Coagulopathy (due to heparin, etc): major risk factor
Gastrointestinal Perforation
Hypotension/Sepsis
Neisseria Meningitidis (see Neisseria Meningitidis, [[Neisseria Meningitidis]]): classic association of meningococcemia with increased risk of adrenal hemorrhage
Aminoglutethimide (Cytadren) (see Aminoglutethimide, [[Aminoglutethimide]])
Abiraterone (Zytiga) (see Abiraterone, [[Abiraterone]])
Pharmacology
Inhibits CYP17A1 enzyme in testicles, adrenal glands, and prostatic cancer -> decreases circulating testosterone levels
Produces mineralocorticoid excess -> side effects of hypokalemia/hypertension
Etomidate (see Etomidate, [[Etomidate]]): inhibits adrenal steroidogenesis
Heparin (see Heparin, [[Heparin]]): the latter three mechanisms below may contribute to the development of hyperkalemia, but heparin does not typically cause adrenal insufficiency (in the absence of adrenal hemorrhage or HIT)
Potential Pharmacologic Mechanisms of Action on Adrenal Gland/Kidney
Adrenal hemorrhage (see above under “Adrenal Hemorrhage/Infarction”)
Decreased aldosterone synthesis
Atrophy of the adrenocortical zona glomerulosa
Decreased in number and affinity of aldosterone II receptors
Features of Adrenal Dysfunction in Critical Illness [MEDLINE]
Suppressed Expression/Activity of Cortisol-Metabolizing Enzymes, Resulting in Decreased Cortisol Degradation
Hypercortisolemia: elevated total and free cortisol
Corticotropin Suppression
Diagnosis
Cortrosyn Stimulation Test
Performed at any time of day/can be performed at least 24 hrs after HC dose, but not after prednisone dose
Baseline Cortisol -> Cortrosyn 250 ug IV (25 U) -> Cortisol 1hr later
Normal Response: Cortisol >18 µg/dL (Surviving Sepsis Campaign and Am Coll Crit Care Med suggest adequacy with increment >9 µg/dL)
Depressed responses may be seen in critically ill patients
Clinical Syndromes
Primary Adrenal Insufficiency Syndromes: manifest signs of both glucocorticoid deficiency + mineralocorticoid deficiency
Manifests adrenal androgen deficiency
Skin Findings: hyperpigmentation is characteristic of primary adrenal insufficiency (due to excess ACTH stimulation of melanocytes)
Acute adrenal insufficiency is more common in primary adrenal insufficiency (due to loss of both glucocorticoids + mineralocorticoids)
Secondary Adrenal Insufficiency Syndromes: manifest signs of only glucorticoid deficiency (since the adrenal gland itself is intact and capable of responding to stimulation from the renin-angiotensin-aldosterone axis)
Manifests adrenal androgen deficiency
Skin Findings: alabaster-like paleness of skin (due to lack of ACTH stimulation of melanocytes)
In cases with hypotahalamic-pituitary disease, patients may also manifest clinical signs associated with other endocrine axes (thyroid, gonadal, growth hormone, prolactin) or visual impairment due to pituitary tumor compressing the optic chiasm
Exogenous Glucocorticoid Administration Syndrome
Patients present with manifestions of glucocorticoid deficiency (if glucocorticoids are discontinued abruptly) + Cushingoid appearance (due to prior exposure to glucocorticoids)
2006 Cochrane review: in relative adrenal insufficiency, if used for at least 5 days (with at least 200 mg/day), there is a 20% decrease in mortality (with no increased risk of superinfection, GI bleeding, or hyperglycemia)
Fludrocortisone (Florinef): 50 ug PO QD
2002 JAMA study (Annane, et al): Fludro+HC had lower 28-day mortality than HC alone
However, randomized trial is needed to determine if fludro is necessary
2008 Surviving Sepsis Guidelines
Use Hydrocortisone (<300 mg qday) for septic shock, only if unresponsive to fluids/pressors
Don’t use cort stim testing to determine who should get steroids (unless another reason to suspect adrenal insufficiency exists)
Hydrocortisone is preferred over dexamethasone
Wean steroids with wean of pressors
Fludrocortisone is optional, if HC is used
References
Hyperreninemic hypoaldosteronism in the critically ill: a new entity. J Clin Endocrinol Metab. 1981 Oct;53(4):867-73 [MEDLINE]
Reduced cortisol metabolism during critical illness. N Engl J Med. 2013 Apr 18;368(16):1477-88. doi: 10.1056/NEJMoa1214969. Epub 2013 Mar 19 [MEDLINE]
Adrenal dysfunction in critically ill patients. N Engl J Med 2013;368(16):1547-1548 [MEDLINE]
