Cushing's%20syndrome Management

• Withdrawal of corticosteroids should be individualized considering patient's general health status, stability of disease being treated and drug regimen being used
• Goal: Use a rate of change that will prevent both recurrence of activity of the underlying disease and symptoms of cortisol deficiency due to persistent hypothalamic-pituitary axis suppression

Corticosteroid Withdrawal Method After Prolonged Therapy Based on Cortisol Measurements

• Tapering dose incrementally from supraphysiologic or pharmacologic to physiologic doses
  • Physiologic doses of glucocorticoid are equivalent to Prednisone 5-7.5 mg/day or Hydrocortisone 15-20 mg/day

Prednisone dose (mg/day)	Duration of Glucocorticoid Therapy
	≤3 weeks	>3 weeks
≥7.5	Can discontinue	Reduce dose rapidly (eg 2.5 mg every 3-4 days then reduce by 1 mg/day every 2-4 weeks)
5-7.5		Reduce dose by 1 mg/day every 2-4 weeks or convert Prednisone 5 mg to Hydrocortisone 20 mg then reduce by 2.5 mg/week to 10 mg/day Assess morning cortisol after 2-3 months of Hydrocortisone 10 mg/day: -  Cortisol <85 nmol/L (<3 mcg/dL): Continue Hydrocortisone & re-evaluate after 4-6 weeks -  Cortisol 85-275 nmol/L (3-10 mcg/dL): Continue Hydrocortisone & conduct further tests such as ACTH stimulation or re-evaluate after 4-6 weeks -  Cortisol >275-500 nmol/L (>10-18 mcg/dL): Discontinue Hydrocortisone & monitor for signs & symptoms of adrenal suppression -  Cortisol >500 nmol/L (>18 mcg/dL): Discontinue Hydrocortisone Perform ACTH stimulation test when cortisol level is ≥200 nmol/L (7.4 mcg/dL): -  Peak cortisol >500 nmol/L: Discontinue glucocorticoid -  Peak cortisol <500 nmol/L: Glucocorticoid required in times of stress or illness until normal ACTH response is attained
<5		Reduce dose by 1 mg/day every 2-4 weeks

References: Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013 Aug;9(1):30.
Nieman LK, Biller BM, Findling JW, et al. Treatment of cushing's syndrome: an Endocrine Society clinical practice guideline. J. Clin Endocrinol Metab. 2015 Aug;100(8):2807-2831.
Stewart PM, Newell-Price JDC. The adrenal cortex: In: Melmed S, Polonsky KS, Larsen P, et al. Williams Textbook of Endocrinology. 13th edition. Philadelphia, PA: Saunders, Elsevier. 2016. 489-555.

Alternative Methods

Percentage Method:

• Tapering dosage by stable decrements of 10-20% every 1-2 weeks from an initial dose of Prednisone ≥40 mg/day or Hydrocortisone ≥100 mg/day

Alternate-day Method:

• Tapering Prednisone dosage by decrements of 1-2 mg on alternate days

• Measure serum sodium during the first 5-14 days after transsphenoidal surgery
• Assess free T4 and prolactin within 1-2 weeks post-transsphenoidal surgery to evaluate for overt hypopituitarism
• Postoperative pituitary MRI may also be done within 1-3 months of transsphenoidal surgery