Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naive patients with somatotroph adenomas

Objective: Somatotroph adenomas causing acromegaly are histologically classified into densely granulated (DG) and sparsely granulated (SG) subtypes with different morphology, clinical characteristics and treatment outcomes. Granulation pattern has been reported to co-segregate with a recurrent mutation at codon 49 in growth hormone receptor (GHR) and GSP oncogene. This study examines response to the octreotide suppression test (OST) in relation to granulation pattern and mutation in GHR and GSP. Design: This is a retrospective, single-centre study of 52 patients with pathologically confirmed somatotroph adenoma who were naive to medical therapy presenting between January 2001 and October 2010. Methods: Clinical, radiological and hormonal data at diagnosis were recorded. GHR and GSP were genotyped, granulation pattern determined and response to the OST measured. Results: SG adenomas were larger (P = 0.038), occurred in younger patients (P = 0.029), were more common in females (P = 0.026) and were more invasive (P < 0.0001 and P = 0.001), with diminished responses to the OST (P = 0.007) compared with DG adenomas. GSP mutation was unrelated to granulation pattern but associated with smaller tumours (P = 0.027), producing more GH (P = 0.048) that responded better to the OST (P = 0.022). Codon 49 of GHR was not mutated. Conclusions: Adenoma histological phenotype, not genotype, corresponds to clinical and biochemical characteristics and response to the OST. SG adenomas constitute a clinically more unfavourable subtype but are not associated with GHR mutations in our series. Ascertainment of the adenoma subtype may become an important consideration in the management of acromegaly. European Journal of Endocrinology 168 491-499