CENTRAL PRECOCIOUS PUBERTY IN MULTISYSTEM LANGERHANS CELL HISTIOCYTOSIS: A Case Report

Abstract

The authors describe a girl with multisystem Langerhans cell histiocytosis (LCH) who developed central precocious puberty (CPP). At the age of 19 months she presented with otorrhea and polypoid formations in the ear canal; polyps were removed and LCH suspected. She subsequently developed diabetes insipidus with a documented lesion of the pituitary stalk; she received chemotherapy and began therapy with l-desamino-8-D-argininevasopressin. Growth hormone deficiency was diagnosed at the age of 4.4 years and GH replacement therapy started. The patient has been off therapy for LCH since the age of 6. Signs of pubertal development appeared at 7.5 years (bone age 8 years) and gonadotropin-releasing hormone analog (GnRHa) treatment was started. During the observation period she developed central hypothyroidism. Development of CPP during LCH is extremely rare; to the authors 'knowledge, no patient has been described so far. The authors believe that CPP was secondary to LCH and did not represent a casual finding, even in the absence of hypothalamic-pituitary axis involvement. The presence of preceding lesions producing excessive cytokine levels, with damage on the neurosecretory apparatus that inhibits the GnRH pulse generator, represents the most intriguing hypothesis. The possibility of CPP development should be considered during the follow-up of these patients.

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

“…Nanduri et al [33] reported 1 boy with LCH who had an early onset of puberty requiring treatment with a gonadotropin-releasing hormone analogue for a period of 20 months. Another reported case was a 7.5-year-old girl with multisystem LCH, CDI, GH deficiency, and central hypothyroidism who developed central precocious puberty [66]. Finally, Table 1 describes the frequency of pituitary involvement in the latest paediatric series.…”

Primary Hypothyroidism, Precocious Puberty and Hypothalamic Obesity in Langerhans Cell Histiocytosis

“…The French LCH study group describes gonadotropin deficiency in 12% of children with DI whereas Maghnie et al did not see any abnormal gonadotropin status in the 17 LCH children (11 with multisystem disease) despite one-third being pubertal or postpubertal [1,6]. A single report in the existing English literature describes central precocious puberty in a 7.5-yr-old LCH girl, 6 years after disease onset [7]. The present patient presented with precocious puberty at 5.5 yrs age, 2 years after disease onset.…”

Endocrine features of Langerhans cell histiocytosis in paediatric patients: A 30‐year review

“…While the risk for evolving anterior pituitary hormone deficiencies is ongoing and international guidelines suggest regular growth and pubertal follow-up, there are very limited data on incidence of atypical puberty in LCH. [13][14][15] Bisphosphonate use in LCH has been documented since 1989, to treat bone pain, in addition to improvement of bone mineral density. 16 In this cohort three were noted to have multiple fractures in the setting of LCH.…”