原发性肾上腺疾病

1、Primary Adrenal DiseaseBriana Patterson, M.D.Fellow, Pediatric EndocrinologyEmory University School of MedicineObjectiveslNormal adrenal physiologylCommon causes of primary adrenal insufficiencylEvaluation of suspected adrenal insufficiencylAcute and chronic management issuesNormal AdrenalsAdrenal C

2、ortexZona Glomerulosa: MineralocorticoidsZona Fasiculata: GlucocorticoidsZona Reticularis: AndrogensMedullaAdrenal HistologyCapsuleGlomerulosaFasiculataReticularisMedullaAdrenal physiology 1:HPA axisAdrenal physiology 2:Renin-angiotensin systemSteroid BiosynthesisACTHCholesterolProgesteronePregnenol

3、oneCorticosterone DOC18-OH-CorticosteroneAldosteroneStAR, 20,22-desmolase3HSD21-hydroxylase11-hydroxylase18-hydroxylase18-oxidase17-OH-Pregnenolone17-OH-ProgesteroneDHEAAndrostenedione17-hydroxylase17-hydroxylase3HSDTestosteroneEstroneEstradiolaromatasearomatase17HSD17HSD3HSD17,20-lyase17,20-lyase11

4、-deoxycortisolCortisol21-hydroxylase11-hydroxylasePrimary adrenal insufficiency:EtiologiesAcquiredlAutoimmunelAIDSlTuberculosislBilateral injurylHemorrhagelNecrosislMetastasislIdiopathicCongenitallCongenital adrenal hyperplasialWolman diseaselAdrenal hypoplasia congenitalAllgrove syndrome (AAA)Syndr

5、omeslAdrenoleukodystrophylKearns-SayrelAutoimmune polyglandular syndrome 1 (APS1)lAPS2Primary adrenal insufficiency:EtiologiesAcquiredlAutoimmunelAIDSlTuberculosislBilateral injurylHemorrhagelNecrosislMetastasislIdiopathicTuberculosisAdrenal Hemorrhage:MeningiococcemiaAddisons Diseasel1st described

6、in 1855 by Dr. Thomas AddisonlRefers to acquired primary adrenal insufficiencylDoes not confer specific etiologylUsually autoimmune (80%)Addisons DiseaseAddisonsNormalPrimary adrenal insufficiency:SymptomslFatiguelWeaknesslOrthostatsislWeight losslPoor appetitelNeuropsychiatriclApathylConfusionlNaus

7、ea, vomitinglAbdominal pain lSalt cravingPrimary adrenal insufficiency:Physical findingslHyperpigmentationlHypotensionlOrthostatic changeslWeak pulseslShocklLoss of axillary/pubic hair (women)Primary adrenal insufficiency:Physical findingsPrimary adrenal insufficiency:Laboratory findingslHyponatremi

8、alHyperkalemialHypoglycemialNarrow cardiac silhouette on CXRlLow voltage EKGPrimary adrenal insufficiency:EtiologiesCongenitallCongenital adrenal hyperplasialWolman diseaselAdrenal hypoplasia congenitalAllgrove syndrome (AAA)21-hydroxylase deficiency: PathophysiologyCAH: PathophysiologyCholesterolPr

9、ogesteronePregnenoloneCorticosterone DOC18-OH-CorticosteroneAldosteroneStAR, 20,22-desmolase3HSD21-hydroxylase11-hydroxylase18-hydroxylase18-oxidase17-OH-Pregnenolone17-OH-ProgesteroneDHEAAndrostenedione17-hydroxylase17-hydroxylase3HSDTestosteroneEstroneEstradiol3HSD17,20-lyase17,20-lyase11-deoxycor

10、tisolCortisol21-hydroxylase11-hydroxylaseCAH: PathophysiologyCholesterolProgesteronePregnenoloneCorticosterone DOC18-OH-CorticosteroneAldosteroneStAR, 20,22-desmolase3HSD21-hydroxylase11-hydroxylase18-hydroxylase18-oxidase17-OH-Pregnenolone17-OH-ProgesteroneDHEAAndrostenedione17-hydroxylase17-hydrox

11、ylase3HSDTestosteroneEstroneEstradiol3HSD17,20-lyase17,20-lyase11-deoxycortisolCortisol21-hydroxylase11-hydroxylase21-hydroxylase deficiency:Physical examlFemales are unremarkable other than genitalialGU exam Clitoromegaly, posterior labial fusion, no vaginal openinglMales appear normal21-hydroxylas

12、e deficiency CAHlClassification based on enzyme activitylClassic lSalt wasting (Complete deficiency)lSimple virilizing (Significant but partial defect)lNon Classic lElevated enzyme levels (Mild deficiency)Primary adrenal insufficiency:EtiologiesSyndromeslAdrenoleukodystrophylKearns-SayrelAutoimmune

13、polyglandular syndrome 1 (APS1)lAPS2Primary adrenal insufficiency:Associated conditionslAutoimmune Polyglandular Syndrome IlHypoparathyroidismlChronic mucocutaneous candidiasislAtrophic gastritislAdrenal insufficiency in childhoodlPernicious anemialVitiligolAIRE mutation lTranscription factorlAffect

14、s immune regulationPrimary adrenal insufficiency:Associated conditionslAutoimmune Polyglandular Syndrome IIlAutoimmune thyroiditislType I diabetes mellituslAdrenal insufficiencylPernicious anemialPremature ovarian failurelGenetic associationslHLA haplotype, CLTA4 EvaluationPrimary adrenal insufficie

15、ncy:Evaluationl0800 cortisol levellACTH levellRandom cortisol in ill patientlACTH stimulation testlSuspected CAHlNeeds special evaluationPrimary adrenal insufficiency:Evaluationl0800 cortisol levellLevels less than 3 mcg/dL are suggestive of AIlLevels greater than 11 mcg/dL exclude AIlACTH levellEle

16、vated in adrenal insufficiencylACTH readily degraded if not properly processedPrimary adrenal insufficiency:EvaluationlRandom cortisol in ill patientl20 mcg/dL reassuringlAdrenal AutoantibodieslACAadrenal cortex antibodylAnti-21-OH-hydroxylase antibodyPrimary adrenal insufficiency:EvaluationACTH Sti

17、mulationlLow dose (1 mcg) testlBaseline and 30 minute cortisol levelslMore physiological ACTH level/stimulationlUseful in central AIlUseful for assessing recovery after chronic steroid treatmentlHigh dose (250 mcg) testlBaseline, 30 and 60 minute levelslCan be done IMlStronger stimulation than 1 mcg

18、 testPrimary adrenal insufficiency:EvaluationACTH StimulationlCortisol peaks are controversiallReported normals range between 16-25 mcg/dllSome providers also look at the magnitude of riselAlso use ACTH to help differentiate primary vs secondary deficiencylSecondary may respond to high dose, but not

19、 lowlPrimary should fail both high and low doseSuspected CAH:EvaluationlNewborn screeninglCall endo before you treatlNeed special evaluationlACTH stimulation can be helpful in well patients with suspected nonclassic diseasel17-OH progesteronel17-OH pregnenolonel11-deoxycortisollDeoxycorticosteronelA

20、ndrostenedionelDHEAlAldosteronelCortisollACTHlPlasma renin activityDiagnosis with 17-OH progesteroneBaseline 20 - 1,000Stimulated 200 - 1,000Baseline 10,000 - 90,000Stimulated 20,000 - 100,000 Baseline 500 - 1,000Stimulated 2,000-15,000TreatmentPrimary adrenal insufficiency:Acute treatmentlNS volume

21、 resusitationlReverse shocklLook for/treat hypoglycemial25% dextroselNew problem, suspected AIlLabssteroidslEstablished patient with AIlSteroidsStress dose steroidslLoading dosel50-100 mg/M2 hydrocortisone IV/IMlSmall/medium/large approachlInfants: Hydrocortisone 25 mglSmall children: Hydrocortisone

22、 50 mglLarger children/teens: Hydrocortisone 100 mglContinue hydrocortisone with 50-100 mg/M2/daylDivide q6-8 hourslMay be 2-3x home dosePrimary adrenal insufficiency:Long term treatmentlDaily glucocorticoid replacement (hydrocortisone)l10-15 mg/m2/day divided TIDlOption to change to prednisone in t

23、een yearslDaily mineralocorticoid replacementlFludrocortisone 0.05-0.2 mg dailylPatient educationlStress coveragelEmergency steroid administrationlIM hydrocortisone (Solucortef Actovial)lMedic Alert IDRelative Steroid PotenciesGlucocorticoid MineralocorticoidHydrocortisone1+Prednisone/Prednisolone3-

24、5+Methylprednisone5-60Dexamethasone25-500Fludrocortisone15-20+Relative Steroid PotenciesGlucocorticoid MineralocorticoidHydrocortisone1+Prednisone/Prednisolone3-5+Methylprednisone5-6-Dexamethasone25-50-Fludrocortisone15-20+When to consider AI:Patients at riskPrimary AIlHistory of TBlRefractory shocklParticularly meningococcal