A 34-year-old woman experiences nausea, abdominal pain, and dizziness after undergoing open reduction and internal fixation of a femur fracture. One year ago, she was diagnosed with systemic lupus erythematosus with significant renal involvement, and she has since been on chronic glucocorticoid therapy with prednisone. The patient was maintained on her usual daily dose of prednisone throughout the perioperative period. Blood pressure is 90/60 mm Hg and pulse is 120/min. Compared to the normal physiologic response to surgery, this patient most likely has which of the following patterns of hypothalamic-pituitary-adrenal axis activity?
This patient is suffering from acute adrenal insufficiency (adrenal crisis) due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis by long-term glucocorticoid therapy. Glucocorticoids suppress the synthesis and release of corticotropin-releasing hormone (CRH) from the hypothalamus and also block its ACTH stimulatory effect on the anterior pituitary. Long-term suppression leads to atrophy of hypothalamic CRH-releasing neurons, pituitary corticotrophic cells, and the adrenal zona reticularis (androgen- producing inner zone) and zona fasciculata (cortisol-producing middle zone).
Chronic glucocorticoid use is characterized by low CRH, ACTH, and cortisol levels that cannot rise in response to stressful situations (eg, infections, surgery) (Choice A). This lack of a stress response can result in relative glucocorticoid deficiency even when the patient's baseline glucocorticoid regimen is maintained. Because glucocorticoids help maintain normal vascular tone (eg, by increasing norepinephrine, renin, and angiotensin vasoconstrictive activity), glucocorticoid deficiency can precipitate hypotension/shock. In such cases, a higher stress dose is needed to compensate for the increased physiologic demands and prevent the development of adrenal crisis.
(Choice B) Increased levels of CRH and ACTH with decreased cortisol suggest primary adrenal insufficiency, as may be seen in autoimmune adrenalitis or bilateral adrenal hemorrhage/infarction. These patients will also have mineralocorticoid deficiency and are at very high risk for adrenal crisis.
(Choice C) Increased CRH with decreased levels of ACTH and cortisol suggest a pituitary disorder. ACTH is secreted by corticotroph cells of the anterior pituitary; damage to the pituitary by a tumor, infarction, or infection can cause decreased release of ACTH, which in turn leads to decreased cortisol production.
(Choice D) Excessive cortisol production from an autonomous adrenal adenoma suppresses CRH and ACTH production by the hypothalamus and pituitary, respectively.
Educational objective:
Suppression of the hypothalamus-pituitary-adrenal axis by glucocorticoid therapy is the most common cause of adrenal insufficiency. In these patients, adrenal crisis can be precipitated by stressful situations (eg, infections, surgery) if the glucocorticoid dose is not increased appropriately.