Practical guidance for stopping glucocorticoids

SUMMARY

Glucocorticoids can be stopped abruptly, without tapering, in patients prescribed them for less than 3 to 4 weeks.

Prolonged glucocorticoid use (more than 3 to 4 weeks) can cause hypothalamic–pituitary–adrenal (HPA) axis suppression, necessitating gradual stopping (tapering) to prevent the consequences of adrenal insufficiency.

For some patients on prolonged glucocorticoids, the dosage can be tapered and stopped without testing serum cortisol concentrations.

For some patients on prolonged glucocorticoids, morning serum cortisol testing can be used to assess HPA axis recovery and guide glucocorticoid cessation.

Further testing of the HPA axis, with an adrenocorticotrophic hormone stimulation test, and referral to endocrinology services may be required in patients with repeated low cortisol concentrations despite a prolonged period at a physiological glucocorticoid dose.

 

Introduction

Cortisol is the main endogenous glucocorticoid in humans. It is produced in the zona fasciculata of the adrenal cortex and regulates widespread functions in the human body. Because of their potent anti-inflammatory action, synthetic glucocorticoids are commonly prescribed systemically to treat a range of inflammatory and autoimmune conditions. This article provides a practical framework for how to abruptly stop, or taper and stop, glucocorticoid therapy. The decision to taper or abruptly stop glucocorticoids is usually made when the underlying disease process that warranted treatment (the therapeutic indication) is controlled. In this article, we assume the aim is to stop glucocorticoid therapy. Prolonged use of glucocorticoids can cause significant complications, including suppression of the hypothalamic–pituitary–adrenal (HPA) axis (Figure 1).^1-3 Potential HPA axis suppression necessitates a structured approach to tapering and stopping glucocorticoid therapy, with careful attention to screening for and managing adrenal insufficiency and recognising withdrawal symptoms.⁴ Although there is a paucity of high-quality studies in this area, a recent clinical guideline from the European Society of Endocrinology and Endocrine Society has provided insights that will assist clinicians in managing glucocorticoid tapering and cessation.⁵

 

Commonly prescribed glucocorticoids

Commonly used synthetic glucocorticoids share structural similarities, but differ in their glucocorticoid and mineralocorticoid activity, serum half-life, duration of action and indications for clinical use (Table 1).⁶

Table 1 Pharmacological characteristics of commonly prescribed glucocorticoids⁶

	Hydrocortisone	Prednisolone or prednisone [NB1]	Dexamethasone
Relative glucocorticoid activity	1	4	20 to 30
Relative mineralocorticoid activity	1	0.6	0
Physiological dose (mg/day)	20	5	0.75
Serum half-life (hours)	1.5 to 2	2 to 3.5	3 to 4.5
Duration of action (hours)	8 to 12	18 to 36	36 to 54
Examples of common clinical use	adrenal replacement	anti-inflammatory agent	reduction of malignancy-related oedema
NB1: Prednisone is a prodrug that is converted in the liver to prednisolone.

 

Stopping glucocorticoids: abruptly or tapered?

When the underlying condition is treated, the primary determinant of whether to stop abruptly or taper gradually is the duration of glucocorticoid therapy (Figure 2).⁵

Patients prescribed glucocorticoids for up to 3 to 4 weeks, even at relatively high doses, rarely develop significant and sustained HPA axis suppression.⁷ As a result, measurement of serum cortisol is not required and therefore, once the clinical decision has been made that therapeutic steroids are no longer needed, they can be stopped abruptly, that is with no tapering.

An average 70 kg adult produces approximately 10 to 20 mg of the endogenous glucocorticoid cortisol every 24 hours, which equates to 2.5 to 5 mg of prednisolone per day.⁸ Patients prescribed a supraphysiological exogenous dose of glucocorticoids for more than 3 to 4 weeks can switch off endogenous cortisol production. In these patients, if glucocorticoid treatment is abruptly stopped, there is a risk of adrenal crisis. If the patient does not have underlying pituitary or adrenal disease, a tapering schedule usually allows the HPA axis to recover and prevents withdrawal symptoms.⁹ The tapering schedule should consider the likelihood of HPA axis suppression, medical comorbidities, and the risk of precipitating a flare in the underlying disease.

How to taper glucocorticoids

For patients on glucocorticoids for longer than 3 to 4 weeks, tapering glucocorticoids should be considered in 2 main phases. The initial phase is to reduce the glucocorticoid dose to near physiological levels (e.g. prednisolone 5 mg/day). In this phase, the primary determinant of the rate of glucocorticoid lowering is the effect on the underlying disease process for which the glucocorticoid was prescribed. The glucocorticoid dose should be tapered as rapidly as possible, while aiming to avoid a relapse of the underlying disease. In patients with complications of glucocorticoid therapy, such as hyperglycaemia, mood disturbance or fractures, a more rapid taper to physiological glucocorticoid levels may be required.

Once the glucocorticoid dose has been reduced to near-physiological concentrations, the rate of taper often needs to be slowed to allow progressive recovery of hypothalamic-releasing factors which stimulate pulsatile adrenocorticotrophic (ACTH) hormone secretion, leading eventually to reversal of adrenal atrophy and return of normal cortisol secretion. The European Society of Endocrinology and Endocrine Society guideline recommends 2 potential approaches to further taper glucocorticoids, based on whether or not to use cortisol testing to monitor HPA recovery.⁵

Tapering without serum cortisol testing

In many patients, glucocorticoids can be further tapered and stopped, without cortisol testing, provided the patient is educated about potential clinical manifestations of adrenal insufficiency and appropriately monitored (Table 2). There are few studies to inform the rate of glucocorticoid tapering in this phase, and there is variability between health conditions and individuals but, in general, it should be slower in patients who have been taking glucocorticoids for longer or who have been prescribed higher cumulative glucocorticoid doses. For example, a potential regimen for a patient who has been on prednisolone for more than 6 months is to reduce the daily prednisolone dose from 5 mg to cessation by 1 mg every month. Some authors recommend that prednisolone should be changed to hydrocortisone before tapering, as the shorter duration of biological action may facilitate recovery of the HPA axis.¹⁰ However, evidence to support this recommendation is limited and a recent study reported that most patients can be successfully weaned off prednisolone.¹¹ If patients are prescribed hydrocortisone, a similar regimen for dose reduction below 20 mg can be used (e.g. reduce daily hydrocortisone dose by 4 mg every month).

Tapering with serum cortisol testing

Once the glucocorticoid is at a physiological dose, the alternative approach to tapering is to measure morning cortisol concentrations, to inform the need for and rate of tapering. This approach may benefit patients who have been prescribed glucocorticoids for a relatively short duration or patients who develop symptoms indicative of adrenal insufficiency as the glucocorticoid dose is reduced, to taper and stop more rapidly (Table 2). A morning serum cortisol concentration should be measured between 8 and 10 am, prior to taking the morning dose of hydrocortisone or prednisolone. Morning cortisol should not be measured in patients prescribed dexamethasone as its longer biological half-life and duration of action will cause HPA suppression. If clinically appropriate, patients on dexamethasone can be switched to an equivalent dose of prednisolone or hydrocortisone before measuring cortisol.¹² The clinician should also be aware of factors that can affect the interpretation of the measurement, such as altered circadian pattern, and conditions that increase corticosteroid-binding globulin, such as oral estrogen therapy and pregnancy.^13,14

Table 2 Clinical features of glucocorticoid withdrawal syndrome, adrenal insufficiency and underlying disease flare

	Glucocorticoid withdrawal syndrome	Adrenal insufficiency	Underlying disease flare
Symptoms	Fatigue, malaise, sleep disturbance, arthralgia	Fatigue, malaise, nausea, arthralgia	Fatigue, malaise, disease-specific symptoms
Signs	May be signs of glucocorticoid excess	Postural hypotension, weight loss	Disease-specific signs
Laboratory	Normal electrolytes	Hyponatraemia, hypoglycaemia	Rise in inflammatory markers, disease-specific indicators of flare of underlying disease
Glucocorticoid dose and timing of symptom onset	Any point during the taper, often at a prednisolone dose below 15 mg/day [NB1]	Prednisolone dose less than 5 mg/day [NB1], or during intercurrent illness	Any point during glucocorticoid taper, especially if rapid dose reduction
HPA axis testing	Rarely indicated if prednisolone dose is above 5 mg/day	Low morning cortisol and low ACTH	Rarely indicated if prednisolone dose is above 5 mg/day
ACTH = adrenocorticotrophic hormone; HPA = hypothalamic–pituitary–adrenal NB1: Or equivalent dose of another glucocorticoid (see Table 1 for relative activity of commonly prescribed glucocorticoids).

Morning cortisol results occur on a continuum, with a higher value more indicative of HPA axis recovery. The European Society of Endocrinology and Endocrine Society guideline provides advice regarding thresholds that can be applied to interpretation of morning cortisol results in patients tapering glucocorticoids.⁵ If a morning cortisol concentration is above 300 nanomol/L during glucocorticoid taper, then the HPA axis has probably recovered and the glucocorticoid can be stopped without further tapering. If the cortisol concentration is between 150 and 300 nanomol/L, HPA axis recovery is possible. The guideline recommends that a physiological dose of glucocorticoids should be continued, and morning cortisol retested in a few weeks. In select patients it may be reasonable to continue glucocorticoid taper, especially if the cortisol concentration is in the upper part of this range, or to arrange more definitive assessment of the HPA axis (Figure 2). A morning cortisol concentration less than 150 nanomol/L is suggestive of ongoing HPA axis suppression and the guideline recommends a physiological dose of glucocorticoid should be continued.¹⁵ Morning cortisol should be retested in a few months, to allow more time for HPA axis recovery.

For patients with persistent intermediate results, an ACTH_1-24 (cosyntropin) stimulation test can provide additional information. The test should be performed prior to the morning dose of hydrocortisone or prednisolone. It involves administering synthetic ACTH_1-24 (cosyntropin) and measuring serum cortisol concentrations 30 and 60 minutes later. The peak cortisol concentration after cosyntropin is used to determine HPA axis status; the threshold that indicates sufficiency is generally 400 to 500 nanomol/L, depending on the cortisol assay used.

 

Distinguishing glucocorticoid withdrawal syndrome, underlying disease flare and adrenal insufficiency

Patients commonly develop symptoms of concern during a glucocorticoid taper. Symptoms such as general malaise, fatigue, nausea, muscle and joint pain, sleep disturbances and mood change can represent a glucocorticoid withdrawal syndrome that arises due to dependence on a supraphysiological glucocorticoid dose.^16-18 This may develop at any point during glucocorticoid taper, but usually when prednisolone is reduced below 15 mg daily (or equivalent).

It is important to distinguish a glucocorticoid withdrawal syndrome from a flare in the underlying disease or adrenal insufficiency, as symptoms may overlap (Table 2). Other clinical and biochemical features may assist in distinguishing between these conditions. For example, postural hypotension is a clinical sign indicative of adrenal insufficiency, while disease-specific features may indicate a flare of an underlying condition (e.g. synovitis in a patient with rheumatoid arthritis). Laboratory analysis is often unremarkable in patients with glucocorticoid withdrawal syndrome, whereas hyponatraemia and hypoglycaemia can indicate adrenal insufficiency, and a rise in inflammatory markers can suggest an underlying disease flare.

The glucocorticoid dose provides insight into the aetiology of symptoms during tapering. Adrenal insufficiency will generally only develop if the prednisolone dose is below 5 mg/day, unless there is an intercurrent illness which can precipitate an adrenal crisis. Patients with an adrenal crisis during glucocorticoid taper will have a low morning cortisol and ACTH, indicative of secondary adrenal insufficiency. Symptoms that develop on a supraphysiological glucocorticoid dose (e.g. prednisolone above 5 mg/day) usually represent a glucocorticoid withdrawal syndrome or underlying disease flare. Both conditions are more likely to occur during a rapid glucocorticoid taper, and the glucocorticoid dose should be increased until symptoms resolve, then tapered less rapidly.¹⁷ In patients on long-term glucocorticoids at prednisolone doses above 5 mg/day (or equivalent), measuring a morning cortisol is rarely helpful, as cortisol will be low because of long-term supraphysiological glucocorticoid dosing, and a low cortisol concentration does not distinguish between these 3 conditions.

 

Sick-day dosing of glucocorticoids

Cortisol concentrations are increased during physiological stress in response to a rise in corticotrophin-releasing hormone that stimulates the HPA axis (Figure 1). This rise in cortisol is necessary to maintain cardiovascular stability, and fluid and electrolyte balance, and to regulate the immune response during intercurrent illness. Sick-day or stress dosing of glucocorticoids during periods of physiological stress, such as illness, surgery or trauma, is essential for patients on long-term glucocorticoids, as they may not appropriately increase endogenous cortisol production. It is critical that patients tapering glucocorticoids are educated regarding the ongoing importance of sick-day management. They should be provided with a written plan for periods of mild, moderate and severe illness and be offered a medic alert bracelet.¹⁹

For mild illness, patients taking more than 10 mg prednisolone equivalent do not require stress dosing. Patients on physiological and sub-physiological doses should increase their prednisolone dose to 10 mg/day for a few days until their illness has passed.²⁰ Patients with moderate to severe physiological stress, or with an illness that impairs absorption, should increase their prednisolone dose to 3 times the physiological dose (e.g. prednisolone 15 mg/day), and gradually taper to their usual dose as their illness improves. If the patient is unable to swallow prednisolone, they should be switched to a parenteral glucocorticoid formulation such as hydrocortisone.¹⁹

 

Adrenal crisis

Adrenal crisis can be life threatening and warrants urgent management. Symptoms suggestive of adrenal crisis include hypotension, light-headedness, nausea and abdominal pain. Adrenal crisis can be precipitated by any medical or surgical stress in a patient who does not have an intact HPA axis to respond appropriately to physiological stress. Failure to recognise adrenal crisis can lead to shock and eventual death.²¹ Treatment entails fluid resuscitation, and administration of hydrocortisone 100 mg intravenous followed by 200 mg over 24 hours in 3 to 4 divided doses, or a continuous intravenous infusion of 200 mg over 24 hours. The precipitant, if present, should also be managed.²²

 

When to refer to an endocrinologist

While most patients on glucocorticoid therapy can be managed in primary care, certain scenarios warrant referral to an endocrinologist. These include patients whose HPA axis does not recover after 12 months of physiological dosing, those with persistent indeterminate results, those with a history of adrenal crisis or those with complex clinical presentations. In these scenarios, an ACTH stimulation test can be performed.²³ Furthermore, patients with complications of glucocorticoid therapy, such as inadequately controlled diabetes or recurrent fractures despite appropriate first-line osteoporotic treatment, can also be referred for management of these comorbidities.

 

Conclusion

The management of stopping glucocorticoids, either abruptly or by tapering, requires a nuanced approach to prevent adrenal insufficiency and withdrawal symptoms, while ensuring adequate control of the underlying disease. Cortisol testing for HPA axis function may be required in some cases following prolonged glucocorticoid therapy. Recognising and managing withdrawal syndrome and providing appropriate stress dosing are critical components of care. Patient education is vital to enhance safety, confidence and appropriate clinical outcomes.

This article was finalised on 17 July 2025.

Conflicts of interest: Faran Khalili has received honoraria from Boehringer, Novo Nordisk and AstraZeneca for lectures on sodium-glucose co-transporter 2 inhibitors in diabetes and glucagon-like peptide-1 agonist therapy for weight management.

Morton Burt has no conflicts to declare.

This article is peer reviewed.

 

References

1. Nicolaides NC, Pavlaki AN, Maria Alexandra MA, Chrousos GP. Glucocorticoid Therapy and Adrenal Suppression. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al. Endotext. South Dartmouth (MA); 2000.
2. Alexandraki KI, Kaltsas GA, Chrousos GP. Adrenal Suppression. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, et al. Endotext. South Dartmouth (MA); 2000.
3. Drouin J, Trifiro MA, Plante RK, Nemer M, Eriksson P, Wrange O. Glucocorticoid receptor binding to a specific DNA sequence is required for hormone-dependent repression of pro-opiomelanocortin gene transcription. Mol Cell Biol 1989;9:5305-14.
4. Glucocorticoid induced adrenal insufficiency. BMJ 2021;374:n1936.
5. Beuschlein F, Else T, Bancos I, Hahner S, Hamidi O, van Hulsteijn L, et al. European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency. J Clin Endocrinol Metab 2024;109:1657-83.
6. Maggio MC, Miniaci A, Gallizzi R, Civino A. "Neuroimmunoendocrinology" in Children with Rheumatic Diseases: How Glucocorticoids Are the Orchestra Director. Int J Mol Sci 2023;24.
7. Henzen C, Suter A, Lerch E, Urbinelli R, Schorno XH, Briner VA. Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment. Lancet 2000;355:542-5.
8. Esteban NV, Loughlin T, Yergey AL, Zawadzki JK, Booth JD, Winterer JC, et al. Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. J Clin Endocrinol Metab 1991;72:39-45.
9. Priya G, Laway BA, Ayyagari M, Gupta M, Bhat GHK, Dutta D. The Glucocorticoid Taper: A Primer for the Clinicians. Indian J Endocrinol Metab 2024;28:350-62.
10. Suehs CM, Menzies-Gow A, Price D, Bleecker ER, Canonica GW, Gurnell M, et al. Expert Consensus on the Tapering of Oral Corticosteroids for the Treatment of Asthma. A Delphi Study. Am J Respir Crit Care Med 2021;203:871-81.
11. Arshad MF, Elder C, Newell-Price J, Ross R, Debono M. A Retrospective Study on Weaning Glucocorticoids and Recovery of the Hypothalamic-Pituitary-Adrenal Axis. J Clin Endocrinol Metab 2024;109:e2031-e7.
12. Meikle AW, Tyler FH. Potency and duration of action of glucocorticoids. Effects of hydrocortisone, prednisone and dexamethasone on human pituitary-adrenal function. Am J Med 1977;63:200-7.
13. Brum MCB, Senger MB, Schnorr CC, Ehlert LR, Rodrigues TDC. Effect of night-shift work on cortisol circadian rhythm and melatonin levels. Sleep Sci 2022;15:143-8.
14. Kalaria T, Buch H, Agarwal M, Chaudhari R, Gherman-Ciolac C, Chopra R, et al. Morning serum cortisol is superior to salivary cortisone and cortisol in predicting normal adrenal function in suspected adrenal insufficiency. Clin Endocrinol (Oxf) 2022;96:916-8.
15. Kazlauskaite R, Evans AT, Villabona CV, Abdu TA, Ambrosi B, Atkinson AB, et al. Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 2008;93:4245-53.
16. Zhang CD, Li D, Singh S, Suresh M, Thangamuthu K, Nathani R, et al. Glucocorticoid withdrawal syndrome following surgical remission of endogenous hypercortisolism: a longitudinal observational study. Eur J Endocrinol 2023;188:592-602.
17. Theiler-Schwetz V, Prete A. Glucocorticoid withdrawal syndrome: what to expect and how to manage. Curr Opin Endocrinol Diabetes Obes 2023;30:167-74.
18. Komminoth M, Donath MY, Hepprich M, Schuetz P, Blum CA, Mueller B, et al. Glucocorticoid withdrawal and glucocorticoid-induced adrenal insufficiency: Study protocol of the randomized controlled <<TOASST" (Taper Or Abrupt Steroid STop) multicenter trial. PLoS One 2023;18:e0281585.
19. Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016;101:364-89.
20. Simpson H, Tomlinson J, Wass J, Dean J, Arlt W. Guidance for the prevention and emergency management of adult patients with adrenal insufficiency. Clin Med (Lond) 2020;20:371-8.
21. Lousada LM, Mendonca BB, Bachega T. Adrenal crisis and mortality rate in adrenal insufficiency and congenital adrenal hyperplasia. Arch Endocrinol Metab 2021;65:488-94.
22. Bancos I, Hahner S, Tomlinson J, Arlt W. Diagnosis and management of adrenal insufficiency. Lancet Diabetes Endocrinol 2015;3:216-26.
23. Oelkers W. Adrenal insufficiency. N Engl J Med 1996;335:1206-12.