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Clinical Implications of Residual Growth Hormone (GH) Response to Provocative Testing in Adults with Severe GH Deficiency

Department of Endocrinology (G.B.), Christie Hospital, Manchester M20 4BX, United Kingdom; Department of Medical Endocrinology (A.K.R., U.F.-R), Rigshospitalet, 2100 Copenhagen, Denmark; Neuroendocrine Unit (B.M.K.B.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114; Department of Neurosurgery (M.B.), University of Erlangen-Nuernberg, 91045 Erlangen, Germany; Medical Department (K.F.), Pfizer GmbH, 76139 Karlsruhe, Germany; Departments of Women’s and Children’s Health (B.J.), and of Pharmacy (M.K.-H.), Uppsala University, 751 05 Uppsala, Sweden; KIGS/KIMS/ACROSTUDY Medical Outcomes (M.K.-H.), Pfizer Health AB, 190 91 Sollentuna, Sweden; Department of Endocrinology (D.M.), University Hospital Saint-Luc, 1200 Bruxelles, Belgium; EndoScience (B.S.), 80337 Munich, Germany; and Department of Endocrinology (A.T.), University Hospital National Health Service Foundation Trust, Birmingham B15 2TH, United Kingdom

Address all correspondence and requests for reprints to: Georg Brabant, Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, United Kingdom. E-mail: georg.brabant{at}manchester.ac.uk.

Context: The diagnosis of GH deficiency (GHD) in adults is based on provocative tests of GH release, all influenced by clinical factors. It is unknown whether the amount of residual GH reserve under the cutoff value has any physiological implication.

Objectives: We used a large pharmacoepidemiological database of adult GHD (KIMS) and tested the impact of confounding factors on GH release of no greater than 3 µg/liter after an insulin tolerance test (ITT) and evaluated its potential physiological role.

Design, Settings, and Patients: A total of 1098 patients fulfilled the criteria of having a GH peak of no greater than 3 µg/liter during ITT as well as documented IGF-I levels.

Outcomes: The impact of underlying hypothalamic-pituitary disease, age, gender, body weight, as well as treatment modalities such as irradiation on peak GH level to ITT was evaluated, and the correlations between GH peak and targets of GH action were analyzed.

Results: The GH response to ITT was regulated by gender, age, and the number of additional pituitary deficiencies. In a multivariate evaluation, the extent of hypothalamic-pituitary dysfunction was the most important single predictor of GH peak in ITT. GH peaks in ITT were positively related to IGF-I levels and high-density lipoprotein-cholesterol, as well as inversely to triglycerides.

Conclusions: Even in adult severe GHD, GH release appears to be regulated by factors defined to play an important role in normal GH secretion. The impact of very low GH release on IGF-I and lipid parameters indicates a persistent physiological role of low GH concentrations in severely affected patients with GHD.