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Title: Direct Evidence for Beneficial Effect of Growth Hormone Replacement on Mortality in Adults With Deficiency: Presented at ECE

"Direct Evidence for Beneficial Effect of Growth Hormone Replacement on Mortality in Adults With Deficiency: Presented at ECE"

By Chris Berrie BERLIN -- May 7, 2008 -- Levels of insulin growth factor I (IGF-I) correlate with mortality rates in patients with severe growth hormone deficiency (GHD) on growth hormone (GH) replacement therapy, researchers reported here at the 10th European Congress of Endocrinology (ECE). This therapy therefore appears to have beneficial effects on mortality in these patients, said coinvestigator Maria Koltowska-Häggström, MD, PhD, Project Director, Pfizer International Metabolic Database KIGS/KIMS Outcomes Research, Pfizer Health AB, Stockholm, Sweden. "Since the early 1990s, there have been a number of studies suggesting that in patients with hypopituitaries who were on the conventional replacement therapy for other hormones there were higher [standardised mortality ratios]," she said during her presentation on May 5. Previous studies have established the beneficial effects on the cardiovascular risk profile of GH replacement in adults with severe GHD, she said. The aim of the current study was to compare the mortality rate relative to the general population among hypopituitary patients who receive GH in addition to conventional hormone replacement and to determine the variation in mortality rates according to levels of IGF-I. The study analysed data from 9,610 patients with GH deficiency extracted from the KIMS database (mean age, 44 years; male, 53%). Their major aetiologies included nonfunctioning pituitary adenoma (26.7% of patients), idiopathic GHD (15.5%), craniopharyngioma (12.1%), prolactinoma (9.7%), and malignancies (8.6%). The analysis expressed a standardised mortality ratio (SMR) as an observed-over-expected number of cases, with numbers calculated according to general population rates, with stratification for age, gender, and country-region. IGF-I was expressed as a standard deviation score (SDS), taking into account age and gender in the healthy reference standard. With a mean follow-up of 3.9 years, all-cause mortality was 257 deaths in the total study population versus 255.1 expected deaths from the external population (SMR: 1.01; 95% confidence interval [CI], 0.89-1.14). This SMR ratio was modified significantly according to age attained during follow-up (<45 years, 4.35; 45-69 years, 0.84; >=70 years, 0.64; [P trend <.0001).

Significantly increased mortality rates in the study population were seen for: females (1.36; 95% CI, 1.10-1.66); diabetes insipidus (1.66; 95% CI, 1.31-2.07); craniopharyngioma (2.00; 95% CI, 1.40-2.77); and malignancy as underlying disease (3.03; 95% CI, 2.15-4.16). Nonfunctioning pituitary adenoma was associated with significantly decreased SMR (0.57; 95% CI, 0.45-0.72).

Although no significant deviations in SMR were seen for other variables, maintenance levels of IGF-I at 1 year in patients taking GH replacement therapy were significantly associated with the SMR analysed from 1 year onwards (P-trend < .0001).

Indeed, in the linear regression analysis, and taking into account all the significant explanatory variables, the SMR decreased significantly, with an increase in IGF-I SDS of 14.5% per unit at the 1-year visit (P = .003).

"There was a very strong significant correlation between SMR and IGF-I levels," Dr. Koltowska-Häggström indicated. "If they were low, SMR was high, and if they were closer to the norm, that was better."

Database access approval and statistical support was supplied by Pfizer Inc.

[Presentation title: Total and Cause-Specific Mortality in Patients From the KIMS Database: Direct Evidence for a Beneficial Effect of GH Replacement Therapy on Mortality in Adult GH-Deficient Patients. Abstract P404]

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