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

Giulia Carosi,Giulia Del Sindaco,Elisa Sala,Alessandra Mangone,Giovanna Mantovani,Roberta Mungari,Emanuele Ferrante,Arianna Cremaschi,Maura Arosio

doi:10.1530/eje-21-0024

Abstract

ObjectiveHigh insulin-like growth factor 1 (IGF-1) and unsuppressed growth hormone (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).DesignRetrospective cohort study.MethodsWe 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.ResultsAt 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).ConclusionsIn patients presenting high IGF-1 but GHn < 0.4 μg/L, a hormonal progression is improbable, likely excluding classical acromegaly in 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 of this group is advised.

Highlights

Is a rare disease resulting from chronic exposure to high levels of growth hormone (GH) and its main mediator, insulin-like growth factor 1 (IGF1)
According to the international criteria, we considered in glucose metabolism alterations (GMA) impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM) [2, 28]
The other 28 patients (52.8%) had insulin-like growth factor 1 (IGF-1) measured for a variety of reasons, including seven pituitary adenomas (5 pituitary incidentalomas, macroadenomas conditioning neuroophthalmological symptoms), 11 suspected hypopituitarism (4 hypogonadism, 3 hypothyroidism, 2 GH-deficiency, 1 diabetes insipidus, 1 hypoadrenalism), three empty sella, one suspected Cushing disease, one sellar meningioma, one hyperprolactinemia, four other endocrinopathies (1 hyperandrogenism, 1 MEN-1, 1 adrenal tumor, 1 thyroid cancer)

Summary

Introduction

Is a rare disease resulting from chronic exposure to high levels of growth hormone (GH) and its main mediator, insulin-like growth factor 1 (IGF1). Increased morbidity and mortality are well documented in patients with active disease, mainly due to cardiovascular, neoplastic, respiratory, and metabolic comorbidities [3, 4, 5, 6]. The evaluation of IGF-1 is recommended as a screening test for acromegaly. In the presence of high IGF1, the diagnosis has to be confirmed by an inadequate GH suppression after an oral glucose tolerance test (OGTT). OGTT is generally diagnostic in the majority of patients. Some series reported acromegalic patients with adequate GH suppression [7, 8, 9, 10, 11, 12, 13]

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