SAT-444 Pituitary Function and the Response to GH Replacement Therapy in Patients with Histiocytosis: Analysis of the Pfizer International Metabolic Database (KIMS)

Abstract

Introduction: Langerhans Cell Histiocytosis (LCH) is a rare infiltrative disease with granulomatous deposits sometimes involving the hypothalamus-pituitary axis, with endocrine manifestations that includes diabetes insipidus (DI) and growth hormone deficiency (GHD) as the most prevalent consequences in both adult- and childhood onset patients. Anterior pituitary dysfunction, although well recognized, has been reported in only 5-20% of patients and most clinical information is primarily described in pediatric patients (Kaltsas G et al. JCEM 85: 1370-1376, 2000) with little information on pituitary function in adults with LCH. Objective: To analyze the safety and effectiveness of GH replacement treatment in adult patients with GHD and LCH. Patients and Methods: Patients with LCH naïve/semi-naïve to GH replacement therapy with baseline (BL) and at least 1 year of follow-up data, enrolled in KIMS were studied. Data are presented as mean (SD) or percentage (%). Effectiveness GH data are presented as change after 1 year treatment (mean, 95% CI). P<0.05 was considered as statistically significant. Results: At BL, 57 adults with LCH (27 with childhood onset), 54% women, mean age at GHD onset 30 (15) yr, at KIMS entry 35 (12) yr; IGF-I SDS and total cholesterol (mmol/L) were -2.3 (1.8) and 5.7 (1.2), respectively; BMI kg/m², 28.5 (7.3) and waist circumference, 93.8 (16.5) cm. DI was diagnosed in 87% of LCH patients and additional pituitary deficiencies included LH/FSH (64%), TSH (56%), and ACTH (47%). One yr cross-sectional values for GH dose (n=37; mg/d) was 0.39 (0.21) and for IGF-I SDS -0.5 (-1.2 to 0.2). First yr delta for patients with LCH included total cholesterol (mmol/L) -0.9 (-1.5 to -0.3; p<0.05); AGHDA-Quality of Life (QoL) score (reduction indicating improved QoL; n=24) was -2.8 (-5.3 to -0.3; p<0.05) and change in waist circumference was -0.7 cm (-3.1 to 1.6; not statistically significant). Twenty-two serious adverse events (SAEs) were reported in 11 patients during 297 patient-years (74.1/1000 pyrs), 14 of these 22 SAEs were associated with hospitalization (7 out of 11 patients), 4 reports indicated no hospitalization and 4 reports had missing value on hospitalization. No new safety signals were reported. Conclusion: Pituitary deficiencies were more frequently observed in patients with LHC and concomitant GHD than previously recognized supporting a systematic hormonal evaluation in these patients. GH replacement therapy (for 1 year) was safe and improved metabolic variables and quality of life.