Endocrine Abstracts

Introduction

Langherans Cell Histiocytosis (LCH) is a rare disease due to a neoplastic proliferation of Langerhans-type cells. Hypothalamic-pituitary (HP) involvement may occur in 20–40% of the patients, presenting with diabetes insipidus (DI) and/or anterior pituitary dysfunction. Typically, such abnormalities are permanent and unresponsive to systemic treatment of LCH. We report the case of a young woman with pulmonary and HP localizations, and significant endocrinological improvement during indomethacin treatment leading to a spontaneous, premature multiple birth.

Case report

A 26-yr old female, smoker, was diagnosed with pulmonary LCH due to respiratory symptoms, that improved after stopping smoking. Six years later, she presented polyuria (up to 8000 cc/24 h), leading to the diagnosis of DI, due to LCH localization on the pituitary stalk. Desmopressin therapy was started, up to 180 mg/day. In the same year, she stopped estrogen-progestin contraception, with a 7-months secondary amenorrhea. Endocrine investigation revealed a normoprolactinemic hypogonadotrophic hypogonadism with GH deficiency and normal thyroid and adrenal functions. Stimulation with GnRH (100 mg) showed a mild and late response and she was put on hormone replacement therapy (HRT). A few months later, indomethacin was started (up to 50 mg three times a day) and the doses of desmopressin was progressively reduced to 60 mg/day. HRT was discontinued because the patient wanted to have a baby but amenorrhea recurred, despite a clear increase in estrogen secretion and basal and GnRH-induced gonadotropin secretion. Medically assisted procreation failed three times even though she progressively recovered irregular menses. One year after the last attempt, at the age of 38, she had a spontaneous pregnancy and delivered two healthy premature monozygotic twins (at 33 weeks). Indomethacin was withdrawn at the beginning of pregnancy. She breastfed for two months and resumed menstruation.

Discussion

Little is known about the recovery of pituitary function after systemic treatment of LCH, with only a few reports of spontaneous DI recovery and a single case of gonadotroph deficiency recovery 3 years after the last course of glucocorticoids. In our case the improvement of DI and recovery of reproductive function occurred during indomethacin treatment.

Conclusion

To the best of our knowledge this is the first report of significant endocrinological improvement occurring during indomethacin treatment, which has recently shown to be effective in bone localizations through the inhibition of prostaglandins production. This observation indicates that HP dysfunction may be reversible and supports further studies to evaluate the potential role of indomethacin in this localization.