What medications are used for a patient with adrenal insufficiency, particularly why prednisone is used as replacement therapy, in a patient already taking pregabalin for neuropathic pain?

Medications for Adrenal Insufficiency and Why Prednisone is Used

Hydrocortisone is the preferred first-line glucocorticoid for adrenal insufficiency replacement therapy, but prednisone serves as an alternative option for select patients who experience marked energy fluctuations throughout the day or have compliance issues with multiple daily hydrocortisone doses. 1

Primary Medications Used in Adrenal Insufficiency

Glucocorticoid Replacement

Hydrocortisone (First-Line)

• Standard dosing: 15-25 mg daily in divided doses (typically 10 mg at 7:00 AM, 5 mg at 12:00 PM, and 2.5-5 mg at 4:00 PM) 1, 2
• Hydrocortisone is preferred because it most closely mimics the body's natural cortisol rhythm and has a shorter half-life, allowing for physiologic replacement 1
• Alternative regimens include 15+5 mg, 10+10 mg, or 10+5+5 mg depending on individual response 1

Cortisone Acetate (Alternative)

• Dosing: 25-37.5 mg daily in divided doses 1
• Requires conversion to cortisol in the liver, making it less predictable than hydrocortisone 1

Prednisone/Prednisolone (Selective Use)

• Dosing: 3-5 mg daily, typically 4-5 mg on awakening, or 3 mg on awakening and 1-2 mg at 14:00 hours 1, 2
• Equivalency: Prednisone 5 mg = Hydrocortisone 20 mg 3

Mineralocorticoid Replacement (Primary Adrenal Insufficiency Only)

Fludrocortisone

• Dosing: 50-200 µg daily, though up to 500 µg daily may be needed in younger adults or during the last trimester of pregnancy 1, 2
• Required only in primary adrenal insufficiency because secondary adrenal insufficiency preserves the renin-angiotensin-aldosterone system 1
• Unrestricted sodium salt intake is essential alongside fludrocortisone therapy 1

Why Prednisone is Used: Specific Clinical Scenarios

Rationale for Prednisone Selection

Prednisone should only be considered in specific circumstances: 1

1. Marked fluctuations in energy or well-being over the course of the day that cannot be managed with hydrocortisone timing adjustments 1

2. Compliance problems with the multiple daily dosing required for hydrocortisone (prednisone allows once or twice daily dosing) 1

3. When hydrocortisone or cortisone acetate is not tolerated 1

Advantages of Prednisone

• Longer half-life allows once or twice daily dosing, improving adherence in patients who struggle with three or four daily doses 1
• More stable plasma levels throughout the day, which may benefit patients with severe energy dips between hydrocortisone doses 1

Critical Limitations of Prednisone

Dexamethasone should be avoided for chronic replacement therapy because it has no mineralocorticoid activity and is inadequate for primary adrenal insufficiency 1, 3

• Prednisone has minimal mineralocorticoid activity compared to hydrocortisone, so patients with primary adrenal insufficiency still require fludrocortisone 1
• The longer half-life means less physiologic cortisol rhythm replication 1
• Switching from prednisone to hydrocortisone for chronic replacement reduces cumulative glucocorticoid exposure and associated complications, with significant reduction in mortality 4

Important Considerations for Patients on Pregabalin

There are no significant drug interactions between pregabalin and glucocorticoid replacement therapy (hydrocortisone, prednisone, or fludrocortisone). 1

However, be aware of medications that DO affect glucocorticoid metabolism:

• Anti-epileptics, barbiturates, antituberculosis drugs, antifungal medications, etomidate, and topiramate increase hydrocortisone requirements 1
• Grapefruit juice and liquorice decrease hydrocortisone requirements 1

Monitoring Glucocorticoid Replacement

Monitoring relies predominantly on clinical assessment, not laboratory parameters 1

Signs of Over-Replacement

• Weight gain, insomnia, peripheral edema 1

Signs of Under-Replacement

• Lethargy, nausea, poor appetite, weight loss, increased pigmentation with uneven distribution 1

Practical Monitoring Approach

• Detailed questioning about daily tablet intake, general feelings of energy and "get up and go," mental concentration, daytime somnolence, and changes in pigmentation 1
• Information about low points or dips in energy during the day and knowledge of bedtime and ease of falling asleep 1

Critical Patient Education Requirements

All patients with adrenal insufficiency must have: 3, 2

• Emergency hydrocortisone injection kit (100 mg) for self-administration with proper training 3
• Medical alert bracelet/necklace and steroid emergency card 3
• Instructions to double or triple their usual dose during illness, fever, or physical stress 2

Stress Dosing Protocol

• For mild to moderate stress (febrile illness, minor procedures): double the regular oral maintenance dose 3
• For major stress or adrenal crisis: hydrocortisone 100 mg IV bolus immediately, followed by continuous infusion of 200 mg over 24 hours 1, 3

Common Pitfalls to Avoid

• Never delay treatment of suspected adrenal crisis for diagnostic procedures—treat immediately with IV hydrocortisone 100 mg and 0.9% saline infusion 1, 2
• Always start corticosteroids BEFORE other hormone replacements (thyroid, testosterone, estrogen), as these accelerate cortisol clearance and can precipitate adrenal crisis 3
• Do not rely on plasma ACTH and serum cortisol for glucocorticoid dose adjustment in established replacement therapy 1
• The absence of hyperkalemia cannot rule out adrenal insufficiency, as it occurs in only ~50% of cases 2