cushing's%20syndrome
CUSHING'S SYNDROME
Cushing’s syndrome is a condition which is due to prolonged exposure of the body tissue to excess cortisol (glucocorticoid hormone).
Laboratory tests and radiological findings confirm diagnosis and determine the actual cause of Cushing's syndrome.
Endogenous adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome has adrenal hypersecretion due to adrenal adenoma, adrenal carcinoma, micronodular hyperplasia, and macronodular hyperplasia.
Exogenous ACTH-independent Cushing's syndrome has adrenal hypersecretion due to iatrogenic causes (eg drug-induced, corticosteroid use).

Cushing's%20syndrome Management

Gradual Withdrawal of Corticosteroids

  • 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

 

Follow Up

  • 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
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