Context: The diagnosis of growth hormone 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 cut-off value has any physiological implication.

Objectives: We used a large pharmaco-epidemiological database of adult GHD (KIMS) and tested the impact of confounding factors on GH release 3µg/l following an insulin tolerance test (ITT) and evaluated its potential physiological role.

Design, settings and patients: 1098 patients fulfilled the criteria of having a GH peak 3µg/l 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 analysed.

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 to HDL-cholesterol as well as inversely to triglycerides.

Conclusion: Even in severe adult 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.