Clinical and hormonal findings in patients presenting with high IGF-1 and growth hormone suppression after oral glucose load: a retrospective cohort study

Abstract

Objective: high IGF-1 and unsuppressed GH levels after glucose load confirm the diagnosis of acromegaly. Management of patients with conflicting results could be challenging. Our aim was to evaluate the clinical and hormonal evolution over a long follow-up in patients with high IGF-1 but normal GH nadir (GHn<0.4 μg/L according to the latest guidelines). Design: retrospective cohort study. Methods: we enrolled 53 patients presenting high IGF-1 and GHn<0.4 μg/L, assessed because of clinical suspicion of acromegaly or in other endocrinological contexts (e.g., pituitary incidentaloma). Clinical and hormonal data collected at the first and last visit were analyzed. Results: at the first evaluation, the mean age was 54.1±15.4 years, 34/53 were females, median IGF-1 and GHn were +3.1 SDS and 0.06 μg/L, respectively. In the whole group, over a median time of 6 years, IGF-1 and GHn levels did not significantly change (IGF-1 mean of differences -0.58, p=0.15; GHn +0.03, p=0.29). In patients with clinical features of acromegaly, the prevalence of acromegalic comorbidities was higher than in the others (median of 3 vs 1 comorbidities per patient, p=0.005), especially malignancies (36% vs 6%, p=0.03), and the clinical worsening overtime was more pronounced (4 vs 1 comorbidities at the last visit). Conclusions: in patients presenting high IGF-1 but GHn<0.4 μg/L, a hormonal progression is improbable, likely excluding classical acromegaly on its early stage. However, despite persistently low GH nadir values, patients with acromegalic features present more acromegalic comorbidities whose rate increases over time. Close clinical surveillance in this group is advised.

Characteristics and treatment outcomes of micromegaly – acromegaly with apparently normal basal GH: A retrospective study and literature review

“…Although our results differ from some studies that used higher normal bGH cutoff levels (Dimaraki et al 2002;Ribeiro-Oliveira et al 2011;Butz et al 2016;Gomes et al 2019), they coincide with the results of Machado et al (2008) and Espinosa de los Monteros et al (2018) (5.9% and 3%, respectively) (Table 3). It is important to note that few studies have defined micromegaly as high IGF-I level and nadir postglucose GH <0.4 ng/mL (Subbarayan et al 2012;Carosi et al 2021). Carosi et al (2021) have described twenty-five patients with acromegalic features with high IGF-I and nadir post-glucose GH <0.4 ng/mL ("micromegalic group"), comparing them with twenty-eight patients with high IGF-I levels and nadir post-glucose GH <0.4 ng/mL despite no clear clinical suspicion of acromegaly (Carosi et al 2021).…”

“…It is important to note that few studies have defined micromegaly as high IGF-I level and nadir postglucose GH <0.4 ng/mL (Subbarayan et al 2012;Carosi et al 2021). Carosi et al (2021) have described twenty-five patients with acromegalic features with high IGF-I and nadir post-glucose GH <0.4 ng/mL ("micromegalic group"), comparing them with twenty-eight patients with high IGF-I levels and nadir post-glucose GH <0.4 ng/mL despite no clear clinical suspicion of acromegaly (Carosi et al 2021). Interestingly, they found that the coexistence of acromegalic features and a nadir post-glucose GH ≥0.1 ng/mL were strongly associated with the presence of a high rate of acromegalic comorbidities (sensitivity=50%; specificity=86%) (Carosi et al 2021).…”

“…Carosi et al (2021) have described twenty-five patients with acromegalic features with high IGF-I and nadir post-glucose GH <0.4 ng/mL ("micromegalic group"), comparing them with twenty-eight patients with high IGF-I levels and nadir post-glucose GH <0.4 ng/mL despite no clear clinical suspicion of acromegaly (Carosi et al 2021). Interestingly, they found that the coexistence of acromegalic features and a nadir post-glucose GH ≥0.1 ng/mL were strongly associated with the presence of a high rate of acromegalic comorbidities (sensitivity=50%; specificity=86%) (Carosi et al 2021). Subbarayan et al (2012) have reported three patients with acromegaly with nadir post-glucose GH <0.4 ng/mL out of a total of 101 patients with acromegaly, finding a comparable micromegaly prevalence (3/101, 3.0%) (Subbarayan et al 2012).…”

Elevated insulin‐like growth factor‐1 in patients without clinical evidence of acromegaly

“…5 At present, the widely accepted diagnostic workup for acromegaly includes a screening IGF-1 and, if elevated, an oral glucose tolerance test (OGTT) with GH nadir of >1 μg/L or >0.4 μg/L depending on assay methodology. 6,7 The 2014 Endocrine Society Guidelines suggest using a GH cut off <1 μg/L is sufficient to exclude the diagnosis. 2 There are published series however, of patients with clinical features and histological evidence of acromegaly with elevated IGF-1 but adequate GH suppression during OGTT before treatment, leading to the term 'micromegaly'.…”

“…8 Case-based observations and previous studies suggest that elevated IGF-1 occurs in patients without clinical acromegaly. 7 Elevated IGF-1 in those without acromegaly has the potential to create unnecessary anxiety for patients, diagnostic uncertainty in clinical practice and can lead to financial costs for additional investigations. A retrospective case-control study was conducted to identify the frequency of IGF-1 elevation in a cohort of patients without clinically suspected GH excess in a single state-based reference laboratory (Pathology Queensland) over a 24-month period using the Diasorin Liaison XL chemiluminescence immunoassay.…”