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Adrenal insufficiency ( AI )

Adrenal insufficiency
adrenal crisis
adrenal insufficiency
primary
secondary adrenal insufficiency
adrenal insufficiency
primary secondary tertiary adrenal
insufficiency 1
1 adrenal insufficiency

Primary adrenal insufficiency (Addison's disease)

Autoimmune adrenalitis (idiopathic)
- Isolated
- Polyglandular autoimmune syndrome type I II
Infection
- Tuberculosis
- Systemic fungal infection (histoplasmosis, cryptococosis, blastomycosis)
- AIDS (cytomegalo virus, bacteria, protozoa)
Adrenal hemorrhage, necrosis, infarction
- Infection : meningococcemia, pseudomonas( Waterhouse-Friderichsen
syndrome)
- Anticoagulant therapy
- Antiphospholipid syndrome
Malignancy
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- Metastasis (lung, breast, kidney)

- Lymphoma
Surgical removal
Drugs : ketoconazole, fluconazole, phenytion, metyrapone, aminoglutethimide,
mitotane
Congenital adrenal hyperplasia
Adrenomyeloneuropathy
Familial glucocorticoid deficiency / resistance

Secondary adrenal insufficiency

Pituitary or metastatic tumor
Craniopharyngioma
Infection
- Tuberculosis
- Histoplasmosis
Pituitary surgery or radiation
Postpartum pituitary necrosis (Sheehan's syndrome)
Necrosis or bleeding into pituitary macroadenoma
Lymphocytic hypophysitis
Sarcoidosis
Histiocytosis X
Empty sella syndrome
Pituitary or adrenal surgery for Cushing's syndrome (transient )

Tertiary adrenal insufficiency

Long term glucocorticiod therapy
Lesion of the pituitary stalk or hypothalamus
Head trauma
Cranial radiation
: Oelkers W 1996:1207.
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Primary adrenal insufficiency ( Addisons disease )

Autoimmune adrenalitis ( idiopathic)
70-80 primary AI (isolated)
( polyglandular autoimmune syndrome )

Infection granulomatous disease ( tuberculosis )
histoplasmosis cryptococcosis blastomycosis

cytomegalovirus necrotizing adrenalitis
Metastatic carcinoma

lymphoma
Adrenal hemorrhage , necrosis , thrombosis anticoagulant
warfarin , heparin meningococcemia pseudomonas ( WaterhouseFriderichsen syndrome ) antiphospholipid syndrome
Surgery :

Cushings
disease
Drugs : AI

cortisol ketoconazole ,flucomazole, phenytoin, metyrapone,
aminoglutethimide cytotoxic mitotane
Congenital adrenal hyperplasia cortisol
cortisol
Adrenomyeloneuropathy
x-linked recessive long-chain fatty acids

AI
Fanrelial glucocorticoid deficiency resistance

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Secondary adrenal insufficiency

hypopituitarism
(Sheehans syndrome)
craniopharyngioma
lymphocytic hypophysitis, sarcoidosis, histiocytosis X
Tertiary adrenal insufficiency

AI
corticotropin releasing hormone (CRH) ACTH cortisol

2
1. Chronic adrenal insufficiency
primary AI

zona glomerulosa ( aldosterone)

zona fasciculata ( cortisol)

zona reticularis ( androgen) 3

90
aldosterone
(postural hypotension) 2
secondary primay AI
hyperpigmentation
TSH
gonadotropin (FSH, LH)
growth hormone
fine wrinkling tertiary AI

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Cushings syndrome
secondary tertiary AI
bitemporal hemianopia
AI 2
2 Clinical manifestations of Adrenal Insufficiency
Primary , secondary and tertiary adrenal insufficiency
Tiredness, weakness, mental depression
Anorexia, weight loss
Dizziness, orthostatic hypotension
Nausea, vomitting, diarrhea
Hyponatremia, hypoglycemia, mild normochromic normocytic anemia,
lymphocytosis, eosinophilia
Primary adrenal insufficiency and associated disorders
Hyperpigmentation
Hyperkalemia
Vitiligo
Autoimmune thyroid disease
Central nervous system symptoms in adrenomyeloneuropathy
Secondary and tertiary adrenal insufficiency
Pale skin without marked anemia
Amenorrhea, decrease libido and potency
Scanty axillary and pubic hair
Small testicles
Secondary hypothyroidism
Prepubertal growth deficit, delayed puberty
Headache, visual symptoms
Diabetic insipidus
: Oelkers W.1996:1207.
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2. Acute adrenal insufficiency (adrenal crisis)

Adrenal crisis
primary,
secondary tertiary AI

hypoglycemia hyponatremia hyperkalemia metabolic acidosis

chronic AI adrenal crisis


1.)
2.)
3.)
Cushings syndrome hypothalamic-pituitaryadrenal axis
adrenal crisis adrenal hemorrhage, necrosis
thrombosis meningococcemia, pseudomonas, anticoagulant,
postpartum pituitary necrosis (Sheehans syndrome), necrosis bleeding
(pituitary apoplexy)

AI

AI
AI

cortisol ACTH (8.00-9.00) plasma cortisol < 5 g/dl
plasma cortisol 20 g/dl AI
plasma ACTH cortisol primary AI
plasma ACTH cortisol secondary tertiary AI
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AI dynamic test
1. Rapid ACTH stimulation test

- cortisol 8.00 .
- Cosyntropin 250 g
8.00 .
- cortisol 30 60

plasma cortisol 20 g/dl 7 g/dl

baseline plasma cortisol 20 g/dl AI
AI dexamethasone

2. Insulin induced hypoglycemia

- 0.9% normal saline

short acting insulin 0.05-0.1 unit/kg
- plasma glucose cortisol 0, 30, 60, 90, 120,

plasma glucose < 40 mg/dl cortisol 20 g/dl

primary AI

3. Short metyrapone test

- metyrapone 30 mg/kg 24.00 .

- cortisol 11-deoxycortisol 8.00 .

cortisol 8 g/dl metyrapone

11-deoxycortisol 7 g/dl (200 nmol/L)
metyrapone test

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AI primary, secondary tertiary

AI
1. secondary tertiary AI hyperpigmentation
plasma ACTH

Cushings syndrome
2.
primary AI
- Complete blood count :
normochromic normocytic megaloblastic anemia pernicious anemia
polyglandular autoimmune syndrome lymphocytosiseosinophilia

- Blood chemistry : fasting hypoglycemia,

hyponatremia, hyperkalemia, hyperchloremic metabolic acidosis hyponatremia
glucocorticoid ADH hyperkalemia
aldosterone hypercalcemia

- cortisol ACTH cortisol
ACTH
- Adrenal autoantibody : autoimmune adrenalitis
- : x-ray abdomen calcification
CT scan abdomen
lymphoma
Secondary tertiary AI
primary AI
hyperkalemia aldosterone ACTH , hyperkalemia
hypercalcemia
: CT-scan MRI

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3.
Prolong ACTH stimulation test
primary AI secondary tertiary AI

1

- cortisol baseline
- Cosyntropin 250 g 8 48

- cortisol 8 48
: primary AI cortisol secondary
tertiary AI cortisol 20 g/dl
2

- cortisol 8.00 . 1, 2, 3, 4, 5
14.00 . 3 5
- 8.00 . cortosyn depot 1 mg

: primary AI cortisol secondary
tertiary AI cortisol cortisol 14.00 . (6
dose ) 20 g/dl
ACTH

Corticotropin releasing hormone (CRH) test
secondary tertiary AI

- 4
- cortisol ACTH 15, 0, 15, 30,45, 60, 90
120 CRH 1 g/kg
: ACTH 2-4 base line cortisol
20 g/dl 20-30 CRH
secondary AI ACTH tertiary AI
ACTH
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adrenal insufficiency
Diagnostic approach to suspected adrenal insufficiency
Basal plasma ACTH, cortisol
30-min low-dose ACTH stimulation test

Normal

No adrenal
insufficiency

Low cortisol
Low ACTH
Secondary or tertiary
adrenal insufficiency

Low cortisol
Low ACTH
Primary adrenal
Insufficiency

Prolong ACTH stimulation test

Cortisol response

No cortisol response

Secondary or tertiary
Adrenal insufficiency

Primary adrenal
Insufficiency

CRH stimulation test

Exaggerated and prolonged

ACTH response

Absent or subnormal
ACTH response

Tertiary
adrenal insufficiency

Secondary
adrenal insufficiency

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1.Adrenal crisis

Emergency treatment
1.
18 20 glucose,
electrolyte, cortisol, ACTH ,CBC
2.
0.9% Nacl 5% dextrose/NSS 2000-3000 cc.
load vital signs, urine output, CVP
vital signs
(pulmonary rales, crepitation)
3.
hydrocortisone 100 mg
hydrocortisone 300 mg in 5% dextrose/NSS IV drip in 24 hours hydrocortisone 100 mg.
8 hours dexamethasone 4 mg.
( 12-18
plasma urine cortisol ACTH stimulation test)
24
adrenal crisis
: mineralocorticoid
sodium retention

hydrocortisone
mineralocorticoid

4. General supportive care
Subacute treatment
1. 0.9% NaCl 5% dextrose/NSS
24-48

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2. hydrocortisone 300 mg. 200 mg. 100 mg.

1-3 vital signs 24
3. adrenal crisis
4. adrenal insufficiency
rapid ACTH stimulation test insulin
induced hypoglycemia
2. Chronic adrenal insufficiency
AI
primary AI glucocorticoid mineralocorticoid
fludrocortisone ( Flurinef ) 0.1 mg. -1 cortisone
acetate
secondary tertiary AI glucocorticoid
prednisolone ( 5mg. ) 5-7.5 mg. 1
3 dexamethasone 0.5 mg.


adrenal crisis chronic adrenal
insufficiency
chronic adrenal insufficiency glucocorticoid
mineralocorticoid physiologic dose physiologic stress
adrenal crisis
Minor stress at home (minor febrile, viral type illness)
- glucocorticoid 3
3
- mineralocorticoid

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Major stress at hospital/surgery (severe febrile illness, sepsis, myocardial infarction)

- glucocorticoid 10 hydrocortisone 100 mg.
8 hydrocortisone 100 mg.
8 24
- stress

other stress
- stress hydrocortisone 50 mg.
prednisolone 10 mg. dexamethasone 2 mg.

- stress barium enema, endoscope, arteriography
hydrocortisone 100 mg. dexamethasone 4 mg.
1
-

1. Burke CW. Primary adrenocortical failure. In : Grossman A ed. Clinical Endocrinology.
London : Blackwell Scientific Publications 1992:393-404.
2. Nerup J. Addisons disease clinical studies : A report of 108 casses. Acta Endocrinol
1974;76:127-41.
3. Oelkers W. Adrenal Insufficiency. N Engl J Med 1996; 335(16):1206-12.
4. Vita JA, Silverberg SJ, Goland RS, et al. Clinical clues to the cause of Addisons
disease. Am J Med 1958;78:461-6.
5. Williams GH, Dluhy RG. Hypofunction of adrenal cortex. In Harrisons Principle of
Internal Medicine 14th eds. Philadelphia 1998:547-65.

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