FP20-5 Development of Multiple Pituitary Hormone Deficiencies (MPHD) in Pediatric Patients Originally Diagnosed with Isolated GH Deficiency (IGHD) due to Organic Causes

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP20-Growth: Clinical Trials & Observational Studies
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:05 AM
Room 122 (Moscone Center)

Poster Board SUN-628
Christopher J Child*1, Cheri L Deal2, Alan G Zimmermann3, Charmian A Quigley3, Ron G Rosenfeld4, Stenvert L Drop5, Gordon B Cutler Jr.6 and Werner F. Blum7
1Eli Lilly and Company, Windlesham, United Kingdom, 2Sainte-Justine Hospital, Montreal, QC, Canada, 3Eli Lilly and Company, Indianapolis, IN, 4Oregon Health & Science University, 5Sophia Childrens Hosp, Rotterdam, Netherlands, 6Eli Lilly and Company, Deltaville, VA, 7Eli Lilly and Company, Bad Homburg, Germany
Patients (pts) originally diagnosed with IGHD due to an organic cause (e.g. congenital pituitary anomaly, or intracranial tumor and/or its treatment) may develop additional pituitary hormone deficiencies (PHDs) later in life. This analysis aimed to identify factors that predict development of MPHD and to characterize their time course.

Newly diagnosed PHDs were identified during follow-up of 716 pediatric pts with organic IGHD in the GeNeSIS prospective, multinational observational study (510 with congenital, 204 with acquired and 2 with unknown GHD cause). PHDs were ascertained by check box on case report forms, reports of adverse events, or initiation of replacement therapy.

During mean±SD follow-up of 3.3±2.9 years (yr), ≥1 additional PHD was reported for 71 of the 716 pts (10%). Limiting the time window of observation to pts with at least 3.5 yr follow-up or development of MPHD within 4.5yr (“4 yr cohort”), resulted in 290 pts (mean±SD follow-up of 5.8±2.3 yr), of whom 60 (21%) were reported to develop ≥1 additional PHD. Of 80 pts with acquired GHD in the 4 yr cohort, 27 (34%) developed MPHD (21/50 [42%] of those with GHD due to intracranial tumor), compared with 33/210 (16%) with GHD due to congenital causes (22/121 [18%] of those with abnormal pituitary development). Comparison of pts in the 4 yr cohort who developed MPHD vs. those who did not, showed the following significant differences (p by ANOVA): age at diagnosis of GHD: 8.2±4.4 vs. 6.8±3.7 yr, p=0.017; age at start of GH: 9.0±4.3 vs. 7.4±3.6 yr, p=0.005; baseline IGF-I SDS: -4.4±2.1 vs. -2.9±2.1), p=0.007; additionally median (Q1;Q3) maximum stimulated GH peak was 1.6 (0.6;3.3) vs. 4.9 (2.7;7.9) μg/L, p<0.001 (with GH peak ≤5 µg/L: 87% vs. 54%, p<0.001). Interestingly, 4 pts who developed MPHD had peak GH >10 µg/L. Deficiency of TSH was the most frequent (73%), followed by LH/FSH (23%), ACTH (15%), and ADH (10%); 80% of MPHD pts had 1 additional PHD diagnosed during 4.5yr follow-up, 18% had 2 and 2% had 3. In the entire population the time (yr) from diagnosis of GHD to the first additional PHD [median (Q1;Q3)] was 1.0 (0.9;2.3) for ADH, 1.9 (1.7;2.8) for ACTH, 2.4 (1.0;3.6) for TSH, and 6.0 (2.5;7.3) for LH/FSH. Multivariable logistic regression modeling identified the following significant (p<0.05) predictors for development of MPHD: female gender, older baseline age, longer follow-up time, and lower stimulated GH peak.

Pts with organic IGHD, especially those with more severe GHD, and those with acquired causes, are at high risk of developing MPHD.  However, even after 4 yr of observation the majority (79%) of pts had not (yet) manifested additional PHDs, and as signs and symptoms of additional PHDs may be delayed, long-term monitoring of pituitary function is recommended.

Disclosure: CJC: Employee, Eli Lilly & Company, Employee, Eli Lilly & Company. CLD: Medical Advisory Board Member, Eli Lilly & Company. AGZ: Employee, Eli Lilly & Company, Employee, Eli Lilly & Company. CAQ: Employee, Eli Lilly & Company, Employee, Eli Lilly & Company. RGR: Medical Advisory Board Member, Eli Lilly & Company. SLD: Medical Advisory Board Member, Eli Lilly & Company. GBC Jr.: , Eli Lilly & Company, , Eli Lilly & Company. WFB: Employee, Eli Lilly & Company, Employee, Eli Lilly & Company.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Sponsored by Eli Lilly and Company