Endocrine Abstracts

EEC is a multisystemic disease secondary to a clonal histiocyte proliferation of non-Langerhans cells due to hyperactivation of the MAPK/ERK signaling pathway, with somatic BRAF V600E mutation present in 50% of cases with therapeutic implications. Between 50% of patients develop endocrinopathies, the most frequent being central diabetes insipidus (CDI). We present the case of a 42-year-old woman, diagnosed with CDI in 1998 without family history, treated with DDAVP [MRI: absence of neurohypophysis, normal pituitary stalk), negative AVP gene and hypergonadotropic hypogonadism since the age of 39 years. In 2019 she developed acute renal failure (GFR 20 ml/min/1.73 m²) and HTA, bilateral grade IV hydronephrosis due to bilateral perirenal infiltrative process. She required a double J catheter and subsequent bilateral nephrostomy without improvement of renal function. She had associated blastic bone lesions in axial and appendicular skeleton. During the diagnostic process she developed gait ataxia, dysarthria and dysphagia. In view of the suspicion of multisystemic disease of histiocytic origin, a bone biopsy of the sacral lesion (not profitable) was conducted and biopsy of the perirenal infiltrative tissue showed proliferation of histiocytes (CD68 positive, S100 and CD1 negative, no Langerhans phenotype) compatible with EEC and presence of BRAF V600E mutation in molecular analysis. The PET-CT extension study (18FDG) showed cerebral hyperenhancement predominantly in the posterior fossa, generalized bone involvement and pathological uptake in bilateral perirenal fat, retroperitoneal, left adrenal, gonads, pulmonary artery, interatrial septum and pericardial thickening. Bone marrow biopsy showed grade 3 myelofibrosis without myeloproliferative syndrome criteria. The presence of BRAFV600E mutation allowed treatment with Vemurafenib without side effects despite renal failure, with clinical improvement and reduction of lesions in PET-CT at 8 weeks of treatment. At the 5th month, after worsening of the neurological symptoms (pyramidocerebellar syndrome), she was treated with IV dexamethasone and second line with Drabrafenib-Trametinib was started (2020). Clinical neurological improvement was confirmed a few weeks after initiation, her nystagmus, dysarthria, dysmetria, and gait improved remarkably, and progressive reduction of pathological uptakes at brain and renal level during follow-up with FDG-F18. In 2021 she was diagnosed with central hypothyroidism and somatotropic deficit, renal function has remained stable and nephrostomies have been closed (2022). The patient continues with the combination of BRAF and MEK inhibitors. She has also developed several endocrinopathies over time: CID as first manifestation 21 years earlier, adenohypophyseal deficits, gonadal involvement with amenorrhea and unilateral adrenal involvement. Prognosis depends on the neurological and cardiological evolution.