History and exam
Key diagnostic factors
common
presence of risk factors
A history of exposure to glucocorticoid therapy is key to the diagnosis of adrenal suppression. High potency, supraphysiological doses of glucocorticosteroid, and prolonged duration of glucocorticoid treatment increase the risk. Patients may need prompting: for example, asking specifically about eye drops, nasal sprays, inhalers for breathing problems, or injections for pain.
sudden cessation or rapid tapering of glucocorticoids
Patients who have received high corticosteroid doses for prolonged periods and whose treatment is suddenly stopped or rapidly weaned might present with symptoms of adrenal insufficiency.
uncommon
acute circulatory collapse with hypotension and tachycardia
Patients at risk of adrenal suppression can present with an acute adrenal crisis if glucocorticoid treatment is suddenly ceased or if it is not increased during periods of increased stress (e.g., febrile illness, trauma, or surgery). Patients with adrenal crisis present with collapse due to hypovolemic shock, hypotension, postural dizziness, and tachycardia and should be treated urgently.[32] Tests may be taken as baseline, but diagnostic tests should not delay treatment.[32]
Other diagnostic factors
common
lassitude and generalised constitutional symptoms
These are non-specific symptoms associated with adrenal insufficiency. They include fatigue, anorexia, weight loss, nausea and vomiting, dizzinesss or orthostatic symptoms, myalgia or arthralgia. Abdominal pain may be present and can be mild or severe enough to lead to a misdiagnosis of acute abdomen.[7][32]
history of weight gain and increased appetite
These are non-specific symptoms associated with Cushing's syndrome.[34] Not all patients appear cushingoid, so a high index of suspicion for adrenal suppression is necessary.
history of depression, agitation, or sleep disorders
These are non-specific symptoms associated with Cushing's syndrome.[34] Not all patients appear cushingoid, so a high index of suspicion for adrenal suppression is necessary.
cushingoid examination features
Patients receiving supraphysiological doses of oral glucocorticoids for corticosteroid-responsive illnesses may develop a cushingoid appearance (moon facies, facial plethora, dorsocervical fat pad, bruising, violaceous abdominal striae, thin skin, proximal muscle weakness, and centripetal obesity).[34] This should prompt recognition of possible hypothalamic-pituitary-adrenal (HPA) axis suppression. HPA axis suppression has been described after only 4 to 5 days of corticosteroid therapy.
Not all patients appear cushingoid, so a high index of suspicion for adrenal suppression is necessary.
history of difficult-to-control diabetes or hypertension
absence of hyperpigmentation or autoimmune stigmata
Helps distinguish from adrenal insufficiency due to Addison's disease (primary adrenal insufficiency).
For example, vitiligo is typically absent.
uncommon
medroxyprogesterone use
Although the most frequent inciting event for adrenal suppression is the use of exogenous glucocorticoids, medroxyprogesterone has also been linked with adrenal suppression.[17]
history of treatment for endogenous Cushing's syndrome
A unilateral adrenal adenoma or carcinoma causing Cushing's syndrome can suppress the hypothalamic-pituitary-adrenal axis. Adrenal suppression can be manifest for a period after surgical removal.[19][20]
In addition, after removal of a pituitary tumour in Cushing's disease (Cushing's syndrome secondary to an adrenocorticotropic hormone (ACTH)-secreting pituitary tumour), the remaining ACTH-secreting cells in the pituitary gland may be sluggish in their recovery, resulting in a period of adrenal suppression and necessitating glucocorticoid supplementation.
Risk factors
strong
systemic glucocorticoid administration
Systemic (oral and intravenous) glucocorticoids in supraphysiological doses are well known to cause adrenal suppression.[1][7]
Doses of glucocorticoids equivalent to prednisolone 5 to 7.5 mg/day (5 mg once daily in the morning, or 5 mg in the morning and 2.5 mg in the evening) or less, are generally considered physiological replacement doses. Physiological doses are used, for example, to treat adrenal insufficiency stemming from Addison's disease or from pituitary surgery.
high potency or dose of exogenous glucocorticoids
Potent glucocorticoids (such as dexamethasone or betamethasone) are more likely than less potent formulations (such as prednisolone) to cause adrenal suppression.[22] High doses of glucocorticoids can cause adrenal suppression even after brief exposure.
The dose of supraphysiological exogenous corticosteroids that might result in adrenal suppression is variable and may depend on a variety of factors such as duration of exposure and patient health.[1] In studies on the effects of inhaled corticosteroids, the risk of adrenal suppression increased with higher doses.[11][12]
prolonged glucocorticoid treatment (e.g., >3 weeks)
In one study of patients receiving systemic glucocorticoids for chronic obstructive pulmonary disease exacerbation, more patients had a blunted peak cortisol response to adrenocorticotropic hormone stimulation at day 14 compared with day 1.[23] Some reports have suggested that adrenal suppression can occur as early as 4 to 5 days after starting glucocorticoids, but that recovery is also rapid when the duration of corticosteroid treatment is <1 week.[24][25] However, even a single intra-articular injection has been reported to cause adrenal suppression.[26][27] Moreover, repeated intra-articular glucocorticoid administration may result in adrenal suppression for several months.[9]
local glucocorticoid administration
Local routes of administration were developed with the hope of targeting the specific underlying organ or condition for which the corticosteroid is needed. However, local administration may result in adrenal suppression.
Of the local administration routes, inhaled corticosteroids seem to be cited most often, but this may stem from physician and patient awareness.[11][12] Intra-articular and epidural administration routes are less recognised, perhaps because of infrequency of use or lack of awareness by patients that they have received glucocorticoids.[9][10][28]
Intranasal and topical administration routes are also reported causes of adrenal suppression.[14] Those at higher risk of systemic absorption of topical corticosteroids include children, those with an impaired cutaneous barrier, and those with corticosteroids applied over large areas or under occlusion.[15]
megestrol use
Megestrol, often given as an appetite stimulant, has been reported to cause decreased cortisol responses after adrenocorticotropic hormone stimulation testing.[16] Patients may present with either Cushing's syndrome or adrenal insufficiency.
weak
non-physiological scheduling of glucocorticoid dose
Mimicking the normal diurnal rhythm by giving short-acting glucocorticoids in the morning decreases the chance of developing adrenal suppression.[7] Alternate-day scheduling also confers less risk of suppression.[1] Giving corticosteroids late in the day or at night may inhibit the diurnal surge of adrenocorticotropic hormone release, increasing the risk of adrenal suppression.
medroxyprogesterone use
Medroxyprogesterone has been reported to decrease plasma cortisol or adrenocorticotropic hormone (ACTH) levels, and some reports show a reduced response to ACTH stimulation tests.[17] Reports have been mostly in patients receiving medroxyprogesterone as part of cancer therapy, especially women.
Use of this content is subject to our disclaimer