ADRENAL INSUFFICIENCY &

ADRENAL CRISIS

Emergency Medicine Ch 217

By Judith Tintinalli, MD

Presentation by Jack Hay, DO

12/15/05
 Introduction
• Medulla secretes epinephrine and
norepinephrine into adrenal veins when
stimulated
• Cortex secretes steroids regulating
metabolism, vascular tone, cardiac
contractility, TBW/Na/K balance,
androgenic function
 Adrenal Physiology
• Cyclic secretion controlled by time of day,
HPA axis, renin-angiotensin system, serum
potassium levels
• Stress increases basal glucocorticoid and
mineralcorticoid levels 5-10 fold
– Occurs within minutes
 Adrenal Failure
• Basal failure results in adrenal insufficiency
– Leads to insidious wasting disease
• Stress failure results in adrenal crisis
• Life-threatening
• Absence of glucocorticoids is most critical
 Corticosteroids
• Three classes (by effect):
– Glucocorticoids
– Mineralcorticoids
– Androgenic steroids
 Glucocorticoids
• Regulate fat, glucose, protein metabolism
• Catecholamine and -adrenergic receptor
synthesis
• Maintain vascular tone and cardiac
contractility
• Control endothelial integrity/vascular
permeability
 Glucocorticoids
• Cortisol
– Controlled by HPA axis
– Hypothalamus  CRH and arginine
vasopressin in circadian rhythm (max 2-4am)
– Anterior Pituitary  ACTH
– Adrenal cortex  cortisol
– Peak @ 8am; declines throughout day
 Glucocorticoids
• Cortisol
– 25mg produced daily (non-stressed)
– 5-10% free and physiologically active
– Remainder bound to cortisol-binding globulin
• Becomes uncoupled in times of stress
– Negatively feeds back to control hypothalamus
• Role in adrenal insufficiency
 Mineralcorticoids
• Regulated via renin-angiotensin system &
serum potassium levels
– Diminished GFR  juxtaglomerular apparatus
release of prorenin
– Aldosterone release  Na & H2O resorption at
distal tubules (K is lost)
– Minor hyperkalemia can stimulate aldosterone
secretion directly
 Adrenal Androgens
• Controlled by ACTH
• Diurnal pattern (like cortisol)
• Significant source of androgens in females
– Can cause signs/symptoms seen in adrenal
insufficiency
 Adrenal Insufficiency
• Primary = failure of adrenal glands
• Secondary = failure of HPA axis
– Usually due to chronic exogenous
glucocorticoid administration
– pituitary failure
• Tertiary = Hypothalamic dysfunction
 Primary Adrenal Insufficiency
• Loss of all three types of adrenal steroids
• 90% of glands must be destroyed to manifest
clinically
– High functional reserve
• Adrenoleukodystrophy = X-linked inherited d/o of
very-long-chain fatty acid metabolism
– Progressive neurological symptoms from
demyelination
 Primary Adrenal Insufficiency
• Addison disease = m.c. autoimmune d/o
• Thrombosis/hemorrhage
– Sepsis, DIC, antiphospholipid syndrome
• Infiltrative diseases
– Bilateral cancer metastasis
– Amyloidosis, hemosiderosis (rare)
 Primary Adrenal Insufficiency
• TB = m.c. infectious cause worldwide
• HIV = m.c. infectious cause in US
– 50% have degree of destruction
– Only 5% have clinical symptoms of A.I.
– CMV infection, ketoconazole use, macrophage-
released cytokines are risk factors
Secondary Adrenal Insufficiency

• HPA axis failure

– deficiency of glucocorticoids and adrenal androgens
– mineralcorticoids are unaffected
• #1 cause=chronic exogenous glucocorticoid
– suppresses diurnal CRH/AV release
– both time- and dose-related
– reversible
• recovery may take up to a year
Secondary Adrenal Insufficiency

• Less common causes

– Postpartum necrosis (Sheehan syndrome)
– Adenoma hemorrhage(s)
– Pituitary destruction from head trauma
– typically have associated focal neurological
changes, visual deficits, diabetes insipidus or
panhypopituitarism
Secondary Adrenal Insufficiency

MYTHBUSTERS!
• Short course (2-3 weeks) is unlikely to
suppress the HPA axis
• Daily doses of prednisone 5mg or less are
unlikely to cause secondary insufficiency
 Chronic Insufficiency
CLINICAL PRESENTATION
• Nonspecific
– Fatigue, anorexia, weight loss, loss of libido
• Neurological
– Headaches, visual changes, diabetes insipidus
• Gastrointestinal
– Pain, nausea, vomiting, diarrhea
 Chronic Insufficiency
CLINICAL PRESENTATION
• Hypotension/Orthostasis
• Cachexia
– Thin axillary and pubic hair in women
• Hypoglycemia
• Normocytic anemia, lymphocytosis,
eosinophilia
 Chronic Insufficiency
CLINICAL PRESENTATION
• Hyperpigmentation
– Pressure points, axillae, palmar creases,
perineum, oral mucosa
– Usually seen early in primary AI
• Pallor out of proportion to anemia
– Seen in secondary AI
 Chronic Insufficiency
CLINICAL PRESENTATION
• Hyponatremia
– Primary = lack of aldosterone & Na wasting
– Secondary = vasopressin secretion & H2O loss
• Hyperkalemia
– Only occurs in primary
– mild with associated azotemia & met acidosis
 Adrenal Crisis
CLINICAL PRESENTATION
• Life-threatening emergency
• May be primary or secondary
• HYPOTENSION
– Typically resistant to catecholamine and IVF
resuscitation
 Adrenal Crisis
CLINICAL PRESENTATION
• Abrupt adrenal failure usually from gland
hemorrhage or thrombosis
– Anticoagulation
– DIC
– Sepsis (Waterhouse-Friderichsen syndrome)
– Usually have abdominal and flank pain
– Can resemble ruptured AAA!!!
 Adrenal Crisis
CLINICAL PRESENTATION
• Catastrophic HPA axis failure
– Head trauma
– Hemorrhage of pituitary adenoma
– Post-partum herniation (Sheehan syndrome)
– Usually neurological deficits, headaches, visual
field cuts and diabetes insipidus
 Diagnosis
• Short corticotropin stim test
– Get baseline level
– Inject 250gm cosyntropin (IV or IM)
– Measure plasma cortisol level in 60 minutes
– Excluded if basal or test level is > 525 nmol/L
• Plasma cortisol levels between 8am-9am
– Level <83 nmol/L rules IN
– Level >525 nmol/L rules OUT
 Treatment – stable patient
• Admit to internist for stim test

“Other tests of adrenal function are much too time-

consuming and cumbersome to warrant their use
in the ED” – the Tint-ster
 Treatment – stress or rescue
• Base the dose of suppressive therapy on the
severity of the stressful even (Table 217-3)
• Use glucocorticoids only (no mineralcorticoids)
• 100mg bolus of IV hydrocortisone followed by
infusion of 200mg IV over next 24 hours
• Correct volume and sugar deficits with D5NS
• Dexamethasone is of no utility
 Summary
• “Unexplained hyponatremia and
hyperkalemia in the setting of hypotension
unresponsive to catecholamine and fluid
administration… should receive 100mg
hydrocortisone intravenously.”
 Questions
1. Failure of the adrenal gland to secrete basal levels of
steroids results in adrenal insufficiency. T/F
2. TB is the most common infectious cause of adrenal
insufficiency in the US. T/F
3. Excess cortisol inhibits CRH and AV secretion leading
to adrenal failure. T/F
4. Hyponatremia and hyperkalemia are only seen in adrenal
crisis and not in chronic adrenal insufficiency. T/F
5. High dose steroids for treatment of adrenal crisis should
only be given after a positive corticotropin stim test. T/F
 Answers
1. T
2. F – TB is most common worldwide but it is HIV in the
US (less than 5% with failure will have clinical AI).
3. T
4. F – hyperkalemia occurs only in secondary chronic AI
(versus primary AI) but hyponatremia and hyperkalemia
are common in both insufficiency and acute crisis– vitals
and history dictate acute versus chronic.
5. F – takes too long. Give steroids to the unstable patient
with high suspicion.