Is a 45-year-old patient who takes prednisone (corticosteroid) for rheumatoid arthritis experiencing primary, secondary, or tertiary hypocortisolism (adrenal insufficiency)?

Tertiary Adrenal Insufficiency in a Patient Taking Prednisone for Rheumatoid Arthritis

The 45-year-old patient taking prednisone for rheumatoid arthritis is experiencing tertiary adrenal insufficiency, which is the most common form of adrenal insufficiency caused by exogenous glucocorticoid therapy suppressing the hypothalamic-pituitary-adrenal axis. 1, 2

Understanding Adrenal Insufficiency Types

Adrenal insufficiency can be classified into three types:

1. Primary adrenal insufficiency (Addison's disease):

   • Direct failure of the adrenal glands
   • Laboratory findings: Low cortisol, high ACTH, low aldosterone, high renin
   • Clinical features: Hyperpigmentation, salt cravings, hyponatremia, hyperkalemia 2

2. Secondary adrenal insufficiency:

   • Failure at the pituitary level (ACTH deficiency)
   • Laboratory findings: Low cortisol, low ACTH, normal electrolytes
   • No hyperpigmentation 2

3. Tertiary adrenal insufficiency:

   • Failure at the hypothalamic level or due to exogenous glucocorticoid therapy
   • Laboratory findings: Low cortisol, low ACTH, normal electrolytes
   • Most common cause is chronic glucocorticoid therapy 1, 2

Mechanism in This Patient

The patient's chronic prednisone use for rheumatoid arthritis has likely caused tertiary adrenal insufficiency through:

• Suppression of the hypothalamic-pituitary-adrenal (HPA) axis
• Negative feedback inhibition of corticotropin-releasing hormone (CRH) from the hypothalamus
• Subsequent reduction in ACTH production from the pituitary
• Resulting in adrenal cortex atrophy and decreased endogenous cortisol production 1, 3

Evidence in Rheumatoid Arthritis Patients

Research shows that up to 48% of rheumatoid arthritis patients on long-term glucocorticoid therapy develop adrenal insufficiency, even with doses as low as 5 mg of prednisolone daily 4. This is particularly concerning because:

• The adrenal suppression can persist for up to 12 months after discontinuation of therapy 3
• Patients may be unable to mount an appropriate stress response during illness, surgery, or other physiological stressors 1
• Even patients on stable DMARDs who relapse upon small reductions in glucocorticoid dose often show impaired adrenal cortex reserve 5

Clinical Implications and Management

For this patient:

1. Diagnosis confirmation:

   • Morning serum cortisol and ACTH levels
   • ACTH stimulation test (Synacthen test) after 48 hours of prednisone pause 4
   • Cortisol levels <110 nmol/L (<4 μg/dL) with low ACTH strongly suggest tertiary adrenal insufficiency 2, 6

2. Management during continued therapy:

   • Continue maintenance prednisone at the lowest effective dose
   • Implement stress dosing during illness, surgery, or other stressors:
     • Minor stress: Double or triple the usual daily dose
     • Moderate stress: Hydrocortisone 50-75 mg/day in divided doses
     • Severe stress: Hydrocortisone 100 mg IV immediately, then 100-300 mg/day 2

3. Patient education:

   • Medical alert identification
   • Steroid emergency card
   • Recognition of adrenal crisis symptoms
   • Stress dose adjustments 2

4. Tapering considerations:

   • Gradual reduction to minimize risk of adrenal crisis
   • Monitor for symptoms of adrenal insufficiency
   • Consider endocrinology consultation for tapering plan 3

Important Cautions

• Never abruptly discontinue prednisone in this patient as it could precipitate an adrenal crisis 3
• Patients with rheumatoid arthritis may have intrinsically compromised adrenal reserve even before glucocorticoid therapy, making them more vulnerable 7
• The risk of adrenal insufficiency does not correlate with duration of treatment, making it unpredictable 4
• Even low-dose prednisone (5 mg daily) can cause significant adrenal suppression 4

This patient requires careful monitoring of adrenal function, especially if any changes to their glucocorticoid regimen are planned, and should be educated about stress dosing to prevent potentially life-threatening adrenal crisis.