Adrenal Failure

Hypotension, hyperkalemia, hypercalcemia, hyperpigmentation.

CAUSES

disease of the adrenal glands (primary adrenal failure, Addison's disease),

deficiency of cortisol and aldosterone and elevated plasma adrenocorticotropic hormone (ACTH)

ACTH deficiency caused by disorders of the pituitary or hypothalamus (secondary adrenal failure), with deficiency of cortisol alone.

Primary adrenal failure

most often is due to autoimmune adrenalitis, which may be associated with other endocrine deficits (e.g., hypothyroidism). Infections of the adrenal gland such as tuberculosis and histoplasmosis also may cause adrenal failure.

Hemorrhagic adrenal infarction may occur in the postoperative period, in coagulation disorders and hypercoagulable states, and in sepsis. Adrenal hemorrhage often causes abdominal or flank pain and fever; CT scan of the abdomen reveals high-density bilateral adrenal masses.

Adrenoleukodystrophy causes adrenal failure in young males.

Adrenal failure may develop in patients with AIDS, caused by disseminated cytomegalovirus, mycobacterial or fungal infection, adrenal lymphoma, or treatment with ketoconazole, which inhibits steroid hormone synthesis.

Secondary adrenal failure

is due most often to glucocorticoid therapy; ACTH suppression may persist for a year after therapy is stopped.

Any disorder of the pituitary or hypothalamus can cause ACTH deficiency, but usually other evidence of these disorders can be seen.

Clinical findings.

anorexia, nausea, vomiting, weight loss, weakness, and fatigue.

Orthostatic hypotension and hyponatremia are common.

shock may suddenly develop that is fatal unless treated promptly. ADRENAL CRISIS

All these symptoms are due to cortisol deficiency and occur in primary and in secondary adrenal failure

Hyperpigmentation (due to marked ACTH excess) and hyperkalemia and volume depletion (due to aldosterone deficiency) occur only in primary adrenal failure.

adrenal crisis

triggered by illness, injury, or surgery..

Diagnosis.

The short cosyntropin (Cortrosyn) stimulation test is used for diagnosis.

Cosyntropin, 250 mu g, is given IV or IM,

plasma cortisol is measured 30 minutes later.

normal response : stimulated plasma cortisol > 20 mu g/dl.

This test detects primary and secondary adrenal failure, except within a few weeks of onset of pituitary dysfunction

Primary vs secondary adrenal failure

PRIMARY: Hyperkalemia, hyperpigmentation, or other autoimmune endocrine deficits

SECONDARY: deficits of other pituitary hormones, symptoms of a pituitary mass (e.g., headache, visual field loss), or known pituitary or hypothalamic disease. Radiographic evidence of adrenal enlargement or calcification indicates that the cause is infection or hemorrhage.

plasma ACTH level primary adrenal failure (in which it is elevated markedly)

secondary adrenal failure. Most cases of primary adrenal failure are due to autoimmune adrenalitis, but other causes should be considered.

Therapy for adrenal failure

Adrenal crisis with hypotension must be treated immediately. Patients should be evaluated for an underlying illness that precipitated the crisis.

If the diagnosis of adrenal failure is known

hydrocortisone, 50 mg IV q8h The dose of hydrocortisone is decreased gradually over several days as symptoms and any precipitating illness resolve, then is changed to oral maintenance therapy.

0.9% saline with 5% dextrose should be infused rapidly until hypotension is corrected

Mineralocorticoid replacement is not needed until the dose of hydrocortisone is less than 100 mg/day.

If the diagnosis of adrenal failure has not been established

single dose of dexamethasone, 10 mg IV and a rapid infusion of 0.9% saline with 5% dextrose should be started.

A Cortrosyn stimulation test should be performed

Dexamethasone is used because it does not interfere with subsequent measurements of cortisol.

After the 30-minute plasma cortisol measurement, hydrocortisone, 50 mg IV q8h, should be given until the test result is known.

Maintenance therapy

all patients with adrenal failure necessitates cortisol replacement with prednisone

most patients with primary adrenal failure also require replacement of aldosterone with fludrocortisone.

Prednisone, 5 mg PO every morning and 2.5 mg PO every evening, should be started. The dose is adjusted to eliminate symptoms and signs of cortisol deficiency or excess, with most patients requiring between 5 mg PO every morning and 5 mg PO bid.

Concomitant therapy with rifampin, phenytoin, or phenobarbital accelerates glucocorticoid metabolism and increases the dose requirement.

During illness, injury, or the perioperative period, the dose of prednisone must be increased. For minor illnesses, the patient should double the dose for 3 days. If the illness resolves, the maintenance dose is resumed.

Vomiting requires immediate medical attention, with IV glucocorticoid therapy and IV fluid. Patients can be given a prefilled syringe of dexamethasone, 4 mg, to be self-administered IM for vomiting or severe illness if medical care is not immediately available.

For severe illness or injury, hydrocortisone, 50 mg IV q8h, should be given, with the dose tapered as severity of illness wanes. The same regimen is used in patients undergoing surgery, with the first dose of hydrocortisone given preoperatively. Usually, the dose can be reduced to maintenance therapy 3-4 days after uncomplicated surgery.

In primary adrenal failure, fludrocortisone, 0.1 mg PO qd, should be given, along with liberal salt intake. The dose is adjusted to maintain BP (supine and standing) and serum potassium within the normal range; the usual dosage is 0.05-0.3 mg PO qd.

Patients should be educated in management of their disease, including adjustment of prednisone dose during illness. They should wear a medical identification tag or bracelet.