MON-095 - Erdheim-Chester Disease Presenting as Panhypopituitarism: A Rare Cause of Central Endocrine Failure

Erdheim–Chester disease (ECD) is a rare non–Langerhans cell histiocytosis characterized by CD68+ CD1a− histiocytes and alterations in the MAPK pathway. Central nervous system (CNS) involvement is uncommon but frequently affects the hypothalamic–pituitary axis and is linked to worse outcomes. In published cohorts, diabetes insipidus (DI) is the most common endocrine manifestation, and anterior pituitary deficits may evolve with infundibular/hypothalamic infiltration. CNS-restricted ECD is a rare diagnosis that requires biopsy with immunophenotyping and molecular profiling to confirm ECD and guide targeted therapy.

A 23-year-old previously healthy woman developed headaches, dizziness, nausea, and back pain over two months, followed by progressive fatigue, polydipsia, and severe polyuria with large-volume voids every 15–30 minutes. She later developed visual loss and encephalopathy, prompting emergency evaluation. MRI demonstrated an enhancing hypothalamic/suprasellar mass and a lesion in the fourth ventricle with obstructive hydrocephalus. She underwent external ventricular drain placement, ventriculoperitoneal shunt, and suboccipital craniotomy with C1 laminectomy. Initial pathology of the 4th ventricle lesion suggested a glial neoplasm; she then underwent another biopsy of hypothalamic/infundibular tissue and demonstrated a histiocyte-rich infiltrate consistent with ECD (CD68+, CD1a−).
She developed panhypopituitarism; DI with variable response to intranasal/oral desmopressin and eventual need for intravenous desmopressin due to unreliable enteral absorption with close Na monitoring; central hypothyroidism treated with levothyroxine via PEG; and secondary adrenal insufficiency treated with hydrocortisone. Other pituitary axis workup showed normal Prolactin level at (24 ng/mL), while LH, FSH, and IGF-1 were suppressed. FDG-PET showed FDG-avid disease confined to the suprasellar region, hypothalamus, and fourth ventricle without extracranial lesions. Next-generation sequencing identified mutations in KRAS and TP53. She received cobimetinib, focal radiation, intra-arterial melphalan, and pembrolizumab. Despite treatment, her course was complicated by seizures, progressive neurologic decline, and worsening radiographic findings.

CNS-predominant ECD can present in young adults with acute encephalopathy and severe hypothalamic–pituitary failure despite the absence of systemic disease. Early endocrine co-management is essential for DI and pituitary hormone replacement. Isolated CNS involvement and adverse molecular features may predict limited response to targeted and immune-based therapies, underscoring the need for early recognition and multidisciplinary care.

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