Cranial Diabetes Insipidus With Mediastinal Adenopathy: What Are the Possibilities?

Abstract

INTRODUCTION: We present a case of a middle aged Chinese male who was diagnosed clinically to have motor neurone disease (MND) in 2011. He presented 2 years later with cranial diabetes insipidus and was found to have a diffuse infiltrative disease affecting multiple organs. We describe a case of a rare condition - non-Langerhans cell histiocytosis (Erdheim-Chester Disease) CASE PRESENTATION: A 49-year-old Chinese male, previously healthy and a non-smoker, was diagnosed to have motor neurone disease in 2011 when he presented with dysarthria, dysphagia and limb <<weakness>>. He was admitted intensive care unit 2 years later for hypoxemic respiratory failure. He was also found at the time to have polyuria with significant hypernatremia (152mmol/L) and raised serum osmolality (306 mmol/kg) with inappropriately low urine osmolality (152mmol/kg). A CT angiogram of the pulmonary arteries was done for the suspicion of possible pulmonary embolism as the cause of hypoxemia was not fully accounted for, only to find a conglomerate of hilar and mediastinal lymph nodes with diffuse pulmonary infiltrates and a small number of lung cysts, predominantly upper lobe in distribution. A clinical diagnosis of cranial diabetes insipidus was made, and neuroimaging confirmed nodular thickening of the pituitary stalk suggestive of pituitary hypophysitis. Bronchoscopy with endobronchial ultrasound guided biopsy of the lymph node showed non-necrotizing granulomatous inflammation. Microbiological studies including induced sputum and lymph node needle aspiration samples sent for gram-stain, acid-fast bacilli and mycobacterial cultures were negative. HIV screen was negative. Prolactin levels were normal (335mIU/L). As the diagnosis of motor neurone disease was questioned at that point, repeat EMG and nerve conduction studies were performed which were normal. Lumbar puncture showed no evidence of aseptic meningitis and protein level was normal. Microbiology for bacteria, mycobacteria and fungi, as well as cytology and flow cytometry for lymphoma were negative. A provisional diagnosis of sarcoidosis was made, with plans to obtain biopsy confirmation of granulomas in a second organ site. Repeat imaging of the thorax extending to the abdomen showed worsening necrotic lymphadenopathy (mediastinal and retroperitoneal), and a diffusely infiltrative process extending along the right posterior pericardium, partially encasing the superior vena cava and encapsulating the aortic arch, descending aorta, imaged iliac vessels and both kidneys. Based on the clinical findings, a diagnosis of Erdheim-Chester Disease was suspected. Long bone x-rays confirmed the presence of sclerotic foci in a bilateral, symmetrical distribution in the metadiaphyses. Mediastinoscopy with lymph node biopsy was performed at the same sitting as a bone biopsy of the left distal radius, with the former intended to exclude concomitant lymphoma. Lymph node biopsy only showed necrotizing granulomatous inflammation with negative stains for acid fast bacilli. Bone biopsy revealed osteosclerosis with chronic inflammation and focal aggregates of xanthomatous histiocytes. They stained positive for CD68 (stained negatively for other molecular markers - S-100, CD1a and CD117), confirming our diagnosis. A referral was made to the hematologist and patient was started on pegylated interferon-alpha. DISCUSSION: The first case of Erdheim Chester Disease (ECD) was reported in 1930. It is a rare condition and about half of the patients affected have extraskeletal manifestations, including involvement of the hypothalamus-pituitary axis, lung, heart, skin, liver, retroperitoneum, spleen, and orbit. This case illustrates the difficulties in diagnosing a rare condition, Erdheim-Chester Disease, where multiple biopsies were non-conclusive. Previous isolated case reports involved patients with long bone pain which was absent in our patient.A high index of suspicion based on the clinical and radiological picture, and finally supported by pathology, is often needed to secure the diagnosis. CONCLUSIONS: This is