Endocrine Abstracts (2009) 20 P523

Development of multiple pituitary hormone deficiency (MPHD) in pediatric patients originally diagnosed with isolated GH deficiency (IsGHD)

Werner Blum1, Cheri Deal2, Alan Zimmermann3, Elena Shavrikova4, Catherine Sampson5, Anja Ignatenko4, Christopher Child6 & Ron Rosenfeld7

1Eli Lilly and Company, Bad Homburg, Germany; 2University of Montreal, Montreal, Canada; 3Eli lilly and Company, Indianapolis, Indiana, USA; 4Pharma Support Inc., St Petersburg, Russian Federation; 5i3 Statprobe, Cary, North Carolina, USA; 6Eli Lilly and Company, Windlesham, UK; 7Lucile Packard Foundation and ProteoGenix Inc., Palo Alto, California, USA.

Patients originally diagnosed with IsGHD may develop additional pituitary hormone deficiencies later in life. This study aimed to identify factors that predict development of MPHD and to characterize the time course of specific hormone deficiencies. Pediatric patients with IsGHD were from an observational study (GeNeSIS). Additional hormone deficiency during follow-up was accepted, if indicated by check box on the case report forms, by an adverse event or by starting replacement therapy. Baseline characteristics of patients with at least 2 year follow-up (n=2161) suggested more severe GHD in those who developed MPHD vs. those who did not (n=108 vs 2053; mean (S.D.), P by ANOVA): age at diagnosis (8.2 (4.2) vs 9.1 (3.6) year, P=0.019), height SDS (−3.1 (1.4) vs −2.5 (0.9), P<0.001), stimulated GH peak (median (Q1; Q3)) (2.6 (1.0; 5.5) vs 7.4 (4.7; 9.9) μg/l, P<0.001). Limiting the window of observation to patients with at least 3.5 years follow-up or development of MPHD within 4.5 years revealed significantly different proportions of patients who developed MPHD in the various diagnostic sub-groups: all GHD (116/1058, 11%), idiopathic (60/785, 8%), congenital (29/128, 23%), acquired (19/48, 40%), abnormal pituitary development (20/71, 28%). Deficiency of TSH was the most frequent (75%), followed by LH/FSH (16%), ADH (10%) and ACTH (10%); no PRL deficiency; 90% had 1 additional hormone deficiency and 10% had 2. In the entire population the time (years) from diagnosis of GHD to the additional hormone deficiency (median (Q1; Q3)) was 0.9 (0.4; 2.8) for ADH, 1.4 (0.8; 3.1) for TSH, 1.8 (1.4; 2.7) for ACTH, and 5.4 (2.5; 8.6) for LH/FSH. Logistic multiple regression modeling identified the following significant (P<0.001) predictors for development of MPHD (odds ratio(95% CI)): organic cause of GHD (3.6 (2.2–6.0)) and low stimulated GH peak (0.5(0.4–0.6)).

Conclusion: In patients with IsGHD additional pituitary hormone deficiencies may develop especially in those with organic cause and severe GHD. Therefore, patients with IsGHD require continuous monitoring for development of MPHD.

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