52

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
- Metastasis (lung, breast, kidney)
- Lymphoma
Surgical removal
Drugs : ketoconazole, fluconazole, phenytion, metyrapone, aminoglutethimide,
mitotane
Congenital adrenal hyperplasia
Adrenomyeloneuropathy
Familial glucocorticoid deficiency / resistance

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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.

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 ( Waterhouse-
Friderichsen syndrome ) antiphospholipid syndrome

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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

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
3
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

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fine wrinkling tertiary AI

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.

2. Acute adrenal insufficiency (adrenal crisis)

Adrenal crisis
primary, secondary
tertiary AI

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hypoglycemia hyponatremia
hyperkalemia metabolic acidosis

chronic AI
adrenal crisis



1.)
2.)
3.)
Cushings syndrome hypothalamic-pituitary-adrenal 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
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

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- 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

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 lymphocytosis eosinophilia
- 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

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: CT-scan MRI

3.
Prolong ACTH stimulation test
primary AI secondary tertiary AI


- cortisol baseline
1
- 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

adrenal insufficiency

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Diagnostic approach to suspected adrenal insufficiency

Basal plasma ACTH, cortisol

30-min low-dose ACTH stimulation test

Normal Low cortisol Low cortisol

Low ACTH Low ACTH

No adrenal Secondary or tertiary Primary adrenal

insufficiency adrenal insufficiency Insufficiency

Prolong ACTH stimulation test

Cortisol response No cortisol response

Secondary or tertiary Primary adrenal

Adrenal insufficiency Insufficiency

CRH stimulation test

Exaggerated and prolonged Absent or subnormal ACTH

ACTH response response

Tertiary Secondary
adrenal insufficiency 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
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.

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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

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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