Erdheim-Chester Disease and Adrenal Insufficiency

Presentation Number: OR03-6
Date of Presentation: April 2nd, 2017

Fady Hannah-Shmouni*1, Louisa Boyd2, Georgios Papadakis3, Amit Tirosh4, Kevin O’Brien2, Brent S. Abel5, Monica C. Skarulis5, William A Gahl6 and Juvianee I. Estrada-Veras2
1Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 2NHGRI, 3National Institutes of Health, 4National Institutes of Health, Bethesda, MD, 5DEOB, NIDDK, NIH, 6National Institutes of Health (NIH), Bethesda, MD


Objective: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis resulting in chronic and uncontrolled inflammation with surrounding fibrosis. ECD involves multiple organ systems, including the HPA axis (1). The majority of patients harbor the BRAF V600E mutation (2). We describe the clinical, radiographic, and genetic findings from patients with ECD and with or without primary or central adrenal insufficiency (AI).

Methods: A prospective cohort study of 61 consecutive patients with ECD (46 males, 54.3 ± 10.8 years) was conducted at the National Institutes of Health (NIH) under NHGRI protocol 11-HG-0207. Clinical, radiographic, and genetic characteristics were assessed. All patients underwent evaluation of AI using a morning cortisol of <5 µg/dL in combination with ACTH, as a preliminary test. Confirmation with corticotropin stimulation was used if clinically or biochemically indicated.

Results: Adrenal gland and pituitary/stalk infiltration was present in 18/61 (29.5%) and 9/61 (14.8%) of patients with ECD on CT or MRI, respectively. The presence of both was observed in 6/61 (9.8%). Twenty-eight patients (28/61, 45.9%) had no infiltration in the HPA axis. Twelve patients (12/61, 19.7%) had a prior diagnosis of AI due to ECD. Infiltration was seen in the adrenal glands (primary AI; 6/12, 50%), pituitary/stalk (central AI; 4/12, 33.3%), or both (2/12, 16.7%). No patient presented with adrenal crisis as the initial manifestation of ECD, although all patients with AI (100%) reported lack of education toward sick day rules prior to their first visit. Glucocorticoid replacement therapy was not required in 15/23 (65%) patients with adrenal gland infiltration (AM cortisol 14 ± 4 μg/dL) or in 8/14 (57%) patients with pituitary/stalk infiltration (AM cortisol 15.8 ± 4.7 μg/dL). Mineralocorticoid replacement therapy was not required in all patients (100%). Thirty-one patients (31/57, 54%) harbored the BRAF V600E mutation, and were more likely to have adrenal gland infiltration (58.1% vs. 19.2%; odds ratio [OR] 5.8, 95% confidence interval [CI] 1.7-19.5, P=0.004), with comparable rates for pituitary/stalk infiltration (25.8% vs. 23.1%; OR 1.2, 95% CI 0.3-3.9, P=0.8) and AI (38.7% vs. 26.9%; OR 1.7, 95% CI 0.6-5.3, P=0.3).

Conclusions: Infiltrative processes of the HPA axis in patients with ECD tend to favor the adrenal glands in BRAF-positive patients, without influencing the rates of AI. At the time of the analysis in this cohort, the majority of patients with HPA axis infiltration did not require glucocorticoid or mineralocorticoid replacement therapy. Patients with ECD should be educated on the risk for, and the management of, AI, and followed closely by an experienced physician.


Nothing to Disclose: FH, LB, GP, AT, KO, BSA, MCS, WAG, JIE