Endocrine Abstracts

Introduction: The diagnosis of acromegaly is confirmed in the presence of high IGF-1 levels and inadequate suppression of growth hormone (GH) after glucose load. According to guidelines, a GH nadir (GHn)>0.4 ng/ml is considered diagnostic with ultrasensitive assays. However, some acromegalic patients with lower GHn, also called ‘micromegalic’, are reported, but a systematic collection of their clinical features is unavailable.

Aim of the study: The main aim was to characterize a group of patients with high IGF1--levels but GHn < 0.4 ng/ml, focusing on acromegalic clinical features and comorbidities. The second one was to evaluate the clinical and hormonal progression over time.

Materials and methods: We performed a longitudinal retrospective study, including 49 patients referred to the Endocrinology Unit of the Ospedale Maggiore Policlinico, from 2009 to 2019, who presented high IGF-1 levels and GHn <0.4 ng/ml. GH was measured with an ultrasensitive assay. Data on typical acromegalic clinical features, comorbidities, pituitary imaging, IGF-1, GHn and GH random were collected, both at the time of the first finding of high IGF1 (diagnosis) and at the last follow up (FU).

Results: At diagnosis, mean age was 53.9 ± 16 s.d. years and 30/49 were females. Diagnostic evaluations started because of acromegalic facies in 45%, pituitary disease in 43% and various endocrinopathies in other ones. Patients with acromegalic facies showed a high prevalence of comorbidities, overlapping with those of classic acromegaly: glucose metabolism alterations in 82 vs 44% in patients with facies and without facies respectively, hypertension in 59 vs 28%, goiter in 50 vs 28%, carpal tunnel in 41 vs 4%, neoplasms in 41 vs 12%, cardiopathy in 36 vs 20%, colonic polyposis in 23 vs 16% (note that only 14 colonoscopies were performed). The ANOVA analysis showed that patients with a higher number of comorbidities had higher GHn levels (P 0.036) and GHn > 0.1 ng/ml was strongly associated with the presence of specific comorbidities (carpal tunnel OR 5.4, goiter OR 4.8 etc.). Pituitary imaging was available in 41/49 showing an adenoma in 16/41 (4 macro, 16 microadenomas) with other 4 new microadenomas at the last FU. Mean FU was 4.4 ± 3.2 years and we observed an increase of some comorbidities (hypertension + 20%, neoplasms + 20% and goiter + 16%), while IGF1 and GH levels did not significantly change.

Conclusions: Patients with acromegalic features, high IGF1 levels but a GH nadi r < 0.4 ng/ml, also called ‘micromegalic’, seem to clinically overlap with classic acromegaly. In our group, acromegalic facies and GHn > 0.1 ng/ml are strongly associated with comorbidities that, unlike IGF1 and GH, seem to worsen over time.