Clinical, biological, radiological, and pathological comparison of sparsely and densely granulated somatotroph adenomas: a single center experience from a cohort of 131 patients with acromegaly.

PURPOSE: Growth hormone-producing pituitary adenomas are divided into two clinically relevant histologic subtypes, densely (DG-A) and sparsely (SG-A) granulated. Histologic subtype was evaluated in a large cohort of patients with acromegaly, separating DG-A and SG-A, and correlated with clinicopathological characteristics. METHODS: Patients with acromegaly undergoing surgery as initial therapy between 1995 and 2015 were identified. Histologic subtype was determined by keratin expression pattern with CAM5.2 and correlated with clinical and imaging parameters, somatostatin receptor subtype 2 (SST2) expression, post-surgical remission rate, and application of a prognostic scoring system incorporating proliferation and invasiveness. RESULTS: One hundred thirty-one patients were included. Tumors were classified as DG-A (75, 57.3%), SG-A (29, 22.1%), intermediate (I-A) (9, 6.9%), and unclassified (18, 13.7%) when CAM5.2 was negative. DG-A and I-A were combined for analysis (DG/I-A) and compared to SG-A. Age, gender, proliferation, and post-surgical remission did not differ. SG-A were larger [2 vs. 1.5 cm (median), p = 0.03], more frequently invasive [65.5% vs. 32.9%, p = 0.004], associated with higher MRI T2-weighted signal ratio [1.01 vs. 0.82 (median), p = 0.01], showed lower SST2 expression (p < 0.0001), and scored higher in the prognostic classification (p = 0.004). Surgical remission occurred in 41.7% DG/I-A and 41.4% SG-A (p = 1.0). On multivariate analysis, absence of invasion (p = 0.009) and lower pre-operative IGF-1 index (p = 0.0002) were associated with post-surgical remission. CONCLUSION: CAM5.2 allowed distinction between DG/I-A and SG-A in most but not all cases. Histologic subtype did not predict surgical outcome. Absence of invasion and lower pre-operative IGF-1 index were the only significant predictors of post-surgical remission in this cohort.

NECESSITY OF MULTIMODAL TREATMENT OF ACROMEGALY AND OUTCOMES.

OBJECTIVE: Uncontrolled acromegaly is associated with increased morbidity and mortality. Despite multimodal therapeutic options, adequate control can be challenging and lead to prolonged exposure to growth hormone excess. The aim of this study was to assess treatment patterns and outcomes in patients with acromegaly following surgery at a single institution. METHODS: A retrospective analysis of response to treatment modalities for patients with a new diagnosis of acromegaly at the Mayo Clinic in Rochester, Minnesota, from 1995-2015. RESULTS: A total of 245 patients with newly diagnosed acromegaly (mean age at diagnosis, 47 ± 14 years; mean follow-up, 5.5 ± 5 years) were evaluated. Primary surgical intervention was performed in 236 patients; 117 (54%) did not achieve remission. Among those with ≥3 months follow-up, 76/217 (35%) patients required three or more forms of treatment. Mean tumor size at diagnosis was 1.6 ± 0.8 cm (80% macroadenomas), and 35% (75/217) had cavernous sinus invasion on pre-operative imaging. The most common second-line treatment was radiation treatment (RT) (50%, 59/117). Among those with persistent disease following surgery, a normal insulin-like growth factor 1 (IGF-1) was achieved in 52% (61/117), with a median time to acromegaly control of 4.5 years. The rate of IGF-1 normalization was 2.1-fold higher in those who received RT compared to those who did not. CONCLUSION: In patients with persistent acromegaly following surgery, multiple treatment modalities, including RT, may be required to achieve remission. Treatment outcome uncertainty and the need for multiple interventions add to the disease burden associated with persistent acromegaly. ABBREVIATIONS: CI = confidence interval; GH = growth hormone; IGF-1 = insulin like growth factor-1; KM = Kaplan-Meier; RT = radiation treatment.

Pregnancy-related hypophysitis revisited.

OBJECTIVE: The aim of the study is to assess the distinguishing features of pregnancy-related hypophysitis (PR-Hy) compared to non-pregnancy autoimmune hypophysitis and to evaluate the changing therapeutic approaches and outcomes in PR-Hy over time. DESIGN: Retrospective analysis of all published cases with PR-Hy and 6 own cases. METHODS: A PubMed search was performed and abstracts screened for publications with information on cases with PR-Hy from which full-text review was performed. Clinical features, diagnostic findings, and outcome in relation to treatment modalities in PR-Hy were assessed. RESULTS: One hundred and forty-eight cases with PR-Hy were identified. PR-Hy was significantly delimited from non-PR-Hy by the frequent occurrence of the chiasmal syndrome (50% vs 13%, P < .0001), higher rate of intrasellar origin (94% vs 74%, P = .0005), lower rate of pituitary stalk involvement (39% vs 86%, P < .0001), and low rate of diabetes insipidus (12% vs 54%, P < .0001). The role of surgery in PR-Hy decreased over time while noninvasive treatment modalities increased. The recurrence rate after high-dose glucocorticoid therapy (33%) was high and exceeded that of surgery (2%) and conservative management (2%). In contrast to initial reports on PR-Hy, recent literature regarding outcome of mother's and child's health was positive. The frequency of spontaneous preterm delivery was not increased. Recurrent PR-Hy in a subsequent pregnancy was reported in only two females. CONCLUSION: PR-Hy has distinct features that delineate the disorder from non-PR-Hy. With increasing experience in diagnosis, availability of adequate replacement therapy, and improved treatment modalities, PR-Hy has lost its threat and the outcome is encouraging.