1、Primary Adrenal Disease,Briana Patterson, M.D. Fellow, Pediatric Endocrinology Emory University School of Medicine,Objectives,Normal adrenal physiology Common causes of primary adrenal insufficiency Evaluation of suspected adrenal insufficiency Acute and chronic management issues,Normal Adrenals,Adr
2、enal Cortex,Zona Glomerulosa: Mineralocorticoids Zona Fasiculata: Glucocorticoids Zona Reticularis: Androgens,Adrenal Histology,Capsule,Glomerulosa,Fasiculata,Reticularis,Medulla,Adrenal physiology 1: HPA axis,Adrenal physiology 2: Renin-angiotensin system,Steroid Biosynthesis,Primary adrenal insuff
3、iciency: Etiologies,Acquired Autoimmune AIDS Tuberculosis Bilateral injury Hemorrhage Necrosis Metastasis Idiopathic,Congenital Congenital adrenal hyperplasia Wolman disease Adrenal hypoplasia congenita Allgrove syndrome (AAA),Syndromes Adrenoleukodystrophy Kearns-Sayre Autoimmune polyglandular synd
4、rome 1 (APS1) APS2,Primary adrenal insufficiency: Etiologies,Acquired Autoimmune AIDS Tuberculosis Bilateral injury Hemorrhage Necrosis Metastasis Idiopathic,Tuberculosis,Adrenal Hemorrhage: Meningiococcemia,Addisons Disease,1st described in 1855 by Dr. Thomas Addison Refers to acquired primary adre
5、nal insufficiency Does not confer specific etiology Usually autoimmune (80%),Addisons Disease,Addisons,Normal,Primary adrenal insufficiency: Symptoms,Fatigue Weakness Orthostatsis Weight loss Poor appetite Neuropsychiatric Apathy Confusion Nausea, vomiting Abdominal pain Salt craving,Primary adrenal
6、 insufficiency: Physical findings,Hyperpigmentation Hypotension Orthostatic changes Weak pulses Shock Loss of axillary/pubic hair (women),Primary adrenal insufficiency: Physical findings,Primary adrenal insufficiency: Laboratory findings,Hyponatremia Hyperkalemia Hypoglycemia Narrow cardiac silhouet
7、te on CXR Low voltage EKG,Primary adrenal insufficiency: Etiologies,Congenital Congenital adrenal hyperplasia Wolman disease Adrenal hypoplasia congenita Allgrove syndrome (AAA),21-hydroxylase deficiency: Pathophysiology,Testosterone,CAH: Pathophysiology,CAH: Pathophysiology,21-hydroxylase deficienc
8、y: Physical exam,Females are unremarkable other than genitalia GU exam Clitoromegaly, posterior labial fusion, no vaginal opening Males appear normal,21-hydroxylase deficiency CAH,Classification based on enzyme activity Classic Salt wasting (Complete deficiency) Simple virilizing (Significant but pa
9、rtial defect) Non Classic Elevated enzyme levels (Mild deficiency),Primary adrenal insufficiency: Etiologies,Syndromes Adrenoleukodystrophy Kearns-Sayre Autoimmune polyglandular syndrome 1 (APS1) APS2,Primary adrenal insufficiency: Associated conditions,Autoimmune Polyglandular Syndrome I Hypoparath
10、yroidism Chronic mucocutaneous candidiasis Atrophic gastritis Adrenal insufficiency in childhood Pernicious anemia Vitiligo AIRE mutation Transcription factor Affects immune regulation,Primary adrenal insufficiency: Associated conditions,Autoimmune Polyglandular Syndrome II Autoimmune thyroiditis Ty
11、pe I diabetes mellitus Adrenal insufficiency Pernicious anemia Premature ovarian failure Genetic associations HLA haplotype, CLTA4,Evaluation,Primary adrenal insufficiency: Evaluation,0800 cortisol level ACTH level Random cortisol in ill patient ACTH stimulation test Suspected CAH Needs special eval
12、uation,Primary adrenal insufficiency: Evaluation,0800 cortisol level Levels less than 3 mcg/dL are suggestive of AI Levels greater than 11 mcg/dL exclude AI ACTH level Elevated in adrenal insufficiency ACTH readily degraded if not properly processed,Primary adrenal insufficiency: Evaluation,Random c
13、ortisol in ill patient 20 mcg/dL reassuringAdrenal Autoantibodies ACAadrenal cortex antibody Anti-21-OH-hydroxylase antibody,Primary adrenal insufficiency: EvaluationACTH Stimulation,Low dose (1 mcg) test Baseline and 30 minute cortisol levels More physiological ACTH level/stimulation Useful in cent
14、ral AI Useful for assessing recovery after chronic steroid treatment High dose (250 mcg) test Baseline, 30 and 60 minute levels Can be done IM Stronger stimulation than 1 mcg test,Primary adrenal insufficiency: EvaluationACTH Stimulation,Cortisol peaks are controversial Reported normals range betwee
15、n 16-25 mcg/dl Some providers also look at the magnitude of rise Also use ACTH to help differentiate primary vs secondary deficiency Secondary may respond to high dose, but not low Primary should fail both high and low dose,Suspected CAH: Evaluation,Newborn screening Call endo before you treat Need
16、special evaluation ACTH stimulation can be helpful in well patients with suspected nonclassic disease,17-OH progesterone 17-OH pregnenolone 11-deoxycortisol Deoxycorticosterone Androstenedione DHEA Aldosterone Cortisol ACTH Plasma renin activity,Diagnosis with 17-OH progesterone,Baseline 20 - 1,000
17、Stimulated 200 - 1,000,Baseline 10,000 - 90,000 Stimulated 20,000 - 100,000,Baseline 500 - 1,000 Stimulated 2,000-15,000,Treatment,Primary adrenal insufficiency: Acute treatment,NS volume resusitation Reverse shock Look for/treat hypoglycemia 25% dextrose New problem, suspected AI Labssteroids Estab
18、lished patient with AI Steroids,Stress dose steroids,Loading dose 50-100 mg/M2 hydrocortisone IV/IM Small/medium/large approach Infants: Hydrocortisone 25 mg Small children: Hydrocortisone 50 mg Larger children/teens: Hydrocortisone 100 mg Continue hydrocortisone with 50-100 mg/M2/day Divide q6-8 ho
19、urs May be 2-3x home dose,Primary adrenal insufficiency: Long term treatment,Daily glucocorticoid replacement (hydrocortisone) 10-15 mg/m2/day divided TID Option to change to prednisone in teen years Daily mineralocorticoid replacement Fludrocortisone 0.05-0.2 mg daily Patient education Stress cover
20、age Emergency steroid administration IM hydrocortisone (Solucortef Actovial) Medic Alert ID,Relative Steroid Potencies,Relative Steroid Potencies,When to consider AI: Patients at riskPrimary AI,History of TB Refractory shock Particularly meningococcal disease Dehydration/shock with hyperpigmentation
21、 Neonate with vomiting/dehydration/shock Other autoimmune endocrine disease History consistent with APS1 Immunodeficiency/chronic mucocutaneous candidiasis,When to consider AI: Patients at riskSecondary AI,Pituitary trauma/surgery Brain tumor Craniopharyngioma Suprasellar germ cell tumor Infiltrativ
22、e pituitary disease Sarcoidosis Histiocytosis Congenital pituitary abnormalities May have progressive loss of corticotroph function Chronic glucocorticoid therapy,Adrenal Insufficiency Summary,May be primary or secondary May be congenital or acquired Treatment is relatively simple Diagnosis is often controversial Baseline cortisol/ACTH before steroids ACTH stim test if possible Additional testing if CAH is suspected Dont forget to check the blood sugar!,
