Hydrocortisone Replacement in Patients With Secondary Adrenal Insufficiency (SUPREME CORT)

A Randomized Double Blind Cross-over Study of the Effects of Low Dose and High Dose Hydrocortisone Replacement Therapy on Cognition, Quality of Life, Metabolic Profile and Somatosensation in Patients With Secondary Adrenal Insufficiency

The aim of this study is to investigate whether a physiologically low hydrocortisone (HC) dose is better for cognition as compared to a physiologically high HC dose. In addition, quality of life, metabolic profile and somatosensation will be described in relation to HC dose.

• Rationale: A wide variety in hydrocortisone (HC) substitution dose-regimens are considered physiological for patients with adrenal insufficiency. However, it is likely that cognition is negatively influenced by higher cortisol exposure to the brain. No studies have been performed to assess the effects of treatment regimens with a low physiological HC substitution dose on cognition in comparison to a high physiological HC substitution dose. These treatment regimens should take body weight and multiple dosing into account. In addition, substitution doses should be monitored by clinical evaluation and biochemical analysis for adverse effects associated with over- or under-replacement.
• Intervention: Patients with secondary adrenal insufficiency will be randomized in two groups to receive either a low dose HC (0.2-0.3 mg/kg body weight) for 10 weeks followed by 10 weeks of high dose HC (0.4-0.6 mg/kg body weight) or vice versa. At baseline and after both treatment periods, patients will be tested.

Inclusion Criteria:

• Patients with secondary adrenal insufficiency.
• Age ≥ 18 - 75 years
• ≥ One year after tumor treatment with surgery and/or radiotherapy
• On stable concomitant medications for at least six months prior to entry of study
• Body weight 50-100 kg

Exclusion Criteria:

• Inability of legal consent
• Documented cognitive impairment
• Drug abuse/dependence
• History of / current psychiatric disorders
• Use of anti-epileptics (e.g. carbamezapine)
• Cushing Disease
• Type 1 diabetes or Type 2 diabetes with medication known to induce hypoglycemia (f.e. Sulfonylurea derivatives
• Current treatment for second malignancy
• Have a significant medical condition (e.g. hepatic, respiratory, or cardiovascular) which, in the opinion of the investigator, may interfere with the interpretation of results and safety or efficacy evaluations.
• A history of frequent hypocortisolism
• Hospitalization during study
• Work in shifts