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adrenal insufficiency

Etiology: 1) 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 2) secondary - pituitary or hypothalamic pathology. - failure of ACTH secretion (pituitary insufficiency) - glucocorticoid use most common cause of secondary adrenal insufficiency) [1] - 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: 1) acute adrenal insufficiency a) anemia b) hypotension, orthostasis c) acute onset abdominal, back or flank pain may occur with adrenal hemorrhage [1,7] 2) chronic adrenal insufficiency a) symptoms - weakness & fatigue (100%) - anorexia (100%) - nausea/vomiting & diarrhea - muscle, joint & abdominal pain (10%) - postural dizziness - salt craving [2] b) signs - weight loss (100%) - hyperpigmentation (90%, primary adrenal insufficiency only, ACTH high) [1] - orthostatic hypotension (90%) - adrenal calcification (10%, primary disease) - vitiligo (5%, primary disease) Laboratory: 1) serum cortisol; serum albumin; serum free cortisol a) 8 AM serum cortisol < 3 ug/dL confirms adrenal insufficiency [1] b) 8 AM serum cortisol > 18 ug/dL excludes adrenal insufficiency [1] c) a random serum cortisol > 12 mg/dL in critically ill patients with low serum albumin makes adrenal insufficiency unlikely [6] 2) serum cortisol & serum aldosterone are low 3) plasma ACTH is high in primary adrenal insufficiency - next diagnostic test after adrenal insufficiency confirmed [1] 4) plasma renin activity is high 5) basic metabolic panel a) serum glucose: hypoglycemia b) serum sodium: hyponatremia (except when due to pituitary insufficiency) [1] c) serum potassium: - hyperkalemia (except when due to pituitary insufficiency) [1] d) serum calcium: hypercalcemia [1] e) serum bicarbonate: metabolic acidosis (mild) [12] 6) 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 [1] - a stimulated serum cortisol of > 18 ug/dL excludes adrenal insufficiency [1] - not needed when AM serum cortisol < 3 ug/dL [1] 7) 24 hour urinary free cortisol is low 8) 21-hydroxylase Ab in serum for autoimmune adrenalitis 9) complete blood count: - eosinophilia [1] - anemia with adrenal hemorrhage 10) see ARUP consult [5] 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 Management: 1) adrenal crisis characterized by hypotension & acute infection - hydrocortisone 100 mg IV 2) administration of glucocorticoids to patients with septic shock or early ARDS should be based on clinical criteria, not on results from ACTH stimulation tests [4] 3) 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) 4) 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 5) septic shock & early ARDS: a) dosage unclear b) 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 c) fludrocortisone 50 ug PO QD optional d) dexamethasone not recommended for treatment of septic shock or ARDS. 6) dexamethasone* 4 mg + IV saline for acute adrenal insufficiency without waiting for serum cortisol & plasma ACTH results [1]. * dexamethasone does not interfere with serum cortisol measurement [1] see Addison's disease (primary adrenal failure) for chronic adrenal insufficiency

Interactions

disease interactions

Related

adrenal (suprarenal) gland

Specific

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

General

adrenal gland disease chronic endocrine disease hormone deficiency

References

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  2. Brender E, Lynm C, Glass RM. Adrenal Insufficiency JAMA 294:2528, 2005 PMID: 16287965
  3. Annane D et al, Diagnosis of adrenal insufficiency in severe sepsis and septic shock. Am J Respir Crit Care Med 2006, 174:1319 PMID: 16973979 - Meyer NJ and Hall JB Relative adrenal insufficiency in the ICU: Can we at least make the diagnosis? Am J Respir Crit Care Med 2006, 174:1282 PMID: 17158285
  4. Marik PE et al, Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: Consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 2008 Jun; 36:1937 PMID: 18496365
  5. ARUP Consult: Adrenal Insufficiency The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/adrenal-insufficiency - ARUP Consult: Adrenal Insufficiency Testing Algorithm https://arupconsult.com/algorithm/adrenal-insufficiency-testing-algorithm
  6. Arafah BM. Hypothalamic pituitary adrenal function during critical illness: limitations of current assessment methods. J Clin Endocrinol Metab. 2006 Oct;91(10):3725-45 PMID: 16882746
  7. Bornstein SR. Predisposing factors for adrenal insufficiency. N Engl J Med. 2009 May 28;360(22):2328-39 PMID: 19474430
  8. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  9. Bakalov VK, Vanderhoof VH, Bondy CA, Nelson LM. Adrenal antibodies detect asymptomatic auto-immune adrenal insufficiency in young women with spontaneous premature ovarian failure. Hum Reprod. 2002 Aug;17(8):2096-100. PMID: 12151443 Free Article
  10. Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol. 2015 Mar;3(3):216-26. Review. PMID: 25098712
  11. Pazderska A, Pearce SH. Adrenal insufficiency - recognition and management. Clin Med (Lond). 2017 Jun;17(3):258-262. Review. PMID: 28572228 Free PMC Article
  12. NEJM Knowledge+ Endocrinology