January 31, 2018
2 min read

Once-daily hydrocortisone therapy improves metabolic profile in adrenal insufficiency

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Valentina Guarnotta
Valentina Guarnotta

Patients with primary and secondary adrenal insufficiency who received once-daily, dual-release hydrocortisone therapy for 3 years experienced decreases in BMI, waist circumference and HbA1c, with the added benefit of improved insulin secretion and sensitivity for patients with adrenal insufficiency and prediabetes, study findings show.

“Conventional [glucocorticoid] treatment, hydrocortisone or cortisone acetate, requires two to three daily doses to maintain adequate serum cortisol levels, with the highest dose administered in the morning and a lower dose in the afternoon and, if required, in the evening,” Valentina Guarnotta, MD, PhD, professor of endocrinology, diabetes and metabolism at the University of Palermo, Italy, and colleagues wrote in the study background. “However, this conventional dosage scheme has been demonstrated to expose patients to supraphysiological levels of cortisol. Overexposure to [glucocorticoids] has been demonstrated to increase metabolic dysfunction, hypertension, sleep pattern disturbance and cardiometabolic risk, resulting in impaired quality of life and enhancing mortality and morbidity.”

In a retrospective study, Guarnotta and colleagues analyzed data from 49 adults with primary (n = 13) or secondary (n = 36) adrenal insufficiency for at least 2 years who were prescribed conventional glucocorticoid treatment at baseline. Within the cohort, 24 patients had prediabetes (14 women; mean age, 51 years; mean BMI, 32.6 kg/m²) and 25 patients had normal glucose tolerance (15 women; mean age, 52 years; mean BMI, 25.1 kg/m²). Patients were switched from conventional therapy to a once-daily, dual-release hydrocortisone therapy for 36 months (Plenadren, Shire Italy), designed with an immediate-release fraction of hydrocortisone in the outer layer of the tablet and an extended-release fraction in the core. Patients underwent a clinical and metabolic evaluation, including an assessment of insulin secretion and insulin sensitivity, at baseline and 12, 24 and 36 months.

At 36 months, patients with adrenal insufficiency and prediabetes and those with adrenal insufficiency and normal glucose tolerance each experienced a decrease in BMI (P < .001 and P = .017, respectively), waist circumference (P < .001 and P = .008, respectively) and HbA1c (P = .017 and P = .034, respectively) and a decrease in HDL cholesterol (P = .043 for both). However, in patients with adrenal insufficiency and prediabetes, researchers observed an additional decrease in insulinemia (P = .014), area under the curve for insulin (P = .038) and visceral adiposity index (P = .001), concomitant with an increase in the oral disposition index (P = .041) and the Matsuda index of insulin sensitivity (P = .038).

Researchers observed no between-group differences for patients when stratified by primary or secondary adrenal insufficiency, they noted.

“This drug can be used in all patients, but notably, those patients who have high risk to develop diabetes mellitus can benefit from this treatment,” Guarnotta told Endocrine Today. “I think that larger and prospective studies should be conducted to support our results.”

The findings follow a similar, short-term study by other researchers of 89 patients with primary or secondary adrenal insufficiency assigned to the same once-daily hydrocortisone therapy for 24 weeks published in December. As Endocrine Today previously reported, patients assigned to once-daily therapy experienced fewer infections and improved metabolic control and reported a higher quality of life vs. patients prescribed conventional therapy. The number of proinflammatory monocytes was reduced by nearly 50% at 24 weeks in the once-daily group vs. the conventional therapy group, and the once-daily group reported fewer mild infections and fewer influenza or influenza-like events vs. the conventional therapy group. – by Regina Schaffer

For more information:

Valentina Guarnotta, MD, PhD, can be reached at the University of Palermo, biomedical Department of Internal and Specialist Medicine, Piazza delle Cliniche 2, 90127, Palermo, Italy; email: valentina.guarnotta@unipa.it.

Disclosures: The authors report no relevant financial disclosures.