HPA Axis Dysfuncon in Obesity - GDX

HPAAxisDysfunc.oninObesityMelanieDorion,AGNP

TheviewsandopinionsexpressedhereinaresolelythoseofthepresenteranddonotnecessarilyrepresentthoseofGenovaDiagnos=cs.Thus,GenovaDiagnos=csdoesnotacceptliabilityforconsequencesofanyac=onstakenonthebasisoftheinforma=onprovided.

MichaelChapman,NDMedicalEduca.onSpecialist-Asheville

MelanieDorion,AGNP

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•  Reviewcontribu=ngfactorsinweightgain•  DiscussresearchonHPAaxisdysfunc=oninobesity•  DiscussothercausesofHPAaxisdysfunc=on•  Introducetherapeu=cop=onsfocusingonadrenalsupport

Objec.ves

ObesityandWeightGainAreMul.factorial!!!•  Dietandlifestyle•  Hormonalinfluences

–  Thyroid,Insulin,Cor=sol,Lep=n•  Nutri=onaldeficiencies

–  VitaminD,Omega-3faVyacids

•  Immuneandgutdysbiosis•  Gene=cs/epigene.cs•  Neurobehavioral•  ...

Contribu.ngFactorsinWeightGain

TheHormonalComponent

https://commons.wikimedia.org/wiki/File:HPA_Axis_Diagram_(Brian_M_Sweis_2012).png

Hypothalamic-Pituitary-Adrenal (HPA) Axis

Mul.pleStudiesHaveLookedatThis-Conflic.ngResults!•  SomeshowgreaterACTHresponsesothersnot•  Circula=ngcor=sollevelsnotconsistentlyelevated•  Lowmorningcor=solbuthighurinarycor=sol•  Possibleexplana=ons

–  smallsamplesizes,–  singlegenderandsingleethnicity–  =ssuespecificaltera=onsincor=solmetabolism

(onlyproperlytestedbyadipose=ssuebiopsy=NOTprac=cal)

HPAAxisandObesity

GeneralPaQerns•  GreaterabdominalfatisassociatedwithgreaterresponsivityoftheHPAaxis•  Upregula=onofcor=soloutputinadipocytes

–  duetogreaterexpressionof11β-hydroxysteroiddehydrogenasetype1(11β-HSD1)•  Downregula=onofcor=solinhepa=c=ssue•  “OverallBMIappearstoalsoberelatedtoahyper-responsiveHPAaxisinmany

butnotallstudies,suchaswhenacutereac=vityisexamined.”(Rodriguez,2015)

WhatisReallyHappening??

HPAAxis-Adrenals

Lucassen A. & Cizza G. Curr Obes Rep. 2012 December ; 1(4): 208–215.

UrinarylevelsofTHF(tetrahydrocor=sol)andTHE(tetrahydrocor=sone)areusuallyincreasedinobesesubjects.

•  IncreasedHSD1ac=vityinadipose=ssueanddecreasedinhepa=c=ssue•  IncreasedurinaryTHEindicatesincreasedcatabolismofcor=sol=

increasedcor=solclearance•  Hyper-responsiveHPAaxisinobesitybutlessresponsivetosuppression

tests(dexamethasonesuppressiontest)•  Hyperac=veSNSincentralobesity•  Weightlossleadsto

–  DecreasedHSD1ac=vity–  Decrease5α-reductaseac=vity

TakeHomePointsfromLucassen&Cizza

“HigherBMIandWCareassociatedwithneuroendocrinedysregula.on[…].”

Champaneri S., et. al. Obesity (Silver Spring). 2013 Jan;21(1):E56-63.

MESA

Study

•  Fortheen.recohort,bothBMIandWCwerenega.velycorrelatedwithawakeningcor.sol

•  THM(tetrahydrometabolites)andTHE(tetrahydrocor=sone)posi=velycorrelatedwithBMIandWC

•  Amongpar=cipantswithDM:–  Cor=solcurveparameterssugges=veofhigherHPAaxisac=vity–  Dysfunc=onwereassociatedwithhigherHbA1c

MESAStudyOutcomes

•  Chronicstress–physicaloremo=onal•  Sleepdisorders

–  Notonlydoesobesitycontributetosleepproblems,butsleepproblemscanalsocontributetoobesity–chickenortheegg??

–  Inadults,OSAises=matedtobeashighas45%inobesesubjects=es=mated18millionAmericanshaveOSA–YIKES!

–  Poorsleepandsleepdepriva=ondecreasesglucosetolerance,decreaseslep=n,increasescor=solandmayincreaseappe=te

•  Inflamma=on(IL-6upregulatesHSD1expression)•  Mooddisorders•  Lowcaloriediets•  Thyroiddisorder

OtherCausesofHPAAxisDysfunc.on

“Restric.ngcaloriesincreasedthetotaloutputofcor.sol,andmonitoringcaloriesincreasedperceivedstress”

Rela.onshipbetweenAdrenals&Thyroid

FactorsThatAffectThyroidFunc.on

HPAAxisTes.ng

Source: Genova Diagnostics

WhatTesttoOrder?

Serum?

Saliva?

Urine?

http://www.townsendletter.com/Jan2014/hormone0114.html

24HourUrinePanels

•  Alwaysincludecor=sol!•  Measuresunboundhormone

reflec=ngbioavailableforms•  Allowmetabolitestobeevaluated•  Accountforthefulldayandnight

ofhormonalsecre=on–removesfalsehighs/lowsd/tcircumstances

•  Lowmineralocor=coidsareaclearindicatorofchronicHPAaxisdysfunc=on

SalivaryTes.ng

•  4samples•  Measuresfreehormone•  Diurnalcurve•  DHEAmeasurement

•  Sleepdisorders–  Notonlydoesobesitycontributetosleepproblems,

butsleepproblemscanalsocontributetoobesity–chickenortheegg??

–  Inadults,OSAises=matedtobe~25%,andashighas45%inobesesubjects=es=mated18millionAmericansOSA–YIKES!

–  Poorsleepandsleepdepriva=ondecreasesglucosetolerance,decreaseslep=n,increasescor=solandmayincreaseappe=te

–  RLS•  Mooddisorders

OtherCausesofHPAAxisDysfunc.on

1318_5148227

Diurnalsalivarycor.solisassociatedwithbodymassindexandwaistcircumference

Champaneri S., et. al. Obesity (Silver Spring). 2013 Jan;21(1):E56-63.

•  EpworthandBerlinscreenings

ScreeningandTes.ngforSleepandMoodDisorders

http://sleepapnea.org/wp-content/uploads/2017/02/ESS-PDF-1990-97.pdf

•  BeckDepressionScale,PHQ-2,PHQ-9

ScreeningandTes.ngforSleepandMoodDisorders

http://www.hr.ucdavis.edu/asap/pdf_files/Beck_Depression_Inventory.pdf

ThyroidTes.ngLookforOp.malLevels,notSimply“Normal”

•  TSH<2.5•  FT4>1.3•  FT3>3.0•  rT3<20

ReverseT3• OccupiessamereceptorsitesasFT3• Increasedin:

– Mitochondrialdysfunc=on(InsulinResistance,DM,Lyme,fibro,etc.)–  Elevatedcor=sol–  SeandFedeficiencies(wantferri=n>50)

Management

AlwaysStartwithDietandLifestyle!

•  Carbohydrateconscious:aboutor<120gofnetcarbs/day•  Lowcarbohydrate:<100gofnetcarbs/day•  Ketogenic:<60-40gofnetcarbs/day

Netcarbs:(totalcarbohydrate–fiber)Readthefoodlabels!

DietaryRecommenda.ons:LowerCarbohydrate,ModerateProteinandHigherFat

Management

•  Lifestyle–  Improvesleep!Orrefertosleepspecialist

–  Movementandexercise–  Deepbreathingandmindfulnessdaily–  Daylightexposurefirstthinginthemorningandthroughouttheday

•  “Tiredandwired”pa=ent–  Phospha=dylserineinarernoon&qHS–  GABA:200-250mgor125mgsublingual–  Homeopathics(EX:CalmsForte)

•  Others–  Magnesium–  P5P

Management

Mind/BodyTherapies•  HeartRateVariability(HRV),

morningHR•  HeartMath•  Medita=on/prayer•  Cogni=veBehavioralTherapy,

EFT,etc•  MovementTherapies

(Yoga,TaiChi,QiGong)Reproduced from http://alessandroferretti.co.uk/

•  Adaptogens–  Ashwagandha(Withaniasomnifera)–  Rhodiola(Rhodiolarosea)–  Schisandra(Schisandrachinensis)–  Asianginseng(Panax)–  Siberianginseng/Eleuthro(Eleutroccocussen=cosus)

•  Cau=oninpa=entswithanxiety

•  Nervines–  Oats(Avenasa5va)–  Gotukola(Centellaasia5ca)

•  Others–  Woodbetony(Stachysoff.):=n½-1dropperTID

BotanicalSupport

Image: Creative Commons

•  Licoriceandturmericandgreentea,OhMy!

Management-11β-HSD1Inhibitors

JSteroidBiochemMolBiol.2009Feb;113(3-5):248-52.PLoSOne.2014Jan3;9(1):e84468.

•  Licoriceandturmericandgreentea,OhMy!•  Salicylate

Management-11β-HSD1Inhibitors

Diabetes.2012 Apr;61(4):790-6. https://www.ncbi.nlm.nih.gov/pubmed/22357964

Significantproblem!51%ofU.S.adults>65yohavepre-dm•  Insulinpromoteslipogenesisandpreventslipolysis

–  Elevatedinsulin(insulinresistance)=difficultfatloss!•  Berberine:1-2000mg/dindivideddoseswithfood•  Chromium:1-2000mcg/dindivideddoseswithfood•  Cinnamon:1-6g/dayindivideddoses

InsulinResistance

The American Journal of Medicine, 2008;121:519-524 N Engl J Med 2005;353:1454-62.

http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf

Case1

70YOFemalePresentsforWeightManagementandFa.gue

•  6+yearsofdebilita=ngfa=gueandongoingconsistentslowweightgain•  Hasseenmanytradi=onalandintegra=veprovidersw/omuchrelief•  Currentsymptoms:GI(bloa=ng,cramping,diarrhea),fa=gue,brainfog,

memoryissues,mmweakness,stress/anxiety•  PastHistory:etohabuse,Lymedisease,OSA,lowFe•  BMI30,othervitalswnl•  Labs

–  Nutri=onalandhormonalpanels–  Reac=vatedmono–  ++Celiacgene=cs–  ElevatedANA–  Otherlabswnl

CaseHistory

•  IMhydroxoB12andoralBsinclP5P•  Con=nueweeklyhighCIVswithmagnesiumandglutathionepush•  Herbaladaptogeniccomboinam•  GutsupportandGlutenfreeandlowercarbdiet–nomorenightlyTriscuits!!!

–  discussedKetogenicdiet–maynotbeappropriaterightnowgiventheexhaus=on•  Dailygentleexercisewitheitherpilates,yogaorwalking/hiking•  Deepbreathing/medita=ondaily–ateveryredlightforexample•  FasterEFTwithaprac==oner

Management

•  Atthetwoweekfollow-up,pa=entreportsfeelingmoreenergythanhasinyears

•  Atthefourweekfollow-up,shecon=nuestofeelbeVerandweightgainhasstopped

Follow-up

285_2731421

Case218YOFemalePresentsforWeightManagementandSleepIssues

•  3+yearswithsteadyweightgain,sleepissues(hardtofallasleepandfrequentwakings)andfa=gue/focusisues

•  Meds:Lexapro,TrazodoneqHS,Adderall,Synthroid•  Supplements:mul=,Bcomplex,melatoninqHS•  Diet:StandardAmericanDiet(SAD)•  Exercise:none•  Vitals:BMI33,othervitalswnl•  Labs

–  Thyroid:lowfT3,sub-op=malfT4–  Pre-dmA1c5.7–  Otherslabswnl

CaseHistory

•  Changeindiet:lowcarb,lowgrain,glutenfree,cutsugars•  Sleephygiene•  TaperofftheTrazodone,startmagnesiumqHS•  Stopcurrentpharmacybrandmul=andBcomplex,startMitoCoreandberberine•  StopSynthroidandswitchtoNatureThroidandslightincreaseindose•  Walk15-30min3-4x/wk

Management

•  Vitals:weightisup,othervitalswnl•  OffTrazodone,easiertofallasleepbuts=llwaking,s=llusingmelatonin•  FeelsslightlybeVerinthemorning,easiertogetup•  Walkingafewdaysperweekandconsideringjoiningthelocalgym

•  Ordersalivarycor=sol

6WeekFollow-Up

•  FurtherdiscussionintoHx–  Moldexposure,s=lllivesinthesamehouse,nomoldremedia=on–  Sharesbedroomw/hersisterwhosnoresandsleepswithanightlight

•  Management–  Gethometestedformold–  Sleepinanotherroomorlosethenightlight–  Adrenalsupportcombo–  AddCor=solManagerqHS–  Integratemedita=on/guidedmedita=onbeforebed

Follow-UpandManagement

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MichaelChapman,NDModerator

MelanieDorion,AGNPPresenter

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Welookforwardtohearingfromyou!

Addi.onalQues.ons?

June28,2017–WarrenBrown,NDPresents:

SpecialtyDiagnos5csforMen’sHealth:GoingBeyondthePSARegisterforupcomingLIVEGDXWebinarsonlineatWWW.GDX.NET

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HPA Axis Dysfuncon in Obesity - GDX