Dual-release hydrocortisone improves body composition and the glucometabolic profile in patients with secondary adrenal insufficiency

Endocrine. 2024 Jun;84(3):1182-1192. doi: 10.1007/s12020-024-03711-9. Epub 2024 Feb 12.

Abstract

Purpose: Studies have suggested improved metabolic profiles in patients with adrenal insufficiency treated with dual-release hydrocortisone (DR-HC) compared with conventional hydrocortisone (C-HC). This study investigates the effect of DR-HC compared with C-HC treatment on five health variables: diurnal salivary cortisol/cortisone, body composition, bone health, glucose metabolism, lipids, and blood pressure.

Methods: Prospective study of 27 participants (24 men) with secondary adrenal insufficiency with measurements during stable C-HC and 16 weeks after treatment switch to DR-HC.

Outcomes: Diurnal salivary-cortisol/cortisone, body composition assessed by Dual-Energy X-ray absorptiometry scan, bone status indices (serum type I N-terminal procollagen [PINP], collagen type I cross-linked C-telopeptide [CTX], osteocalcin, receptor activator kappa-B [RANK] ligand, osteoprotegerin, and sclerostin), lipids, haemoglobin A1c (HbA1c), and 24-hour blood pressure.

Results: After the switch to DR-HC, the diurnal salivary-cortisol area under the curve (AUC) decreased non-significantly (mean difference: -55.9 nmol/L/day, P = 0.06). The salivary-cortisone-AUC was unchanged. Late-evening salivary-cortisol and cortisone were lower (-1.6 and -1.7 nmol/L, P = 0.002 and 0.004). Total and abdominal fat mass (-1.5 and -0.5 kg, P = 0.003 and 0.02), HbA1c (-1.2 mmol/mol, P = 0.02), and osteocalcin decreased (-7.0 µg/L, P = 0.03) whereas sclerostin increased (+41.1 pg/mL, P = 0.0001). The remaining bone status indices, lipids, and blood pressure were unchanged.

Conclusion: This study suggests that switching to DR-HC leads to lower late-evening cortisol/cortisone exposure and a more favourable metabolic profile and body composition. In contrast, decreased osteocalcin with increasing sclerostin might indicate a negative impact on bones.

Clinical trial registration: EudraCT201400203932.

Keywords: Adrenal insufficiency; Body composition; Diurnal cortisol secretion; Dual-release hydrocortisone; Glucose metabolism.

MeSH terms

  • Adrenal Insufficiency* / drug therapy
  • Adrenal Insufficiency* / metabolism
  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • Body Composition* / drug effects
  • Cortisone / administration & dosage
  • Cortisone / metabolism
  • Delayed-Action Preparations
  • Female
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hydrocortisone* / blood
  • Male
  • Middle Aged
  • Prospective Studies
  • Saliva / chemistry
  • Saliva / metabolism
  • Treatment Outcome

Substances

  • Hydrocortisone
  • Blood Glucose
  • Cortisone
  • Delayed-Action Preparations
  • Glycated Hemoglobin