The Many Faces of Acromegaly: Understanding Its Clinical and Biological Heterogeneity

Acromegaly, in 95% of cases resulting from a PitNET that hypersecretes growth hormone (GH), is constantly revisited in the literature due to the repercussions on morbidity and mortality and difficulties that persist in early diagnosis.

To shorten the interval between the onset of acromegaly manifestations and the diagnosis, our goal was to summarize the main situations that deviate from the typical presentation of the disease, highlighting the variability in phenotypic features, biochemical findings, and GH tumor expression. These non-classic findings contribute to the difficulties in managing the disease. The narrative literature review emphasized the diversity of presentations and recent and relevant publications.

The diagnosis of acromegaly can be challenging due to atypical clinical and biochemical presentations. Clinically, difficulties arise from the continuum of facial feature changes, which depend on several factors, including varying tissue sensitivity to excess GH. Biochemically, challenges include discordant GH and IGF-1 values, GH suppressibility in response to glucose, and borderline IGF-1 levels. There is also a wide range of immunohistochemical GH expressions in acromegaly, from complete absence of GH to rare multihormonal combinations. Awareness of these atypical forms of acromegaly presentation can improve early recognition and lead to timely diagnosis and management.