adrenal insufficiency

Etiology

• primary
  • bilateral adrenal destruction
    • autoimmune adrenalitis (most common cause)
    • infections: tuberbulosis, histoplasmosis
  • bilateral adrenal hemorrhage
    • anticoagulation
  • lymphoma
  • sarcoidosis
  • metastases to the adrenals
  • agents that inhibit steroid synthesis
    • ketoconazole
    • adrenolytic agents
    • etomidate
    • metyrapone
  • agents that induce cortisol metabolism
    • rifampin
    • phenytoin
    • phenobarbital
• secondary
  • pituitary or hypothalamic pathology.
    • failure of ACTH secretion (pituitary insufficiency)
      • glucocorticoid use most common cause of secondary adrenal insufficiency)
        • recent discontinuation of corticosteroid therapy, & up to 1 year after corticosteroid withdrawal
        • failure to increase chronic corticosteroid therapy in times of stress

* also see Addison's disease

Clinical manifestations

• acute adrenal insufficiency
  • anemia
  • hypotension, orthostasis
  • acute onset abdominal, back or flank pain may occur with adrenal hemorrhage
• chronic adrenal insufficiency
  • symptoms
    • weakness & fatigue (100%)
    • anorexia (100%)
    • nausea/vomiting & diarrhea
    • muscle, joint & abdominal pain (10%)
    • postural dizziness
    • salt craving
  • signs
    • weight loss (100%)
    • hyperpigmentation (90%, primary adrenal insufficiency only, ACTH high)
    • orthostatic hypotension (90%)
    • adrenal calcification (10%, primary disease)
    • vitiligo (5%, primary disease)

Laboratory

• serum cortisol; serum albumin; serum free cortisol
  • 8 AM serum cortisol < 3 ug/dL confirms adrenal insufficiency
  • 8 AM serum cortisol > 18 ug/dL excludes adrenal insufficiency
  • a random serum cortisol > 12 mg/dL in critically ill patients with low serum albumin makes adrenal insufficiency unlikely
• serum cortisol & serum aldosterone are low
• plasma ACTH is high in primary adrenal insufficiency
  • next diagnostic test after adrenal insufficiency confirmed
• plasma renin activity is high
• basic metabolic panel
  • serum glucose: hypoglycemia
  • serum sodium: hyponatremia (except when due to pituitary insufficiency)
  • serum potassium:
    • hyperkalemia (except when due to pituitary insufficiency)
  • serum calcium: hypercalcemia
  • serum bicarbonate: metabolic acidosis (mild)
• cosyntropin stimulation test confirms diagnosis in patients with low or non-diagnostic serum cortisol
  • most useful when AM serum cortisol is 4-12 ug/dL
  • a stimulated serum cortisol of > 18 ug/dL excludes adrenal insufficiency
  • not needed when AM serum cortisol < 3 ug/dL
• 24 hour urinary free cortisol is low
• 21-hydroxylase Ab in serum for autoimmune adrenalitis
• complete blood count:
  • eosinophilia
  • anemia with adrenal hemorrhage
• see ARUP consult

Radiology

• CT of abdomen (plasma ACTH high)*
  • adrenal often appear atrophic with autoimmune adrenalitis
  • adrenals may be enlarged or normal in size with tuberculosis
  • adrenals enlarge with lymphoma, sarcoidosis, histoplasmosis, bilateral adrenal hemorrhage
• MRI of pituitary (plasma ACTH low)*

* laboratory confirmed adrenal insufficiency

Complications

• disease interaction(s) of hypothyroidism with adrenal insufficiency

Management

• adrenal crisis characterized by hypotension & acute infection
  • hydrocortisone 100 mg IV
• administration of glucocorticoids to patients with septic shock or early ARDS should be based on clinical criteria, not on results from ACTH stimulation tests
• consider hydrocortisone for septic shock, especially with poor response fluid resuscitation & vasopressors
  • hydrocortisone 200 mg IV daily divided QID, or as bolus of 100 mg followed by continuous infusion at 10 mg/hour (240 mg daily)
• consider glucocorticoids in moderate doses for patients with early severe ARDS (PaO2/FiO2 <200) & before day 14 in patients with refractory ARDS
  • methylprednisolone 1 mg/kg daily IV continuous infusion
• septic shock & early ARDS:
  • dosage unclear
  • duration:
    • least 7 days before glucocorticoids are tapered (assuming no recurrence of sepsis or shock),
    • early ARDS, least 14 days before tapering begins
    • taper slowly
    • never stop abruptly
  • fludrocortisone 50 ug PO QD optional
  • dexamethasone not recommended for treatment of septic shock or ARDS.
• dexamethasone* 4 mg + IV saline for acute adrenal insufficiency without waiting for serum cortisol & plasma ACTH results.

* dexamethasone does not interfere with serum cortisol measurement

see Addison's disease (primary adrenal failure) for chronic adrenal insufficiency

More general terms

• adrenal gland disease
• chronic endocrine disease
• hormone deficiency

More specific terms

• Addison's disease (primary adrenal failure)
• adrenocortical insufficiency
• adrenomedullary insufficiency
• congenital adrenal hypoplasia
• secondary adrenal insufficiency (SAI)
• Waterhouse-Friderichsen syndrome

Additional terms

• adrenal (suprarenal) gland

Patient information

adrenal insufficiency patient information