Primary Adrenal Disease

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Primary Adrenal Disease

• Briana Patterson, M.D.
• Fellow, Pediatric Endocrinology
• Emory University School of Medicine

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Objectives

• Normal adrenal physiology
• Common causes of primary adrenal insufficiency
• Evaluation of suspected adrenal insufficiency
• Acute and chronic management issues

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Normal Adrenals
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Adrenal Cortex
Zona Glomerulosa Mineralocorticoids Zona
Fasiculata Glucocorticoids Zona Reticularis
Androgens
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Adrenal Histology
Glomerulosa
Reticularis
Capsule
Fasiculata
Medulla
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Adrenal physiology 1HPA axis
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Adrenal physiology 2Renin-angiotensin system
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Steroid Biosynthesis
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Primary adrenal insufficiencyEtiologies

• 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 syndrome 1 (APS1)
• APS2

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Primary adrenal insufficiencyEtiologies

• Acquired
• Autoimmune
• AIDS
• Tuberculosis
• Bilateral injury
• Hemorrhage
• Necrosis
• Metastasis
• Idiopathic

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Tuberculosis
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Adrenal HemorrhageMeningiococcemia
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Addisons Disease

• 1st described in 1855 by Dr. Thomas Addison
• Refers to acquired primary adrenal insufficiency
• Does not confer specific etiology
• Usually autoimmune (80)

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Addisons Disease
Addisons
Normal
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Primary adrenal insufficiencySymptoms

• Fatigue
• Weakness
• Orthostatsis
• Weight loss
• Poor appetite
• Neuropsychiatric
• Apathy
• Confusion
• Nausea, vomiting
• Abdominal pain
• Salt craving

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Primary adrenal insufficiencyPhysical findings

• Hyperpigmentation
• Hypotension
• Orthostatic changes
• Weak pulses
• Shock
• Loss of axillary/pubic hair (women)

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Primary adrenal insufficiencyPhysical findings
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Primary adrenal insufficiencyLaboratory findings

• Hyponatremia
• Hyperkalemia
• Hypoglycemia
• Narrow cardiac silhouette on CXR
• Low voltage EKG

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Primary adrenal insufficiencyEtiologies

• Congenital
• Congenital adrenal hyperplasia
• Wolman disease
• Adrenal hypoplasia congenita
• Allgrove syndrome (AAA)

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21-hydroxylase deficiency Pathophysiology
Testosterone
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CAH Pathophysiology
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CAH Pathophysiology
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21-hydroxylase deficiencyPhysical exam

• Females are unremarkable other than genitalia
• GU exam Clitoromegaly, posterior labial fusion,
  no vaginal opening
• Males appear normal

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21-hydroxylase deficiency CAH

• Classification based on enzyme activity
• Classic
• Salt wasting (Complete deficiency)
• Simple virilizing (Significant but partial
  defect)
• Non Classic
• Elevated enzyme levels (Mild deficiency)

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Primary adrenal insufficiencyEtiologies

• Syndromes
• Adrenoleukodystrophy
• Kearns-Sayre
• Autoimmune polyglandular syndrome 1 (APS1)
• APS2

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Primary adrenal insufficiencyAssociated
conditions

• Autoimmune Polyglandular Syndrome I
• Hypoparathyroidism
• Chronic mucocutaneous candidiasis
• Atrophic gastritis
• Adrenal insufficiency in childhood
• Pernicious anemia
• Vitiligo
• AIRE mutation
• Transcription factor
• Affects immune regulation

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Primary adrenal insufficiencyAssociated
conditions

• Autoimmune Polyglandular Syndrome II
• Autoimmune thyroiditis
• Type I diabetes mellitus
• Adrenal insufficiency
• Pernicious anemia
• Premature ovarian failure
• Genetic associations
• HLA haplotype, CLTA4

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Evaluation
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Primary adrenal insufficiencyEvaluation

• 0800 cortisol level
• ACTH level
• Random cortisol in ill patient
• ACTH stimulation test
• Suspected CAH
• Needs special evaluation

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Primary adrenal insufficiencyEvaluation

• 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

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Primary adrenal insufficiencyEvaluation

• Random cortisol in ill patient
• gt20 mcg/dL reassuring
• Adrenal Autoantibodies
• ACAadrenal cortex antibody
• Anti-21-OH-hydroxylase antibody

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Primary adrenal insufficiencyEvaluationACTH
Stimulation

• Low dose (1 mcg) test
• Baseline and 30 minute cortisol levels
• More physiological ACTH level/stimulation
• Useful in central 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

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Primary adrenal insufficiencyEvaluationACTH
Stimulation

• Cortisol peaks are controversial
• Reported normals range between 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

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Suspected CAHEvaluation

• Newborn screening
• Call endo before you treat
• Need 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

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Diagnosis with 17-OH progesterone
Baseline 10,000 - 90,000 Stimulated
20,000 - 100,000
Baseline 500 - 1,000 Stimulated
2,000-15,000
Baseline 20 - 1,000 Stimulated 200
- 1,000
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Treatment
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Primary adrenal insufficiencyAcute treatment

• NS volume resusitation
• Reverse shock
• Look for/treat hypoglycemia
• 25 dextrose
• New problem, suspected AI
• Labs?steroids
• Established patient with AI
• Steroids

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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 hours
• May be 2-3x home dose

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Primary adrenal insufficiencyLong 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 coverage
• Emergency steroid administration
• IM hydrocortisone (Solucortef Actovial)
• Medic Alert ID

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Relative Steroid Potencies
Glucocorticoid Mineralocorticoid
Hydrocortisone 1
Prednisone/ Prednisolone 3-5
Methylprednisone 5-6 0
Dexamethasone 25-50 0
Fludrocortisone 15-20
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Relative Steroid Potencies
Glucocorticoid Mineralocorticoid
Hydrocortisone 1
Prednisone/ Prednisolone 3-5
Methylprednisone 5-6 -
Dexamethasone 25-50 -
Fludrocortisone 15-20
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When to consider AIPatients at riskPrimary AI

• History of TB
• Refractory shock
• Particularly meningococcal disease
• Dehydration/shock with hyperpigmentation
• Neonate with vomiting/dehydration/shock
• Other autoimmune endocrine disease
• History consistent with APS1
• Immunodeficiency/chronic mucocutaneous candidiasis

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When to consider AIPatients at riskSecondary AI

• Pituitary trauma/surgery
• Brain tumor
• Craniopharyngioma
• Suprasellar germ cell tumor
• Infiltrative pituitary disease
• Sarcoidosis
• Histiocytosis
• Congenital pituitary abnormalities
• May have progressive loss of corticotroph
  function
• Chronic glucocorticoid therapy

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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!