Endocrine Abstracts (2008) 16 P425

Tests of growth hormone (GH) status in severe GH deficiency: do they identify a similar phenotype? Insight from the KIMS database

Andrew Toogood1, George Brabant2, Michael Buchfelder3, Ulla Feldt-Rasmussen4, Maria Koltowska-Haggstrom5, Bjorn Jonsson6, Æse Krogh Rasmussen4, Dominique Maiter7, Bernhard Saller8 & Beverly Biller9

1Department of Medicine, Queen Elizabeth Hospital, Birmingham, UK; 2Department of Endocrinology, Christie Hospital, Manchester, UK; 3Neurochirurgische Klinik, Universität Erlangen-Nürnberg, Erlangen, Germany; 4Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark; 5KIMS Medical Outcomes, Pfizer Endocrine Care, Stockholm, Sweden; 6Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden; 7Faculte de Medecine, UCL, Brussels, Belgium; 8Pfizer Global Pharmaceuticals, EBT Endocrine Care, London, UK; 9Neuroendocrine Unit, Massachusetts General Hospital, Boston, USA.

A GH peak of 3 μg/l during the insulin tolerance test (ITT) is considered the gold standard for identifying adults with severe GH deficiency. Alternative stimuli such as arginine (AST) and glucagon (GST) are also employed but produce lower GH peaks than the ITT in normal subjects. Despite this, 3 μg/l is used as the diagnostic threshold for these tests, raising the possibility that severe GH deficiency is being diagnosed inappropriately.

We studied 4584 patients enrolled in KIMS (3070 underwent an ITT, 1320 an AST and 910 a GST at diagnosis) to determine whether these patients exhibited a similar phenotype. Interquartile ranges of GH peaks achieved during the ITT were determined (1st <0.12, 2nd 0.13–0.39, 3rd 0.4–0.99, 4th 1.0–3.0 μg/l). These limits were applied to the AST and GST. Comparisons were made in the 1st and 4th quartiles between the AST vs ITT and GST vs ITT for the following clinical variables: BMI, IGF-I SDS, cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, waist:hip ratio and quality of life (QoL-AGHDA). quartile. AST vs ITT: BMI was higher (30.6 vs 28.8 kg/m2, P<0.0001) in the AST group. GST vs ITT: IGF-I SDS was lower (-1.9 vs -2.8, P=0.003), HDL was higher (1.1 vs 1.2 mmol/l, P=0.025) and triglycerides were lower (2.7 vs 2.3 mmol/l, P=0.003) in the ITT group. quartile. AST vs ITT: BMI was higher in the AST group (29.0 vs 28.0 kg/m2, P=0.035). GST vs ITT: Quality of life was worse in the GST group (15 vs 12, P<0.0001).

None of the other parameters was significantly affected in either quartile.

Using a diagnostic threshold of 3 μg/l, the AST and GST identified GHD patients with similar features to those defined by the ITT. This is reassuring for future studies on the impact of GH replacement in the KIMS database.