MON-003 - Asynchronous Multisite Langerhans Cell Histiocytosis Presenting with Pituitary Dysfunction and Delayed Vulvar Disease

Background:
Langerhans cell histiocytosis (LCH) is a rare clonal histiocytic neoplasm that frequently involves the hypothalamic–pituitary axis. In adults, arginine vasopressin (AVP) deficiency (formerly central diabetes insipidus) is often the earliest manifestation and may precede diagnosis by years. Pituitary stalk thickening is characteristic but not pathognomonic in LCH and may remain stable over time. Cutaneous involvement occurs in approximately 33–40% of patients, yet vulvar LCH is exceptionally rare and genital disease is not highlighted in NCCN guidelines.

Case:
A previously healthy 30-year-old woman presented with abrupt onset polyuria and polydipsia. Evaluation demonstrated hypotonic polyuria (urine specific gravity 1.001, urine osmolality 45 mOsm/kg), consistent with AVP deficiency requiring desmopressin. Initial monitoring of other endocrine labs was unremarkable. Pituitary MRI revealed mild infundibular thickening with loss of normal tapering measuring up to 3.5 millimeters and a small posterior pituitary T1-hyperintense, T2-hypointense hypoenhancing lesion consistent with a Rathke cleft cyst. Extensive evaluation for alternative inflammatory and granulomatous etiologies, including sarcoidosis, did not identify an underlying cause.
Over subsequent years, she developed progressive anterior pituitary dysfunction, including hypogonadotropic hypogonadism with secondary amenorrhea and infertility, requiring in vitro fertilization to achieve pregnancy. During pregnancy, her AVP deficiency was managed with an increased dose of her desmopressin without complications. Serial MRIs throughout the years demonstrated stability of the infundibular thickening and posterior pituitary lesion.
Seven years after initial presentation, she developed chronic vulvar ulcerations refractory to antimicrobial therapy, ultimately leading to biopsy-confirmed LCH with CD1a and langerin positivity. Whole-body PET/CT demonstrated no metabolically active systemic disease. She was treated with methotrexate with good cutaneous disease control. Multidisciplinary review concluded that the longstanding pituitary stalk abnormality and AVP deficiency represented hypothalamic-pituitary LCH with delayed extra-pituitary manifestation.

Results:
This case demonstrates AVP deficiency as the earliest manifestation of adult LCH, preceding cutaneous disease by seven years, with progressive anterior pituitary dysfunction manifesting as amenorrhea and infertility, despite stable pituitary imaging.

Conclusion:
AVP deficiency with unexplained pituitary stalk thickening warrants prolonged surveillance for LCH, as extra-pituitary disease may emerge years later and establish the diagnosis. Early recognition is critical given the permanence of pituitary hormone deficits and the long-term implications for reproductive and endocrine health.

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