Restarting Hydrocortisone After Abrupt Discontinuation

Clinical Context and Management

• The Endocrine Society recommends that patients who have been off hydrocortisone therapy for only one week should restart at the same dose immediately, as the body may not have fully adapted to the loss of exogenous steroids, and the risk of adrenal crisis is significant 1, 2
• Patients with adrenal insufficiency are at risk for hypotension, particularly postural hypotension, and should be evaluated for this symptom before restarting hydrocortisone, as recommended by the American College of Endocrinology 1, 3
• The European Society of Endocrinology suggests that patients with adrenal insufficiency should be monitored for weight loss, fatigue, nausea, and hypoglycemia, as these are common symptoms of adrenal insufficiency 1, 3

Laboratory Testing and Interpretation

• The American Association of Clinical Endocrinologists recommends checking serum sodium and potassium levels to evaluate for electrolyte abnormalities suggesting mineralocorticoid deficiency, before or immediately after restarting hydrocortisone 1, 3
• Blood glucose levels should be checked to rule out hypoglycemia, as recommended by the Endocrine Society 3
• Morning cortisol and ACTH levels should be measured to assess whether the HPA axis has recovered, although this may not be diagnostic in patients already taking hydrocortisone, as noted by the American College of Endocrinology 4

Ongoing Monitoring and Patient Education

• The American College of Endocrinology recommends monitoring patients for return of normal energy, stable weight, and normal blood pressure after restarting hydrocortisone, and adjusting the dose as needed 1, 3
• Patients should be educated on stress dosing to prevent adrenal crisis, including doubling the usual dose during minor illness, using emergency hydrocortisone injection if vomiting or unable to take oral medication, and seeking immediate medical attention for severe illness, trauma, or surgery, as recommended by the Endocrine Society 1, 2, 4

Critical Considerations

• The European Society of Endocrinology recommends that patients with primary adrenal insufficiency should not attempt to "taper up" the dose, but rather restart at full replacement dose immediately, and should not assume HPA axis recovery after only one week off steroids, as this typically takes months 1, 2
• Mineralocorticoid replacement (fludrocortisone) should not be forgotten if this is primary adrenal insufficiency, as hydrocortisone alone does not provide adequate mineralocorticoid activity at physiologic doses, as noted by the American College of Endocrinology 1, 2

Recovery of Adrenal Function After Corticosteroid Treatment

Introduction to Adrenal Insufficiency

• The American College of Physicians recommends understanding the difference between primary and secondary adrenal insufficiency, as primary adrenal insufficiency does not recover and requires lifelong treatment, whereas secondary adrenal insufficiency can recover after stopping exogenous corticosteroids 5, 6, 7

Diagnosis and Treatment

• The Endocrine Society suggests that primary adrenal insufficiency, such as Addison's disease, is characterized by a deficiency in both cortisol and aldosterone, and the problem lies within the adrenal gland itself 5, 6
• Secondary or tertiary adrenal insufficiency is caused by the suppression of the hypothalamic-pituitary-adrenal axis due to exogenous corticosteroids, and the problem lies in the pituitary gland or hypothalamus, not the adrenal gland 5, 6
• The Journal of Clinical Oncology recommends testing adrenal function 3 months after treatment with hydrocortisone, and using tests such as the ACTH stimulation test or morning cortisol levels, although these may not be accurate in patients taking corticosteroids 7, 8

Risk of Adrenal Crisis

• The American Academy of Clinical Endocrinologists warns that patients are at risk of adrenal crisis during any physical stress until the hypothalamic-pituitary-adrenal axis has fully recovered, with a reported incidence of 6-8 cases per 100 patients per year 5, 6, 9
• The mortality rate is increased, with a reported 2.19-fold increase for men and 2.86-fold increase for women 5, 6, 9

Patient Education

• The European Society of Endocrinology recommends that all patients should receive instructions on stress doses, including doubling the usual dose during minor illness, and using hydrocortisone injections in cases of vomiting or severe illness 10, 7
• Patients should also be educated on the use of emergency hydrocortisone injections, and should wear a medical alert bracelet or carry a card indicating their adrenal insufficiency 10, 7

Likelihood of Adrenal Crisis When Stress‑Dose Steroids Are Omitted in Patients on Chronic Glucocorticoids

1. Risk of Adrenal Suppression from Chronic Prednisolone

• Chronic oral prednisolone at 7–14 mg daily for an extended period reliably suppresses the hypothalamic‑pituitary‑adrenal (HPA) axis. 11, 12
• A daily prednisolone dose ≥ 5 mg for longer than one month constitutes an adrenal‑suppressive regimen in a substantial proportion of adults. 11, 12
• Short Synacthen testing shows that roughly 33‑50 % of patients receiving 5–20 mg prednisolone daily fail to mount an adequate cortisol response, indicating insufficient adrenal reserve. 11, 12

2. Physiological Stressors and the Need for Dose Escalation

• Infections, particularly respiratory infections with fever, precipitate about 50 % of adrenal crises in individuals with adrenal insufficiency. 11
• During the first episode of pneumonia, doubling the prednisolone dose from 7 mg to 14 mg (stress‑dose steroids) was an appropriate response to the physiological stress. 11
• Even a modest increase to 10 mg prednisolone (higher than the baseline 7 mg) was insufficient to meet the cortisol demand of acute pneumonia, underscoring the need for larger stress‑dose adjustments. 11, 12

3. Guideline Recommendations for Stress‑Dose Steroid Management

• UK guidelines issued by the Association of Anaesthetists, the Royal College of Physicians, and the Society for Endocrinology state that physiological glucocorticoid replacement must not be interrupted and that the daily dose should be increased during periods of physiological stress. 11
• The same guidelines advise that, when uncertainty exists about the necessity of additional glucocorticoids, clinicians should administer them (“if in doubt, give”). 12

4. Clinical Consequences of Omitted Stress‑Dose Steroids

• Failure to double the prednisolone dose during the second pneumonia episode—a recommendation that was medically appropriate and guideline‑concordant—had a very high likelihood of contributing to the ensuing adrenal crisis. 11, 12
• In a prospective 2‑year follow‑up of 423 patients with adrenal insufficiency, two deaths occurred during adrenal crises, highlighting the potentially fatal outcome of inadequate stress‑dose coverage. 11

5. Common Pitfalls in Hospital Settings

• Omission or under‑dosing of glucocorticoids during hospitalization is a recognized precipitant of adrenal crisis. 11
• Ward nursing staff may overlook or dismiss early warning signs of glucocorticoid under‑replacement in ill patients, increasing the risk of crisis. 11

Stress‑Dose Glucocorticoid Management for Patients on Chronic Low‑Dose Prednisolone

Risk of HPA‑Axis Suppression

• HPA‑axis suppression is expected in any patient receiving >7.5 mg prednisolone‑equivalent daily for >3 weeks, and it can also occur at lower doses; therefore clinicians should anticipate reduced adrenal reserve in this population. 13, 14

Triggers Requiring Dose Escalation

• Physiological stressors that mandate stress‑dose glucocorticoids include respiratory infections with fever, gastro‑enteritis with vomiting or diarrhoea, trauma, surgical procedures, or any acute illness producing significant systemic symptoms. 13, 14

Doubling‑Dose Protocol for Low‑Dose Therapy

• For patients on ≤5 mg prednisolone daily, the dose should be doubled for the entire period of the acute illness—typically 2–3 days for minor illnesses and continued until symptoms have resolved. No taper is needed after short‑term escalation. 13, 14

Guideline Recommendation (EULAR)

• The European League Against Rheumatism (EULAR) guideline explicitly advises that patients on chronic glucocorticoid therapy receive adequate glucocorticoid replacement during acute stress, recommending an increase in dosage for approximately 3 days based on clinical judgement. (Expert consensus) 13, 14

Patient Education Imperative

• Patients must be informed that chronic prednisolone suppresses adrenal responsiveness to stress, making stress‑dose supplementation essential during acute illness. 13, 14