Discordant GH and IGF-1 Results in Treated Acromegaly: Impact of GH Cutoffs and Mean Values Assessment

Abstract

Context Discordant GH and IGF-1 values are frequent in acromegaly. Objective To evaluate the impact of different GH cut-offs on discordance rate. To investigate whether the mean of consecutive GH measurements impact discordance rate when matched to the last available IGF-1 value. Design Retrospective study. Setting Referral centre for pituitary diseases. Patients Ninety acromegaly patients with at least three consecutive evaluations for GH and IGF-1 using the same assay in the same laboratory (median follow-up 13 years). Interventions Multimodal treatment of acromegaly. Main outcome measures Single fasting GH (GHf) and IGF-1 (IGF-1f). Mean of three GH measurements (GHm), collected during consecutive routine patients’ evaluations. Results At last evaluation GHf values were 1.99 ± 2.79 µg/L and age-adjusted IGF-1f 0.86 ± 0.44 xULN (mean ± SD). Discordance rate using GHf was 52.2% (cut-off 1 µg/L) and 35.6% (cut-off 2.5 µg/L) (p=0.025). “High GH” discordance was more common for GHf <1.0 µg/L, while “high IGF-1” was predominant for GHf <2.5 µg/L (p<0.0001). Using GHm mitigated the impact of GH cut-offs on discordance (GHm <1.0 µg/L: 43.3%; GHm <2.5 µg/L: 38.9%; p=0.265). At ROC curve analysis, both GHf and GHm were poor predictors of IGF-1f normalization (AUC=0.611 and AUC=0.645, respectively). The prevalence of disease-related comorbidities did not significantly differ between controlled, discordant, and active disease patients. Discussion GH/IGF-1 discordance strongly depends on GH cut-offs. The use of GHm lessen the impact of GH cut-offs. Measurement of fasting GH levels (both GHf and GHm) is a poor predictor of IGF-1f normalization in our cohort.

Clinical and Radiological Predictors of Biochemical Response to First-Line Treatment With Somatostatin Receptor Ligands in Acromegaly: A Real-Life Perspective

“…We focused on IGF-1 since most recent Consensus Statements on acromegaly suggest it as the main target hormone to monitor disease activity (10), being more constant than GH in a single measurement, without showing significant circadian variations (46)(47)(48).…”

Octreotide and Pasireotide Combination Treatment in Somatotroph Tumor Cells: Predominant Role of SST2 in Mediating Ligand Effects

“…GH excess results in high circulating levels of insulin-like growth factor-1 (IGF-1), hence leading to increased patients’ morbidity and mortality [ 1 ]. Therefore, a primary aim of acromegaly management is to reach normal age-adjusted IGF-1 levels, as well as safe GH values (defined as random GH <1 µg/L or <2.5 µg/L, according to the sensitivity of the assays) [ 2 , 3 ].…”

Mean GH profile is more accurate than single fasting GH in the evaluation of acromegaly disease control during somatostatin receptor ligands therapy

“…Previous studies found quite similar cut-offs: Cozzi et al found out that normal IGF-I was predicted by the GH value of 1.8 µg/l in males and 2.4 µg/l in females [ 26 ]; according to Campana et al, instead, the best-fitting single fasting GH cut-off was1.63 µg/l [ 27 ].…”

“…A more recent study by Campana et al suggested using the mean of 3 GH measurements collected during consecutive routine patients’ evaluations, as it mitigates the impact of GH cutoffs on discordance with IGF-I [ 27 ].…”