Endocrine Abstracts

Somatotroph adenomas causing acromegaly are histologically classified into densely and sparsely granulated subtypes and an intermediate, mixed type. Although the different subtypes are not currently taken into account when making decisions about the management of acromegaly, there is growing evidence that the subtypes represent clinically different entities.

In a cohort (n=52) of somatostatin-naïve patients with acromegaly, sparsely granulated adenomas were larger (P=0.038), found predominantly in younger (P=0.029), female patients (P=0.026) and exhibited higher proliferation indices and invasion of surrounding structures (P<0.0001 and P=0.001). Sparsely granulated adenomas also showed diminished responses to the octreotide suppression test compared to the densely granulated subtype (P=0.007). Codons 201 and 227 of Gsα and codon 49 of GHR were sequenced and the mutation status compared to clinical characteristics. There were no mutations at codon 49 of GHR in this cohort and mutation in Gsα did not co-segregate with granulation pattern. However, Gsα mutation was associated with smaller tumours (P=0.027) with a greater production of growth hormone (P=0.048) and more common satisfactory response to the octreotide suppression test (P=0.022). Immunohistochemical characterisation of the adherens junction complex in a subset of this cohort revealed an intact complex at the cell membranes of densely granulated adenomas that was disrupted in the sparsely granulated subtype. Disruption of cell–cell adhesion may underlie the poorly cohesive and more invasive features of sparsely granulated adenomas.

The granulation pattern of somatotroph adenomas is associated with differing clinical, histological and biochemical characteristics in this cohort. The sparsely granulated subtype represents a larger, more invasive tumour with disrupted cell–cell adhesion. Determination of the adenoma subtype may become an important consideration in the management of acromegaly.

Declaration of funding

This work was supported by the NIHR Oxford Biomedical Research Centre.