Metabolic Effects of Cortisone Acetate vs Hydrocortisone in Patients With Secondary Adrenal Insufficiency

Elise Ekstrand; Daniela Esposito; Oskar Ragnarsson; Jörgen Isgaard; Gudmundur Johannsson


J Endo Soc. 2020;4(12) 

In This Article

Abstract and Introduction


Context: Pharmacokinetic properties of cortisone acetate (CA) and hydrocortisone (HC) differ because CA needs to be converted into cortisol to become active.

Objective: This work analyzed the metabolic consequences of switching CA to an equivalent daily dose of HC in patients with secondary adrenal insufficiency (SAI).

Design: This was a post hoc analysis from a prospective study including individuals with hypopituitarism receiving growth hormone replacement. Data were collected before and after a switch from CA to an equivalent dose of HC (switch group). Two control groups were included: patients continuing CA replacement (CA control group) and adrenal-sufficient hypopituitary patients (AS control group).

Results: The analysis included 229 patients: 105, 31, and 93 in the switch, CA control, and AS control groups, respectively. After the change from CA to HC, increases in mean body weight (1.2 kg; P < .05), waist circumference (2.9 cm; P < .001), body fat measured by dual-energy x-ray absorptiometry (1.3 kg; P < .001), and glycated hemoglobin (0.3%; P < .05) were recorded in the switch group. The increase in mean waist circumference was greater than in the AS control group (0.9 cm; P < .05). Mean body fat increased in the switch group but not in the CA control group (–0.7 kg; P < .05).

Conclusions: A switch from CA to an equivalent dose of HC was associated with a worsened metabolic profile, suggesting that HC has a more powerful metabolic action than CA based on the assumption that 20 mg HC equals 25 mg CA.


Approximately 75% of European patients with adrenal insufficiency (AI) receive hydrocortisone (HC) for glucocorticoid (GC) replacement.[1] In some countries, however, cortisone acetate (CA) is more commonly used. The pharmacokinetic profiles of HC and CA differ. HC is the chemical equivalent of endogenous cortisol and, thus, is a biologically active GC, whereas CA requires conversion to cortisol by the enzyme 11-β-hydroxysteroid dehydrogenase type 1 to become active. Therefore, orally administered CA has a delayed peak of serum cortisol concentration compared to HC.

The dose of GC replacement has a strong impact on metabolic outcome in patients with secondary AI (SAI), irrespective of GC type.[2,3] However, the type of GC may also influence metabolic outcome.[2] The conventional treatment for replacement therapy in patients with AI consists of HC or CA, divided into 2 or 3 oral doses per day, as recommended by current guidelines.[4] As the standard and most widely used conversion ratio for HC:CA is 4:5, the hydrocortisone equivalent (HCeq) dose of 20 mg HC is 25 mg of CA. This conversion ratio, however, is based on data from older in vitro studies comparing the anti-inflammatory potency of GCs.[5–8] There is limited information comparing the in vivo metabolic effects of various GCs during oral administration. In a previous study,[2] the use of CA was associated with more favorable glucose metabolism, with glycated hemoglobin (HbA1c) levels being lower than in patients treated with HC. Thus, HC may have a more potent metabolic effect than the assumed equivalent dose of CA.

In Sweden, CA was the conventional GC used for replacement therapy in patients with AI until 2001, when it was withdrawn from the market by the manufacturer and HC was approved by the Swedish Medical Products Agency. We were therefore able, in an ongoing prospective study,[9,10] to follow patients with hypopituitarism through a period during which most patients were switched from CA to HC. The aim of this study was to assess the consequent metabolic effects of the change in GC replacement in patients with SAI.