HPA Suppression and Vomiting in Chronic Low-Dose Prednisolone
Yes, HPA axis suppression can cause nausea and vomiting, and this is a recognized clinical manifestation of adrenal insufficiency that occurs in 20-62% of affected patients. 1
Clinical Presentation of HPA Suppression
Nausea and vomiting are cardinal symptoms of adrenal insufficiency, whether from primary adrenal disease or secondary HPA suppression. 1 The gastrointestinal symptoms occur because:
- Morning nausea and lack of appetite are particularly common in adrenal insufficiency and often represent under-replacement or inadequate endogenous cortisol production 1
- Nausea occurs in 20-62% of patients with adrenal insufficiency, frequently accompanied by vomiting, poor appetite, and weight loss 1
- Severe vomiting and/or diarrhea are common presenting symptoms of acute adrenal crisis, which can be life-threatening 1
Risk with Chronic Low-Dose Prednisolone
Daily prednisolone doses ≥5 mg for longer than 1 month can cause HPA axis suppression in a significant proportion of adults. 2
- Approximately one-third to one-half of patients taking 5-20 mg prednisolone daily demonstrate inadequate adrenal cortisol reserve on testing 2, 1
- Although a precise dose-response relationship cannot be demonstrated, 5 mg prednisolone represents an adrenal suppressive dose in many patients 2
- The suppression is iatrogenic secondary (or tertiary) adrenal insufficiency caused by chronic glucocorticoid administration 2
Distinguishing HPA Suppression from Other Causes
The key clinical context is whether the patient has symptoms during periods of physiological stress or illness when cortisol demands increase:
- Unexplained collapse, hypotension, and gastrointestinal symptoms (vomiting or diarrhea) should immediately raise suspicion for adrenal insufficiency 1
- Under-replacement or inadequate cortisol production is characterized by lethargy, nausea, poor appetite, weight loss, and increased pigmentation 1
- Hyponatremia is present in 90% of newly diagnosed adrenal insufficiency cases, though the absence of hyperkalemia cannot rule out the diagnosis as it occurs in only ~50% of cases 1
Diagnostic Approach
Morning cortisol measurements in patients actively taking prednisolone are not diagnostic because the assay measures both endogenous cortisol and therapeutic steroids. 1
- Patients on corticosteroids will have low morning cortisol as a result of iatrogenic secondary adrenal insufficiency—this is expected and not diagnostic 1
- Laboratory confirmation of adrenal insufficiency should not be attempted until corticosteroid treatment is ready to be discontinued and sufficient washout time has elapsed 1
- The cosyntropin stimulation test is the gold standard for confirming adrenal insufficiency when initial results are indeterminate, with a peak cortisol <500 nmol/L (<18 μg/dL) being diagnostic 1
Critical Management Considerations
If the patient is clinically unstable with suspected adrenal crisis, treatment must never be delayed for diagnostic procedures. 2, 1
- Give 100 mg IV hydrocortisone immediately plus 0.9% saline infusion at 1 L/hour if adrenal crisis is suspected 1
- In cases of clinical uncertainty with ongoing steroid use, opt for empiric glucocorticoid replacement and test for ongoing need at 3 months rather than attempting diagnostic testing while on steroids 1
- All patients with glucocorticoid-dependent conditions are at risk of adrenal crisis as a consequence of surgical stress or illness 2
Common Pitfalls to Avoid
- Do not rely on electrolyte abnormalities alone—between 10-20% of patients have mild or moderate hypercalcemia at presentation, and some may have normal electrolytes 1
- Do not assume adequate adrenal function in patients on chronic prednisolone ≥5 mg daily, even if they appear clinically well at baseline 2
- Do not attempt diagnostic testing while the patient is still taking prednisolone or immediately after stopping, as this will yield false results showing "adrenal insufficiency" that simply reflects expected HPA suppression 1