10/5/2012

1

ClinicalCorrectionforAdrenalandNeurotransmitterImbalances

ErinLommen,NDCEO&AssociateMedicalDirectorLabrixClinicalServices,Inc.Restorative2012

UnderstandthephasesofadrenaldysfunctionastheyrelatetoHPAandneuroendocrineactivity

ReviewHPAaxisandbrainphysiologyasitpertainstotheregulationofadrenalfunction

ObtainanoverviewofPTSDanditsramificationsasabasisforunderstandingroutineclinicalpresentationandtreatment

LearnnewtreatmentprotocolsbasedonadvancedprinciplesandrefineexistingtreatmentapproachesforthesuccessfultreatmentofHPAaxisdysfunctionandneuroendocrineimbalances.

Angina Asthma AutoImmunediseases Alzheimer's Cancer Cardiovasculardisease ChronicFatiguesyndrome DepressionandAnxiety Diabetes(adultonset,typeII) Fibromyalgia

Headaches Hypertension Hormonalimbalances Immunesuppression Irritableboweldisease Inflammatoryboweldisease Menstrualirregularities Premenstrualtension Rheumatoidarthritis Ulcerativecolitis Ulcers

Rheumatoidarthritisisassociatedwithlowcortisollevels.

RA symptomsofpainworseinthemorningandimprovingasthedaygoeson.

Theflatteningoftheirdiurnalrhythmisthoughttoplayaroleinthedisease.

LowdosecortisoltherapyhelpssymptomaticallywithRAandimprovestheslowingoftheprogressionofthedisease.

Stressasariskfactorinthepathogenesisofrheumatoidarthritis.Cutolo M,StraubRH.Neuroimmunomodulation. 2006;13(56):27782.Epub 2007Aug6.

10/5/2012

2

Engaginginamemorytaskactivatestheimmune

systemPassivelywatchingaviolentvideoweakensimmunity

OhioStateUniversityPsychophysiology,SeptemberOctober2001

dramaticallyincreasestheabilityofexogenouschemicalstopassthroughthebloodbrainbarrier.DuringtheGulfWar,Israelisoldierstookadrugtoprotectthemselvesfromchemicalandbiologicalweapons.Thispharmaceuticalagenunderusualcircumstances,isnotexpectedtocrosstheBBB,butresearchersobservedthatwiththestressofwar

Nearly25%ofthesoldierscomplainedofheadaches,nausea,anddizziness(symptomswhichoccuronlyifthedrugreachesthebrain).

HenceanincreasedthepermeabilityoftheBBB...

JournalofAppliedPsychology,October2000

GaryEvansandenvironmentalpsychologistsatCornellfoundthatlowlevelnoiseinopenstyleofficesresultedinhigherlevelsofstress,andlowertaskmotivation.

Fortyexperiencedfemaleclericalworkers(averageage37)wereassignedtoathreehourworkstudy toeitheraquietofficeoronewithlowintensityusualambientofficenoise(includingspeech).

Theworkersinthenoiseinclusiveenvironmentsexperienced:

significantlyhigherlevelsofstress(asmeasuredbyurinaryepinephrine)

made40%fewerattemptstosolveanunsolvablepuzzle,andmadeonlyhalfasmanyergonomicadjustmentstotheirworkstations,comparedtotheircolleaguesinquietoffices.

Thesimulatedopenofficenoiseelevatedworkers'urinaryepinephrinelevels,isindicativeofmotivationaldeficits:Participantswerealsolesslikelytomakeergonomic,posturaladjustmentsintheircomputerworkstationwhileworkingundernoisy,relativetoquiet,conditions.Posturalinvarianceisariskfactorformusculoskeletaldisorder.

Althoughparticipantsinthenoiseconditionperceivedtheirworksettingassignificantlynoisierthanthoseworkingunderquietconditionsdid,thegroupsdidnotdifferinperceivedstress.Pointstopotentialhealthconsequencesoflongtermexposuretolowintensityofficenoise

Evans,GaryW.;Johnson,DanaJournalofAppliedPsychology,Vol.85(5),Oct2000,779783.

Includedinnoiserelatedproblems: highbloodpressure pepticulcers cardiovasculardeaths strokes suicides degradationoftheimmunesystem, impairmentoflearning increaseinaggression decreaseincooperation

NewYorkTimes,March6,1990

SerotoninModulationofSensoryInputstotheLateralAmygdala:DependencyonCorticosterone, JournalofNeuroscience,15November1998,18(22)95299538,GraceEStutzmann,BruceSMcEwenandJosephELedoux

10/5/2012

3

Medicalinsider.com

Hypoadrenia (ICD10255.7billablediagnosis)code

Couldtherebeadditionalconsiderationsforwhatleadstohypoadrenia?

ICD10:F43.1isnotabillablediagnosiscodeandcannotbeusedtoindicateamedicaldiagnosis.

PTSDisamentalhealthconditionthat'striggeredbyaterrifyingevent.

Symptomsmayincludeflashbacks,nightmaresandsevereanxiety,aswellasuncontrollablethoughtsabouttheevent.

DysfunctionoftheHPAaxisinthestressresponsehasbeendocumentedinanumberofpsychiatricdisorders(Loetal.,2008;Pariante andLightman,2008;Sinha,2008),includingPTSD.

10/5/2012

4

Experienceoftraumaorterror responseinvolvedisintensefear,horrororasenseofhelplessness Reliveexperiencesoftheevent,suchashavingdistressingimagesand

memories,upsettingdreams,flashbacksorevenphysicalreactions Attemptstoavoidsituationsorthingsthatremindthemofthetraumatic

eventorfeelasenseofemotionalnumbness feelingasifconstantlyonguardoralertforsignsofdanger,whichmay

makeitdifficulttosleeporconcentrate symptomslastlongerthanonemonth Thesymptomscausesignificantdistressinlifeorinterferewithabilitytogo

aboutyournormaldailytasks Staysawayfromplaces,events,orobjectsthatareremindersofthe

experience Feelingemotionallynumb Feelingstrongguilt,depression,orworry Losinginterestinactivitiesthatwereenjoyableinthepast Havingtroublerememberingthedangerousevent.

Beingeasilystartled Feelingtenseoronedge Havingdifficultysleeping,and/orhavingangryoutbursts. Angerandirritability Guilt,shame,orselfblame Substanceabuse Feelingsofmistrustandbetrayal Depressionandhopelessness Suicidalthoughtsandfeelings Feelingalienatedandalone Physicalachesandpains Strongfoodcravings(sugarandsimplecarbohydrate)

6.8%USApopulation Maybeashighas24%insubpopulations(military)

Kessleretal2005ab Millikenetal2007

ArecentmetaanalysisnotedthatlowerlevelsofbasalcortisolinplasmaandserumwerefoundinpatientswithPTSDcomparedtohealthycontrolswithnopriortraumaexposure,butnotnecessarilycomparedtocontrolswithahistoryoftraumaexposure(Meewisse etal.,2007).

YehudaandcolleaguesdemonstratedthatcombatveteranswithPTSDshowedgreatercortisolsuppressionthandidcombatveteranswithoutPTSDornormalcontrols(Yehudaetal.,1995)

Fatigue Weakness Unexplainedhairloss Nervousness Difficultybuildingmuscle Irritability Mentaldepression Difficultygainingweight Apprehension Hypoglycemia Palpitations(heart fluttering) Inability toconcentrate Excessivehunger Tendencytowards

inflammation Momentsofconfusion

Indigestion Feelingsoffrustration Poormemory Alternatingdiarrheaand

constipation Osteoporosis Lackofenergy

Autoimmunediseases Lightheadedness Dizzinessthatoccursuponstanding

Poorresistancetoinfections Lowbloodpressure Insomnia Food/inhalant allergies PMS Cravings forsweets Dryandthin skin Headaches Scantyperspiration Alcoholintolerance Lowbodytemperature

Developmentofthehumanadrenalzona reticularis:morphometricandimmunohistochemical studiesfrombirthtoadolescence.Hui XG,Akahira J,SuzukiT,Nio M,NakamuraY,SuzukiH,RaineyWE,Sasano H.JEndocrinol. 2009Nov;203(2):24152.Epub 2009Sep1.

MaternalseparationwithinthefirsttwoweeksafterdeliveryinducespermanentheightenedsensitivityoftheadrenalcortextoACTH.

Notonlythat,developmentofcortisolreceptorsthroughoutthebrainarepermanentlyinfluencedwhenbabiesaredeprivedofmaternalhandlingthefirstweeksoflife.

Thisresultsinanalteredcortisolresponsiveness,alteredstressregulation,alteredbehavioraladaptationandacceleratedbrainaging.

10/5/2012

5

EarlyHumanDevelopmentVolume84,Issue10 ,Pages689697,October2008

PrenatalSSRIexposurealteredHPAstressresponsepatternsandreducedearlyeveningbasalcortisollevels.

Thesefindingssuggestanearlyprogrammingeffectofantenatalmaternalmood,prenatalSSRIexposureandpostnatalmaternalcaregivingontheHPAsystem.

Thestressresponsesystemtoappropriatelyreact,adaptandrecoverfromthetraumaticevent.

NumerousbiologicalpathwayshavebeenimplicatedintheabnormalpathophysiologyofPTSD

CRHCorticotropinReleasingHormone HPAhypothalamicpituitaryAxis Noradrenergicnorepinephrine Serotonergicserotonin Glutamatergicglutamine

10/5/2012

6

Lifestylechanges(sedentary,increasedsugarandsimplecarbs)

Electronicinformationage(morescreengazinglessexercise)

Modernlife Morestimuli

"WorkersintheUnitedStatesareputtinginmorehoursthananyoneelseintheindustrializedworld." LawrenceJeffJohnson thechieflabormarketeconomist.

http://archives.cnn.com/2001/CAREER/trends/08/30/ilo.study/.August31,2001Posted:2:07AMEDT(0607GMT)

CRHactsasbothastresshormoneandaneurotransmitter.

CRHsecretionisincreasedincasesofanxietydisordersandsomeformsofdepression.

EuropeanJournalofPharmacologyin2008FlorianHolsboerandMarcusIsing

CRHisnotexclusivelyproducedinthehypothalamus:1. peripheralinflammatorysites2. inthethecaandstromalcellsaswellasincellsof

thecorporalutea3. cellsoftheendometrium

(ADHispresentwithCRHinsomehypothalamiccellsandisoftenreleasedsimultaneouslywithCRHandsynergizeswithit).

IsthekeyregulatoroftheHPAaxis Alsoexertsmajorinfluenceonthewakeandsleepcycle CRHinducesincreasedwakingCRHisexcitatoryinthelocusceruleus (LC),amygdala,hippocampus,cerebralcortex,andsomeportionsofthehypothalamus.

10/5/2012

7

Inhumans,themajorityofthestudiessuggestthatthesleepofyoungindividualsisratherresistanttothearousingeffectsofCRH.

Incontrast,middleagedindividualsrespondedtoanequivalentdoseofCRHwithsignificantlymorewakefulnessandsuppressionofslowwavesleepcomparedtobaseline.

Basedonthesefindings,weconcludedthatmiddleagedmenshowincreasedvulnerabilityofsleeptostresshormones,possiblyresultinginimpairmentsinthequalityofsleepduringperiodsofstress.

Thesefindingssuggestthatchangesinsleepphysiologyassociatedwithmiddleageplayasignificantroleinthemarkedincreaseofprevalenceofinsomniainmiddleage.Also,peripheraladministrationofCRHisassociatedwithaREMsuppression,whichisstrongerintheyoungthaninthemiddleaged.

ourfindingsshowanimportantroleoffibroblastexpressedCRHintheproliferation,migration,andcytokineproductionofthesecellsprocessesassociatedwiththeskinresponsetoinjury.

OurdatasuggestthattheimmunomodulatoryeffectsofCRHmayincludeanimportant,albeitnotexploredyet,roleinepidermaltissueremodelingandregenerationandmaintenanceoftissuehomeostasis.

HumanCRH wasaseffectiveasACTH atstimulatingDHEA production;however,itwas70%lesspotentthanACTH atstimulatingcortisolproduction,indicatingthatitsactionswerepreferentiallydirectedtowardincreasingDHEAsynthesis.

TheJournalofClinicalEndocrinologyandMetabolismMay5,1998 CorticotropinReleasingHormoneDirectlyandPreferentiallyStimulatesDehydroepiandrosterone SulfateSecretionbyHumanFetalAdrenalCorticalCells1RogerSmith,SamMesiano,EngChengChan,ShaneBrownandRobertB.Jaffe

Regulatedbycorticotropinreleasinghormone(CRH)fromthehypothalamus

Increasesinresponsetolowlevelsofcirculatingcortisol

AlsoIncreasesinresponseto: Stress Fever AcuteHypoglycemia

WaterdeprivationincreasesACTHsecretionandadrenalsensitivitytoACTH

Newborns Geneticpolymorphism somepeoplemaypossessreceptorsontheadrenalglandthatarelesssensitivetoACTH.Thisisthoughttobeseenmoreofteninatopic individuals.

Teenagersdiurnalrhythmshiftsby12hours,withacortisolgraphpeakingatbetween9and10am(ratherthan68am).

Adrenalinnervationfromtheadrenalmedullafacilitatestheadrenalresponseduringstress.

(Chronobiol Int.2007;24(5):96990.Diurnalandseasonalcortisol,testosterone,andDHEArhythmsinboysandgirlsduringpuberty.Matchock RL,DornLD,Susman EJ.)

10/5/2012

8

Withinthefirst3monthsofbirththefetalzonevirtuallydisappearsandproductionofDHEAceases.

Theproductionofcortisolandaldosteroneremainsconstanthoweverandtheadrenalcortexappearstohaveonlytwozones:Zonafasciculata andtheZonaglomerulosa.

Developmentofthehumanadrenalzona reticularis:morphometricandimmunohistochemical studiesfrombirthtoadolescence.Hui XG,Akahira J,SuzukiT,Nio M,NakamuraY,SuzukiH,RaineyWE,Sasano H.JEndocrinol. 2009Nov;203(2):24152.Epub 2009Sep1.

Attention Learning Memory

(Wolf,2008).(Sargant andSlater,1940).

thereisalargebodyofevidencetosuggestthatthisfunctioningisaltered,andtheremayinfactbehyperactivenoradrenergicfunctioninPTSD.(evidencesupportsautonomichyperactivityinPTSD)

FurthermorethereareimportantreciprocalinteractionsthatexistbetweentheserotoninandNEsystems.ThefiringofNEneuronsintheLCisundertonicinhibitionbyprojectionsfromthedorsalraphe nucleus.TheuseofSSRIswhicheffectivelyallowincreased5HTtobereleasedindirectlyenhancesthisinhibitorytone(Szabo andBlier,2001)whichmaybeakeyfactoryinimprovingthehyperadrenergic stateinPTSD,andthedownstreamimprovementinamygdala activation.

10/5/2012

9

Synapse. 2001Dec15;42(4):20312.Serotonin(1A)receptorligands actonnorepinephrine neuronfiringthroughexcitatory

aminoacidandGABA(A)receptors:amicroiontophoretic studyintheratlocuscoeruleus.

Szabo ST,Blier P.SourceNeurobiologicalPsychiatryUnit,McGillUniversity,Montral,Canada.

RevealselevatedurineNElevelscomparedtohealthycontrolsinmilitarypersonnelwithPTSD

Oneofthemostimportantfunctionsofnorepinephrineisitsroleasthe neurotransmitter releasedfromthe sympatheticneurons affectingtheheart.

Anincreaseinnorepinephrinefromthesympatheticnervoussystemincreasestherateofcontractions.

Asa stresshormone,norepinephrineaffectspartsofthebrain,suchasthe amygdala,where attention andresponsesarecontrolled.

Alongwith epinephrine,norepinephrinealsounderliesthe fightorflightresponse,directlyincreasing heartrate,triggeringthereleaseof glucosefromenergystores,andincreasingbloodflowto skeletalmuscle.Itincreasesthebrain'soxygensupply.

Norepinephrinecanalsosuppressneuroinflammation whenreleaseddiffuselyinthebrainfromthe locusceruleus.

IndividualswiththisdisorderappeartodisplayabnormalitiesindifferentmeasuresofNEalongwithhypersensitiveadrenergicreceptorssuggestiveofanoverallenhancednoradrenergicstate.TheproposedneuralcircuitryimplicatedinPTSDisalsoinfluencedbythesecatecholaminergicalterations.IncreasedNAmaycontributenotonlytotheenhancedfearacquisitionandconditioningresponsesbytheamygdala,butalsotolossofprefrontalcontrolovertheamygdalathusimpairingextinctionofthefearresponse.

Studiesofglucocorticoids (GCs)andmemoryhaverevealedthatduringacutestress,elevatedGClevelsworkinconcertwithnoradrenergicactivationtoenhancetheprocessofencodingandconsolidatingemotionalmemories(Rozendaal etal.,2006).

OnemodelthathasbeenputforthhypothesizesthatthemPFC whichnormallyhasinhibitorycontroloverthenoradrenergicneuronsoftheLCandovertheHPAaxis,isrenderedineffectiveattimesofacutestressthuspermittingenhancedstimulationoftheamygdalabyGCsandNE,whichinturnenhancesencodingandconsolidationofthetraumaticmemory(Hurlemann,2008).

AdrenergicreceptorsinindividualswithchronicPTSDareparticularlysensitivetostimulationandpronetohyperactivity.

10/5/2012

10

SerotoninmodulatesHPAaxisandLongtermtreatmentwithSSRIappearstodecreaseHPAresponsivenessatthepituitarylevel

JNeuroendocrinol. 1999Jun;11(6):46571.Acuteandlongtermtreatmentswiththeselective

serotoninreuptakeinhibitorcitaloprammodulatetheHPAaxisactivityatdifferentlevelsinmalerats.

JensenJB,JessopDS,Harbuz MS,Mrk A,SnchezC,Mikkelsen JD.

Source:DepartmentofClinicalBiochemistry,Bispebjerg Hospital,Copenhagen,Denmark.jej@lundbeck.com

Incontrasttotheenhancingeffectsonencoding,similarlyelevatedGClevelsmayimpairdelayedmemoryretrieval,particularlyforemotionallyarousingmaterial(Buchananetal.,2006),againinthecontextofnoradrenergicactivationwithintheBLA.AninvertedUshapedcurvehasthusbeenproposedtoexplainhowmemoryretrievalisaffectedbycortisolconcentrations(Wolf,2008)andthisinturnmayexplainwhyindividualswithPTSDhavedifficultysubsequentlyrememberingcertainaspectsofthetrauma.

PrimaryexcitatoryneurotransmitterintheCNS PlayaroleinthepathophysiologyofPTSDinpartviaitsactions

ontheHPAaxis ViathemodulationofCRHreleaseinresponsetostress Changesinglutamatelevelsplayakeyroleininitiationand

maintenanceoftheHPAresponse. Hyperglutamatergic statemaybeimplicatedinPTSD Isalsothoughttoplayafundamentalroleinmemoryformation,

(akeyprocessofPTSD). Followingtraumaticevents,elevatedglutamatelevelsmayserve

toencodeandconsolidatetraumaticmemories,butalsoenhancehippocampaldamage(Joca etal.,2007).

PhasesofAdrenalDysfunction

10/5/2012

11

Stimulatesfatdepositsandcanresultinweightgain. Increasedfataccumulationaroundwaist. Increasesbloodpressure. Increasesproteinbreakdownthatcanleadtomuscle

loss. Causesdemineralizationofbonethatcanleadto

osteoporosis. Interfereswithskin'sabilitytoregenerationandheal. Causesdemineralizationofbonethatcanleadto

osteoporosis. Interfereswithskin'sabilitytoregenerationandheal. Cortisolisapowerfulantiinflammatoryagent.

SalivaryAdrenalProfile BasicNeurotransmitters Thyroidfunctiontests BasalBodytemps

Beforebeginninganytreatmentprotocolontheadrenalglandsaclinicalhistoryshouldbetakenandtestingshouldbedone.1.Saliva2. Serum3. Urine

10/5/2012

12

DiurnalCortisol=4Cortisols(AM,Noon,Eve,PM) 30minutes(afterawakening) Beforelunch Beforedinner Beforebedtime(preferablyatleastonehourafter

dinner).

DHEA(NOTDHEAS)*Totaloffivehormonetests

LabrixClinicalServicesETL,2008

Cortisol Awakening Response

0

5

10

15

20

25

0 15 30 45 60 75

Time post awakening (minutes)

Cor

tisol

(nm

ol/L

)

SalivaryCortisol:ABetterMeasureofAdrenalCorticalFunctionThanSerum.ViningRF,etal.AnnClinBiochem (1983)20:32935.

VenipunctureCausesRapidRiseinPlasmaACTH.Meeran Ketal.BrJClinPract (1993)47(5):2467.

SalivaryCortisol AnAlternativetoSerumCortisolDeterminationsinDynamicFunctionTests.AardalErikssonE,etal.ClinChem LabMed(1998)36(4):215222.

HormoneProfilesinHumansExperiencingMilitarySurvivalTraining.MorganCA,etal.BiolPsychiatry(2000)47:891901.

SalivaryCortisolDeterminedbyEnzymeImmunoassayisPreferabletoSerumTotalCortisolforAssessmentofDynamicHypothalamicPituitaryAdrenalAxisActivity.Gozansky WS,etal.ClinEndocrin (2005)63:336341.

Urine 13hoursafterrising(not1st morningvoid) Serotonin,norepinephrine,epinephrine,dopamine,glutamate,GABA

Received7June2010Receivedinrevisedform21July2010Accepted30July2010ReviewNeurotransmittersexcretedintheurineasbiomarkersofnervoussystemactivity:ValidityandclinicalapplicabilityDavidT.Marc,JosephW.Ailts,DanielleC.AiltsCampeau,MichaelJ.Bull,KellyL.Olson

Hydrocortisone(physiologicdosing)

DHEA Melatonin VitaminC VitaminB5 VitaminB6 VitaminE PhosphorylatedSerine 5 HTP LTyrosine LTheanine

Traceminerals Zinc Manganese Selenium Chromium Molybdenum Copper Iodine

Rhodiola Ashwagandha Panax Ginseng SiberianGinseng

Bioessays. 2008Aug;30(8):74456.Whatgoesonbehindcloseddoors:physiologicalversuspharmacologicalsteroidhormoneactions.Simons SSJr.SteroidHormonesSection,Bldg 10,Room8N307B,NIDDK/CEB,NIH,Bethesda,MD208921772,USA.

Phase0

Multivitamin/MultimineralOmega3EFAsVitaminD,IodineandProbiotics

10/5/2012

13

Phase1

PhosphorylatedSerine100mgTIDorattimeswhenelevatedVitaminsB5(500mg)TID,B6(50mg)TID,C(1000mg)TIDMelatonin(16mg)qhs ifcortisollevelselevatedatnightDHEA*Lifestylemodification:Deepbreathing,stressmanagement,exercise,optimaldietetc.

Phase2

VitaminsB5(500mg)TID,B6(50mg)TID,C(1000mg)TIDAdrenalglandularand/orherbaladaptogens inmorningandatnoon*AminoAcids:5HTP,ltyrosine,ltheanineLifestylemodification:Deepbreathing,stressmanagement,exercise,optimaldietetc.

Phase3

VitaminsB5(500mg)TID,B6(50mg)TID,C(1000mg)TIDAdrenalglandularand/orherbaladaptogens inmorningandatnoon.hydrocortisonesupplementation510mginAMand510mgatnoonMelatoninAminoAcids;5HTP,ltyrosine,ltheanineLifestylemodification:Deepbreathing,stressmanagement,exercise,optimaldietetc.

3options: Rx Compoundedcortisol Glandularstandardized

glandularRx

Tabletsareavailablefororaladministrationinthreestrengths:eachtabletcontainseither5mg,10mg,or20mgofcortisol.

Inactiveingredients:calciumstearate,cornstarch,lactose,mineraloil,sorbic acid,sucrose.

HOWSUPPLIEDTabletsareavailableinthefollowingstrengthsandpackagesizes:5mg(white,round,scored,imprintedCORTEF5)Bottlesof5010mg(white,round,scored,imprintedCORTEF10)Bottlesof10020mg(white,round,scored,imprintedCORTEF20)Bottlesof100 Rx

Cortisolcanbecompounded(intoanydoseyouchoose).

Especiallywhengivingthepatientdosesdifferentthan5mg,10mgor20mg

Canhaveregularreleaseandsustainedreleaseblend

(70:30ratio 70%reg.cortisol:30%slowreleaseagent)

10/5/2012

14

Sometimesstandardizedeachpelletcontains2.45mg ofcortisol.

Otheringredientsinclude:driedadrenalcortex,Echinacea,Prunus spp,Lomatium dissectumroot,lactoseandlactase.SampleDosingSchedule

I.30minutesafterawakening:14pellets(2.57.5mgcortisol)2.4hourslaterorbeforenoon:14pellets(2.57.5mgcortisol)3.321(am7.5mg,noon5.0mg,midafternoon2.55.0mg)

glandular

Shorthalflife 8to12hours1. Cortisone2. Cortisol

Cortisolismetabolizedinmosttissues,butprimarilyinthelivertobiologicallyinactivecompounds.Thehalflifeofcortisolmaybeprolongedinpatientswithhypothyroidism.

Inactivemetabolitesareexcretedbythekidneys.Negligibleamountsareexcretedinbile.

0.5mgofdexamethazone =15mgcortisol Inadexamethazone suppressiontestusually1mgof

dex isgivenorally(i.e,30mgcortisol). 5mgprednisone=20mgcortisol Anormalstartingdoseofprednisoneisbetween5

60mg/day. MultipleSclerosistreatmentstartsat200mg/dayand

tapersto80mg/day.Cortisol

(hydrocortisone)Cortisone Prednisone Dexamethasone

20mg 25mg 5mg 0.75mg

Lowdosephysiologicalcortisolsupplementationdoesnotproducesignsorsymptomsofglucocorticoidexcessandhasnotbeenshowntocauseclinicallysignificantadrenalsuppression.20mgoforalhydrocortisonehasfarlessglucocorticoideffectonboneforexample,than5mgofprednisone(jodar 03)Studieshaveshownthat10mgand40mgofhydrocortisone(theamountincreasesdependinguponbodyweight(Mah 2004)doesnotcauseboneloss,suppressionofimmunesystem,weightgain,elevatedbloodsugar,elevatedbloodpressurethinningskin,easybruisingorsuppressionofendogenouscortisolproduction(Wichers 1999,McConnell2002,Danowski1962,SafeUsesofCortisolbyWilliamMck JefferiesMD)

Hypothalamopituitaryadrenalaxisdysfunctioninchronicfatiguesyndrome,andtheeffectsoflowdosehydrocortisonetherapy. evidencesupportspreviousfindingsofimpairedadrenalcortical

responsivity inCFS. lowdosehydrocortisonesupplementationisabletoincreasetheoverall

cortisolthroughput,suggestingthatthereisnot(over28d)acompensatoryswitchingoffofendogenouscortisolproduction.

thosewhorespondedtotreatment,hadasignificantdecreaseinfatigueascomparedtonormalpopulationlevels,therewasacorrespondingnormalizationofthebluntedcortisolresponsetohCRH challenge.

1. JClinEndocrinolMetab. 2001Aug;86(8):35455 leareAJ,MiellJ,HeapE,Sookdeo S,YoungL,Malhi GS,O'Keane V.

2. Jefferies,WilliamMcK.MD.SafeUsesofCortisol3rdeditionCharlesCThomasPublisher.LTD.ISBN0398075018

3. ThelowdoseACTHtestinchronicfatiguesyndromeandinhealthLucindaV.Scott1,SamiMedbak2,TimothyG.Dinan3Articlefirstpublishedonline:4JAN2002DOI: 10.1046/j.13652265.1998.00418.xClinicalEndocrinologyVolume48,Issue6,pages733737,June1998

4. LowDoseHydrocortisoneforTreatmentofChronicFatigueSyndromeARandomizedControlledTrialRobinMcKenzie,MD;AnnOFallon,RN;JanetDale,RN,MPH;MarkDemitrack,MD;Geetika Sharma,MD;Maria Deloria;DiegoGarciaBorreguero,MD;WilliamBlackwelder,PhD;StephenE.Straus,MD

10/5/2012

15

TheamountofDHEAneededtobringamalewithAddisonsdiseaseintonormalphysiologicalrangeis5070mg(Huntetal.2000).

Ifyouarefollowingphysiological(notreplacement)dosesyouwouldlikelynotexceed: Males2550mg/day Females1025mg/day

Improvementinmoodandfatigueafterdehydroepiandrosterone replacementinAddison'sdiseaseinarandomized,doubleblindtrial. Hunt PJ,etal.JClinEndocrinolMetab. 2000Dec;85(12):46506.

Secretedbythepinealgland Regulatescircadianrhythmandinducesleep. Cushing'ssyndromewasshowntohavesignificantlylowerlevelscomparedtohealthycontrolgroups.

Studiesalsohaveshownthatnightlyadministrationof2mgofmelatoninhavesupportedadrenalrecoveryafter6monthsofadministration

(Soszynskietal.1989;Brulsetal.2000;Pawlikowskietal.2002).

Ofallthevitaminsandmineralsinvolvedinadrenalmetabolism,vitaminCisprobablythemostimportant.Infact,themorecortisolmade,themorevitaminCused.VitaminCissoessentialtotheadrenalhormonecascadeandthemanufactureofadrenalsteroidhormones1

StudiesshowthatvitaminCcanattenuateandinfluencecortisol,inducinganantiinflammatoryresponsetoprolongedexerciseandstress.VitaminChasbeenshowntoreducetheelevationofcortisolinresponsetoheavyexercise.Inhumanstudies,3000mgofvitaminCdailymitigatedariseinbloodpressure,cortisol,andsubjectiveresponsetoacutepsychologicalstress

1)Dr.JamesL.WilsonistheauthorofAdrenalFatigue:The21stCenturyStressSyndrome.In19982)DiLuigietal.2001;Petersetal.2001a,2001b;Brodyetal.2002).

(CoA)thebasisfortheproductionofhemoglobin,bile,sexandadrenalsteroids,cholesterol,andotherbrainchemicalsandneurotransmitters.

Pantothenicaciddeficiencyresultsinadrenalinsufficiency,whichischaracterizedbyfatigue,headache,sleepdisturbances,nausea,andabdominaldiscomfort

PantothenicAcidAndPantethine,MichaelLam,MD,MPH(Tarasovetal.1985;Smithetal.1996;Murrayetal.1997).

B6(pyridoxine) isalsoacoenzymeinseveralofthebiochemicalpathwaysintheadrenalcascadeandplaysaroleinthefunctioningofthehypothalamic/pituitary/adrenal(HPA)axisthatmodulatesadrenalactivityandthestressresponse.

JamesWilsonwebsite2010

Absorbsandneutralizesthesedamagingfreeradicalmoleculesinsidetheadrenalglands(VitaminCenhancesvitaminEsactivityinsidethecellbyregeneratingthecapacityofvitaminEtosequesterthefreeradicals).

WorkshandinhandwithVit.Ctokeeptheadrenalcascadefunctioning.

HighamountsofvitaminEarenecessaryinorderfortheadrenalstomaintainhighlevelsofsteroidproductionandrecoveradequately.

Bieri,JG;Evarts(1974)."Tocopherol:metabolism,biologicalactivityandsignificanceinhumanvitaminEnutrition".AmericanJournalofClinicalNutrition 27 (9):980986.PMID 4472121

10/5/2012

16

SevenForestsSanQi17(26tablets) StJohnss Wort (300mg) 5HTP(100mg*) LTheanine (50200mg) Melatonin16*mg Chamomile,ValerianRoot(asdirected)

Normalizeyoursleep Sleepmore Sleepattherighttimes(lightdarkcircadian

rhythms) Sleeplater(until8:30or9am) Balancehormones;adrenalsand

estrogen/progesterone Book:LightsOut

Takenonemptystomach30minutesawayfromfood

CrossthebloodbrainbarrierandinteractwithHPAaxisandneurotransmitterregulationThemonoamineneurotransmittersserotonin,dopamine,norepinephrine,andepinephrinedonotcrossthebloodbrainbarrier;therefore,peripheraladministrationoftheseneurotransmitterswillnotincreasecentralnervoussystemneurotransmitterlevels.Theaminoacidprecursorsoftheseneurotransmittersdocrossthebloodbrainbarrier.TheonlywaytoincreasecentralnervoussystemneurotransmitterlevelsisthroughadministrationofaminoacidPrecursors.

MartyHinz MDFoodandNutritionindiseaseManagement,Ch 29,pp465483 Birdsall TC.5Hydroxytryptophan:aclinicallyeffectiveserotoninprecursor.Altern MedRev.1998Aug;3(4):271280. PyleAC,Argyropoulos SV,NuttDJ.Theroleofserotonininpanic:evidencefromtryptophandepletionstudies.Acta

Neuropsychiatrica 2004;16:7984

Aphospholipid thatisastructuralcomponentofthebiologicalmembranesinanimalsandplants.

BluntstheHPAsensitivitybyalteringACTHandcortisol responses

(Monteleoneetal.1990;Kelly1999;Bentonetal.2001).

Alsoknownasoxitriptan Anaturallyoccurringaminoacid Chemicalprecursoraswellasmetabolicintermediateinthebiosynthesisoftheserotoninandmelatoninfromtrytophan

Chronicstressalsoactsinthebraintodecreaseserotonin.Serotoninactsinthebraintoenhancetheeffectsofleptin inthehypothalamus.

Adv Exp MedBiol. 1996;398:3739.Fibromyalgiaandmigraine,twofacesofthesamemechanism.Serotoninasthecommonclueforpathogenesisandtherapy.Nicolodi M,Sicuteri F.Interuniversity CentreofNeurochemistry,UniversityUnit,Florence,Italy.

Notconsideredanessentialaminoacidbecausethebodycansynthesizethisfromphenylalanine

Convertedintodopamineandnorepinephrine Underepisodesofstress,thebodymaynothavethecapacitytoproduceenoughtyrosinefromphenylalanine;therefore,supplementationsupportshormoneandNTproduction

IncreasesalertnessandmentalclarityIntJGenMed2011Hinz etal,publisherandlicenseeDoveMedicalPressLtd.AminoacidmanagementofParkinsonsdisease:acasestudyMartyHinz,1 AlvinStein,2 andThomasUncini31ClinicalResearch,NeuroResearch Clinics,Inc.,CapeCoral,FL,USA;2SteinOrthopedicAssociates,Plantation,FL,USA;3DBSLabs,Duluth,MN,USACorrespondence:MartyHinz,1008DolphinDr,CapeCoral,FL33904,USA,Tel+12186262220,Fax+12186261638,Emailmarty@hinzmd.com

10/5/2012

17

Glutamicacidanalogderivative Aminoacidfoundingreentea Producesacalmingeffectinthebrain. Increasinggammaaminobutyric acid(GABA)(relaxer

andcreatesasenseofwellbeing). Helpmodulatemood Reducementalandphysical Improvescognition

Abeetal.1995;Kobayashietal.1998;Juneja etal.1999GomezRamirezM;Higgins,BA;Rycroft,JA;Owen,GN;Mahoney,J;Shpaner,M;Foxe,JJ(2007)."TheDeploymentofIntersensory SelectiveAttention:AHighdensityElectricalMappingStudyoftheEffectsofTheanine".ClinNeuropharmacol 30 (1):2538.KimuraK,Ozeki M,Juneja L,Ohira H(2007)."LTheanine reducespsychologicalandphysiologicalstressresponses".BiolPsychol 74 (1):3945.doi:10.1016/j.biopsycho.2006.06.006.PMID 16930802.HaskellCF,KennedyDO,MilneAL,Wesnes KA,Scholey AB(2008)."Theeffectsofltheanine,caffeineandtheircombinationoncognitionandmood".BiolPsychol 77 (2):11322

Antioxidantactivity Liverprotectionandantitoxin

activity Improvedbloodsugar

metabolism Lesscravingforalcoholor

sugar Improvedimmuneresistance Increasedenergyandstamina Improvedmuscletone

Increasedstrength Fasterrecovery Betterfocusand

concentration Lessanxiety Bettersleep Bettermotivationand

productivity Afeelingofwellbeing Bettermoods

Haveanormalizingeffectonthebodyandtobecapableofeithertoningdownorstrengtheningtheactivityofhyperandhypofunctioningsystems.

Themechanismoftheantistressoradaptogenic activitiesofradixeleutherococciappearstobethreefold. Extractsoftherootshaveanadaptogenic effect

thatproducesanonspecificincreaseinthebodysdefenseagainstexogenousstressfactorsandnoxiouschemicals.

Therootsalsostimulatetheimmunesystem Andpromoteanoverallimprovementinphysical

andmentalperformance."AdaptogensthatHelpwithAdrenalFatigue:GetGoingAgainwithNaturalHerbalRemedieshttp://www.suite101.com/content/adaptogensthathelpwithadrenalfatiguea162757#ixzz1EWWOrDIz

Alargestudyreviewedtheresultsofanumberofclinicaltrialsinvolving2,100healthymenandwomenages19to72.Subjectsweregivendosesofginsengrangingfrom2to16mloffluidextract,33percentethanol,fromonetothreetimesdailyforupto60days.Subjectshadincreasedmentalalertnessandworkoutput,enhancedathleticperformanceandimprovedworkquality.Theyalsoexhibitedanimprovedabilitytowithstandadverseconditionssuchasheat,noise,increasesinworkloadandphysicalexertion.

BullWorldHealthOrgan.1985;63(6):965981. Medicinalplantsintherapy* NormanR.Farnsworth,Olayiwola Akerele,AudreyS.Bingel,

Djaja D.Soejarto,andZhengang Guo

Effectiveatimprovingaperson'sabilitytowithstandstress: Improvedworkperformanceandquality Enhancesmentalfunction Increasesthereleaseofadrenocorticotropichormone(ACTH),whichstimulatesanincreaseinadrenalhormonesecretion.

Counteractstheshrinkageoftheadrenalglandcausedbycorticosteroiddrugs.

Murray,M.&Pizzorno,J.EncyclopediaofNaturalMedicine:499.Rocklin,Calif.:PrimaPublishing,1990.Shibata,S.,etal."Chemistryandpharmacologyofpanax,"EconMedPlantRes,1:21784,1985.

Immunomodulating Modifiesanxietyandotherpsychologicalcomplaints.

Whencortisolistoohigh,itlowersit,andifitistoolow,itraisesit.

Upadhaya,L.,etal."RoleofanindigenousdrugGeriforte onbloodlevelsofbiogenicaminesanditssignificanceinthetreatmentofanxietyneurosis," Acta Nerv Super, 32(1):15,1990.Ghosal,S.,etal."ImmunomodulatoryandCNSeffectsofsitoindosides IXandX,twonewglycowithanolides fromWithania somnifera," Phytother Res, 3(5):2016,1989.Bhattacharya,S.K.,etal."Antistressactivityofsitoindosides VIIandVIII,newacylsterylglycosides fromWithania somnifera," Phytother Res, 1(1):3237,1987.www.smartpublications.com.Wilson,James.Adrenal Fatigue.

10/5/2012

18

Promotesorenhancesimmunesystemfunction Stimulatestheadrenalcortex Inhibitsthebreakdownofadrenalhormonebytheliver,therebyincreasingcorticosteroidlevelsincirculation

Inhibitscortisol'sabilitytopromotethymusatrophy

1ProtocolJournalofBotanicalMedicine,1(4):194.Ayer,Mass.:HerbalResearchPublications,1996.2)Murray,M.&Pizzorno,J.,op.cit.,pp.60,61,67.3)Armanini,D.,Kargbowiak,I.,etal."Affinityofliquorice derivativesformineralocorticoid andglucocorticoid receptors,"Clin Endocrinol,19:60912,1983.

Diminishesfatigue Improvesattentionspan Improvesmemory; Makesworkersmoreproductive. Increasesthecapacityformental/cognitivework

Enhancespermeabilityofthebloodbrainbarriertodopamineandserotonin.

Rhodiola rosea instressinducedfatigue:adoubleblindcrossoverstudyofastandardizedextractSHR5witharepeatedlowdoseregimenonthementalperformanceofhealthyphysiciansduringnightduty.Darbinyan V,Kteyan A,Panossian A,Gabrielian E,WikmanG,WagnerH.Department ofNeurology,ArmenianStateMedicalUniversityPhytomedicine 2000;7(5):36571.

Usetryptophanif5HTPiscausingGIupset Balancing:neurotransmitters,sexhormonesandadrenalfunctionareallinterdependentandcorrectingonepositivelyaffectstheother

Nodirectfeedbackbetweenzona fasciculata andzona reticularistreateachzoneasifseparategland

Treatthepathwayaswellasthelevel TreatHPAdysfunctionfirstthenmayneedtotreathypoadrenia ifpresent

DHEA,melatoninand phosphoylated serinecanbeusedtoquietHPAdysfunction

ACTHisnotstimulatingincreasedandrogensinwomenwithMet.SyndromeandPCOS