Is this patient's Cushing syndrome exogenous or endogenous and what is the risk of adrenal crisis if the steroid is stopped abruptly?

Exogenous Cushing Syndrome with High Risk of Adrenal Crisis

This patient has exogenous Cushing syndrome from chronic steroid use, and abrupt discontinuation poses a life-threatening risk of adrenal crisis due to suppressed hypothalamic-pituitary-adrenal (HPA) axis that requires gradual steroid tapering with replacement therapy. 1, 2

Five Specific Findings Supporting Exogenous Cushing Syndrome

1. History of exogenous steroid administration - The most common cause of Cushing syndrome is exogenous steroid use, which must be excluded first in any evaluation 2, 3. Any documented use of oral, inhaled, topical, or intranasal corticosteroids confirms exogenous etiology 4, 5.

2. Suppressed ACTH levels - Exogenous steroids suppress the HPA axis, resulting in low or undetectable plasma ACTH concentrations, distinguishing it from endogenous ACTH-dependent causes where ACTH is mid-normal to elevated 2, 3. This is pathognomonic for exogenous administration.

3. Low morning cortisol levels - Chronic exogenous steroid use suppresses endogenous cortisol production, resulting in inappropriately low serum cortisol levels (typically <250 nmol/L or <9 mcg/dL) when measured at times when exogenous steroid is not present 6, 4.

4. Cushingoid features without elevated endogenous cortisol production - Physical stigmata of Cushing syndrome (facial plethora, striae, central obesity, easy bruising) present alongside suppressed endogenous cortisol production on 24-hour urinary free cortisol or late-night salivary cortisol testing 2, 3.

5. Specific features unique to exogenous Cushing syndrome - Posterior subcapsular cataracts, glaucoma, avascular necrosis of the femur, and certain psychiatric manifestations are more specific to exogenous rather than endogenous Cushing syndrome 4. These complications help differentiate the etiology.

Adrenal Crisis Risk Assessment

The risk of adrenal crisis with abrupt steroid discontinuation is extremely high and potentially fatal. 1, 4

Mechanism of Risk

• HPA axis suppression - Chronic exogenous glucocorticoid administration suppresses the hypothalamic-pituitary-adrenal axis at multiple levels, preventing normal cortisol production 1, 4. The pituitary stops producing ACTH, and the adrenal glands atrophy from disuse.

• Duration of suppression - Drug-induced secondary adrenocortical insufficiency may persist for months after discontinuation of therapy, with recovery time being highly variable and unpredictable 1, 4. The time taken for HPA axis recovery remains variable among patients.

• Stress vulnerability - During the recovery period, any physiological stress (illness, surgery, trauma) can precipitate acute adrenal crisis because the suppressed axis cannot mount an appropriate cortisol response 1, 7. This represents a life-threatening emergency.

Clinical Manifestations of Adrenal Crisis

• Progressive loss of vasomotor tone and impaired alpha-adrenergic receptor responses to noradrenaline 6
• Orthostatic hypotension progressing to supine hypotension and shock 6
• Hyponatremia, hypoglycemia, and cardiovascular collapse 6
• Fatal outcome if not rapidly corrected with stress-dose glucocorticoids 6, 1

Management Algorithm to Prevent Adrenal Crisis

Immediate Actions

• Never abruptly discontinue steroids - Treatment must involve gradual dose reduction with replacement therapy to allow HPA axis recovery 1, 4

• Initiate replacement doses - Start patients on physiologic replacement doses of prednisone (typically 5-7.5 mg daily) or hydrocortisone (15-25 mg daily in split doses) 6, 4

Tapering Strategy

• Gradual dose reduction - Taper exogenous steroids slowly over weeks to months depending on duration of use 1, 4. The FDA label specifically warns that "drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage" 1.

• Stress dosing education - In any situation of stress occurring during the recovery period, hormone therapy must be reinstituted or increased 1, 7. Patients require 2-3 times their maintenance dose during minor illness and parenteral hydrocortisone for major stress 6.

Monitoring and Safety

• Patient education is mandatory - All patients must wear medical alert identification, carry a steroid emergency card, and have supplies for self-injection of parenteral hydrocortisone 6

• Mineralocorticoid consideration - Since mineralocorticoid secretion may be impaired, salt supplementation and/or fludrocortisone should be administered concurrently in primary adrenal insufficiency 1

• Long-term follow-up - Continue monitoring until HPA axis recovery is confirmed, which may take months and requires periodic ACTH stimulation testing 6, 4

Critical Pitfall to Avoid

The most dangerous error is assuming the patient can simply stop steroids because they have Cushing syndrome features. The paradox is that these patients simultaneously have cortisol excess from exogenous sources AND endogenous cortisol deficiency due to HPA suppression—abrupt cessation removes the exogenous source without allowing time for endogenous production to recover, creating a life-threatening cortisol-deficient state 1, 4.