Abstract
Simple SummaryErdheim–Chester disease (ECD) is a rare histiocytic neoplasm that is frequently associated with hypothalamic–pituitary gland involvement leading to endocrine dysfunctions. Frequently, endocrinopathy is permanent and precedes the diagnosis of ECD and may also develop during the course of treatment. However, the exact nature and frequency of hypothalamic–pituitary involvement are unknown. We studied a natural history cohort of 61 subjects with Erdheim–Chester disease and found abnormal pituitary imaging in 47.5% of cases, associated with panhypopituitarism, diabetes insipidus, and a higher median number of pituitary endocrinopathies. These data confirm and significantly extend previous reports of centrally occurring endocrine dysfunction and highlight the need for routine imaging and systematic assessment of hypothalamic–pituitary endocrine function in patients with ECD.Purpose: We examined abnormal pituitary imaging (API) and associated endocrine dysfunction in subjects with ECD. Methods: A cross-sectional descriptive examination of a natural history cohort study diagnosed with ECD was conducted at a clinical research center. Subjects underwent baseline endocrine tests of anterior and posterior pituitary function and dedicated pituitary gland MRI scans. We determined the frequency of various pituitary imaging abnormalities in ECD and assessed its relationships with age, sex, body mass index (BMI), BRAF V600E status, high sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), pituitary hormone deficits and number, diabetes insipidus (DI), and panhypopituitarism. Results: Our cohort included 61 subjects with ECD [age (SD): 54.3 (10.9) y, 46 males/15 females]. API was present in 47.5% (29/61) of ECD subjects. Loss of the posterior pituitary bright spot (36.1%) followed by thickened pituitary stalk (24.6%), abnormal enhancement (18.0%), and pituitary atrophy (14.8%) were the most common abnormalities. DI and panhypopituitarism were more frequent in subjects with API without differences in age, sex distribution, hsCRP, ESR, and BRAF V600E status compared to normal pituitary imaging. Conclusions: We noted a high burden of API and endocrinopathies in ECD. API was highly associated with the presence of panhypopituitarism and DI. Therefore, a thorough assessment of hypothalamic–pituitary integrity should be considered in subjects with ECD.
Highlights
Erdheim Chester disease (ECD), a non-Langerhans histiocytosis, was initially described by Erdheim and Chester as lipoid granulomatosis in 1930 [1]; it was recently reclassified by the WHO as a neoplasm of histiocytic origin [2]
Subjects presented to the NIH at a mean of 2.9 ± 0.4 years after they were formally diagnosed with ECD and at a mean of 6.6 ± 0.8 years after first signs of ECD had appeared
Pituitary imaging was performed on their initial enrollment visit
Summary
Erdheim Chester disease (ECD), a non-Langerhans histiocytosis, was initially described by Erdheim and Chester as lipoid granulomatosis in 1930 [1]; it was recently reclassified by the WHO as a neoplasm of histiocytic origin [2]. ECD is extremely rare and has been reported a few hundred times in the literature with a mean presenting age of ~53 years, predominantly affecting males [2,3]. NRAS, KRAS, PIK3CA, ARAF, and MAP2K1 defects have been involved in the pathogenesis of ECD [7,8]. Initial clinical manifestations of ECD include ostalgia (50%), neurological symptoms (23%), and diabetes insipidus (DI, 22%), which is the most frequently overlooked symptom [3]. We have previously noted that ECD leads to a wide variety of endocrinopathies such as hypothyroidism, adrenal dysfunction, and hypogonadism [9,10,11,12,13]. ECD can affect the retroperitoneum, pulmonary, cardiovascular, and cutaneous systems [12,14,15,16,17]
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