Objective: Somatotropinomae are classified as densely and sparsely granulated adenomae, which typically exhibit a perinuclear pattern (PP) and a dot pattern (DP) in cytokeratin (CK) immunostaining respectively. Some exhibit a mixed pattern (MP). We studied the relationship between these somatotropinoma subtypes and their clinico-pathological features. Methods: The study population consisted of 141 Japanese acromegalic patients. We evaluated their clinical presentation and their response to provocation tests with TRH and LHRH and to suppression (octreotide) test. Tumour tissues were subjected to immunostaining for CAM-5.2, MIB-1, CD34, E-cadherin (CDH1) and p53 (TP53). In 43 cases (30 non-DP and 13 DP), we analysed gsp mutations (constitutively activating mutations of the G s a protein that is encoded by GNAS gene). Results: The 141 adenomae were categorised into three subtypes based on their CK staining patterns; 30 (21.3%) exhibited DP, 83 (58.9%) exhibited PP, and 28 (19.9%) exhibited MP. Compared with the other subtypes, DP adenomae were significantly larger, and their E-cadherin expression and response to TRH, LHRH and octreotide challenge were lower. The postoperative cure rate tended to be lower in DP adenomae. gsp mutations were detected in 25 of 43 cases examined (58.1%); 20 of the 30 non-DP (66.7%) and 5 of the 13 DP tumours (38.5%) were affected by the mutation. Conclusion: DP somatotropinomae exhibit characteristic features. Compared with the non-DP subtypes, DP adenomae manifested a larger tumour size, a lower incidence of abnormal responses to TRH and LHRH challenge, a poor response to octreotide test and a lower expression of E-cadherin. gsp mutation was not exclusive for non-DP somatotropinomae.

In the course of 4 years, the size of the incidentalomas increased in 40% of 42 patients and became symptomatic in 20%. During the 5-year follow up, pituitary apoplexy developed in 9.5%. These findings may justify early intervention, especially in young individuals with incidentally found macroadenoma.

The incidence of intracranial aneurysm associated with pituitary adenoma is not definitely established although reported higher than in general population. This study was designed to find the existence of such association in a large series of pituitary adenoma cases. A retrospective study of 467 cases of pituitary adenoma (mean age: 41 +/- 15 years) was done. All patients underwent cerebral angiography at least of anterior circulation, detailed hormonal study, and 155 cases had additional magnetic resonance (MR) angiography. Twenty-five cases (5.4%) of pituitary adenoma (mean age 52 years) had intracranial aneurysm, 97% on anterior circulation, and 12% had multiple aneurysms. Two cases presented with aneurysmal rupture and the rest were incidental. Aneurysm was more frequently seen with increasing age (p < 0.001) and the age distribution resembled that of aneurysm among general population. Although the combination was most frequent among nonfunctioning adenoma (8.8%), and least frequent among prolactinoma (2.4%), this association was again due to age factor. There was no association between hormone secretion, size and invasive nature of the tumor. The results showed no association between intracranial aneurysm and pituitary adenoma. Our speculation is that such occurrence is merely a chance factor and the risk is no greater than that among general population.

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