To Treat Adrenal Insufficiency, First Suspect and Detect It
The diagnosis and management of adrenal insufficiency (AI) in the inpatient and critical care settings start with a high index of suspicion. “If you don’t suspect it, you’re not going to detect it,” said Lynnette Nieman, MD.
Symptoms of AI include gastrointestinal (anorexia, abdominal pain, nausea, emesis, diarrhea), fatigue, malaise, weight loss, and joint aches/pains (especially back). Patients with AI may have hyponatremia. Those with primary AI are deficient in both cortisol and aldosterone related to high potassium levels and may also experience hyperpigmentation (commonly found on elbows and knees and sometimes on the creases of the hand) with or without vitiligo. Other pituitary deficits and signs and symptoms of those deficits may occur with secondary AI.
In patients with crisis/acute AI, additional signs and symptoms include orthostatic hypotension, circulatory collapse, fever, and hypoglycemia. “When we are dealing with critical illness-related AI or relative AI, we’re talking about a different kind of situation where we also have shock, but that’s unresponsive to fluid resuscitation and vasopressors, whereas in primary or secondary AI with an acute crisis, those symptoms of hypotension are responsive to fluids and vasopressors,” said Dr. Nieman, senior investigator and head, Endocrine Consult Service, Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.
Medications that can induce primary AI are steroidogenesis inhibitors, ketoconazole, itraconazole, fluconazole, etomidate, and immune checkpoint inhibitors. Medications that may be responsible for secondary AI are opiates, pharmacologic or replacement glucocorticoid (all routes), over-the-counter glucocorticoids (supplements, bleaching cream), megace, and immune checkpoint inhibitors.
AI can also occur in the context of recent pituitary surgery or in patients with autoimmune disease such as hypothyroidism or celiac disease.
In the subacute setting (inpatient service), a diagnosis of AI can be established by stimulation of cortisol 30 or 60 minutes after administration of cortrosyn (synthetic ACTH) at a dosage of 250 µg IV, and the target cortisol level is ≥18 µg/dL (500 nmol/L).
“I recommend getting a baseline plasma ACTH and cortisol. . . . The ACTH helps you distinguish primary AI versus secondary AI,” she said. Additional testing for causes of primary or secondary AI is also recommended if the patient does not have a normal cortisol response.
In the critical care setting, there is no ideal test for true AI; the morning cortisol level generally should be higher than normal (25 µg/dL). Critical illness‐related corticosteroid insufficiency (CIRCI) is a reversible entity caused by glucocorticoid resistance and is diagnosed by corticosteroid reversal of vasopressor‐unresponsive hypotension.
Inpatient management of AI consists of a ”stress dose” of hydrocortisone (50 mg IV every 6 hours), tapering off as patient recovers, transitioning to a “replacement” dose. Hydrocortisone is preferred because it also has mineralocorticoid activity and will replace the aldosterone deficiency if the patient has primary AI. For primary AI, add fludrocortisone, 50 to 150 µg/day.
In the critical care setting, for patients with known AI, or with concern that AI has been precipitated by etomidate, hydrocortisone, 50 to 100 mg IV every 6 hours is recommended. For patients with CIRCI and vasopressor‐unresponsive hypotension, 200 mg/day of hydrocortisone as divided bolus or by continuous IV is recommended. The addition of fludrocortisone or lower hydrocortisone doses or use of other glucocorticoids is controversial in this setting.
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