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Diabetes insipidus associated with Langerhans cell histiocytosis: is it reversible?
1Department of Haematology and Oncology, Hospital for Sick Children, London, England, United Kingdom.
Insights
Diabetes insipidus, characterized by thirst and polyuria, affects a significant portion of children with Langerhans cell histiocytosis (LCH). Current treatments, including DDAVP, do not reverse the condition, highlighting the need for further research.
Area of Science:
- Pediatric Endocrinology
- Oncology
- Nephrology
Background:
- Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disease.
- Posterior pituitary dysfunction, leading to diabetes insipidus (DI), can complicate LCH.
- Thirst and polyuria are key symptoms of DI.
Purpose of the Study:
- To investigate the incidence and characteristics of diabetes insipidus in children with LCH.
- To evaluate the effectiveness of current treatments for DI in this population.
- To assess the long-term outcomes of DI in children with LCH.
Main Methods:
- Retrospective review of 58 children with LCH.
- Water deprivation tests and urinary arginine vasopressin (AVP) measurements to diagnose DI.
- Comparison of 1-desamino-8-D arginine vasopressin (DDAVP) doses at diagnosis and follow-up.
- Documentation of local and systemic treatments received.
Main Results:
- 14% of children with LCH developed thirst and polyuria.
- 10 children had complete DI, and 4 had partial DI.
- No child was able to discontinue DDAVP replacement therapy, even with irradiation or chemotherapy.
- Mean DDAVP dose increased from 9.3 to 18 micrograms daily over 7.8 years.
Conclusions:
- Diabetes insipidus is a significant complication of LCH that often requires lifelong DDAVP treatment.
- Current treatments do not appear to reverse posterior pituitary dysfunction in LCH.
- Precise documentation of DI, including urinary AVP levels, is crucial for evaluating new therapeutic approaches.
Abstract:
Fourteen of 58 (24%) children with Langerhans cell hisiocytosis (LCH) currently attending the Hospital for Sick Children (London) developed thirst and polyuria during the course of their disease. Three had single-system disease confined to bone, and 11 had multisystem disease. The median age at presentation of LCH was 2 years 0 months, and polyuria/polydipsia developed at a median age of 3 years 9 months (range 1 month before diagnosis of LCH to 4 years after diagnosis). Each child had a water deprivation test with measurement of urinary arginine vasopressin (AVP) to document diabetes insipidus. The doses of 1-desamino-8-D arginine vasopressin (DDAVP) required to control symptoms were compared at diagnosis and at a mean follow-up of 7 years 8 months. Local and systemic treatment was recorded. Ten of 14 children were shown to have "complete" diabetes insipidus, whilest the other four had "partial" diabetes insipidus. Seven children were treated with irradiation. with or without systemic chemotherapy, six with systemic chemotherapy only, and one with DDAVP replacement only. No child, including two with partial diabetes insipidus irradiated within 4 weeks of the onset of symptoms, lost symptoms of polyuria/polydypsia and none was able to discontinue DDAVP replacement. One child treated with Etoposide showed a temporary rise in urinary AVP level to within the normal range but still needed DDAVP to control her symptoms. The mean doses of DDAVP at onset of diabetes insipidus and at follow-up were 9.3 micrograms and 18 micrograms daily, respectively. We conclude that the most appropriate treatment for reversing diabetes insipidus complicating Langerhans cell histiocytosis is yet to be determined. Precise documentation of posterior pituitary dysfunction, including measurement of urinary AVP levels, is essential if the effects of new forms of treatment are to be assessed accurately.