Biochemical assessment of disease control in acromegaly: reappraisal of the glucose suppression test in somatostatin analogue (SA) treated patients

Abstract

(1) Patients controlled by somatostatin analog fail to suppress growth hormone in response to both mixed meals and oral glucose tolerance test (2) This phenomenon is likely to result in elevated serum growth hormone levels during everyday life in somatostatin analog-treated patients, (3) We postulate that measuring growth hormone levels during oral glucose tolerance test is useful to unmask potential somatostatin analog under-treatment in the presence of 'safe' insulin-like growth factor-I levels.

Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly: a randomized multicentre study

“…It remains to be tested if a more prolonged study period will translate into detectable changes in QoL or other non-biochemical endpoints. Our observations on insulin, FFA and glucose levels during the OGTT are in accordance with previous studies (11,12,13) and reflect the suppressive effects of SA on insulin secretion. It is also noteworthy that a positive correlation between insulin AUC during OGTT and IGF-I was recorded only in surgery patients, which indirectly supports a suppressive effect of SA on insulin-induced hepatic IGF-I.…”

“…By contrast, we have previously observed that GH nadir levels are significantly elevated in controlled SA patients compared to surgery patients despite comparable IGF-I and GH fasting levels, which were accompanied by worse symptoms and QoL (11). We have also reported that SA patients exhibit elevated GH nadir levels in response to both OGTT and mixed meals as compared to controlled surgery patients carefully matched for IGF-I and gender (12). The reason why GH nadir levels are elevated in SA patients in the presence of controlled IGF-I levels is not fully clarified.…”

“…It is also controversial whether OGTT-based GH nadir levels in SA-treated patients offer useful information as compared to random or fasting GH measurements (10). However, we have observed in two retrospective studies that measuring GH levels during OGTT may unmask potential under-treatment with SA despite IGF-I levels within the target range (11,12).…”

Growth Hormone Response to Oral Glucose Load: From Normal to Pathological Conditions

“…In contrast, another group has questioned the validity of IGF-1 as an adequate marker of disease activity in somatostatin analogue-treated patients, as somatostatin analogues may exert a suppressive effect on hepatic IGF1 production resulting in normal IGF-1 levels despite continued disease activity induced by circulating GH [107-109]. The authors reported significantly higher GH nadir levels along with worse symptoms and quality of life in controlled patients treated with somatostatin analogues compared to surgery despite comparable IGF-I and fasting GH levels [109].…”

“…Dose escalation of somatostatin analogues minimized the discordance between IGF-1 and nadir GH levels with, however, no improvement in quality of life [108]. Furthermore, higher GH nadir levels after an OGTT as well as after mixed meals were observed in patients treated with somatostatin analogues compared to patients successfully treated with surgery and matched to IGF-1 levels suggesting a residual disease activity in somatostatin analogue treated patients despite normalized IGF-I levels [107]. The authors thus conclude that measuring GH levels during OGTT may unmask insufficient disease control with somatostatin analogues despite normalized IGF-I levels.…”