Pulsatile Subcutaneous Hydrocortisone Replacement in Primary Adrenal
                    Insufficiency

Katerina Simunkova; Kristian Løvås; Paal Methlie; Nevena Jovanovic; Ersilia Bifulco; Ingeborg Bronstad; S. L. Lightman; Eystein Sverre Husebye; Marianne Oksnes

doi:10.1055/a-2092-5228

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2023; 55(07): 471-478
DOI: 10.1055/a-2092-5228

Original Article: Endocrine Care

Pulsatile Subcutaneous Hydrocortisone Replacement in Primary Adrenal Insufficiency

Authors

Katerina Simunkova

¹Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway

²Departments of Endocrinology, Haukeland University Hospital, Bergen, Norway
Kristian Løvås

¹Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway

²Departments of Endocrinology, Haukeland University Hospital, Bergen, Norway
Paal Methlie

¹Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway

²Departments of Endocrinology, Haukeland University Hospital, Bergen, Norway
Nevena Jovanovic

²Departments of Endocrinology, Haukeland University Hospital, Bergen, Norway
Ersilia Bifulco

¹Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway
Ingeborg Bronstad

¹Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway
S. L. Lightman

³The Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, United Kingdom of Great Britain and Northern Ireland
Eystein Sverre Husebye

¹Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway

²Departments of Endocrinology, Haukeland University Hospital, Bergen, Norway
Marianne Oksnes

¹Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway

²Departments of Endocrinology, Haukeland University Hospital, Bergen, Norway

Abstract

Pulsatile endogenous cortisol secretion is critical for physiological glucocorticoid gene signaling. Conventional glucocorticoid replacement therapy does not mimic endogenous cortisol pulsing in primary adrenal insufficiency. In an open-labeled, two-week, nonrandomized cross-over study of five patients with adrenal insufficiency (Addison’s disease in two, bilateral adrenalectomy in one, and congenital adrenal hyperplasia in two patients) we compared pulsatile and continuous cortisol pump treatment and conventional oral glucocorticoid therapy with respect to 24-h serum corticosteroid levels and plasma adrenocorticotropic hormone (ACTH). Pulsed pump restored ultradian rhythmicity as demonstrated by five peaks of serum (all patients) and subcutaneous tissue cortisol (four patients). Morning subcutaneous cortisol and cortisone were higher in continuous and pulsed pump treatment than in oral therapy despite nearly similar serum cortisol levels in all treatment arms. ACTH was within the physiological range during pulsed pump treatment in all patients except for slightly elevated levels in the morning hours 04:00–08:00 h. During oral therapy, ACTH was very high in patients with Addison’s disease and suppressed in patients with congenital adrenal hyperplasia. In conclusions, mimicking endogenous cortisol rhythmicity by ultradian subcutaneous infusion of cortisol is feasible. It was superior to both continuous pump and oral therapy in maintaining normal ACTH levels throughout the 24-h cycle. Our results demonstrate a low free cortisol bioavailability on thrice daily oral replacement therapy compared to both types of subcutaneous infusion.

Key words

circadian rhythm - ultradian rhythm - free cortisol - primary adrenal failure - glucocorticoid replacement therapy

Full Text

References

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