Micromegaly: a distinct clinical entity? Insights from a monocentric cohort study.
The term "micromegaly" historically refers to patients with acromegalic features, elevated IGF-1, but normal growth hormone (GH) levels. The physiological mechanism, the appropriate clinical and treatment approaches, as well as its existence as a separate clinical entity are not well-defined.
We retrospectively collected clinical and hormonal data from 30 patients with acromegaly and 30 with micromegaly (displaying high IGF-1 but GH < 0.4 µg/L after glucose load), matched for age and sex. Data about acromegaly related comorbidities were collected (goiter, colonic polyps, malignancies, hypertension, cardiopathy, obstructive-sleep-apnea, carpal tunnel, and hyperglycemia). We performed a laboratory analysis of pituitary tissue samples from both groups, examining GH isoform expression and proliferative rate. We compared data of the two groups and described follow-up and treatment response in micromegalic patients.
Patients with acromegaly exhibited higher IGF-1 values at diagnosis (+8.3 vs. +3.2 SDS, p < 0.01) and higher GH nadir levels after glucose load (6 vs. 0.15 μg/L, p < 0.01). All patients with acromegaly had a detectable pituitary adenoma (70% macroadenomas), whereas 52% of patients with micromegaly showed no evidence of pituitary adenoma. Despite different GH/IGF-1 values, the prevalence of most comorbidities was similar in both groups, except for valve disease and diabetes mellitus, which were more frequent in acromegaly (valvopathy: 42.9% vs. 16.7%, p = 0.006; diabetes: 56.7% vs. 23.3%, p = 0.016, respectively). Laboratory analyses in patients with micromegaly indicated a lower proliferative profile in tumor cells (D3 cyclin expression).
Patients with a clinical diagnosis of acromegaly and high IGF-1 levels but a GH nadir < 0.4 µg/L following glucose load exhibit a high burden of comorbidities and therefore require appropriate screening and follow-up. Therapeutic strategies in these cases should be individualized, considering the frequent absence of neuroradiological findings, which may reflect a lower proliferative profile.
We retrospectively collected clinical and hormonal data from 30 patients with acromegaly and 30 with micromegaly (displaying high IGF-1 but GH < 0.4 µg/L after glucose load), matched for age and sex. Data about acromegaly related comorbidities were collected (goiter, colonic polyps, malignancies, hypertension, cardiopathy, obstructive-sleep-apnea, carpal tunnel, and hyperglycemia). We performed a laboratory analysis of pituitary tissue samples from both groups, examining GH isoform expression and proliferative rate. We compared data of the two groups and described follow-up and treatment response in micromegalic patients.
Patients with acromegaly exhibited higher IGF-1 values at diagnosis (+8.3 vs. +3.2 SDS, p < 0.01) and higher GH nadir levels after glucose load (6 vs. 0.15 μg/L, p < 0.01). All patients with acromegaly had a detectable pituitary adenoma (70% macroadenomas), whereas 52% of patients with micromegaly showed no evidence of pituitary adenoma. Despite different GH/IGF-1 values, the prevalence of most comorbidities was similar in both groups, except for valve disease and diabetes mellitus, which were more frequent in acromegaly (valvopathy: 42.9% vs. 16.7%, p = 0.006; diabetes: 56.7% vs. 23.3%, p = 0.016, respectively). Laboratory analyses in patients with micromegaly indicated a lower proliferative profile in tumor cells (D3 cyclin expression).
Patients with a clinical diagnosis of acromegaly and high IGF-1 levels but a GH nadir < 0.4 µg/L following glucose load exhibit a high burden of comorbidities and therefore require appropriate screening and follow-up. Therapeutic strategies in these cases should be individualized, considering the frequent absence of neuroradiological findings, which may reflect a lower proliferative profile.
Authors
Mangone Mangone, Carosi Carosi, Sala Sala, Marra Marra, Del Sindaco Del Sindaco, Mungari Mungari, Cremaschi Cremaschi, Lotito Lotito, Peverelli Peverelli, Ferrante Ferrante, Mantovani Mantovani
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