English
Source | Pathophysiology | Findings | Comments |
---|---|---|---|
Intrinsic absolute adrenal failure | Absolute failure of component(s) of the HPA axis can be the primary cause of critical illness but is uncommon in ICU populations | ||
Primary | Disease within adrenal cortex | ↓ Cortisol, ↑ ACTH | - Infectious: disseminated TB, HIV, CMV, histoplasmosis, cryptococcus - Adrenal Hemorrhage: DIC, supratherapeutic anticoagulation, trauma, Waterhouse-Friderichsen syndrome - Autoimmune: due to antiadrenal autoimmunity in polyendocrine failure syndrome - Metastatic disease: including lymphoma, lung cancer, breast cancer, melanoma - Adrenoleukodystrophies - Congenital adrenal hypoplasia - Bilateral adrenalectomy - Drug related: rifampin, azoles, etomidate, phenytoin, mitotane |
Secondary | Disease within the anterior pituitary | ↓ cortisol, ↓ ACTH | - Infectious (eg, HIV, TB) - Pituitary tumors - Pituitary surgery trauma - Infarction - Hemorrhage - Infiltrative disorders - Metastatic disease - Drug related (eg, megestrol acetate, opiates, chronic glucocorticoid therapy) |
Tertiary | Disease within hypothalamus | ↓ cortisol, ↓ ACTH | - Mass lesion (eg, craniopharyngioma) - Radiation - Infiltrative lesion (eg, sarcoidosis) - Trauma - Infection (eg, viral encephalitis) - Drug related (eg chronic glucocorticoid therapy) |
Source | Pathophysiology | Findings | Comments |
---|---|---|---|
Absolute/intrinsic adrenal failure: primary | Disease within adrenal cortex | ↓ cortisol (total and free), ↑ ACTH | Absolute failure of the HPA axis can be the primary cause of critical illness but is uncommon in ICU populations |
Absolute/intrinsic adrenal failure: secondary | Disease within anterior pituitary | ↓ cortisol (total and free), ↓ ACTH | Absolute failure of the HPA axis can be the primary cause of critical illness but is uncommon in ICU populations |
Absolute/intrinsic adrenal failure: tertiary | Disease within hypothalamus | ↓ cortisol (total and free), ↓ ACTH | Absolute failure of the HPA axis can be the primary cause of critical illness but is uncommon in ICU populations |
Glucocorticoid withdrawal | A prevalent and specific type of tertiary central adrenal insufficiency that occurs as a result of CRH and ACTH suppression | Low ACTH response to CRH stimulation test | History of recent, frequent, or chronic use of supraphysiologic corticosteroids as might occur for treatment of autoimmune or inflammatory conditions |
CIRCI: acquired central adrenal insufficiency in the ICU | Caused by sustained lack of trophic ACTH signaling | - In patients with prolonged critical illness, requiring ICU care of weeks or longer - This author suggests using gestalt of patient’s history, physical examination, and clinical course, as well as the following laboratory findings: - Free cortisol level less than 2-fold above upper reference limit with associated low plasma ACTH, and - Less than 2-fold increment change in serum free cortisol from baseline with ACTH stimulation test, and/or - Low ACTH response to CRH stimulation test | - Prolonged treatment with opioids or other HPA axis affecting drugs and presence of endogenous glucocorticoid receptor binding ligands (eg, bile acids) may play a role - Concept requires further research |
Relative adrenal failure | Concept is based on supposition of maximally activated adrenal cortex that is unable to produce sufficiently high cortisol in the setting of critical illness | Low cortisol response to ACTH stimulation test | Studies revealed that plasma ACTH is low or low-normal in these patients, and that low total incremental cortisol response to ACTH stimulation test is due to increased cortisol distribution volume, thus refuting the idea of a maximally activated adrenal cortex; therefore, this terminology is a misnomer |
Cerebral trauma or injury | Central adrenal insufficiency22 due to pituitary and/or hypothalamic dysfunction | Pituitary dysfunction occurs in approximately 20%-40% of patients diagnosed with moderate or severe brain injury22 | |
HPA suppressive medications19 | History of use of any known suppressive medication including: - Chronic (or high dose) opioids - Ketoconazole, fluconazole - Megestrol acetate - Aminoglutethimide, trilostane, etomidate - Phenobarbital, phenytoin, rifampin - Anticoagulants, tyrosine kinase inhibitors - Mifepristone - Mitotane | ||
Preexisting latent adrenal insufficiency | Preexisting latent adrenal insufficiency could be unmasked by stress trigger (eg, surgery, infection, trauma) | History of unexplained lethargy, weight loss, or abdominal complaints |
Medication | Dosing | Indication | Comments |
---|---|---|---|
Hydrocortisone | IV 60 mg/day Either as continuous infusion or as bolus of 40 mg AM and 20 mg PM to mimic diurnal rhythm | Substitution dose for suspected adrenal insufficiency in critically ill adults | Recommended by this subject matter expert author |
Hydrocortisone | IV 200 mg/day Dose: 4 x 50 mg bolus injections or as continuous infusion; typically, 5-7 days in duration with taper guided by clinical response | Pharmacologic dose for shock reversal in septic shock states that are refractory to fluid and vasopressor support | In agreement with SCCM/ESICM guidelines2,27 |
Fludrocortisone | 50 mcg via GT once a day | May be combined with 200 mg hydrocortisone per day in acute septic shock | 2 trials that showed mortality benefit used the combination of hydrocortisone with fludrocortisone5,25 |