Growth hormone levels in the diagnosis of growth hormone deficiency in adulthood

Abstract

Current guidelines for the diagnosis of adult growth hormone deficiency (GHD) state that the diagnosis must be proven biochemically by provocative testing that is done within the appropriate clinical context. The need for reliance on provocative testing is based on evidence that the evaluation of spontaneous growth hormone (GH) secretion over 24 h and the measurement of IGF-I and IGFBP-3 levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it has been demonstrated that very low levels in patients highly suspected for GHD (i.e., patients with childhood-onset, severe GHD, or with multiple hypopituitarism acquired in adulthood) may be considered definitive evidence for severe GHD obviating the need for provocative tests. However, normal IGF-I levels do not rule out severe GHD and therefore adults suspected for GHD and with normal IGF-I levels must undergo a provocative test of GH secretion. The insulin tolerance test (ITT) is the test of choice, with severe GHD being defined by a GH peak less than 3 microg/l, the cut-off that distinguishes normal from GHD adults. The ITT is contraindicated in the presence of ischemic heart disease, seizure disorders, and in the elderly. Other tests are as reliable as the ITT, provided they are used with appropriate cut-off limits. Glucagon stimulation, a classical test, and especially new maximal tests such as GHRH in combination with arginine or GHS (i.e., GHRP-6) have well-defined cut-off limits, are reproducible, are independent of age and gender, and are able to distinguish between normal and GHD subjects. The confounding effect of overweight or obesity on the interpretation of the GH response to provocative tests needs to be considered as the somatotropic response to all stimuli is negatively correlated with body mass index. Appropriate cut-offs for lean, overweight, and obese subjects must be used in order to avoid false-positive diagnoses of severe GHD in obese adults.

Does Imatinib Mesylate Therapy Cause Growth Hormone Deficiency?

“…More recently, research has shown that cardiotoxicity is an unanticipated side effect of inhi- bition of c-Abl by imatinib [13] . On the other hand, the combined administration of GHRH with arginine recommended by the consensus guidelines [6] was beyond the scope of the present study. Instead, we used other established and reliable methods, including the GST and the L -dopa test, and IGF-I SDSs and IGFBP-3 SDSs.…”

“…IGF-I levels are a valuable biochemical marker of GH se-cretion. However, it is recommended that the diagnosis of adult GHD be confirmed by a provocation test of GH release [6] . Nearly 70% of these GHD patients showed severe deficiency on the GST.…”

“…3.0 g/l after GST [6] ; (2) IGF-I and IGFBP-3 SDS below -1.8 and -0.9, respectively, with 88% diagnostic efficiency [5] ; (3) IGF-I SDS below -3 in adults over age 28 with 94% specificity [7] ; (4) GH level with a peak value below 1.1 g/l in patients after the L -dopa stimulation test [4] . The L -dopa test was carried out on patients who had basal IGF-I SDS levels above -1.8.…”

The accuracy of diagnostic tests for GH deficiency in adults: a systematic review and meta-analysis

“…Patient characteristics can also influence accuracy of interpretation of GH provocation tests. Obese normal subjects have been shown to exhibit a blunted GH response to provocative stimuli to a degree that sometimes overlaps with the results obtained from severe GH-deficient adults (25). It has, therefore, been suggested that diagnostic cutoff criteria should be adjusted for body mass index to avoid the potential of a false-positive result.…”

Anterior Pituitary Failure

“…Known physiologic factors affecting the dynamic testing of GH secretion include gender, BMI, visceral adiposity, sex steroid status and age [159]. Responses to some secretagogues do not appear to attenuate with age [160].…”