The unresolved riddle of glucocorticoid withdrawal

Abstract

Glucocorticoid (GC) therapy is the most common cause of adrenal insufficiency (AI). The real prevalence of AI after GC is unknown but it could involve more than 30% of patients. Some gene variation has been associated with the variability of hypothalamic-pituitary-adrenal (HPA) axis and this issue could contribute to the individual variation of adrenal function after GC treatment. Symptoms and signs of AI are nonspecific and frequently the diagnosis is delayed. Dosage, duration of treatment, administration route and serum cortisol value are not completely useful to predict AI. Clinical estimation of HPA suppression is difficult and biochemical testing is needed to confirm the diagnosis of AI. The different tapering regimens are based on a very low quality of evidence and considering the sizable individual variation, it is improbable that future research will find a secure GC tapering schedule for all patients. The aim of this review is to address the most important aspects in management of GC withdrawal in light of current knowledge.

Improved salivary cortisol rhythm with dual-release hydrocortisone

“…Secondly, before enrollment patients were treated with different GC (HC or CA); therefore, the pharmacokinetic results obtained (mainly AUC) have to be confirmed in larger series of patients treated with one compound. To obtain solid data, we used anti-inflammatory equivalents, as reported in the Endocrine Society’s guidelines ( 3 ); other equivalent doses are proposed, as the anti-inflammatory equivalents or growth-retarding cortisol equivalents ( 41 , 42 ); however, they are not used worldwide. Furthermore, also a three times daily dosing with conv-HC could improve daily cortisol curve; however, we decided to consider only patients with twice daily GC dosing, to ensure appropriate comparison among HC and CA.…”

Acute Adrenal Insufficiency Precipitated by the Discontinuation of a Betamethasone and Dextrochlorpheniramine Combination: The Diagnostic Utility of an Echocardiographic Assessment of Systemic Vascular Resistance

“…Thus, drug information alerts to unthinking chronic administration to avoid iatrogenic Cushing's syndrome. Withdrawal from glucocorticoid therapy (usually long-term) is a common cause of adrenal insufficiency (9). Thus, a dose reduction or complete discontinuation of long-term Celestamine Ⓡ can precipitate secondary acute adrenal insufficiency due to the suppression of the hypothalamic-pituitary-adrenal axis.…”

“…The accurate prevalence rates of adrenal insufficiency associated with glucocorticoid therapy are unknown; however, approximately 6% of hospitalized patients may have glucocorticoid-induced adrenal insufficiency (3), and presumably ≥30% of patients taking glucocorticoids are affected (9). The glucocorticoid dose or the duration of treatment that can affect adrenal function after glucocorticoid withdrawal cannot be accurately predicted owing to variations between patients (9, 10). In the present case, Celestamine Ⓡ equivalent to a daily dose of 5 mg of prednisolone had been administered for ≥13 years, which was sufficient to inhibit the patient's endogenous hypothalamic-pituitary-adrenal axis.…”

Improved salivary cortisol rhythm with dual-release hydrocortisone

“…Secondly, before enrollment patients were treated with different GC (HC or CA); therefore, the pharmacokinetic results obtained (mainly AUC) have to be confirmed in larger series of patients treated with one compound. To obtain solid data, we used anti-inflammatory equivalents, as reported in the Endocrine Society's guidelines (3); other equivalent doses are proposed, as the anti-inflammatory equivalents or growth-retarding cortisol equivalents (41,42); however, they are not used worldwide. Furthermore, also a three times daily dosing with conv-HC could improve daily cortisol curve; however, we decided to consider only patients with twice daily GC dosing, to ensure appropriate comparison among HC and CA.…”