

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ADAPTOGENSADAPTOGENS: LICORICE ROOT: LICORICE ROOT

Protects mitochondrial function during periods of oxidative stress

Lowers cholesterol Anti-fungal and anti-viral Anti-ulcer Anti-ulcer Decreases abdominal adiposity Reduces adrenal stress Dose 2 – 3 grams daily (200-300 mg of

Glycyrrhiza); ½ tsp solid extract 8am and ¼ tsp at noon

ADAPTOGENSADAPTOGENS: GINSENG: GINSENG

Normalizes cortisol levels Immunostimulant Anti-fatigueg Prevents oxidative stress Improves cognitive performance Anti-depressant Suppresses inflammation and DNA damage

ADAPTOGENSADAPTOGENS: GINSENG: GINSENG

Korean ginseng most potent followed by American ginseng and Siberian ginseng

Use caution in hypertensive patients Use caution in patients on medications for

diabetes, cardiac glycosides, and stimulants For chronic fatigue, 2-4 grams TID Typical dose 2- 8 grams of dried root

daily


HERBAL SUPPLEMENTSHERBAL SUPPLEMENTS

HERBAL SUPPLEMENTSHERBAL SUPPLEMENTS

Berberine

TheanineMelatonin

Seditol

Phosphatidylserine

5-HTP

THEANINETHEANINE

Amino acid extracted from green tea leaves Increases alpha brain wave activity Inhibits LDL oxidation Counteracts stimulatory effects of caffeine Reduces blood pressure

Altern Med Rev. 2005; 10(2): 136-138

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THEANINETHEANINE

Influences the secretion and function: Dopamine Serotonin

Exerts anti-stress effects during an acute stress challenge

Dose dependant presence of brain alpha waves within 40 minutes of ingesting 200 mg

Kimura et al. Biol Psych. 2007; 74: 39-45Kobayashi et al. Nippon Nogeikagaku Kaishi. 1998; 72: 153-157

Altern Med Rev. 2005; 10(2): 136-138

PHOSPHATIDYLSERINEPHOSPHATIDYLSERINE

Ubiquitous phospholipid Only phospholipid in animal cells containing an amino

acidacid Found on the inner leaflet of cell membranes Important in cellular communication and excitability Induces release of acetylcholine, dopamine, and

norepinephrine Dampens stress induced ACTH and cortisol release

Sports Medicine. 36(8):657-69, 2006.

PHOSPHATIDYLSERINEPHOSPHATIDYLSERINE

Supplementation improves mood and stress resistance to acute stressor

Helps prevent chronic stress induced memory loss Blunts chronic stress induced HPA axis activation

Stress. 7(2):119-26, 2004 Jun.

Alternative Medicine Review. 4(4):249-65, 1999 Aug.

Alternative Therapies in Health & Medicine. 4(6):38-43, 1998 Nov.

European Journal of Clinical Pharmacology. 42(4):385-8, 1992.


PHARMACOLOGIC AGENTSPHARMACOLOGIC AGENTS

CORTISOLCORTISOL VS. HYDROCORTISONEVS. HYDROCORTISONE

Hydrocortisone

C2121HH3030OO55C21H28O5

HYDROCORTISONEHYDROCORTISONE Physiologic doses (15 mg) do not increase levels

beyond normal levels Physiologic doses do not cause bone loss, adrenal

suppression, or immune suppression Typical dosing schedule:

10 to15 mg in am 5 to 10 mg at noon 2.5 to 5 mg late afternoon

Holtorf KH. J Chronic Fatigue Syn. 2008; 14(3):1-14

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HYDROCORTISONEHYDROCORTISONE

Improves cellular and humoral immunity Therapeutic trial of low dose hydrocortisone should be

considered in patients with signs and symptoms of adrenal dysfunction, even if test results ‘normal’.

Has been shown to be effective treatment in patients with CFS and fibromyalgia


Cleare AJ. The Lancet. 1999; 353: 455-458

HYDROCORTISONEHYDROCORTISONE

Holtorf and colleagues conducted multi-center trial of 4000 consecutive patients. Conclusion…

“Supplementation has been shown to be a beneficial

and safe alternative with little of no risk as part of a p

multi-system integrative treatment protocol in patients

with fibromyalgia and chronic fatigue syndrome [related

to adrenal dysfunction].”


FLUDROCORTISONEFLUDROCORTISONE

Mineralocorticoid and glucocorticoid activity Can be used to temporarily treat orthostatic

hypotension Potential side effects: hypertension edema Potential side effects: hypertension, edema,

headaches

DHEADHEA

Use caution in patients with low cortisol since it can further lower cortisol levels. Counter-regulatory hormone to cortisol

Typical dose in women 2.5 to 10 mg daily and 25 to 50 mg daily in men

Use 7-keto form in patients who are not testosterone and/or estrogen deficient

DHEADHEA

Has been shown to prevent diabetes, hepatitis, and colon cancer (J Steroid Biochem Mol Biol, Jun 1, 2003; 85(2-5):

469-472)

R l t l b h l f l i t i Replacement may also be helpful in auto-immune diseases, insulin resistance, osteoporosis, and atherosclerosis (Evid Based Compl Alter Med. 2005; 2(3): 413-419)

ADRENAL DYSFUNCTION

CASE STUDIESCASE STUDIES

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CLINICAL CASES: CASE I

66 year old postmenopausal female Symptoms

• Exhaustion• Difficulty losing weight• Dyspepsia• Dyspepsia• Polyarthralgia• Impaired memory• BLE edema• “Pain all over”• Depression• Insomnia

IMPORTANT ASPECTS OF TREATMENTIMPORTANT ASPECTS OF TREATMENT


Past Medical History• Type 2 DM• Asthma• Hypertension

Medications Advair Singulair Mirapex

• Hyperlipidemia• Fibromyalgia• Hypothyroidism• Restless leg syndrome• Esophageal dysmotility• Depression• Chronic insomnia

Ambien Zocor Cymbalta Lexapro Flexeril Kadipex


0.5

0.6

0.7

0.8

0.9

0

0.1

0.2

0.3

0.4

morning noon late day night

Control Patient

CLINICAL CASES: CASE II

41 year old pre-menopausal female Clinical symptoms

FatigueDiffi lt l i g ightDifficulty losing weight

Diffuse joint painDepression Anxiety Irregular menstrual cycles

CLINICAL CASES: CASE II

Past medical history Seasonal allergies

On no prescription medications or supplements

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CLINICAL CASES: CASE II CLINICAL CASES: CASE III

51 year old obese male Clinical symptoms

Daytime fatigueD d dDepressed mood

Impaired concentrationDecreased staminaDiminished libido Insomnia (initiation and propagation)

CLINICAL CASES: CASE III

Past medical history Insulin resistance Dyslipidemia Hypertension

Medications Venlafaxine Metformin Aspirinype te s o

Depression Erectile dysfunction

sp Lipitor Lunesta

CLINICAL CASES: CASE III

CLINICAL CASES: CASE IV

30 year old female Clinical symptoms

• Fatigue• Depressionp• Insomnia• Weight gain• Impaired memory

CLINICAL CASES: CASE IV

Past medical history Unremarkable

Medications YAZ Claritin

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CLINICAL CASES: CASE IV CLINICAL CASES: CASE V

62 y.o. postmenopausal female Symptoms:• Fatigue• Difficulty losing weight• Polyarthralgia• Polyarthralgia• Depression• Anxiety• Insomnia• Sugar cravings• Dyspepsia

CLINICAL CASES: CASE V

Past medical history Degenerative joint

disease Depression

Medications Mobic Citalopram Omeprazole

GERD/Hiatal hernia TAH + BSO R. hip replacement Obesity Metabolic syndrome

Premarin Ambien

CLINICAL CASES: CASE V

adrenal dysfunction ii - educational review systems · review clinically relevant case studies ......

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