(CSEMP021) ISOLATED DIABETES INSIPIDUS: HAVE YOU CONSIDERED ERDHEIM-CHESTER DISEASE?

Abstract:

Background: Isolated Diabetes insipidus can have an elusive diagnosis and histiocytosis is on the differential. Histiocytosis are rare disorders characterized by the accumulation of cells thought to be derived from dendritic cells or macrophages. They can be classified as Langerhans cell histiocytosis (LCH) or non-LCHs like Erdheim-Chester disease (ECD). LCH are common in the pediatric population, while ECD mainly affects adults, more often males. ECD is a neoplastic disease with mutations in MAPK pathway and can involves multiple organ systems including cardiac, pulmonary, endocrine, retroperitoneal, skin and skeletal manifestations. In recent years a somatic mutation in the BRAF V600E gene has been identified in both LCH and ECD tissue infiltrates, suggesting a common origin of both histiocytosis, and shedding light on new treatment options for ECD which was previously considered an aggressive histiocytic disorder with poor response to therapy.

Case presentation: A 41-year-old female initially referred to Endocrinology with polyuria and polydipsia found to have central diabetes insipidus, later developed central hypogonadism and hyperprolactinemia. MRI sella shows thickened pituitary stalk consistent with lymphocytic hypophysitis. Patient was started on desmopressin however despite increasing doses (0.6mg PO QID) and a trial of prednisone had no significant improvement. 3 years later she developed fevers NYD and was found to have significant periorbital xanthelasma; macular skin lesions on ankles and flanks; and bony pain with imaging showing osteosclerosis. Biopsy of the skin lesions revealed Langerhans cell histiocytosis, positive for BRAF V600E mutation. Given the constellation of symptoms including recurrent fevers, hypophysitis, serositis, osteosclerosis and xanthelasma, together with skin biopsy results, she was diagnosed with LCH with ECD clinical features. For management, she was initially started on first line chemotherapy with Cladribine with no clinical or radiographic improvement noted. Next step would be to start targeted therapy with Dabrafenib, a BRAF inhibitor.

Discussion: This case illustrates a rare presentation of concomitant occurrence of both LCH and ECD in the same patient, and posed significant diagnostic challenges to her care team. Central diabetes insipidus is the most common endocrinopathy associated with ECD, and usually appears early in the disease course. Therefore an initial diagnosis of isolated diabetes insipidus, together with other features such as xanthelasma palpebrarum and bony pain with osteosclerosis, may prompt towards further testing for ECD. Given the rare and aggressive nature of ECD, early diagnosis is crucial to begin treatment and slow disease progression.