SAT-054 - Hypothalamic Involvement in Erdheim-Chester Disease

Introduction
Erdheim–Chester disease (ECD) is a rare non–Langerhans cell histiocytosis characterized by multisystem infiltration of foamy histiocytes. Involvement of the hypothalamic–pituitary axis is well described but diagnostically challenging, particularly in young adults. We report a case of ECD presenting with severe hypothalamic involvement, hypopituitarism, and hypothalamic obesity.

Case Presentation
A 26-year-old male presented with dizziness, nausea, vomiting, headache, and urinary incontinence. Initial labs showed hypothyroidism (FT4 0.4 ng/dL, TSH 11.31 mIU/L), prompting treatment with levothyroxine. MRI revealed a 6.4-cm infiltrative midline hypothalamic lesion. Endocrine workup demonstrated cortisol 2.2 µg/dL with inappropriately normal ACTH 9.8 pg/mL, DHEA-S 10 µg/dL, undetectable gonadotropins (LH < 0.1 IU/L, FSH < 0.9 IU/L), testosterone 2 ng/dL, and IGF-1 37 ng/mL (Z –5.5), consistent with hypopituitarism. Hypernatremia and hyperosmolality with polyuria, polydipsia, and dilute urine established ADH deficiency. Prolactin was mildly elevated (33.5 µg/L), and low FT4 with TSH suggested a hypothalamic etiology (tertiary).

He was started on desmopressin and stress-dose glucocorticoids before brain biopsy with mesh cranioplasty. Histopathology showed fibrohistiocytic proliferation, CD163/CD68 positive and negative for CD1a, BRAF, ALK, β-catenin, and S100, raising concern for ECD. He was discharged on levothyroxine, physiologic hydrocortisone, and desmopressin. At outpatient one month follow-up, he reported hyperphagia with rapid 6-kg weight gain.

Discussion
ECD frequently involves the hypothalamic–pituitary axis, causing irreversible endocrine dysfunction. Beyond hypopituitarism and ADH deficiency, hypothalamic lesions can disrupt appetite regulation. Infiltration of the arcuate, ventromedial, and paraventricular nuclei impairs satiety signaling, leading to hyperphagia and hypothalamic obesity. In this patient, rapid post-discharge weight gain was temporally associated with extensive hypothalamic involvement and unlikely due to thyroid or physiologic glucocorticoid replacement alone. Biopsy findings of fibrohistiocytic proliferation were supportive but not definitive, underscoring the diagnostic challenge.

Conclusion
This case highlights the diverse endocrine and metabolic consequences of hypothalamic involvement in ECD. Beyond hypopituitarism and ADH deficiency, hypothalamic lesions may drive hyperphagia and rapid weight gain. Early recognition and longitudinal metabolic surveillance are essential to optimize outcomes.

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