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Langerhans Cell Histiocytosis Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Presentation of LCH in Children


Endocrine system

Diabetes insipidus, caused by LCH-induced damage to the antidiuretic hormone-secreting cells of the posterior pituitary, is the most frequent endocrine manifestation in LCH.[31] MRI scans usually show nodularity and/or thickening of the pituitary stalk and loss of the pituitary bright spot on T2-weighted images. Pituitary biopsies are rarely done and usually only when the stalk is greater than 6.5 mm or there is a hypothalamic mass.[32] Pituitary disease is often associated with other sites of involvement; in order to avoid biopsy of the pituitary, these sites can be biopsied to establish the diagnosis.

Approximately 4% of LCH patients present with an apparently idiopathic presentation of diabetes insipidus before other lesions of LCH are identified. A review of pediatric patients presenting with idiopathic central diabetes insipidus showed that 19% eventually developed manifestations of LCH.[33] Approximately 50% of patients who present with isolated diabetes insipidus as the initial manifestation of LCH either have anterior pituitary deficits at the time of diagnosis or develop them within 10 years of diabetes insipidus onset.[34,35] These included secondary amenorrhea, panhypopituitarism, growth hormone deficiency, hypoadrenalism, and abnormalities of gonadotropins.

Patients with diabetes insipidus due to LCH have a 50% to 80% chance of developing other lesions diagnostic of LCH within 1 year of diabetes insipidus onset, including bone, lung, and skin.[32,34] A study of 589 patients with LCH revealed the 10-year risk of pituitary involvement was 24%.[31] No decrease in incidence of diabetes insipidus was seen in chemotherapy-treated patients, but this may reflect the length of the therapy and/or the number of drugs used.[32] Using longer therapy and more drugs, the German-Austrian-Dutch (Deutsche Arbeits-gemeinschaft für Leukaemieforschung und-therapie im Kindesalter [DAL]) Group found the cumulative incidence to be 12%.[36,37] Diabetes insipidus followed initial LCH diagnosis at a mean of 1 year and growth hormone deficiency occurred 5 years later. The incidence of diabetes insipidus was lower in patients treated with more intensive chemotherapy regimens on the LCH-III and JLSG-96 and JLSG-02 studies in Japan (8.9% for multisystem patients) than on the LCH-I and LCH-II studies (14.2%).[37,38,39,40] Fifty-six percent of diabetes insipidus patients will develop anterior pituitary hormone deficiencies (growth, thyroid, or gonadal-stimulating hormones) within 10 years of the onset of diabetes insipidus. Diabetes insipidus occurs in 11% of patients treated with multiagent chemotherapy and in up to 50% of patients treated less aggressively.[35,41]

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