Endocrine manifestations in a cohort of 63 adulthood and childhood onset patients with Langerhans cell histiocytosis

Abstract

Objective Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm which can infiltrate any organ or tissue. Endocrine involvement has mostly been described in case reports and small retrospective studies. We aimed to describe endocrine manifestations in a large cohort of adulthood onset (AO) and childhood onset (CO) patients with LCH. Design Single-center observational study conducted between January 2002 and December 2017 at Pitié-Salpêtrière University Hospital (Paris, France), a tertiary care hospital. Method Clinical, biological and morphological evaluations of pituitary, gonadal, adrenal and thyroid function evaluations performed in 63 consecutive patients with LCH (AO patients: 40, CO patients: 23). Fifty-eight patients underwent follow-up assessments. Results Complete pituitary evaluation was performed in 38/63 patients (60.3%); at least one anterior pituitary dysfunction (APD) was found in 63.2% of them. In this subgroup of patients, the most prevalent deficiencies were diabetes insipidus (DI) and GHD (55.3% each), followed by gonadotropin deficiency (34.2%) and thyrotropin deficiency (23.7%). In the subgroup of the 25 incompletely evaluated patients, we found DI in 44%, GHD in 50%, gonadotropin deficiency in 30.4% and thyrotropin deficiency in 16%. APD was more common in CO patients (P = 0.003) but was not systematically associated with DI regardless of the age of onset. Endocrine dysfunction was most often permanent; moreover, occurrence of new deficiencies has been described during follow-up. Conclusion The spectrum of endocrine disorders appears to be large in LCH (both in AO and CO patients) and should be evaluated carefully at diagnosis and during follow-up. APD was not always associated with DI.

Paediatric Langerhans Cell Histiocytosis Disease: Long-Term Sequelae in the Hypothalamic Endocrine System

“…Other anterior pituitary hormones can be affected in a variable proportion and commonly in association. In accordance with LCH adult patients [32, 61, 62], Nanduri et al [33] and Sagna et al [47] reported GH and gonadotropin deficiencies (D) as the more frequent most common endocrine deficiencies seen after CDI. In the Argentinean paediatric cohort [57], GHD (45.4%) and thyroid hormone D (34%) were the most frequent APD associated with CDI, followed by gonadotropins D (27%) and corticotrophin-releasing hormone (ACTH) D (9%).…”

“…However, in the latest years, after the implementation of more aggressive and long treatments in MS disease, the reported incidence has significantly decreased, and it is estimated between 11.5 and 24% [9, 16, 38, 43-46]. Surprisingly, this is not the case in a recently study by Sagna et al [47], since a higher incidence of CDI (74%) in a cohort of 23 LCH children was reported.…”

“…Thyroid hormone deficiency can also occur secondary to infiltration of the thyroid by Langerhans cells [32, 63, 64]. Moderately hyperprolactinaemia which can be attributed to PS infiltration has been occasionally reported [29, 47]. However, it has not been studied systematically in the different reports.…”

Diabetes insipidus secondary to sellar/parasellar lesions

“…Involvement of two or more organs at diagnosis of LCH is the most important risk factor for DI, with a 4.7‐fold increased risk as opposed to patients with single organ involvement. Importantly, lesions in the craniofacial area, especially in the region of the ears, eyes and oral cavity, carry a significantly increased risk for DI; LCH‐related DI is usually permanent 59,74 . However, pituitary involvement may be reversible in some patients with LCH if it is observed and treated before the development of DI, whereas the effect of treatment with targeted therapies in patients presenting with early pituitary involvement has not as yet been studied in detail 75 .…”

“…Importantly, lesions in the craniofacial area, especially in the region of the ears, eyes and oral cavity, carry a significantly increased risk for DI; LCHrelated DI is usually permanent. 59,74 However, pituitary involvement may be reversible in some patients with LCH if it is observed and treated before the development of DI, whereas the effect of treatment with targeted therapies in patients presenting with early pituitary involvement has not as yet been studied in detail. 75 Some previous studies have shown that the prevalence of DI in patients with LCH has been found to be greater than 40%, approaching 94%…”