Endocrine Abstracts

Context: Glucocorticoid-induced adrenal insufficiency is the most frequent type of adrenal insufficiency, but its symptomatology has not been thoroughly studied.

Objective: To describe the predominant symptoms experienced by patients with glucocorticoid-induced adrenal insufficiency and rate these symptoms’ significance for patients’ perceived need for supplemental hydrocortisone stress dose.

Methods: The 80 symptoms in the Patient-Reported Outcomes version of the common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire, were presented to 11 endocrinologists from four Danish tertiary endocrine referral centres. The endocrinologists rated the symptoms’ relevance and could add additional symptoms. Symptoms with a mean score ≥1 (“minor relevance”) were evaluated by a Delphi panel including 3 senior investigators who excluded symptoms found irrelevant for a need for hydrocortisone stress doses. The remaining items were presented to adult patients with longstanding glucocorticoid-induced adrenal insufficiency receiving hydrocortisone replacement treatment. During interviews, participants first described their symptoms of glucocorticoid-induced adrenal insufficiency and subsequently rated the PRO-CTCAE symptoms from 1 (completely irrelevant) to 5 (very important) according to the significance in realising the need of hydrocortisone stress doses. New symptoms were added for the next participants to rate. Importance scores were calculated as the percentage of the participants experiencing the symptom times the mean significance rating.

Results: The PRO-CTCAE symptom review by 11 endocrinologists identified 17 relevant symptoms of glucocorticoid-induced adrenal insufficiency. The Delphi round removed three symptoms. Thirty patients (20 women) were included with mean (SD) age 58.4 (14.2) years and with median (range) duration of glucocorticoid-induced adrenal insufficiency of 5 (0.5-31) years, after glucocorticoid treatment of mainly asthma and rheumatological disorders. They reviewed the 14 symptoms and added 14 symptoms. The symptoms most frequently experienced were fatigue (87%), feeling generally unwell (80%), weariness (80%), difficulty concentrating (63%), and nausea (60%). The symptoms with the highest mean significance scores were dizziness (4.33), nausea (4.29), vomiting (4.20), fatigue (4.15), and feeling generally unwell (4.09). The symptoms with the highest importance scores were fatigue (360), feeling generally unwell( 325), weariness (293), nausea (253), and difficulty concentrating (250).

Conclusions: The presented new knowledge of the patients’ self-perceived symptoms of glucocorticoid-induced adrenal insufficiency can improve the clinical understanding of the condition. Additionally, this systematically investigation of symptoms has led to the development of a symptom measurement tool used in two ongoing clinical trials on glucocorticoid-induced adrenal insufficiency.

Funding: Achieved from the Novo Nordisk Foundation as part of a collaborative grant entitled "DOUBLE EDGE – Characterization and mitigation of adverse effects of glucocorticoid treatment"(NNF20OC0063280).