A.C.O. S. Giovanni - Addolorata - Roma, Italia
ADRENAL INSUFFICIENCY AND ADRENAL CRISIS
TABLE: Pathogenesis of Primary Adrenal Insufficiency
TABLE: Pathogenesis of Secondary or Tertiary Adrenal Insuffciency
TABLE: Steroid Equivalents
The Authors examined adrenal insufficiency
Adrenal insufficiency consists of decreased levels of or absent hormones
produced by the adrenal glands and results from structural or functional
lesions of the adrenal cortex, the anterior pituitary gland, or the hypothalamus.
Deficit of adrenal hormones may manifest clinically as a chronic, insidious
disorder, or as an acute, life-threatening emergency. Therapy of adrenal
insufficiency is specific and includes replacement of the deficient hormones.
Chronic adrenal insufficiency is due to a variety of causes. It may be
primary (Addison's disease), due to failure of the adrenal glands. It
may also occur secondarily because of failure of the pituitary gland (hypopituitarism)
or as a tertiary insufficiency due to hypothalamic dysfunction. Iatrogenic
adrenal suppression from chronic steroid use is termed iatrogenic tertiary
adrenal insufficiency. Acute adrenal insufficiency (adrenal crisis) may
result from certain acute events, or when a person with chronic adrenal
insufficiency is subjected to stress and exhausts reserve adrenal hormones,
or when replacement hormone medication is discontinued.
PATHOPHYSIOLOGY OF THE ADRENAL GLANDS
The adrenal glands are divisble into the cortex and medulla. The adrenal cortex is essential for life and produces glucocorticoid, mineralocorticoid, and androgenic steroid hormones. The medulla secretes the catecholamines epinephrine and norepinephrine, largely under neural control. No definite clinical condition has been ascribed to hypofunction of the adrenal medulla. Most of the manifestations of adrenal insufficiency occur when the physiologic requirement for glucocorticoid and mineralocorticoid hormones exceeds the capacity of the adrenal glands to produce them.
Cortisol
The major glucocorticoid is cortisol, which is secreted in response to
direct stimulation by adrenocorticotropic hormone (ACTH) from the anterior
pituitary gland. Secretion of ACTH is governed by the hormone corticotropin-releasing
factor (CRF) from the hypothalamus. This normally occurs with a diurnal
rhythm, with the highest levels in the morning and the lowest levels in
the late evening. Upon stimulation by ACTH, the adrenal glands respond
in minutes to secrete cortisol in direct proportion to the ACTH concentration.
Cortisol is normally secreted at the rate of 20 to 25 mg/day. Through
negative feedback inhibition, the plasma cortisol level acts to suppress
ACTH release.
By an undefined mechanism, stress factors such as anoxia, trauma, infections,
and hypoglycemia can also trigger CRF and ACTH release and produce cortisol
levels several times normal. The release of CRF in response to stress
is resistant to suppression through negative feedback inhibition.
Cortisol is a potent hormone and affects the metabolism of most body tissues.
In general, cortisol acts to maintain blood glucose levels by decreasing
glucose uptake at extrahepatic sites and by providing precursors for gluconeogenesis
via protein and fat breakdown. Cortisol governs the distribution of water
between extracellular and intracellular compartments and possesses a minor
sodium-retaining effect. It also acts to enhance the pressor effects of
catecholamines on heart muscle and arterioles. In supraphysiologic amounts,
cortisol inhibits inflammatory and allergic reactions. Finally, through
negative feedback inhibition, cortisol suppresses the secretion of ACTH
and melanocyte-stimulating hormone (MSH) from the anterior pituitary gland.
Aldosterone
The major mineralocorticoid is aldosterone. The renin-angiotensin system
and plasma potassium concentration regulate aldosterone through negative
feedback loops. These mechanisms are probably of equal importance and
far more important than the minor aldosterone-stimulating effect of ACTH.
Aldosterone acts to increase sodium reabsorption and potassium excretion,
primarily in the distal tubules of the kidneys. Other tissue effects of
aldosterone are minor in comparison with its regulation of sodium and
potassium levels.
Androgens
Androgenic hormone production by the adrenal glands is regulated by ACTH
and is trivial in men in comparison with the production of these hormones
by the gonads. In women, however, androgens from the adrenal glands do
contribute a significant proportion to androgen metabolism.
Idiopathic
Primary adrenal insufficiency, or Addison's disease, is due to disease
or destruction of the adrenal cortex and has a wide variety of causes
(see Table -1). Approximately 90 percent of the adrenal cortex must be
involved before clinical manifestations of adrenal failure result. Idiopathic
atrophy of the adrenal glands is the leading cause of chronic adrenal
insufficiency. Idiopathic adrenal insufficiency has been further divided
into autoimmune (70 to 75 percent) and truly idiopathic (25 to 30 percent).
There is an overwhelming association between idiopathic adrenal insufficiency
and other autoimmune diseases. Associated diseases include diabetes mellitus,
Hashimoto's thyroiditis, pernicious anemia, and primary ovarian failure.
Other investigators have reported frequent association with hypoparathyroidism,
chronic active hepatitis, malabsorption, chronic mucocutaneous candidiasis,
alopecia, and vitiligo.
Infiltrative or Infectious
Adrenal tuberculosis has declined in frequency as a cause of Addison's
disease but is still reported to be a cause in 17 to 21 percent of the
cases. Fungal infections and other infiltrative processes are infrequent
causes of adrenal insufficiency during active, disseminated disease. Adrenal
insufficiency as a complication of the acquired immunodeficiency syndrome
(AIDS) has been reported. Infectious infiltration of the adrenal glands
with Mycobacterium avium or M. intracellulare or with cytomegalovirus
may have caused the adrenal failure. Metastatic carcinoma in the adrenal
glands is a relatively frequent finding at autopsy in patients with certain
carcinomas, but it only rarely causes adrenal insufficiency.
Bilateral Adrenal Hemorrhage
Bilateral adrenal gland hemorrhage (adrenal apoplexy) is rare. In general,
patients with a serious underlying condition whose adrenal glands are
stressed are at risk for this complication. Stress-stimulated adrenal
glands are hemorrhage prone. The association between adrenal hemorrhage
and anticoagulant therapy with heparin and dicumarol is well established.
Adrenal hemorrhage in this setting is most likely to occur between the
third and eighteenth day of anticoagulation. Sudden deterioration with
hypotension and pain in the flank, costovertebral angle, or epigastrium
should suggest this disastrous event. Associated findings may include
fever, nausea, vomiting, and disturbed sensorium. Computed tomography
and ultrasound can assist in establishing this diagnosis. Other stressful
events that have been associated with adrenal hemorrhage include surgery,
trauma, burns, convulsions, pregnancy, and adrenal vein thrombosis.
Adrenal crisis as a consequence of adrenal hemorrhage also occurs with
overwhelming septicemia and in the newborn. Fulminant septicemia with
meningococcus, pneumococcus, staphylococcus, streptococcus, Haemophilus
influenzae, and gram-negative organ-isms has been reported to cause adrenal
hemorrhage. The Waterhouse-Friderichsen syndrome is a life-threatening
disorder resulting from overwhelming septicemia due to meningococcemia.
The pa-tient is acutely ill and has shaking chills, severe headache, and
a petechial rash that may progress to extensive purpura. Bilateral adrenal
gland hemorrhage frequently occurs with this disorder. Vascular collapse
and death may result unless the patient is promptly treated.
Miscellaneous
Another cause of primary adrenal failure is bilateral adrenalectomy for
metastatic breast or prostate cancer or for Cushing's syndrome. Following
such a procedure the patient is totally dependent upon replacement corticosteroids
for life. Chemotherapeutic agents such as mitotane (o,p?-DDD) used in
treatment of Cushing's disease can produce adrenal failure. Other drugs
such as methadone, rifampin, and ketoconazole have been reported to cause
adrenal insufficiency. Finally, rare congenital and inherited disorders
can cause adrenal insufficiency.
In children, adrenal insufficiency is due to rare congenital causes or
to acquired lesions of the hypothalamus, pituitary or adrenal cortex.
By far, the most common cause of acquired chronic adrenal insufficiency
is autoimmune destruction of the adrenal glands. Type I autoimmune polyendocrinopathy
manifests with chronic mucocutaneous candidiasis, hypoparathyroidism and
Addison's disease. Type II autoimmune disease presents with adrenal failure
in association with thyroid disorder or insulin dependent diabetes mellitus.
Infections account for approximately 20 percent of the cases of pediatric
adrenal insufficiency. Among those are infiltrative destruction of the
gland by fungal infections and tuberculosis. Hemorrhage into the adrenal
glands may occur in the neonatal period as a consequence of a complicated
labor or asphyxia. Another cause of adrenal gland hemorrhage is the Waterhouse-Friderichsen
syndrome resulting from meningococcemia and producting shock. Finally,
about one-third of patients with adrenoleukodystrophy will develop adrenal
insufficiency, usually after 4 years of age.
Clinical Presentation
The clinical manifestations of chronic adrenal insufficiency develop gradually
with subtle signs and symptoms that provide a diagnostic challenge. The
clinical presentation of Addison's disease can be explained on the basis
of a deficiency of cortisol and aldosterone and a lack of feedback suppression
of ACTH and MSH.
Cortisol deficiency manifests clinically with anorexia, nausea, vomiting,
lethargy, hypoglycemia with fasting, and inability to withstand even minor
stresses without shock. The ability to excrete a free water load is also
impaired and can lead to water intoxication. Lack of aldosterone results
in impaired ability to conserve sodium and excrete potassium. The patient
with aldosterone deficiency presents with sodium depletion, dehydration,
hypotension, postural syncope, and decreased cardiac size and output.
Renal blood flow is decreased, and azotemia may develop. Hyperkalemia
is commonly seen but rarely is severe. Lack of suppression of ACTH and
MSH secretion occurs because of deficient cortisol levels and results
in increased pigmentation.
The overall clinical picture of a patient with Addison's disease is that
of one who is weak and lethargic, with loss of vigor, and fatigue on exertion.
The patient may have a feeble tachycardic pulse. Postural hypotension
and syncope are common. In spite of hypotension, the extremities usually
remain warm. Heart sounds may be soft or almost inaudible on auscultation.
Gastrointestinal (GI) symptoms are a prominent feature of chronic adrenal
insufficiency and include anorexia, nausea, vomiting, weight loss, abdominal
pain, and sometimes diarrhea.
Cutaneous manifestations of Addison's disease include increased brownish
pigmentation over exposed body areas such as the face, neck, arms, and
dorsum of the hands, and over friction or pressure points such as the
elbows, knees, fingers, toes, and nipples. Pigmentation of mucous membranes,
darkening of nevi and hair, and longitudinal pigmented bands in the nails
may be seen. Vitiligo, mucocutaneous candidiasis, and alopecia may occur
with Addison's disease that has an autoimmune cause. Women with Addison's
disease may exhibit decreased growth of axillary and pubic hair because
of adrenal androgen deficiency. This is not seen in men because of adequate
testicular androgen.
Mentally these patients vary from alert to confused. Unconsciousness is
rare unless the condition is preterminal. The sensory modalities of taste,
olfaction, and hearing may be increased. Hyperkalemic paralysis is a rare,
emergent complication of adrenal insufficiency; the patient presents with
a rapidly ascending muscular weakness which leads to flaccid quadriplegia.
Treatment of this complication consists of the intravenous administration
of glucose and insulin or bicarbonate.
Laboratory
The usual laboratory findings in patients with primary adrenal insufficiency
include hyponatremia, hyperkalemia, hypoglycemia, and azotemia. Hyponatremia
is usually mild to moderate, and severe hyponatremia (?120 mEq/L) is rare.
Hyperkalemia is usually mild, and the potassium level rarely exceeds 7
mEq/L. Initial potassium levels may be normal or low if protracted vomiting
has occurred. Rarely, hyperkalemia may be severe and cause cardiac arrhythmia
or paralysis.
Hypoglycemia is infrequent in adults with chronic adrenal insufficiency
in the absence of infection, fever or alcohol ingestion. Moderate elevation
of the blood urea nitrogen (BUN) level may occur because of dehydration
secondary to aldosterone deficiency. Azotemia is usually reversible with
rehydration.
Electrocardiographic changes include flat or inverted T waves, a prolonged
QT interval, low voltage, a prolonged PR or QRS interval, and a depressed
ST segment. The ECG changes reflective of hyperkalemia may also be present.
The chest x-ray film may show a small, narrow cardiac silhouette due to
decreased intravascular volume. A flat plate film of the abdomen may show
adrenal calcification, which is most commonly due to tuberculosis but
may occur with infection or hemorrhage.
SECONDARY AND TERTIARY ADRENAL INSUFFICIENCY
Secondary adrenal insufficiency
may be due to disease or destruction of the pituitary gland, and tertiary
insufficiency due to hypothalamic dysfunction, resulting in impaired capacity
of the pituitary to secrete ACTH. Those disorders responsible for secondary
or tertiary adrenal failure are listed in Table -2.
The most common cause of tertiary adrenal insufficiency and adrenal crisis
is iatrogenic adrenal suppression from prolonged steroid use. Rapid withdrawal
of steroids from patients with adrenal atrophy secondary to chronic steroid
use may result in collapse and death, especially under circumstances of
increased stress. Exogenous administration of glucocorticoids may cause
hypothalamic-pituitary-adrenal (HPA) suppression and subsequent adrenal
atrophy. This complication has been reported to occur not only with oral
steroids but also with those given by the intrathecal, topical, and inhalant
routes.
The mechanism of continued adrenal atrophy following discontinuation of
exogenous steroids may be a failure of normal diurnal release of CRF.
Stress-induced release of ACTH may remain intact, but the atrophic adrenal
glands are unable to secrete sufficient cortisol to meet the physiologic
requirements in response to stress. The shortest time interval or the
smallest dose at which HPA suppression occurs is unknown. As a general
rule, there is no suppression regardless of the dose if its duration of
use is less than three weeks. In addition, there is no suppression if
the dose is ?10 mg of prednisone regardless of the duration unless it
is given on an h.s. timetable. Any patient who is on more than 20 mg of
prednisone for greater than three weeks is suppressed and should have
the necessary precautions taken.
Following prolonged supraphysiologic dosages of steroids, it may take
up to 6 to 12 months for recovery of HPA function when steroids are withdrawn
completely. Until complete recovery has occurred, it is wise to assume
the patient will need basal steroid therapy and supplementary therapy
during intercurrent illness or stress. Adrenal suppression must be suspected
based upon the history of prior steroid use. When in doubt about the HPA
status of a seriously ill or deteriorating patient, steroids should be
given.
Clinical Presentation
Significant clinical and laboratory differences exist between patients
with primary and those with secondary adrenal insufficiency. With secondary
adrenal failure, the capacity of the pituitary to secrete ACTH is impaired.
The level of aldosterone is largely unaffected because of its regulation
by the renin-angiotensin system and the plasma potassium concentration.
The clinical manifestations of secondary adrenal failure are due to insufficiency
of cortisol and adrenal androgens. In addition, insufficiency of other
anterior pituitary hormones such as growth hormone, thyroid hormone, and
gonadotropic hormone may cause clinical abnormalities.
Patients with secondary adrenal insufficiency are better able to tolerate
sodium deprivation without developing shock. This is true because of intact
aldosterone secretion. Hyponatremia, hyperkalemia, and azotemia are not
prominent features of secondary failure. Hypoglycemia, however, may be
more common in patients with hypopituitarism because of concomitant growth
hormone deficiency. Hyperpigmentation does not occur with secondary failure
because ACTH and MSH are eliminated at their source, the pituitary gland.
Finally, with secondary failure, men as well as women may exhibit signs
of androgen deficiency because of insufficient gonadotopic hormone from
the pituitary.
Primary adrenal insufficiency is diagnosed by demonstrating a low baseline
plasma cortisol level and failure to increase this level in response to
exogenous administration of ACTH. Any patient who has cortisol level of
>20 microg/dl does not have adrenal insufficiency of any type. Failure
to respond to ACTH stimulation occurs because the adrenal cortex is damaged
or destroyed and has no functional capacity to respond. Secondary adrenal
insufficiency is diagnosed by demonstrating low plasma cortisol and urinary
metabolite levels that increase in a stepwise fashion with repetitive
ACTH stimulation over a period of days. A variety of tests to assess the
integrity of the HPA axis are available.
A rapid screening test can reliably distinguish patients with normal adrenal
function from those with adrenal insufficiency. This test is based on
the fact that adrenal response to a single injection of ACTH is maximal
within 1 h. Plasma for measurement of baseline cortisol level is drawn,
and then 25 units of corticotropin (synthetic ACTH) is administered subcutaneously,
intramuscularly, or intravenously. Another plasma cortisol level is obtained
30 to 60 min later. Normal persons should respond with a doubling of the
baseline cortisol level, unless the patient has an already existing high
basal level due to stress or some other factor. In this instance, the
cortisol level would not double but the patient could still have normal
physiology. Patients with primary adrenal insufficiency show no increase
in plasma cortisol levels, whereas those with secondary adrenal failure
may show no, or a slight, response to corticotropin. A normal response
is defined by a peak cortisol value of greater than or equal to 20 microg/dL.
However, both falsely normal and abnormal rapid ACTH test results have
been reported. This test should be used as a screening test, or to assess
adrenal reserve in patients previously receiving steroids, but not as
a diagnostic test for adrenocortical failure. A more prolonged period
of ACTH stimulation is necessary to confirm adrenal failure and to reliably
distinguish primary from secondary adrenal insufficiency. However, measurement
of ACTH will also help clarify this differential and will be less labor-intensive.
Glucocorticoid
Therapy of primary adrenal insufficiency consists of replacement of cortisol
and aldosterone, and, on occasion, supplemental androgen therapy in the
female patient. The usual maintenance dosage for glucocorticoid replacement
varies from 20 to 37.5 mg of cortisol per day. Various preparations may
be used (see Table -3 for steroid equivalents). A generally accepted dosage
schedule is 5 mg of prednisone in the morning followed by 2.5 mg of prednisone
in the afternoon. This simulates the normal diurnal variation of cortisol
secretion. A few patients, especially large active men, may require a
total daily dose of 10 mg of prednisone for optimum response.
Another treatment alternative is 5 mg of prednisone h.s. or 15 to 20 mg
of hydrocortisone on awakening and 5 to 10 mg in the early afternoon.
Finally, once a day dosing for prednisone is sufficient.
Mineralocorticoid
Mineralocorticoid replacement in patients with primary adrenal insufficiency
can be achieved by administration of the synthetic mineralocorticoid fludrocortisone
acetate, 0.05 to 0.2 mg/day orally. This dosage should be appropriately
reduced in patients in whom hypertension develops. It is also important
for the patient with Addison's disease to maintain an adequate dietary
salt intake.
Androgen
The woman with primary adrenal insufficiency may show signs of androgen
deficiency such as decreased growth of axillary and pubic hair. Supplemental
androgen therapy can be achieved with 2 to 5 mg of fluoxymesterone orally
per day.
Secondary Insufficiency
Treatment of secondary adrenal insufficiency differs from that of primary
adrenal insufficiency with regard to mineralocorticoid and androgen replacement.
Patients with secondary adrenal failure usually do not require mineralocorticoid
therapy and can maintain salt and fluid balance with a diet generous in
sodium chloride. In the presence of hypotension, however, supplementary
fludrocortisone acetate, 0.05 to 0.1 mg/day, is indicated. Evidence of
androgen insufficiency may occur with male and female patients with hypopituitarism.
Sufficient androgen in the female patient can be achieved with 2 to 5
mg of fluoxymesterone orally per day. Larger dosages of this preparation
or long-acting testosterone (Depo-Testosterone) can be used in the male
patient. Patients with secondary insufficiency will also require thyroid
hormone replacement.
Adrenal crisis is an acute,
life-threatening emergency that must be suspected and treated based upon
clinical impression. It is due primarily to cortisol insufficiency and
to a lesser extent, aldosterone insufficiency, and occurs when the physiologic
demand for these hormones exceeds the capacity of the adrenal glands to
produce them.
Adrenal reserve may be exhausted in patients with chronic adrenal insufficiency
when they are subjected to intercurrent illness or stress. These patients
should be taught to respond to minor febrile illness or stress by increasing
their glucocorticoid dose by 2 to 3 times the usual dose for a few days
during the illness. Mineralocorticoid dose does not need to be changed.
During an emergency from severe trauma or stress, dexamethasone 4 mg IM
can be self-administered. A variety of conditions may precipitate crisis;
these include major or minor infections, trauma, surgery, burns, pregnancy,
hypermetabolic states such as hyperthyroidism, and drugs, especially hypnotics
or general anesthetics. Adrenal crisis may also occur in patients with
chronic adrenal failure if the patient fails to or is unable to take replacement
steroid medication. The most common cause of adrenal crisis is abrupt
withdrawal of steroids from a patient with iatrogenic adrenal suppression
due to prolonged steroid use. Finally, bilateral adrenal gland hemorrhage
from fulminant septicemia or other causes can produce adrenal crisis.
Clinical Presentation
The clinical manifestations of adrenal crisis are due primarily to insufficiency
of cortisol and to a lesser extent, insufficiency of aldosterone. Patients
appear acutely ill. They are profoundly weak and may be confused. Hypotension,
especially postural hypotension, is usual. Circulatory collapse may be
profound. The pulse is feeble and rapid, and heart sounds may be soft.
Temperature elevation is common but may be due to underlying infection.
Anorexia, nausea, vomiting, and abdominal pain are almost universal. The
abdominal pain may be severe, simulating an acute abdomen. Patients in
crisis may exhibit increased motor activity which can progress to delirium
or seizures.
Laboratory findings vary. The serum sodium level is usually moderately
decreased but may be normal. Potassium levels may be normal or slightly
increased. Rarely the potassium concentration may be markedly increased,
and this can cause cardiac arrhythmias or hyperkalemic paralysis. Hypoglycemia
is characteristic and can be severe.
Treatment
Treatment must be instituted promptly based upon clinical impression and
should not be delayed for confirmatory testing of adrenal function. Therapeutic
measures in treatment of adrenal crisis include replacement of fluids
and sodium, administration of glucocorticoid, correction of hypotension
and hypoglycemia, reduction of hyperkalemia, and identification and treatment
of a precipitating cause of the crisis.
Fluids
A rapid infusion of 5% dextrose and isotonic saline should be started
immediately. This acts to correct dehydration, hypotension, hyponatremia,
and hypoglycemia. The extracellular volume deficit in the average adult
in adrenal crisis is approximately 20 percent, or 3 L. The first liter
should be given over 1 h, and 2 or 3 L may be required during the first
8 h of therapy. The functional capacity of the cardiovascular system is
reduced with adrenal insufficiency, and the usual precautions with the
rapid administration of saline should be observed.
Steroids
A water-soluable glucocorticoid should be administered promptly. As soon
as the diagnosis of adrenal crisis is entertained, 100 mg of hydrocortisone
sodium succinate (Solu-Cortef) or phosphate should be given in an intravenous
bolus. In addition, 100 mg of hydrocortisone should be added to the intravenous
solution. Usually, 200 mg of hydrocortisone is given every 6 h during
the first 24 h of therapy. Glucocorticoid therapy acts to correct hypotension,
hyponatremia, hyperkalemia, and hypoglycemia.
Mineralcorticoid therapy is not required during initial treatment of adrenal
crisis. High dosages of hydrocortisone provide sufficient mineralocorticoid
effect. As the total dosage of glucocorticoid is reduced below 100 mg/24
h, many patients need supplementary mineralocorticoid, which can be provided
as desoxycorticosterone acetate, 2.5 to 5.0 mg intramuscularly one or
twice daily. If hypotension persists despite adequate volume and corticosteroid
replacement, additional corticosteroid can be given and other causes of
hypotension should be investigated. Vasopressors may be needed to correct
hypotension. Adrenal hemorrhage should be considered, especially if the
patient is receiving anticoagulants.
Simultaneous Treatment and Testing
It is possible to treat adrenal crisis and to perform simultaneous, confirmatory
diagnostic testing for adrenal insufficiency. Physiologic saline is administered,
but instead of hydrocortisone, 4 mg of dexamethasone is added to the infusion.
Additionally, 25 units of corticotropin is added to the solution and this
liter is infused in the first hour. Blood for plasma cortisol assay is
obtained before and at the completion of the infusion. A 24-h urine collection
for measurement of 17-hydroxycorticosteroid (17-OHCS) is collected. Additional
corticotropin is added to subsequent intravenous solutions so that at
least 3 units is infused each hour for 8 h. A third blood specimen for
cortisol assay is obtained between the sixth and eighth hours of intravenous
therapy.
If the patient has primary adrenal insufficiency, all plasma cortisol
levels are low (?15 ?g/dL), and the urinary 17-OHCS is also low, confirming
the inability of the adrenals to respond to ACTH stimulation. An adequate
rise in the plasma cortisol level excludes the diagnosis of adrenal insufficiency.
A response indicative of partially intact adrenocortical reserve excludes
the diagnosis of primary adrenal failure in favor of secondary adrenal
insufficiency, but further testing is required to confirm this diagnosis.
Other methods for simultaneous diagnosis and treatment have been described.
The adrenal crisis should begin to resolve favorably within a few hours
after initiation of appropriate therapy. Intensive treatment and monitoring
should continue for 24 to 48 h. Once the patient's condition has stabilized,
the transition to an oral maintenance program can begin. Usually, 7 to
10 days are required for this transition.
The main causes of death during adrenal crisis are circulatory collapse
and hyperkalemia-induced arrhythmias. Hypoglycemia may contribute to demise
in some cases. With prompt recognition and appropriate treatment, most
patients in adrenal crisis should do well.
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Pathogenesis of Primary Adrenal Insufficiency
- Primary, chronic
- Idiopathic (autoimmune)
Infiltrative or infectious- Tuberculosis
Fungal infections
Sarcoidosis
Amyloidosis
Hemochromatosis
Acquired immunodeficiency syndrome (AIDS)
Neoplastic (metastatic) disease
Adrenoleukodystrophy
- Tuberculosis
- Hemorrhage or infarction
Bilateral adrenalectomy
Drugs
Congenital adrenal hyperplasia
Congenital unresponsiveness to ACTH
- Idiopathic (autoimmune)
- Primary, acute
- Hemorrhage (adrenal
apoplexy)
- Fulminant septicemia
Newborn
Anticoagulants
- Fulminant septicemia
- Discontinuation of replacement
steroids
- Hemorrhage (adrenal
apoplexy)
- Secondary
- Pituitary tumor (chromophobe adenoma, craniopharyngioma,
hamartoma, meningioma, glioma)
Pituitary hemorrhage or vascular accident
Postpartum pituitary infarction (Sheehan's syndrome)
Infiltrative and granulomatous disease- Sarcoidosis
Hemochromatosis
Histiocytosis X
- Sarcoidosis
- Internal carotid artery aneurysm
Head trauma (basilar skull fracture)
Infection (meningitis, cavernous sinus thrombosis)
Hypophysectomy
Pituitary gland irradiation
Isolated ACTH deficiency
- Pituitary tumor (chromophobe adenoma, craniopharyngioma,
- Tertiary
- Iatrogenic HPA suppression due to steroid therapy
Discontinuation of replacement steroids.
- Iatrogenic HPA suppression due to steroid therapy
Drug |
Equivalent |
Na+ |
Short-acting Cortisone |
25 |
2+ |
Hydrocortisone (cortisol) |
20 |
2+ |
Prednisone |
5 |
1+ |
Prednisolone |
5 |
1+ |
Methylprednisolone |
4 |
0 |
Intermediate-acting Triamcinolone |
4 |
0 |
Long-acting Dexamethasone |
0.75 |
0 |
Betamethasone |
0.6 |
0 |