Glucocorticoid Induced Adrenal Insufficiency GI-AI 糖皮质激素引起的肾上腺功能不全

On 12 July BMJ published a concerned article about corticosteroids. “Synthetic glucocorticoids are widely used for their anti-inflammatory and immunosuppressive actions. A possible unwanted effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal axis, which can lead to adrenal insufficiency. Patients with exogenous glucocorticoid use may develop features of Cushing’s syndrome and, subsequently, glucocorticoid withdrawal syndrome when the treatment is tapered down. ” BMJ 2021;374:n1380 [1]

On 19 July 2019, The JAMA hightlighted Steroids Side Effects on Patient Page [2]. Factors affecting the risk of glucocorticoid induced adrenal insufficiency (GI-AI) include the duration of glucocorticoid therapy, mode of administration, glucocorticoid dose and potency, concomitant drugs that interfere with glucocorticoid metabolism, and individual susceptibility.

JAMA steroids

Side effects of oral corticosteroids [1-8]

  1. Fluid retention, causing swelling in your lower legs
  2. High blood pressure
  3. Problems with mood swings, memory, behavior, and other psychological effects, such as confusion or delirium
  4. Upset stomach
  5. Weight gain, with fat deposits in your abdomen, your face and the back of your neck
  6. Elevated pressure in the eyes (glaucoma)
  7. Clouding of the lens in one or both eyes (cataracts)
  8. A round face (moon face)
  9. High blood sugar, which can trigger or worsen diabetes
  10. Increased risk of infections, especially with common bacterial, viral and fungal microorganisms
  11. Thinning bones (osteoporosis) and fractures
  12. Suppressed adrenal gland hormone production that may result in a variety of signs and symptoms, including severe fatigue, loss of appetite, nausea and muscle weakness
  13. Thin skin, bruising and slower wound healing

Side effects of inhaled corticosteroids [1-8]

  1. Fungal infection in the mouth (oral thrush)
  2. Hoarseness

Side effects of topical corticosteroids [9-13]

  1. steroids withdrawal syndroms thin skin, red skin lesions and acne.
  2. erythema, scaling, papules, nodules, desquamation, peeling, and swelling, edema.
  3. the most commonly reported symptoms were burning/stinging (94.6%), pruritus, pain, and diminished tolerance for emollients

Side effects of injected corticosteroids [1-8]

  1. skin thinning
  2. loss of color in the skin
  3. facial flushing, insomnia
  4. high blood sugar.
  5. Doctors usually limit corticosteroid injections to three or four a year, depending on each patient’s situation.

Research Questions

Q: What are the best predictors of glucocorticoid induced adrenal insufficiency and its duration?
A: unknown

Q: What is the best approach to glucocorticoid taper to alleviate glucocorticoid withdrawal syndrome while achieving the quickest recovery of adrenal function?
A: unknown

Q: Are there potential harms associated with oral corticosteroid bursts (oral corticosteroids for 14 or fewer days) in children?
A: 1.4- to 2.2-fold increased risk of GI bleeding, sepsis, and pneumonia within the first month after initiation of corticosteroid therapy that is attenuated during the subsequent 31 to 90 days [14].

Q: How long does topical steroid withdrawal syndrome last?
A: Syndroms take many months to several years to resolve. 76.7% of patients with steroid withdrawal syndrome received complete or partial clearance in 3 months, 12.5% in 6 months, 5.5% in 12 months and 5.1% over 12 months respectively after discontinuation use of steroid [9,15]. Time required to recover is proportionate to the time steroids were used [1].

GIAI bmj

My Thought

Steroids Withdrawl Syndroms may last months to years, and patients report poor quality of life and wellbeing. Steroids withdrawl syndrom is under-recognized as a separate entity, partly because of overlap of SWS symptoms with those of underlying diseases steroids were initially prescribed to treat. When physicians and patients do not recognize steroids withdrawl syndroms as a separate entity, the recovery process can be difficult and prolonged, especially if glucocorticoid doses are increased unnecessarily. In the published evidence so far, very little emphasis has been placed on assessment of the severity of withdrawl syndroms during glucocorticoid taper.

We can see how corticosteroids, which seem to us to be obvious effective medicine, have turned out, in light of recent discoveries, to have been mistakenly abused. These recent discoveries force us to rethink some of our clinical guidelines we had long designed for non-life-threatening skin diseases treatments.



  1. Prete A, Bancos I. Glucocorticoid induced adrenal insufficiency doi:10.1136/bmj.n1380
  2. Grennan D, Wang S. Steroid Side Effects. JAMA. 2019;322(3):282. doi:10.1001/jama.2019.8506
  3. Freyberg  RH, Traeger  CH, Patterson  M, Squires  W, Adams  CH.  Problems of prolonged cortisone treatment for rheumatoid arthritis; further investigations.   J Am Med Assoc. 1951;147(16):1538-1543.
  4. Volmer  T, Effenberger  T, Trautner  C, Buhl  R.  Consequences of long-term oral corticosteroid therapy and its side-effects in severe asthma in adults: a focused review of the impact data in the literature.   Eur Respir J. 2018;52(4):1800703.
  5. Fardet  L, Kassar  A, Cabane  J, Flahault  A.  Corticosteroid-induced adverse events in adults: frequency, screening and prevention.   Drug Saf. 2007;30(10):861-881.
  6. Nashel  DJ.  Is atherosclerosis a complication of long-term corticosteroid treatment?   Am J Med. 1986;80(5):925-929.
  7. Walsh  LJ, Wong  CA, Pringle  M, Tattersfield  AE.  Use of oral corticosteroids in the community and the prevention of secondary osteoporosis: a cross sectional study.   BMJ. 1996;313(7053):344-346.
  8. Van Staa  TP, Leufkens  HG, Abenhaim  L, Zhang  B, Cooper  C.  Use of oral corticosteroids and risk of fractures.   J Bone Miner Res. 2000;15(6):993-1000.
  9. Li AW, Yin ES, Antaya RJ. Topical Corticosteroid Phobia in Atopic Dermatitis: A Systematic Review. JAMA Dermatol. 2017;153(10):1036–1042. doi:10.1001/jamadermatol.2017.2437
  10. Hagar T, Leshem YA, Hannifin JM, etc. (2015) A systematic review of topical corticosteroid withdraw (steroid addiction) in patients with atopic dermatitis and other dermatoses. J Am Acad Dermatol 2015;72:541-549
  11. Belinda Sheary. Topical corticosteroid addiction and withdrawal – An overview for GPs. Australian family Physician. Volume 45, No.6, June 2016 Pages 386-388
  12. Sheary B. Steroid Withdrawal Effects Following Long-term Topical Corticosteroid Use. Dermatitis. 2018;29(4):213‐218. doi:10.1097/DER.0000000000000387
  13. Belinda Sheary. Topical Steroid Withdrawal: A Case Series of 10 Children. Acta Derm Venereol. 2019 May 1;99(6):551-556. doi: 10.2340/00015555-3144.
  14. Yao T, Wang J, Chang S, et al. Association of Oral Corticosteroid Bursts With Severe Adverse Events in Children. JAMA Pediatr. 2021;175(7):723–729. doi:10.1001/jamapediatrics.2021.0433
  15. Hagar T, Leshem YA, Hannifin JM, etc. (2015) A systematic review of topical corticosteroid withdraw (steroid addiction) in patients with atopic dermatitis and other dermatoses. J Am Acad Dermatol 2015;72:541-549