MON-068 - BRAF-Mutated Histiocytosis Presenting with Central DI and Panhypopituitarism

Introduction
Infiltrative hypothalamic–suprasellar lesions can present with panhypopituitarism and central diabetes insipidus (DI), creating an endocrine emergency that may mimic infection, inflammation, or malignancy. Non-Langerhans histiocytosis is an uncommon cause; tissue diagnosis with molecular testing can enable targeted therapy.
Clinical Case
A 34-year-old woman with polycystic ovarian syndrome, prediabetes, infertility, and two miscarriages presented with 1 week of worsening confusion and gait instability after 4 months of low-grade fevers and 14-kg unintentional weight loss. She was hypotensive and somnolent. Sodium was 151 mmol/L (ref 136–144) with serum osmolality of 320 mOsm/kg (ref 275–300) and inappropriately dilute urine Uosm 107 mOsm/kg (ref 50-1200) with low urine sodium < 20 mmol/L, raising concern for central DI. Brain MRI showed a 2.8-cm hypothalamic/optic chiasm mass with infundibular stalk involvement. Endocrine evaluation showed central adrenal insufficiency (cortisol 3.2 µg/dL, ref 2.5–11.9 at 4–8 PM; ACTH 2.6, ref 7.2–63.3), central hypothyroidism (free T4 0.8 ng/dL, ref 0.9–1.7; TSH 1.63, ref 0.27–4.20), and hypogonadotropic hypogonadism (LH < 0.1, ref 2.4–12.6; FSH 1.4, ref 3.5–12.5), with prolactin 32.8 ng/mL (ref 4.4–33.8), overall consistent with panhypopituitarism. She received stress-dose hydrocortisone, followed by desmopressin with carefully titrated free-water replacement, and levothyroxine was started after adrenal replacement was established. The differential at that point included infectious, inflammatory, and neoplastic etiologies. Extensive CSF and blood infectious workup was negative, but PET showed an isolated FDG-avid skull-base lesion corresponding to the brain mass. Stereotactic biopsy was pursued, showing BRAF-mutated non-Langerhans histiocytosis. She continued hormone replacement and was started on dabrafenib/trametinib, with subsequent clinical improvement and interval MRI response.
Clinical Lessons
Hypothalamic/suprasellar lesions can present with a life-threatening combination of central DI and panhypopituitarism. In suspected adrenal insufficiency with DI, treat with glucocorticoids first, then desmopressin with cautious free-water replacement, and only then thyroid hormone. Maintain a broad differential including infectious, inflammatory, and neoplastic infiltrative etiologies, and expedite tissue diagnosis when noninvasive studies are unrevealing. Although rare, non-Langerhans histiocytosis should be considered because mutation testing may enable targeted therapy.

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