Endocrine Abstracts

Case: A 42-year old woman was referred to the endocrinology department for polydipsia and polyuria of sudden onset one month prior to presentation. She drank between 8 and 10 litres of water per day and complained of thirst, asthenia and lighter menstruation under her usual oral contraceptive pill. In addition to contraception she took 50 μg of L-thyroxine for Hashimoto thyroïditis. She had also a medical history of pink-red cutaneous lesions evolving for more than 10 years, first appeared in the axillae. The initial skin biopsy evoked granuloma secondary to aluminium contact but eviction of deodorant did not improve the existing lesions and other granuloma appeared in the sub mammary and inguinal folds. More recent biopsies retained the diagnosis of multiple reticulo-histiocytomas. Systemic involvement was excluded for 5 years by annual bone scintigraphy, chest and abdomen CT. Considering the polyuria-polydipsia syndrome associated with hypernatremia, independently of any deshydratation test (Na 146 mmol/L; N 135–145 mmol/l), diagnosis of central diabetes insipidus was made and patient received DDAVP nasal spray therapy. It allowed rapid improvement of the symptoms and normalization of natremia. Diagnosis was confirmed by a magnetic resonance imaging (MRI) that showed loss of normal hyper intense T1-weighted signal of the posterior pituitary gland, but also thickening of the pituitary stalk and lesion of the right side of the gland mimicking micro adenoma (7*9*9 mm). At this time circulating levels of anterior pituitary hormones were normal, except for mild hyperprolactinemia (PRL 704 μUI/ml; N<500). Gonadal and adrenal axes were difficult to interpret because of the contraceptive pill. After stopping this treatment, patient became amenorrheic and hormonal profile demonstrated hypogonadotropic hypogonadism. Considering the neuroendocrine manifestations, new cutaneous biopsies were performed, revealing CD68+, CD163+S100 CD1a -, CD207-, ALK- histiocytes evoking non-Langerhans histiocytosis (NLH). No BRAF or NRAS mutation was found. The diagnosis of Erdheim-Chester disease (ECD) or xanthoma disseminatum (XD) was thus evoked. Several weeks later, patient complained of polyarthralgia (painful knees and shoulders) and back pain irradiating in both legs. Bone scintigraphy and knee X-rays did not show any lesion. 18F-FDG-PET/CT revealed focal L3 vertebra hypermetabolic lesion and MRI confirmed infiltration of L3 but also to a lesser degree of L5. Biopsy of the L3 vertebral bone confirmed, as for cutaneous biopsy, NLH. Radiological follow-up showed spontaneous regression of pituitary infiltration with persistent thickened stalk, and new small non-hypermetabolic lesions in D12 and L1vertebra. Excepted DDAVP nasal spray, L-thyroxine and oestro-progestogenic substitutions, expectant observation was proposed as the patient was poorly symptomatic and systemic treatment available being heavy and often disappointing.

Discussion: Histiocytoses are rare disorders characterized by the accumulation of dendritic cells, macrophages or monocyte-derived cells in various tissues. These can affect children and adults and be uni- or multifocal, mild or disseminated. NLH distinguishes from Langerhans cell histiocytosis (LCH) by the absence of positivity of CD1a marker on histiocytes.^1,2 LCH and NLH may affect any organ of the body including skin, bones and pituitary gland.^2,3 NLH include a broad spectrum of pathologies including Erdheim-Chester disease (ECD) characterized by bilateral, symmetric cortical osteosclerosis of the diaphyseal and metaphyseal regions in more than 95% of cases^1,2,4, and xanthoma disseminatum (XD) characterized by predominant mucosal and skin involvement.^1,2 Diabetes insipidus can occur in LCH as in NLH and in ECD as in XD. Furthermore, more than 50% of the ECD patients exhibit BRAF-V600E mutation like in LCH supposing a common cellular origin.¹ Differential diagnosis between these different forms of histiocytoses is thus very difficult.

Conclusion: We described the case of a 42-year old woman with histopathologic features of NLH. She had cutaneous eruption and diabetes insipidus compatible with the diagnosis of XD. Female gender and bone involvement rather suggest ECD, but the absence of BRAF mutation and the non-typical bone lesion argue against. Finally, we described a rare cause of diabetes insipidus resulting from indeterminate (between XD and ECD) NLH with pituitary and vertebral involvement.

References: 1. Emile J-F, Abla O, Fraitag S. et al. Revised classification of histiocytes and neoplasms of the macrophage-dendritic cell lineages. Blood 2016, 127: 2672–2681.

2. Weitzman S, Jaffe R, Uncommon histiocytic disorders: The non-Langerhans cell histiocytoses. Pediatr Blood Cancer 2005; 45:256–264.

3. Courtillot C, Laugier Robiolle S, Cohen Aubart F, et al. Endocrine manifestations in a monocentric cohort of 64 patients with Erdheim-Chester disease. J Clin Endocrinol Metab, January 2016, 101(1): 305–313.

4. Diamond Eli L, Dagna L, Hyman D, et al. Consensus guidelines for the diagnosis and clinical management of Erdheim-Chester disease. Blood 2014, 124:483–492.